PMID- 21949453 OWN - NLM STAT- Publisher DA - 20110927 IS - 0138-9130 (Print) IS - 0138-9130 (Linking) VI - 88 IP - 3 DP - 2011 Sep TI - A comment to the paper by Waltman et al., Scientometrics, 87, 467-481, 2011. PG - 1011-1016 AB - In reaction to a previous critique (Opthof and Leydesdorff, J Informetr 4(3):423-430, 2010), the Center for Science and Technology Studies (CWTS) in Leiden proposed to change their old "crown" indicator in citation analysis into a new one. Waltman (Scientometrics 87:467-481, 2011a) argue that this change does not affect rankings at various aggregated levels. However, CWTS data is not publicly available for testing and criticism. Therefore, we comment by using previously published data of Van Raan (Scientometrics 67(3):491-502, 2006) to address the pivotal issue of how the results of citation analysis correlate with the results of peer review. A quality parameter based on peer review was neither significantly correlated with the two parameters developed by the CWTS in the past citations per paper/mean journal citation score (CPP/JCSm) or CPP/FCSm (citations per paper/mean field citation score) nor with the more recently proposed h-index (Hirsch, Proc Natl Acad Sci USA 102(46):16569-16572, 2005). Given the high correlations between the old and new "crown" indicators, one can expect that the lack of correlation with the peer-review based quality indicator applies equally to the newly developed ones. AU - Opthof T AU - Leydesdorff L LA - ENG PT - JOURNAL ARTICLE DEP - 20110617 TA - Scientometrics JT - Scientometrics JID - 7901197 PMC - PMC3153660 EDAT- 2011/09/29 06:00 MHDA- 2011/09/29 06:00 CRDT- 2011/09/28 06:00 PHST- 2011/05/11 [received] PHST- 2011/06/17 [epublish] AID - 10.1007/s11192-011-0424-8 [doi] AID - 424 [pii] PST - ppublish SO - Scientometrics. 2011 Sep;88(3):1011-1016. Epub 2011 Jun 17. PMID- 21793337 OWN - NLM STAT- MEDLINE DA - 20110728 DCOM- 20110809 IS - 0304-4920 (Print) IS - 0304-4920 (Linking) VI - 53 IP - 4 DP - 2010 Aug 31 TI - Impact factor of the Chinese Journal of Physiology in 2009: meet the readers. PG - 268-9 FAU - van der Heyden, Marcel A G AU - van der Heyden MA FAU - Opthof, Tobias AU - Opthof T LA - eng PT - Letter PL - China (Republic : 1949- ) TA - Chin J Physiol JT - The Chinese journal of physiology JID - 7804502 SB - IM MH - *Journal Impact Factor MH - Periodicals as Topic/*statistics & numerical data MH - *Physiology MH - Time Factors EDAT- 2011/07/29 06:00 MHDA- 2011/08/10 06:00 CRDT- 2011/07/29 06:00 PST - ppublish SO - Chin J Physiol. 2010 Aug 31;53(4):268-9. PMID- 21773742 OWN - NLM STAT- In-Data-Review DA - 20110727 IS - 1876-6250 (Electronic) IS - 1568-5888 (Linking) VI - 19 IP - 7-8 DP - 2011 Aug TI - One more time: bibliometric analysis of scientific output remains complicated. PG - 359-60 AD - Department of Clinical and Experimental Cardiology, Heart Failure Research Center, Academic Medical Center, Meibergdreef 9, Room K2-105, 1105, AZ, Amsterdam, the Netherlands, t.opthof@inter.nl.net. FAU - Opthof, T AU - Opthof T FAU - Wilde, A A M AU - Wilde AA LA - eng PT - Journal Article PL - Netherlands TA - Neth Heart J JT - Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation JID - 101095458 PMC - PMC3144329 OID - NLM: PMC3144329 EDAT- 2011/07/21 06:00 MHDA- 2011/07/21 06:00 CRDT- 2011/07/21 06:00 AID - 10.1007/s12471-011-0180-7 [doi] PST - ppublish SO - Neth Heart J. 2011 Aug;19(7-8):359-60. PMID- 21738508 OWN - NLM STAT- PubMed-not-MEDLINE DA - 20110708 DCOM- 20110714 LR - 20110801 IS - 1664-042X (Electronic) IS - 1664-042X (Linking) VI - 2 DP - 2011 TI - A single intracoronary injection of midkine reduces ischemia/reperfusion injury in Swine hearts: a novel therapeutic approach for acute coronary syndrome. PG - 27 AB - Several growth factors are effective for salvaging myocardium and limiting infarct size in experimental studies with small animals. Their benefit in large animals and feasibility in clinical practice remains to be elucidated. We investigated the cardioprotective effect of midkine (MK) in swine subjected to ischemia/reperfusion (I/R). I/R was created by left anterior descending coronary artery occlusion for 45 min using a percutaneous over-the-wire balloon catheter. MK protein was injected as a bolus through the catheter at the initiation of reperfusion [MK-treated (MKT) group]. Saline was injected in controls (CONT). Infarct size/area at risk (24 h after I/R) in MKT was almost five times smaller than in CONT. Echocardiography in MKT revealed a significantly higher percent wall thickening of the interventricular septum, a higher left ventricular (LV) fractional shortening, and a lower E/e(') (ratio of transmitral to annular flow) compared with CONT. LV catheterization in MKT showed a lower LV end-diastolic pressure, and a higher dP/dt(max) compared with CONT. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling-positive myocytes and CD45-positive cell infiltration in the peri-infarct area were significantly less in MKT than in CONT. Here, we demonstrate that a single intracoronary injection of MK protein in swine hearts at the onset of reperfusion dramatically reduces infarct size and ameliorates systolic/diastolic LV function. This beneficial effect is associated with a reduction of apoptotic and inflammatory reactions. MK application during percutaneous coronary intervention may become a promising adjunctive therapy in acute coronary syndromes. AD - Research Institute of Environmental Medicine, Nagoya University Nagoya, Japan. FAU - Ishiguro, Hisaaki AU - Ishiguro H FAU - Horiba, Mitsuru AU - Horiba M FAU - Takenaka, Hiroharu AU - Takenaka H FAU - Sumida, Arihiro AU - Sumida A FAU - Opthof, Tobias AU - Opthof T FAU - Ishiguro, Yuko S AU - Ishiguro YS FAU - Kadomatsu, Kenji AU - Kadomatsu K FAU - Murohara, Toyoaki AU - Murohara T FAU - Kodama, Itsuo AU - Kodama I LA - eng PT - Journal Article DEP - 20110623 PL - Switzerland TA - Front Physiol JT - Frontiers in physiology JID - 101549006 PMC - PMC3125584 OID - NLM: PMC3125584 EDAT- 2011/07/09 06:00 MHDA- 2011/07/09 06:01 CRDT- 2011/07/09 06:00 PHST- 2010/07/02 [received] PHST- 2011/06/04 [accepted] PHST- 2011/06/23 [epublish] AID - 10.3389/fphys.2011.00027 [doi] PST - ppublish SO - Front Physiol. 2011;2:27. Epub 2011 Jun 23. PMID- 21722855 OWN - NLM STAT- In-Process DA - 20110704 IS - 1556-3871 (Electronic) IS - 1547-5271 (Linking) VI - 8 IP - 7 DP - 2011 Jul TI - Rebuttal to M cells are present in the ventricular myocardium. Counterpoint. PG - 1100 AD - Heart Failure Research Center, Academic Medical Center, Amsterdam, The Netherlands. FAU - Janse, Michiel J AU - Janse MJ FAU - Coronel, Ruben AU - Coronel R FAU - Opthof, Tobias AU - Opthof T LA - eng PT - Comment PT - Journal Article PL - United States TA - Heart Rhythm JT - Heart rhythm : the official journal of the Heart Rhythm Society JID - 101200317 SB - IM CON - Heart Rhythm. 2011 Jul;8(7):1099. PMID: 21722854 EDAT- 2011/07/05 06:00 MHDA- 2011/07/05 06:00 CRDT- 2011/07/05 06:00 PHST- 2011/01/23 [received] AID - S1547-5271(11)00541-8 [pii] AID - 10.1016/j.hrthm.2011.04.028 [doi] PST - ppublish SO - Heart Rhythm. 2011 Jul;8(7):1100. PMID- 21700087 OWN - NLM STAT- MEDLINE DA - 20110624 DCOM- 20110824 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 58 IP - 1 DP - 2011 Jun 28 TI - Reconstituted high-density lipoprotein shortens cardiac repolarization. PG - 40-4 AB - OBJECTIVES: We hypothesize that increasing high-density lipoprotein cholesterol (HDL-C) shortens cardiac repolarization. BACKGROUND: HDL-C is inversely associated with sudden death. The relation between HDL-C and repolarization of the heart is unexplored. METHODS: HDL-C was elevated with reconstituted high-density lipoprotein (rHDL). Cardiac repolarization was studied by recording cardiac transmembrane potentials with the patch clamp technique from isolated rabbit cardiomyocytes that were superfused with rHDL. Infusions with rHDL (40 mg/kg body weight) were performed in dyslipidemic patients and healthy volunteers. Electrocardiograms were recorded to assess cardiac repolarization before and 24 h after infusion with rHDL. RESULTS: rHDL as well as purified human apolipoprotein AI shortened repolarization of isolated rabbit cardiomyocytes by approximately 25% (p < 0.05). rHDL infusion shortened the heart rate-corrected QT interval on surface electrocardiograms in all participants (p < 0.001). CONCLUSIONS: rHDL shortens cardiac repolarization. These data provide evidence for a novel mechanism of HDL infusion that may contribute to reduction of sudden cardiac death. CI - Copyright (c) 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. AD - Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands. FAU - Den Ruijter, Hester M AU - Den Ruijter HM FAU - Franssen, Remco AU - Franssen R FAU - Verkerk, Arie O AU - Verkerk AO FAU - van Wijk, Diederik F AU - van Wijk DF FAU - Vaessen, Stefan F AU - Vaessen SF FAU - Holleboom, Adriaan G AU - Holleboom AG FAU - Levels, Johannes H AU - Levels JH FAU - Opthof, Tobias AU - Opthof T FAU - Sungnoon, Rattapong AU - Sungnoon R FAU - Stroes, Erik S AU - Stroes ES FAU - Kuivenhoven, Jan Albert AU - Kuivenhoven JA FAU - Coronel, Ruben AU - Coronel R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 0 (Apolipoprotein A-I) RN - 0 (Cholesterol, HDL) SB - AIM SB - IM CIN - J Am Coll Cardiol. 2011 Jun 28;58(1):45-7. PMID: 21700088 MH - Adult MH - Aged MH - Animals MH - Apolipoprotein A-I/metabolism MH - Atherosclerosis/metabolism MH - Case-Control Studies MH - Cholesterol, HDL/*metabolism MH - Coronary Disease/*physiopathology MH - Death, Sudden MH - Dyslipidemias/metabolism MH - Electrocardiography/methods MH - Female MH - Heart/*physiology MH - Heart Conduction System/*physiopathology MH - Heart Rate MH - Humans MH - Male MH - Middle Aged MH - Myocytes, Cardiac/*cytology MH - Patch-Clamp Techniques MH - Rabbits MH - Ventricular Fibrillation/metabolism EDAT- 2011/06/28 06:00 MHDA- 2011/08/25 06:00 CRDT- 2011/06/25 06:00 PHST- 2010/11/01 [received] PHST- 2010/11/19 [accepted] AID - S0735-1097(11)01345-3 [pii] AID - 10.1016/j.jacc.2010.11.072 [doi] PST - ppublish SO - J Am Coll Cardiol. 2011 Jun 28;58(1):40-4. PMID- 21567267 OWN - NLM STAT- In-Process DA - 20110531 IS - 1741-0444 (Electronic) IS - 0140-0118 (Linking) VI - 49 IP - 6 DP - 2011 Jun TI - Differences in citation frequency of clinical and basic science papers in cardiovascular research. PG - 613-21 AB - In this article, a critical analysis is performed on differences in citation frequency of basic and clinical cardiovascular papers. It appears that the latter papers are cited at about 40% higher frequency. The differences between the largest number of citations of the most cited papers are even larger. It is also demonstrated that the groups of clinical and basic cardiovascular papers are also heterogeneous concerning citation frequency. It is concluded that none of the existing citation indicators appreciates these differences. At this moment these indicators should not be used for quality assessment of individual scientists and scientific niches with small numbers of scientists. FAU - Opthof, Tobias AU - Opthof T LA - eng PT - Editorial DEP - 20110513 PL - United States TA - Med Biol Eng Comput JT - Medical & biological engineering & computing JID - 7704869 SB - IM PMC - PMC3104007 OID - NLM: PMC3104007 EDAT- 2011/05/14 06:00 MHDA- 2011/05/14 06:00 CRDT- 2011/05/14 06:00 PHST- 2011/01/14 [received] PHST- 2011/04/20 [accepted] PHST- 2011/05/13 [aheadofprint] AID - 10.1007/s11517-011-0783-6 [doi] PST - ppublish SO - Med Biol Eng Comput. 2011 Jun;49(6):613-21. Epub 2011 May 13. PMID- 21526387 OWN - NLM STAT- In-Data-Review DA - 20110504 IS - 1876-6250 (Electronic) IS - 1568-5888 (Linking) VI - 19 IP - 5 DP - 2011 May TI - Bibliometric data in clinical cardiology revisited. The case of 37 Dutch professors. PG - 246-55 AB - In this paper, we assess the bibliometric parameters of 37 Dutch professors in clinical cardiology. Those are the Hirsch index (h-index) based on all papers, the h-index based on first authored papers, the number of papers, the number of citations and the citations per paper. A top 10 for each of the five parameters was compiled. In theory, the same 10 professors might appear in each of these top 10s. Alternatively, each of the 37 professors under assessment could appear one or more times. In practice, we found 22 out of these 37 professors in the 5 top 10s. Thus, there is no golden parameter. In addition, there is too much inhomogeneity in citation characteristics even within a relatively homogeneous group of clinical cardiologists. Therefore, citation analysis should be applied with great care in science policy. This is even more important when different fields of medicine are compared in university medical centres. It may be possible to develop better parameters in the future, but the present ones are simply not good enough. Also, we observed a quite remarkable explosion of publications per author which can, paradoxical as it may sound, probably not be interpreted as an increase in productivity of scientists, but as the effect of an increase in the number of co-authors and the strategic effect of networks. AD - Department of Clinical and Experimental Cardiology, Heart Failure Research Center, Academic Medical Center, Meibergdreef 9, Room K2-105, 1105 AZ, Amsterdam, the Netherlands, t.opthof@inter.nl.net. FAU - Opthof, T AU - Opthof T FAU - Wilde, A A M AU - Wilde AA LA - eng PT - Journal Article PL - Netherlands TA - Neth Heart J JT - Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation JID - 101095458 PMC - PMC3087028 OID - NLM: PMC3087028 EDAT- 2011/04/29 06:00 MHDA- 2011/04/29 06:00 CRDT- 2011/04/29 06:00 AID - 10.1007/s12471-011-0128-y [doi] PST - ppublish SO - Neth Heart J. 2011 May;19(5):246-55. PMID- 21241826 OWN - NLM STAT- In-Process DA - 20110530 IS - 1556-3871 (Electronic) IS - 1547-5271 (Linking) VI - 8 IP - 6 DP - 2011 Jun TI - Counterpoint: M cells do not have a functional role in the ventricular myocardium of the intact heart. PG - 934-7 AD - The Experimental Cardiology Group, Center for Heart Failure Research, Academic Medical Center, Amsterdam, The Netherlands. FAU - Janse, Michiel J AU - Janse MJ FAU - Coronel, Ruben AU - Coronel R FAU - Opthof, Tobias AU - Opthof T LA - eng PT - Journal Article DEP - 20110115 PL - United States TA - Heart Rhythm JT - Heart rhythm : the official journal of the Heart Rhythm Society JID - 101200317 SB - IM CIN - Heart Rhythm. 2011 Jul;8(7):1099. PMID: 21722854 CIN - Heart Rhythm. 2011 Jun;8(6):930-3. PMID: 21241824 EDAT- 2011/01/19 06:00 MHDA- 2011/01/19 06:00 CRDT- 2011/01/19 06:00 PHST- 2011/10/12 [received] PHST- 2011/10/15 [accepted] PHST- 2011/01/15 [aheadofprint] AID - S1547-5271(11)00039-7 [pii] AID - 10.1016/j.hrthm.2010.10.048 [doi] PST - ppublish SO - Heart Rhythm. 2011 Jun;8(6):934-7. Epub 2011 Jan 15. PMID- 21187646 OWN - NLM STAT- MEDLINE DA - 20101228 DCOM- 20110411 LR - 20110422 IS - 1880-313X (Electronic) IS - 0388-6107 (Linking) VI - 31 IP - 6 DP - 2010 TI - Glial cell line-derived neurotrophic factor (GDNF) enhances sympathetic neurite growth in rat hearts at early developmental stages. PG - 353-61 AB - Molecular signaling of sympathetic innervation of myocardium is an unresolved issue. The purpose of this study was to investigate the effect of neurotrophic factors on sympathetic neurite growth towards cardiomyocytes. Cardiomyocytes (CMs) and sympathetic neurons (SNs) were isolated from neonatal rat hearts and superior cervical ganglia, and were co-cultured, either in a random or localized way. Neurite growth from SNs toward CMs was assessed by immunohistochemistry for neurofilament M and alpha-actinin in response to neurotrophic factors-nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF) and a chemical repellent, semaphorin 3A. As a result, GDNF as well as NGF and BDNF stimulated neurite growth. GDNF enhanced neurite outgrowth even under the NGF-depleted culture condition, excluding an indirect effect of GDNF via NGF. Quantification of mRNA and protein by real-time PCR and immunohistochemistry at different developmental stages revealed that GDNF is abundantly expressed in the hearts of embryos and neonates, but not in adult hearts. GDNF plays an important role in inducing cardiac sympathetic innervation at the early developmental stages. A possible role in (re)innervation of injured or transplanted or cultured and transplanted myocardium may deserve investigation. AD - Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan. FAU - Miwa, Keiko AU - Miwa K FAU - Lee, Jong-Kook AU - Lee JK FAU - Takagishi, Yoshiko AU - Takagishi Y FAU - Opthof, Tobias AU - Opthof T FAU - Fu, Xianming AU - Fu X FAU - Kodama, Itsuo AU - Kodama I LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Japan TA - Biomed Res JT - Biomedical research (Tokyo, Japan) JID - 8100317 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Ciliary Neurotrophic Factor) RN - 0 (Gdnf protein, rat) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 11003-00-2 (Actinin) RN - 9061-61-4 (Nerve Growth Factor) SB - IM MH - Actinin MH - Animals MH - Animals, Newborn MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cells, Cultured MH - Ciliary Neurotrophic Factor/metabolism MH - Ganglia/cytology MH - Gene Expression Regulation, Developmental MH - Glial Cell Line-Derived Neurotrophic Factor/*metabolism MH - Heart/*embryology MH - Myocytes, Cardiac/*cytology MH - Nerve Growth Factor/metabolism MH - Neurites/*physiology MH - Neurons/metabolism MH - Rats MH - Rats, Wistar MH - Sympathetic Nervous System/*cytology/metabolism EDAT- 2010/12/29 06:00 MHDA- 2011/04/13 06:00 CRDT- 2010/12/29 06:00 AID - JST.JSTAGE/biomedres/31.353 [pii] PST - ppublish SO - Biomed Res. 2010;31(6):353-61. PMID- 21157118 OWN - NLM STAT- MEDLINE DA - 20110124 DCOM- 20110624 IS - 1347-8648 (Electronic) IS - 1347-8613 (Linking) VI - 115 IP - 1 DP - 2011 TI - Bepridil facilitates early termination of spiral-wave reentry in two-dimensional cardiac muscle through an increase of intercellular electrical coupling. PG - 15-26 AB - Bepridil is effective for conversion of atrial fibrillation to sinus rhythm and in the treatment of drug-refractory ventricular tachyarrhythmias. We investigated the effects of bepridil on electrophysiological properties and spiral-wave (SW) reentry in a 2-dimensional ventricular muscle layer of isolated rabbit hearts by optical mapping. Ventricular tachycardia (VT) induced in the presence of bepridil (1 microM) terminated earlier than in the control. Bepridil increased action potential duration (APD) by 5% - 8% under constant pacing and significantly increased the space constant. There was a linear relationship between the wavefront curvature (kappa) and local conduction velocity: LCV = LCV - D.kappa (D, diffusion coefficient; LCV, LCV at kappa = 0). Bepridil significantly increased D and LCV. The regression lines with and without bepridil crossed at kappa = 20 - 40 cm(1), resulting in a paradoxical decrease of LCV at kappa > 40 cm(1). Dye transfer assay in cultured rat cardiomyocytes confirmed that bepridil increased intercellular coupling. SW reentry in the presence of bepridil was characterized by decremental conduction near the rotation center, prominent drift, and self-termination by collision with boundaries. These results indicate that bepridil causes an increase of intercellular coupling and a moderate APD prolongation, and this combination compromises wavefront propagation near the rotation center of SW reentry, leading to its drift and early termination. AD - Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Japan. FAU - Takanari, Hiroki AU - Takanari H FAU - Honjo, Haruo AU - Honjo H FAU - Takemoto, Yoshio AU - Takemoto Y FAU - Suzuki, Tomoyuki AU - Suzuki T FAU - Kato, Sara AU - Kato S FAU - Harada, Masahide AU - Harada M FAU - Okuno, Yusuke AU - Okuno Y FAU - Ashihara, Takashi AU - Ashihara T FAU - Opthof, Tobias AU - Opthof T FAU - Sakuma, Ichiro AU - Sakuma I FAU - Kamiya, Kaichiro AU - Kamiya K FAU - Kodama, Itsuo AU - Kodama I LA - eng PT - In Vitro PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101209 PL - Japan TA - J Pharmacol Sci JT - Journal of pharmacological sciences JID - 101167001 RN - 0 (Anti-Arrhythmia Agents) RN - 64706-54-3 (Bepridil) SB - IM MH - Action Potentials/drug effects MH - Animals MH - Anti-Arrhythmia Agents/*pharmacology MH - Bepridil/*pharmacology/therapeutic use MH - Cells, Cultured MH - Electrophysiological Phenomena/*drug effects MH - Heart/*physiology MH - Heart Conduction System/physiology MH - Myocytes, Cardiac/physiology MH - Rabbits MH - Rats MH - Stimulation, Chemical MH - Tachycardia, Ventricular/drug therapy/physiopathology EDAT- 2010/12/16 06:00 MHDA- 2011/06/28 06:00 CRDT- 2010/12/16 06:00 PHST- 2010/12/09 [aheadofprint] AID - JST.JSTAGE/jphs/10233FP [pii] PST - ppublish SO - J Pharmacol Sci. 2011;115(1):15-26. Epub 2010 Dec 9. PMID- 20551422 OWN - NLM STAT- MEDLINE DA - 20100616 DCOM- 20100709 LR - 20101118 IS - 1941-3084 (Electronic) IS - 1941-3084 (Linking) VI - 3 IP - 3 DP - 2010 Jun 1 TI - The Brugada ECG pattern: a marker of channelopathy, structural heart disease, or neither? Toward a unifying mechanism of the Brugada syndrome. PG - 283-90 AD - Heart Failure Research Center, Department of Cardiology and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. m.g.hoogendijk@amc.uva.nl FAU - Hoogendijk, Mark G AU - Hoogendijk MG FAU - Opthof, Tobias AU - Opthof T FAU - Postema, Pieter G AU - Postema PG FAU - Wilde, Arthur A M AU - Wilde AA FAU - de Bakker, Jacques M T AU - de Bakker JM FAU - Coronel, Ruben AU - Coronel R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United States TA - Circ Arrhythm Electrophysiol JT - Circulation. Arrhythmia and electrophysiology JID - 101474365 RN - 0 (Ion Channels) SB - IM CIN - Circ Arrhythm Electrophysiol. 2010 Jun 1;3(3):280-2. PMID: 20551421 MH - Animals MH - Brugada Syndrome/diagnosis/*etiology/metabolism/physiopathology MH - *Electrocardiography MH - Genetic Predisposition to Disease MH - Heart Diseases/*complications/metabolism/physiopathology MH - Humans MH - Ion Channels/genetics/*metabolism MH - Mutation MH - Predictive Value of Tests MH - Risk Factors RF - 88 EDAT- 2010/06/17 06:00 MHDA- 2010/07/10 06:00 CRDT- 2010/06/17 06:00 AID - 3/3/283 [pii] AID - 10.1161/CIRCEP.110.937029 [doi] PST - ppublish SO - Circ Arrhythm Electrophysiol. 2010 Jun 1;3(3):283-90. PMID- 20385252 OWN - NLM STAT- MEDLINE DA - 20100726 DCOM- 20101215 LR - 20110309 IS - 1556-3871 (Electronic) IS - 1547-5271 (Linking) VI - 7 IP - 8 DP - 2010 Aug TI - Cardiac expression of skeletal muscle sodium channels increases longitudinal conduction velocity in the canine 1-week myocardial infarction. PG - 1104-10 AB - BACKGROUND: Skeletal muscle sodium channel (Nav1.4) expression in border zone myocardium increases action potential upstroke velocity in depolarized isolated tissue. Because resting membrane potential in the 1-week canine infarct is reduced, we hypothesized that conduction velocity (CV) is greater in Nav1.4 dogs compared with in control dogs. OBJECTIVE: The purpose of this study was to measure CV in the infarct border zone border in dogs with and without Nav1.4 expression. METHODS: Adenovirus was injected in the infarct border zone in 34 dogs. The adenovirus incorporated the Nav1.4- and a green fluorescent protein (GFP) gene (Nav1.4 group, n = 16) or only GFP (n = 18). After 1 week, upstroke velocity and CV were measured by sequential microelectrode recordings at 4 and 7 mM [K(+)] in superfused epicardial slabs. High-density in vivo epicardial activation mapping was performed in a subgroup (8 Nav1.4, 6 GFP) at three to four locations in the border zone. Microscopy and antibody staining confirmed GFP or Nav1.4 expression. RESULTS: Infarct sizes were similar between groups (30.6% +/- 3% of left ventricle mass, mean +/- standard error of the mean). Longitudinal CV was greater in Nav1.4 than in GFP sites (58.5 +/- 1.8 vs. 53.3 +/- 1.2 cm/s, 20 and 15 sites, respectively; P <.05). Transverse CV was not different between the groups. In tissue slabs, dV/dt(max) was higher and CV was greater in Nav1.4 than in control at 7 mM [K(+)] (P <.05). Immunohistochemical Nav1.4 staining was seen at the longitudinal ends of the myocytes. CONCLUSION: Nav1.4 channels in myocardium surviving 1 week infarction increases longitudinal but not transverse CV, consistent with the increased dV/dt(max) and with the cellular localization of Nav1.4. CI - Copyright 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved. AD - Experimental Cardiology Group, Center for Heart Failure Research, Academic Medical Center, Amsterdam, The Netherlands. r.coronel@amc.nl FAU - Coronel, Ruben AU - Coronel R FAU - Lau, David H AU - Lau DH FAU - Sosunov, Eugene A AU - Sosunov EA FAU - Janse, Michiel J AU - Janse MJ FAU - Danilo, Peter Jr AU - Danilo P Jr FAU - Anyukhovsky, Evgeny P AU - Anyukhovsky EP FAU - Wilms-Schopman, Francien J G AU - Wilms-Schopman FJ FAU - Opthof, Tobias AU - Opthof T FAU - Shlapakova, Iryna N AU - Shlapakova IN FAU - Ozgen, Nazira AU - Ozgen N FAU - Prestia, Kevin AU - Prestia K FAU - Kryukova, Yelena AU - Kryukova Y FAU - Cohen, Ira S AU - Cohen IS FAU - Robinson, Richard B AU - Robinson RB FAU - Rosen, Michael R AU - Rosen MR LA - eng GR - HL094410/HL/NHLBI NIH HHS/United States GR - R01 HL094410-03/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20100410 PL - United States TA - Heart Rhythm JT - Heart rhythm : the official journal of the Heart Rhythm Society JID - 101200317 RN - 0 (Sodium Channels) SB - IM CIN - Heart Rhythm. 2010 Aug;7(8):1111-2. PMID: 20466071 MH - Action Potentials MH - Animals MH - Disease Models, Animal MH - Dogs MH - Heart Conduction System/*physiopathology MH - Muscle, Skeletal/*physiology MH - Myocardial Infarction/*physiopathology MH - Sodium Channels/*biosynthesis EDAT- 2010/04/14 06:00 MHDA- 2010/12/16 06:00 CRDT- 2010/04/14 06:00 PHST- 2009/12/07 [received] PHST- 2010/04/02 [accepted] PHST- 2010/04/10 [aheadofprint] AID - S1547-5271(10)00345-0 [pii] AID - 10.1016/j.hrthm.2010.04.009 [doi] PST - ppublish SO - Heart Rhythm. 2010 Aug;7(8):1104-10. Epub 2010 Apr 10. PMID- 20180941 OWN - NLM STAT- MEDLINE DA - 20100414 DCOM- 20100729 LR - 20110727 IS - 1476-5381 (Electronic) IS - 0007-1188 (Linking) VI - 159 IP - 7 DP - 2010 Apr TI - The anti-protozoal drug pentamidine blocks KIR2.x-mediated inward rectifier current by entering the cytoplasmic pore region of the channel. PG - 1532-41 AB - Background and purpose: Pentamidine is a drug used in treatment of protozoal infections. Pentamidine treatment may cause sudden cardiac death by provoking cardiac arrhythmias associated with QTc prolongation and U-wave alterations. This proarrhythmic effect was linked to inhibition of hERG trafficking, but not to acute block of ion channels contributing to the action potential. Because the U-wave has been linked to the cardiac inward rectifier current (I(K1)), we examined the action and mechanism of pentamidine-mediated I(K1) block. Experimental approach: Patch clamp measurements of I(K1) were made on cultured adult canine ventricular cardiomyocytes, K(IR)2.1-HEK293 cells and K(IR)2.x inside-out patches. Pentamidine binding to cytoplasmic amino acid residues of K(IR)2.1 channels was studied by molecular modelling. Key results: Pentamidine application (24 h) decreased I(K1) in cultured canine cardiomyocytes and K(IR)2.1-HEK293 cells under whole cell clamp conditions. Pentamidine inhibited I(K1) in K(IR)2.1-HEK293 cells 10 min after application. When applied to the cytoplasmic side under inside-out patch clamp conditions, pentamidine block of I(K1) was acute (IC(50)= 0.17 microM). Molecular modelling predicted pentamidine-channel interactions in the cytoplasmic pore region of K(IR)2.1 at amino acids E224, D259 and E299. Mutation of these conserved residues to alanine reduced pentamidine block of I(K1). Block was independent of the presence of spermine. K(IR)2.2, and K(IR)2.3 based I(K1) was also sensitive to pentamidine blockade. Conclusions and implications: Pentamidine inhibits cardiac I(K1) by interacting with three negatively charged amino acids in the cytoplasmic pore region. Our findings may provide new insights for development of specific I(K1) blocking compounds. AD - Department of Medical Physiology, Division Heart & Lungs, UMCU, Utrecht, The Netherlands. FAU - de Boer, T P AU - de Boer TP FAU - Nalos, L AU - Nalos L FAU - Stary, A AU - Stary A FAU - Kok, B AU - Kok B FAU - Houtman, M J C AU - Houtman MJ FAU - Antoons, G AU - Antoons G FAU - van Veen, T A B AU - van Veen TA FAU - Beekman, J D M AU - Beekman JD FAU - de Groot, B L AU - de Groot BL FAU - Opthof, T AU - Opthof T FAU - Rook, M B AU - Rook MB FAU - Vos, M A AU - Vos MA FAU - van der Heyden, M A G AU - van der Heyden MA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100224 PL - England TA - Br J Pharmacol JT - British journal of pharmacology JID - 7502536 RN - 0 (Antiprotozoal Agents) RN - 0 (Kir2.1 channel) RN - 0 (Potassium Channels, Inwardly Rectifying) RN - 100-33-4 (Pentamidine) SB - IM MH - Animals MH - Antiprotozoal Agents/*pharmacology MH - Blotting, Western MH - Cell Line MH - Cytoplasm/*drug effects/metabolism MH - Dogs MH - Humans MH - Mutation MH - Patch-Clamp Techniques MH - Pentamidine/*pharmacology MH - Potassium Channels, Inwardly Rectifying/*antagonists & inhibitors/genetics PMC - PMC2850409 OID - NLM: PMC2850409 EDAT- 2010/02/26 06:00 MHDA- 2010/07/30 06:00 CRDT- 2010/02/26 06:00 PHST- 2010/02/24 [aheadofprint] AID - BPH658 [pii] AID - 10.1111/j.1476-5381.2010.00658.x [doi] PST - ppublish SO - Br J Pharmacol. 2010 Apr;159(7):1532-41. Epub 2010 Feb 24. PMID- 20147846 OWN - NLM STAT- MEDLINE DA - 20100421 DCOM- 20100927 IS - 1533-4023 (Electronic) IS - 0160-2446 (Linking) VI - 55 IP - 4 DP - 2010 Apr TI - Comparative study of nifekalant versus amiodarone for shock-resistant ventricular fibrillation in out-of-hospital cardiopulmonary arrest patients. PG - 391-8 AB - BACKGROUND: In Japan, intravenous nifekalant (NIF) was often used for direct current cardioversion-resistant ventricular fibrillation (VF), until the use of intravenous amiodarone (AMD) was approved in 2007. The defibrillatory efficacy of NIF and AMD has thus far not been compared for resuscitation. METHODS AND RESULTS: Between August 2007 and April 2009, 403 consecutive out-of-hospital patients with cardiopulmonary arrest were transferred to the Emergency Medical Service of Tokai University. Of these, 30 patients with first defibrillation failure or VF recurrence were enrolled for this NIF/AMD study. The final defibrillation success (and hospital survival rate) was 67% (10/15) in the AMD and 47% (7/15) in the NIF group. The discharge survival rate was 53% (8/15) in the AMD and 21% (4/15) in the NIF group (P = 0.06). Notably, all 4 survivors in the NIF group could take up normal daily life again, whereas this was restricted to only 2 patients from the 11 survivors in the AMD group. The difference is probably partly attributable to longer time from AMD administration to defibrillation success compared with NIF. In the cases of defibrillation failure, VF continued in 4/8 by NIF, however, asystole or pulseless electrical activity occurred in 4/5 patients by AMD. CONCLUSIONS: AMD may be borderline superior over NIF to facilitate defibrillation in out-of-hospital patients with cardiopulmonary arrest. However, from the view point of preservation of brain function, NIF is not inferior to AMD for CPR. AD - Department of Cardiology, Tokai University School of Medicine, Isehara, Japan. mariam@is.icc.u-tokai.ac.jp FAU - Amino, Mari AU - Amino M FAU - Yoshioka, Koichiro AU - Yoshioka K FAU - Opthof, Tobias AU - Opthof T FAU - Morita, Seiji AU - Morita S FAU - Uemura, Shunryo AU - Uemura S FAU - Tamura, Kozo AU - Tamura K FAU - Fukushima, Tomokazu AU - Fukushima T FAU - Higami, Shigeo AU - Higami S FAU - Otsuka, Hiroyuki AU - Otsuka H FAU - Akieda, Kazuki AU - Akieda K FAU - Shima, Makiyoshi AU - Shima M FAU - Fujibayashi, Daisuke AU - Fujibayashi D FAU - Hashida, Tadashi AU - Hashida T FAU - Inokuchi, Sadaki AU - Inokuchi S FAU - Kodama, Itsuo AU - Kodama I FAU - Tanabe, Teruhisa AU - Tanabe T LA - eng PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cardiovasc Pharmacol JT - Journal of cardiovascular pharmacology JID - 7902492 RN - 0 (Anti-Arrhythmia Agents) RN - 0 (Pyrimidinones) RN - 130656-51-8 (MS 551) RN - 1951-25-3 (Amiodarone) SB - IM MH - Aged MH - Amiodarone/administration & dosage/adverse effects/*therapeutic use MH - Anti-Arrhythmia Agents/administration & dosage/adverse effects/therapeutic use MH - Drug Therapy, Combination MH - *Electric Countershock MH - *Emergency Service, Hospital MH - Female MH - Heart Arrest/*drug therapy/etiology/therapy MH - Heart Diseases/complications MH - Humans MH - Male MH - Middle Aged MH - Prognosis MH - Pyrimidinones/administration & dosage/adverse effects/*therapeutic use MH - Survival Analysis MH - Treatment Outcome MH - Ventricular Fibrillation/*drug therapy/etiology/therapy EDAT- 2010/02/12 06:00 MHDA- 2010/09/29 06:00 CRDT- 2010/02/12 06:00 AID - 10.1097/FJC.0b013e3181d3dcc7 [doi] PST - ppublish SO - J Cardiovasc Pharmacol. 2010 Apr;55(4):391-8. PMID- 19969622 OWN - NLM STAT- MEDLINE DA - 20100311 DCOM- 20100624 LR - 20101118 IS - 1755-3245 (Electronic) IS - 0008-6363 (Linking) VI - 86 IP - 1 DP - 2010 Apr 1 TI - Midkine gene transfer after myocardial infarction in rats prevents remodelling and ameliorates cardiac dysfunction. PG - 113-21 AB - AIM: We have previously reported that therapy with midkine (MK) has a protective effect in mouse models of myocardial infarction (MI) and ischemia/reperfusion. The underlying mechanism was proved to be anti-apoptosis and prevention of left ventricular (LV) remodelling following angiogenesis. Here we investigated the effects of overexpression of MK by adenoviral gene transfer on cardiac function and remodelling in an experimental rat MI model. METHODS AND RESULTS: MI was created in male Wistar rats. Adenoviral vectors encoding mouse MK (AdMK) or beta-galactosidase (AdLacZ; as controls) were injected in myocardium at the onset of MI. One week after injection, in vivo adenoviral gene expression was assessed by western blot and histological analysis. After echocardiographic analysis at 4 weeks and haemodynamic analysis at 6 weeks after MI, AdMK animals had better cardiac function compared with AdLacZ animals. Heart weight (HW) and relative HW of AdMK animals were not different from sham-operated animals after 6 weeks, pointing to a very potent effect in the prevention of ischemic cardiomyopathy. In histological studies at 6 weeks after MI, AdMK animals had less fibrosis in the non-infarcted myocardium and higher vascular density in the border-zone area compared with AdLacZ animals. AdMK animals had strongly upregulated levels of phosphorylated extracellular signal-regulated kinase, Akt, PI 3-kinase, and Bcl-2, whereas the level of Bax was downregulated compared with AdLacZ animals. CONCLUSION: Overexpression of MK prevents LV remodelling and ameliorates LV dysfunction by anti-apoptotic and pro-angiogenic effects. MK gene transfer may provide a new therapeutic modality in ischemic cardiomyopathy and ischemic heart failure. AD - Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Huro-cho, Chikusa-ku, Nagoya 464-8601, Japan. FAU - Sumida, Arihiro AU - Sumida A FAU - Horiba, Mitsuru AU - Horiba M FAU - Ishiguro, Hisaaki AU - Ishiguro H FAU - Takenaka, Hiroharu AU - Takenaka H FAU - Ueda, Norihiro AU - Ueda N FAU - Ooboshi, Hiroaki AU - Ooboshi H FAU - Opthof, Tobias AU - Opthof T FAU - Kadomatsu, Kenji AU - Kadomatsu K FAU - Kodama, Itsuo AU - Kodama I LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20091207 PL - England TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Collagen Type I) RN - 0 (Collagen Type III) RN - 0 (Cytokines) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 137497-38-2 (midkine) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Adenoviridae/genetics MH - Animals MH - Apoptosis/physiology MH - Collagen Type I/metabolism MH - Collagen Type III/metabolism MH - Cytokines/*genetics MH - Disease Models, Animal MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Gene Therapy/*methods MH - Gene Transfer Techniques MH - Hemodynamics/physiology MH - Injections, Intralesional MH - Lac Operon MH - Male MH - Mice MH - Myocardial Infarction/pathology/physiopathology/*therapy MH - Myocardium/metabolism/pathology MH - Neovascularization, Physiologic/physiology MH - Phosphatidylinositol 3-Kinases/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - Rats MH - Rats, Wistar MH - Ventricular Dysfunction, Left/pathology/physiopathology/*therapy MH - Ventricular Remodeling/physiology EDAT- 2009/12/09 06:00 MHDA- 2010/06/25 06:00 CRDT- 2009/12/09 06:00 PHST- 2009/12/07 [aheadofprint] PHST- 2010/01/19 [aheadofprint] AID - cvp386 [pii] AID - 10.1093/cvr/cvp386 [doi] PST - ppublish SO - Cardiovasc Res. 2010 Apr 1;86(1):113-21. Epub 2009 Dec 7. PMID- 19939964 OWN - NLM STAT- MEDLINE DA - 20100211 DCOM- 20100426 LR - 20101118 IS - 1755-3245 (Electronic) IS - 0008-6363 (Linking) VI - 85 IP - 4 DP - 2010 Mar 1 TI - Left atrial pressure reduction for mitral stenosis reverses left atrial direction-dependent conduction abnormalities. PG - 711-8 AB - AIMS: Left atrial (LA) stretch-associated electrophysiological changes in patients with mitral stenosis (MS) predispose to atrial fibrillation. We hypothesized that the normalization of the pressure gradient by percutaneous transvenous mitral balloon valvotomy (PTMV) affects LA but not right atrial (RA) conduction, depending on the site of stimulation. Because direction-dependent (asymmetric) changes of conduction may contribute to arrhythmogenesis, we assessed conduction symmetry in MS patients and tested whether it is restored by PTMV. METHODS AND RESULTS: In nine patients with MS, atrial effective refractory period and local activation times (ATs) were determined during stimulation before and after PTMV, with up to four decapolar catheters (LA and RA). Eight patients with ventricular pre-excitation served as controls. ATs at basic cycle length were similar before and after PTMV. With stimulation from either atrium, they were about 45 ms in the ipsilateral atrium and about 115 ms in the contralateral atrium. With premature stimulation, ATs increased dramatically. The shortest ATs were found in the RA with RA stimulation (78 +/- 9 and 80 +/- 6 ns, before and after PTMV). PTMV caused a shortening in LA-ATs (following LA stimulation) from 118 +/- 14 to 82 +/- 5 ms (before and after; P < 0.05). Asymmetry in conduction properties was therefore normalized by PTMV. PTMV led to a decrease in RA-ATs (following LA stimulation) from 196 +/- 11 to 174 +/- 13 ms (P < 0.02). In addition, following RA stimulation, the dispersion in ATs in the LA decreased significantly by PTMV (from 66 +/- 10 to 34 +/- 7 ms; P < 0.02). CONCLUSION: MS is associated with LA conduction delay, increased LA dispersion of conduction, and conduction asymmetry. These changes are immediately reversible by PTMV. AD - Experimental Cardiology Group , Center for Heart Failure Research, Academic Medical Center, rm K2-112, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. r.coronel@amc.uva.nl FAU - Coronel, Ruben AU - Coronel R FAU - Langerveld, Jorina AU - Langerveld J FAU - Boersma, Lucas V A AU - Boersma LV FAU - Wever, Eric F D AU - Wever EF FAU - Bon, Laurens AU - Bon L FAU - van Dessel, Pascal F H M AU - van Dessel PF FAU - Linnenbank, Andre C AU - Linnenbank AC FAU - van Gilst, Wiek H AU - van Gilst WH FAU - Ernst, Sjef M P G AU - Ernst SM FAU - Opthof, Tobias AU - Opthof T FAU - van Hemel, Norbert M AU - van Hemel NM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20091125 PL - England TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM MH - Adult MH - Atrial Fibrillation/physiopathology MH - Atrial Function, Left/*physiology MH - *Balloon Dilation MH - Cardiac Pacing, Artificial MH - Electrocardiography MH - Female MH - Fluoroscopy MH - Heart Conduction System/*physiopathology MH - Humans MH - Male MH - Middle Aged MH - Mitral Valve Stenosis/*physiopathology/radiography/*therapy MH - Refractory Period, Electrophysiological/physiology MH - Ventricular Pressure/physiology EDAT- 2009/11/27 06:00 MHDA- 2010/04/27 06:00 CRDT- 2009/11/27 06:00 PHST- 2009/11/25 [aheadofprint] PHST- 2009/12/19 [aheadofprint] AID - cvp374 [pii] AID - 10.1093/cvr/cvp374 [doi] PST - ppublish SO - Cardiovasc Res. 2010 Mar 1;85(4):711-8. Epub 2009 Nov 25. PMID- 19808447 OWN - NLM STAT- MEDLINE DA - 20091007 DCOM- 20091027 IS - 1941-3084 (Electronic) IS - 1941-3084 (Linking) VI - 2 IP - 1 DP - 2009 Feb TI - Is there a significant transmural gradient in repolarization time in the intact heart?: Repolarization Gradients in the Intact Heart. PG - 89-96 AD - Experimental Cardiology Group, Center for Heart Failure Research, Academic Medical Center, Amsterdam, The Netherlands. FAU - Opthof, Tobias AU - Opthof T FAU - Coronel, Ruben AU - Coronel R FAU - Janse, Michiel J AU - Janse MJ LA - eng PT - Comment PT - Historical Article PT - Journal Article PL - United States TA - Circ Arrhythm Electrophysiol JT - Circulation. Arrhythmia and electrophysiology JID - 101474365 SB - IM CON - Circ Arrhythm Electrophysiol. 2009 Feb;2(1):80-8. PMID: 19808446 MH - Action Potentials MH - Animals MH - *Electrocardiography/history MH - Evidence-Based Medicine MH - Heart Conduction System/*physiopathology MH - Heart Diseases/*diagnosis/history/physiopathology MH - Heart Ventricles/physiopathology MH - History, 20th Century MH - History, 21st Century MH - Humans MH - Kinetics MH - Predictive Value of Tests EDAT- 2009/10/08 06:00 MHDA- 2009/10/29 06:00 CRDT- 2009/10/08 06:00 AID - 2/1/89 [pii] AID - 10.1161/CIRCEP.108.825356 [doi] PST - ppublish SO - Circ Arrhythm Electrophysiol. 2009 Feb;2(1):89-96. PMID- 19560091 OWN - NLM STAT- MEDLINE DA - 20090629 DCOM- 20090930 LR - 20091027 IS - 1556-3871 (Electronic) IS - 1547-5271 (Linking) VI - 6 IP - 7 DP - 2009 Jul TI - There is no transmural heterogeneity in an index of action potential duration in the canine left ventricle. PG - 1028-34 AB - BACKGROUND: Transmural heterogeneity in ventricular repolarization demonstrated in vitro has been difficult to confirm in vivo. Whether this discrepancy reflects a physiological phenomenon or a methodological problem remains a vivid matter of debate despite a plethora of experimental work. Therefore, we have measured the relevant electrophysiological parameters first in vivo and repeated these in the same heart and at identical sites in vitro. Methodological issues were tackled by using both unipolar and bipolar recordings. Physiological issues were explored by measuring both local and functional electrophysiological parameters. METHODS: In 10 healthy dogs, 2 high-resolution needle electrodes were inserted into the left ventricle. Effective refractory periods (ERP) as well as activation recovery intervals (ARI) were determined at each electrode along both needles at basic cycle lengths (BCL) of 850 and 300 ms, respectively. After excision of the heart, ERP and ARI measurements were repeated in the arterially perfused wedge preparations. RESULTS: First, we observed that ERPs and ARIs were significantly shorter in vivo than in vitro. Mean ERPs and ARIs of all muscle layers were relatively uniform throughout the ventricular wall in vivo. The transition from the in vivo to the in vitro preparation was associated with a significant albeit small increase of mean ARIs in the subendocardium, whereas interlayer differences in mean ERPs did not reach statistical significance as in vivo. CONCLUSION: In the intact canine left ventricular wall, a more or less homogeneous distribution in transmural ERP and ARI is present. AD - University of Heidelberg, Department of Cardiology, Heidelberg, Germany. Frederik_Voss@med.uni-heidelberg.de FAU - Voss, Frederik AU - Voss F FAU - Opthof, Tobias AU - Opthof T FAU - Marker, Jens AU - Marker J FAU - Bauer, Alexander AU - Bauer A FAU - Katus, Hugo A AU - Katus HA FAU - Becker, Ruediger AU - Becker R LA - eng PT - Comparative Study PT - Journal Article DEP - 20090320 PL - United States TA - Heart Rhythm JT - Heart rhythm : the official journal of the Heart Rhythm Society JID - 101200317 SB - IM CIN - Heart Rhythm. 2009 Jul;6(7):1035-7. PMID: 19497787 MH - *Action Potentials MH - Animals MH - Dogs MH - Electrodes, Implanted MH - Electrophysiologic Techniques, Cardiac MH - Female MH - Heart Ventricles MH - Male MH - Time Factors MH - Ventricular Function/*physiology EDAT- 2009/06/30 09:00 MHDA- 2009/10/01 06:00 CRDT- 2009/06/30 09:00 PHST- 2008/08/07 [received] PHST- 2009/03/14 [accepted] PHST- 2009/03/20 [aheadofprint] AID - S1547-5271(09)00328-2 [pii] AID - 10.1016/j.hrthm.2009.03.028 [doi] PST - ppublish SO - Heart Rhythm. 2009 Jul;6(7):1028-34. Epub 2009 Mar 20. PMID- 19465555 OWN - NLM STAT- MEDLINE DA - 20090728 DCOM- 20090901 IS - 1522-1539 (Electronic) IS - 0363-6135 (Linking) VI - 297 IP - 2 DP - 2009 Aug TI - Validation of a simple model for the morphology of the T wave in unipolar electrograms. PG - H792-801 AB - Local unipolar electrograms (UEGs) permit assessment of local activation and repolarization times at multiple sites simultaneously. However, UEG-based indexes of local repolarization are still debated, in particular for positive T waves. Previous experimental and computer modeling studies have not been able to terminate the debate. In this study we validate a simple theoretical model of the UEG and use it to explain how repolarization statistics in the UEG relate to those in the action potential. The model reconstructs the UEG by taking the difference between an inverted local action potential and a position-independent remote signal. In normal tissue, this extremely simple model predicts T-wave morphology with surprising accuracy while explaining in a readily understandable way why the instant of repolarization is always related to the steepest upstroke of the UEG, both in positive and negative T waves, and why positive T waves are related to early repolarizing sites, whereas negative T waves are related to late repolarizing sites. AD - Institute of Biomedical Engineering, Universite de Montreal, Montreal, Quebec, Canada. mark@potse.nl FAU - Potse, Mark AU - Potse M FAU - Vinet, Alain AU - Vinet A FAU - Opthof, Tobias AU - Opthof T FAU - Coronel, Ruben AU - Coronel R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Validation Studies DEP - 20090522 PL - United States TA - Am J Physiol Heart Circ Physiol JT - American journal of physiology. Heart and circulatory physiology JID - 100901228 SB - IM MH - Action Potentials/*physiology MH - *Electrocardiography MH - Heart/anatomy & histology/*physiology MH - Humans MH - *Medical Informatics MH - *Models, Cardiovascular MH - Predictive Value of Tests EDAT- 2009/05/26 09:00 MHDA- 2009/09/02 06:00 CRDT- 2009/05/26 09:00 PHST- 2009/05/22 [aheadofprint] AID - 00064.2009 [pii] AID - 10.1152/ajpheart.00064.2009 [doi] PST - ppublish SO - Am J Physiol Heart Circ Physiol. 2009 Aug;297(2):H792-801. Epub 2009 May 22. PMID- 19421360 OWN - NLM STAT- PubMed-not-MEDLINE DA - 20090507 DCOM- 20110714 IS - 1568-5888 (Print) IS - 1568-5888 (Linking) VI - 17 IP - 4 DP - 2009 Apr TI - The Hirsch-index: a simple, new tool for the assessment of scientific output of individual scientists: The case of Dutch professors in clinical cardiology. PG - 145-54 AB - In this brief paper we explore the Hirsch-index together with a couple of other bibliometric parameters for the assessment of the scientific output of 29 Dutch professors in clinical cardiology. It appears that even within such a homogeneous group there is large interindividual variability. Although the differences are quite remarkable, it remains undetermined what they mean; at least it is premature to interpret them as differences in scientific quality. It goes without saying that even more prudence is required when different fields of medicine and life sciences are compared (for example within University Medical Centres). Recent efforts to produce an amalgam of scientific 'productivity', 'relevance' and 'viability' as a surrogate parameter for the assessment of scientific quality, as for example performed in the AMC in Amsterdam, should be discouraged in the absence of a firm scientific base. Unfortunately for politicians and 'managers of science' only reading papers and studying are suitable for quality assessment of scientific output. Citations analyses can't substitute that. (Neth Heart J 2009;17:145-54.). AD - Department of Experimental Cardiology, Center for Heart Failure Research, Academic Medical Center, Amsterdam and Department of Medical Physiology, University medical Center Utrecht, Utrecht, the Netherlands. FAU - Opthof, T AU - Opthof T FAU - Wilde, A A M AU - Wilde AA LA - eng PT - Journal Article PL - Netherlands TA - Neth Heart J JT - Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation JID - 101095458 PMC - PMC2669244 OID - NLM: PMC2669244 EDAT- 2009/05/08 09:00 MHDA- 2009/05/08 09:01 CRDT- 2009/05/08 09:00 PST - ppublish SO - Neth Heart J. 2009 Apr;17(4):145-54. PMID- 19324316 OWN - NLM STAT- MEDLINE DA - 20090327 DCOM- 20090707 LR - 20091027 IS - 1556-3871 (Electronic) IS - 1547-5271 (Linking) VI - 6 IP - 4 DP - 2009 Apr TI - Dispersion of repolarization and arrhythmogenesis. PG - 537-43 AB - BACKGROUND: The relation between induction of arrhythmias and dispersion of repolarization is not completely understood. OBJECTIVE: The purpose of this study was to study the relation between heterogeneity in repolarization and arrhythmogenesis under conditions of selective regional action potential prolongation and shortening. METHODS: Pig hearts were perfused in a Langendorff setup. The left anterior descending artery (LAD) was cannulated and perfused. Sotalol (220 microM) was infused in the aortic cannula, and pinacidil (20 microM) was infused through the LAD, causing a gradient in repolarization time between the two myocardial regions. Premature stimulation was performed from the LAD region. RESULTS: No transmural repolarization gradients developed after infusion of the drugs. High-density epicardial activation/repolarization mapping (176 unipolar electrodes, 2-mm interelectrode spacing) revealed a maximum repolarization gradient of approximately 120 ms over 14 mm. The critical parameter for differentiating between the occurrence of reentry and the mere occurrence of a line of activation block between the two myocardial regions (and no reentry) was not the magnitude of the repolarization gradient but the timing of arrival of the premature activation wave at the distal side of the line of activation block relative to the repolarization time of the premature beat proximal to the line of block. No spontaneous arrhythmias were observed despite the presence of the repolarization gradient. CONCLUSION: It is not the repolarization gradient but the restitution characteristics of the tissue with the shorter action potential, in combination with the time of arrival of the premature wavefront at the distal side of the line of block, that determines the occurrence of reentry. AD - Department of Experimental Cardiology, Center for Heart Failure Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. R.Coronel@amc.uva.nl FAU - Coronel, Ruben AU - Coronel R FAU - Wilms-Schopman, Francien J G AU - Wilms-Schopman FJ FAU - Opthof, Tobias AU - Opthof T FAU - Janse, Michiel J AU - Janse MJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090118 PL - United States TA - Heart Rhythm JT - Heart rhythm : the official journal of the Heart Rhythm Society JID - 101200317 RN - 3930-20-9 (Sotalol) RN - 85371-64-8 (Pinacidil) SB - IM CIN - Heart Rhythm. 2009 Apr;6(4):544-5. PMID: 19324317 MH - Action Potentials/physiology MH - Animals MH - Arrhythmias, Cardiac/*drug therapy/*physiopathology MH - Electrocardiography MH - Electrophysiologic Techniques, Cardiac MH - Heart Conduction System/drug effects/*physiopathology MH - Pinacidil/*pharmacology MH - Sotalol/*pharmacology MH - Swine EDAT- 2009/03/28 09:00 MHDA- 2009/07/08 09:00 CRDT- 2009/03/28 09:00 PHST- 2008/11/20 [received] PHST- 2009/01/09 [accepted] PHST- 2009/01/18 [aheadofprint] AID - S1547-5271(09)00040-X [pii] AID - 10.1016/j.hrthm.2009.01.013 [doi] PST - ppublish SO - Heart Rhythm. 2009 Apr;6(4):537-43. Epub 2009 Jan 18. PMID- 19303369 OWN - NLM STAT- MEDLINE DA - 20090424 DCOM- 20090825 LR - 20091027 IS - 1556-3871 (Electronic) IS - 1547-5271 (Linking) VI - 6 IP - 5 DP - 2009 May TI - Early termination of spiral wave reentry by combined blockade of Na+ and L-type Ca2+ currents in a perfused two-dimensional epicardial layer of rabbit ventricular myocardium. PG - 684-92 AB - BACKGROUND: Modification of spiral wave (SW) reentry by antiarrhythmic drugs is a central issue to be challenged for better understanding of their benefits and risks. OBJECTIVE: We investigated the effects of pilsicainide and/or verapamil, which block sodium and L-type calcium currents (I(Na) and I(Ca,L)), respectively, on SW reentry. METHODS: A two-dimensional epicardial ventricular muscle layer was created in rabbit hearts by cryoablation (n = 32), and action potential signals were analyzed by high-resolution optical mapping. RESULTS: During constant stimulation, pilsicainide (3-5 microM) caused a frequency-dependent decrease of conduction velocity (CV; by 20%-54% at 5 Hz) without affecting action potential duration (APD). Verapamil (3 microM) caused APD shortening (by 16% at 5 Hz) without affecting CV. Ventricular tachycardias (VTs) that were induced were more sustained in the presence of either pilsicainide or verapamil. The incidence of sustained VTs (>30 s)/all VTs per heart was 58% +/- 9% for 5 microM pilsicainide vs. 22% +/- 9% for controls and 62% +/- 10% for 3 microM verapamil vs. 22% +/- 8% for controls. The SWs with pilsicainide were characterized by slower rotation around longer functional block lines (FBLs), whereas those with verapamil were characterized by faster rotation around shorter FBLs. Combined application of 3 microM pilsicainide and 3 microM verapamil resulted in early termination of VTs (sustained VTs/all VTs per heart: 2% +/- 2% vs. 29% +/- 9% for controls); SWs showed extensive drift and decremental conduction, leading to their spontaneous annihilation. CONCLUSION: Blockade of either I(Na) or I(Ca,L) stabilizes SWs in a two-dimensional epicardial layer of rabbit ventricular myocardium to help their persistence, whereas blockade of both currents destabilizes SWs to facilitate their termination. AD - Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan. FAU - Ishiguro, Yuko S AU - Ishiguro YS FAU - Honjo, Haruo AU - Honjo H FAU - Opthof, Tobias AU - Opthof T FAU - Okuno, Yusuke AU - Okuno Y FAU - Nakagawa, Harumichi AU - Nakagawa H FAU - Yamazaki, Masatoshi AU - Yamazaki M FAU - Harada, Masahide AU - Harada M FAU - Takanari, Hiroki AU - Takanari H FAU - Suzuki, Tomoyuki AU - Suzuki T FAU - Morishima, Mikio AU - Morishima M FAU - Sakuma, Ichiro AU - Sakuma I FAU - Kamiya, Kaichiro AU - Kamiya K FAU - Kodama, Itsuo AU - Kodama I LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090121 PL - United States TA - Heart Rhythm JT - Heart rhythm : the official journal of the Heart Rhythm Society JID - 101200317 RN - 0 (Calcium Channel Blockers) RN - 0 (Calcium Channels, L-Type) RN - 0 (Sodium Channel Blockers) RN - 0 (Sodium Channels) RN - 137-58-6 (Lidocaine) RN - 52-53-9 (Verapamil) RN - 88069-49-2 (pilsicainide) SB - IM CIN - Heart Rhythm. 2009 May;6(5):693-5. PMID: 19332392 MH - Animals MH - Calcium Channel Blockers/*therapeutic use MH - Calcium Channels, L-Type/*drug effects MH - Disease Models, Animal MH - Electrophysiologic Techniques, Cardiac MH - Heart Rate/drug effects MH - Heart Ventricles/drug effects/*pathology/physiopathology MH - Lidocaine/*analogs & derivatives/therapeutic use MH - Pericardium/pathology MH - Rabbits MH - Sodium Channel Blockers/*therapeutic use MH - Sodium Channels/drug effects/metabolism MH - Tachycardia, Sinoatrial Nodal Reentry/*drug therapy/metabolism/pathology MH - Treatment Outcome MH - Verapamil/*therapeutic use EDAT- 2009/03/24 09:00 MHDA- 2009/08/26 09:00 CRDT- 2009/03/24 09:00 PHST- 2008/10/11 [received] PHST- 2009/01/17 [accepted] PHST- 2009/01/21 [aheadofprint] AID - S1547-5271(09)00080-0 [pii] AID - 10.1016/j.hrthm.2009.01.022 [doi] PST - ppublish SO - Heart Rhythm. 2009 May;6(5):684-92. Epub 2009 Jan 21. PMID- 19251218 OWN - NLM STAT- MEDLINE DA - 20090302 DCOM- 20090609 LR - 20091027 IS - 1556-3871 (Electronic) IS - 1547-5271 (Linking) VI - 6 IP - 3 DP - 2009 Mar TI - IK1 modulates the U-wave: insights in a 100-year-old enigma. PG - 393-400 AD - Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. FAU - Postema, Pieter G AU - Postema PG FAU - Ritsema van Eck, Henk J AU - Ritsema van Eck HJ FAU - Opthof, Tobias AU - Opthof T FAU - van Herpen, Gerard AU - van Herpen G FAU - van Dessel, Pascal F H M AU - van Dessel PF FAU - Priori, Silvia G AU - Priori SG FAU - Wolpert, Christian AU - Wolpert C FAU - Borggrefe, Martin AU - Borggrefe M FAU - Kors, Jan A AU - Kors JA FAU - Wilde, Arthur A M AU - Wilde AA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20081127 PL - United States TA - Heart Rhythm JT - Heart rhythm : the official journal of the Heart Rhythm Society JID - 101200317 RN - 0 (ERG1 potassium channel) RN - 0 (Ether-A-Go-Go Potassium Channels) RN - 0 (KCNJ2 protein, human) RN - 0 (KCNQ1 Potassium Channel) RN - 0 (KCNQ1 protein, human) RN - 0 (Potassium Channels, Inwardly Rectifying) SB - IM MH - Action Potentials/*physiology MH - Adult MH - Andersen Syndrome/genetics MH - Arrhythmias, Cardiac/genetics/*physiopathology MH - *Electrocardiography MH - Ether-A-Go-Go Potassium Channels/genetics MH - Female MH - Humans MH - KCNQ1 Potassium Channel/genetics MH - Long QT Syndrome/genetics/physiopathology MH - Male MH - Middle Aged MH - Mutation MH - Potassium Channels, Inwardly Rectifying/genetics/*physiology MH - Signal Processing, Computer-Assisted EDAT- 2009/03/03 09:00 MHDA- 2009/06/10 09:00 CRDT- 2009/03/03 09:00 PHST- 2008/09/30 [received] PHST- 2008/11/22 [accepted] PHST- 2008/11/27 [aheadofprint] AID - S1547-5271(08)01179-X [pii] AID - 10.1016/j.hrthm.2008.11.024 [doi] PST - ppublish SO - Heart Rhythm. 2009 Mar;6(3):393-400. Epub 2008 Nov 27. PMID- 19148335 OWN - NLM STAT- PubMed-not-MEDLINE DA - 20090116 DCOM- 20110714 IS - 1568-5888 (Print) IS - 1568-5888 (Linking) VI - 17 IP - 1 DP - 2009 Jan TI - Fraud and misconduct in science: the stem cell seduction: Implications for the peer-review process. PG - 25-9 AB - Scientific misconduct and fraud occur in science. The (anonymous) peer review process serves as goalkeeper of scientific quality rather than scientific integrity. In this brief paper we describe some limitations of the peer-review process. We describe the catastrophic facts of the 'Woo-Suk Hwang fraud case' and raise some ethical concerns about the issue. Finally, we pay attention to plagiarism, autoplagiarism and double publications. (Neth Heart J 2009;17:25-9.). AD - Department of Medical Physiology, University Medical Center, Utrecht, the Netherlands. FAU - van der Heyden, M A G AU - van der Heyden MA FAU - van de Ven, T AU - van de Ven T FAU - Opthof, T AU - Opthof T LA - eng PT - Journal Article PL - Netherlands TA - Neth Heart J JT - Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation JID - 101095458 PMC - PMC2626656 OID - NLM: PMC2626656 EDAT- 2009/01/17 09:00 MHDA- 2009/01/17 09:01 CRDT- 2009/01/17 09:00 PST - ppublish SO - Neth Heart J. 2009 Jan;17(1):25-9. PMID- 19139945 OWN - NLM STAT- MEDLINE DA - 20090413 DCOM- 20090605 IS - 1435-1803 (Electronic) IS - 0300-8428 (Linking) VI - 104 IP - 3 DP - 2009 May TI - The effect of enhanced gap junctional conductance on ventricular conduction in explanted hearts from patients with heart failure. PG - 321-32 AB - AIM: To investigate ventricular conduction and refractoriness before and after application of rotigaptide, an enhancer of gap junctional conductance, to explanted hearts of patients with heart failure (HF). METHODS AND RESULTS: In six explanted perfused hearts of patients with end-stage HF, activation/repolarization mapping was performed and refractory periods (RPs) and activation recovery intervals (ARIs) were measured before and after application of 50 nM rotigaptide. Rotigaptide caused a decrease of RP from 476 +/- 36 to 453 +/- 31 ms (P < 0.05), but did not change ARI-dispersion. During premature activation along the fibers rotigaptide decreased the minimal activation time (AT(min)) and maximal activation time (AT(max)) significantly from 35 +/- 12 to 24 +/- 9 and from 97 +/- 38 to 43 +/- 7 ms, respectively. Rotigaptide did not change AT(min) and AT(max) during activation perpendicular to the fiber direction. After application of rotigaptide conduction curves normalized in five/six recordings when activation was parallel, but destabilized in three/six hearts when activation was perpendicular to fiber direction. The destabilization was associated with local conduction delays rather than with facilitation of conduction. CONCLUSION: Rotigaptide applied to hearts of patients with end-stage HF shortened RPs normalized conduction curves and increased conduction parallel to fiber direction. However, in 50% of the hearts local slowing of conduction with destabilization of conduction (curves) occurs at sites close to the stimulation site, when activation is perpendicular to fiber direction. AD - Experimental Cardiology Group (ECG), Dept. of Experimental Cardiology, Center for Heart Failure Research, Academic Medical Center, Amsterdam, The Netherlands. FAU - Wiegerinck, Rob F AU - Wiegerinck RF FAU - de Bakker, Jacques M T AU - de Bakker JM FAU - Opthof, Tobias AU - Opthof T FAU - de Jonge, Nicolaas AU - de Jonge N FAU - Kirkels, Hans AU - Kirkels H FAU - Wilms-Schopman, Francien J G AU - Wilms-Schopman FJ FAU - Coronel, Ruben AU - Coronel R LA - eng PT - Journal Article DEP - 20090112 PL - Germany TA - Basic Res Cardiol JT - Basic research in cardiology JID - 0360342 RN - 0 (Oligopeptides) RN - 355151-12-1 (rotigaptide) SB - IM MH - Action Potentials/drug effects/physiology MH - Adult MH - Electrophysiology MH - Female MH - Gap Junctions/drug effects/*metabolism MH - Heart Conduction System/drug effects/*physiopathology MH - Heart Failure/*physiopathology MH - Heart Ventricles/drug effects/*physiopathology MH - Humans MH - Male MH - Middle Aged MH - Myocytes, Cardiac/drug effects/physiology MH - Neural Conduction/drug effects/physiology MH - Oligopeptides/pharmacology EDAT- 2009/01/14 09:00 MHDA- 2009/06/06 09:00 CRDT- 2009/01/14 09:00 PHST- 2008/06/20 [received] PHST- 2008/11/24 [accepted] PHST- 2009/01/12 [aheadofprint] AID - 10.1007/s00395-008-0771-7 [doi] PST - ppublish SO - Basic Res Cardiol. 2009 May;104(3):321-32. Epub 2009 Jan 12. PMID- 19112884 OWN - NLM STAT- MEDLINE DA - 20081230 DCOM- 20090202 LR - 20090812 IS - 0304-4920 (Print) IS - 0304-4920 (Linking) VI - 51 IP - 4 DP - 2008 Aug 31 TI - Impact factor of the Chinese Journal of Physiology in 2007: building a strong foundation. PG - 259-60 FAU - Opthof, Tobias AU - Opthof T FAU - van der Heyden, Marcel A G AU - van der Heyden MA LA - eng PT - Letter PL - China (Republic : 1949- ) TA - Chin J Physiol JT - The Chinese journal of physiology JID - 7804502 SB - IM MH - China MH - *Journal Impact Factor MH - Periodicals as Topic/*statistics & numerical data/*trends MH - *Physiology EDAT- 2008/12/31 09:00 MHDA- 2009/02/03 09:00 CRDT- 2008/12/31 09:00 PST - ppublish SO - Chin J Physiol. 2008 Aug 31;51(4):259-60. PMID- 18275974 OWN - NLM STAT- MEDLINE DA - 20080229 DCOM- 20080509 LR - 20081121 IS - 0024-3205 (Print) IS - 0024-3205 (Linking) VI - 82 IP - 11-12 DP - 2008 Mar 12 TI - T-type Ca2+ channel blockers prevent cardiac cell hypertrophy through an inhibition of calcineurin-NFAT3 activation as well as L-type Ca2+ channel blockers. PG - 554-60 AB - T-type Ca2+ channels (TCCs) are involved in cardiac cell growth and proliferation in cultured cardiomyocytes. Underlying molecular mechanisms are not well understood. In this study, we investigated the role of TCCs in signal transduction in cardiac hypertrophy compared with L-type Ca2+ channels (LCCs). Cardiomyocytes dissociated from neonatal mouse ventricles were cultured until stabilization. Cell hypertrophy was induced by reapplication of 1% fatal bovine serum (FBS) following a period (24 h) of FBS depletion. Cell surface area increased from 862+/-73 microm2 to 2153+/-131 microm2 by FBS stimulation in control (250+/-1.8%). T-type Ca2+ current (I(CaT)) was inhibited dose-dependently by kurtoxin (KT) and efonidipine (ED) with IC50 0.07 microM and 3.2 microM, respectively in whole-cell voltage clamp. On the other hand, 1 microM KT which inhibits I(CaT) over 90% did not effect on L-type Ca2+ current (I(CaL)). 10 microM ED had the ability of I(CaL) blockade as well as that of I(CaT) blockade. 3 microM nisoldipine (ND) suppressed I(CaL) by over 80%. The increase in cell surface area following reapplication of FBS as observed in control (250+/-1.8%) was significantly reduced in the presence of 1 microM KT (216+/-1.2%) and virtually abolished in the presence of 10 microM ED (97+/-0.8%) and 3 microM ND (80+/-1.1%). Hypertrophy was associated with an increase in BNP mRNA of 316+/-3.6% in control and this increase was reduced as well in the presence of 1 microM KT (254+/-1.8%) and almost abolished in the presence of 10 microM ED (116+/-1.1%) and 3 muM ND (93+/-0.8%). Immunolabeling showed that translocation of nuclear factor of activated T cells (NFAT3) into the nucleus in response to FBS stimulation was markedly inhibited by either KT or ED as well as ND. Calcineurin phosphatase activity was upregulated 2.2-fold by FBS, but KT, ED and ND decreased this upregulation (1.7-fold, 0.8-fold, and 0.7-fold with KT, ED and ND respectively). These results suggest that blockade of Ca2+ entry into cardiomyocytes via TCCs may block pathophysiological signaling pathways leading to hypertrophy as well as via LCCs. The mechanism may be the inhibition of calcineurin-mediated NFAT3 activation resulting in prevention of its translocation into the nucleus. AD - Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan. mhoriba@riem.nagoya-u.ac.jp FAU - Horiba, Mitsuru AU - Horiba M FAU - Muto, Takao AU - Muto T FAU - Ueda, Norihiro AU - Ueda N FAU - Opthof, Tobias AU - Opthof T FAU - Miwa, Keiko AU - Miwa K FAU - Hojo, Mayumi AU - Hojo M FAU - Lee, Jong-Kook AU - Lee JK FAU - Kamiya, Kaichiro AU - Kamiya K FAU - Kodama, Itsuo AU - Kodama I FAU - Yasui, Kenji AU - Yasui K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071204 PL - England TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Calcium Channel Blockers) RN - 0 (Calcium Channels, L-Type) RN - 0 (Calcium Channels, T-Type) RN - 0 (Dihydropyridines) RN - 0 (NFATC Transcription Factors) RN - 0 (Neurotoxins) RN - 0 (Nitrophenols) RN - 0 (Organophosphorus Compounds) RN - 0 (Scorpion Venoms) RN - 0 (kurtoxin) RN - 111011-53-1 (efonidipine) RN - 114471-18-0 (Natriuretic Peptide, Brain) RN - 63675-72-9 (Nisoldipine) RN - EC 3.1.3.16 (Calcineurin) SB - IM MH - Active Transport, Cell Nucleus/physiology MH - Animals MH - Calcineurin/*metabolism MH - Calcium Channel Blockers/*metabolism/pharmacology MH - Calcium Channels, L-Type/*metabolism MH - Calcium Channels, T-Type/*metabolism MH - Cattle MH - Cells, Cultured MH - Dihydropyridines/metabolism MH - *Hypertrophy MH - Mice MH - *Myocardium/cytology/pathology MH - Myocytes, Cardiac/cytology/*metabolism MH - NFATC Transcription Factors/*metabolism MH - Natriuretic Peptide, Brain/genetics/metabolism MH - Neurotoxins/metabolism MH - Nisoldipine/metabolism MH - Nitrophenols/metabolism MH - Organophosphorus Compounds/metabolism MH - Patch-Clamp Techniques MH - Scorpion Venoms/metabolism EDAT- 2008/02/16 09:00 MHDA- 2008/05/10 09:00 CRDT- 2008/02/16 09:00 PHST- 2007/09/04 [received] PHST- 2007/11/14 [accepted] PHST- 2007/12/04 [aheadofprint] AID - S0024-3205(07)00837-5 [pii] AID - 10.1016/j.lfs.2007.11.010 [doi] PST - ppublish SO - Life Sci. 2008 Mar 12;82(11-12):554-60. Epub 2007 Dec 4. PMID- 18003549 OWN - NLM STAT- MEDLINE DA - 20071116 DCOM- 20080408 LR - 20090611 IS - 1557-170X (Print) IS - 1557-170X (Linking) VI - 2007 DP - 2007 TI - Simulating T-wave parameters of local extracellular electrograms with a whole-heart bidomain reaction-diffusion model: Size matters! PG - 6644-7 AB - As a measure of local repolarization time (T(R)), the instant of maximum slope (T(up)) of the T wave in the local unipolar electrogram is commonly used. Measurement of T(up) can be difficult, especially in positive T waves. These difficulties have led some researchers to propose the instant of maximum downslope (T(down)) as a marker of T(R) when the T wave is positive. To improve understanding of T-wave parameters, we simulated electrograms with a bidomain model of the human heart. To test T-wave parameters, we compared them to T(R) determined from the local membrane potential. We propose a simple model of the electrogram, which we validated by comparison to the bidomain model. With the simple model, it is straightforward to show that the sign of the T wave is almost uniquely determined by T(R). We then used the bidomain model to simulate the effects of a variety of pathologies and technical difficulties, which the simple model could not account for. Generally, T(up) was a much better estimate for T(R) than T(down). Regional fibrosis could attenuate local electrogram components and reduce accuracy of T(up) as a marker for T(R). In fibrotic tissue, T(down) was not related to T(R) at all. This investigation of electrogram slopes required the simulation of extracellular potentials with about 100 times more precision than needed for simulation of visually acceptable waveforms alone. This requirement is more difficult to meet in larger models, but it was actually possible for a human-heart model with 60 million nodes. By sacrificing some spatial resolutions, we kept the computational requirements within acceptable limits for multiple simulations. AD - Research Center, Hopital du Sacre-Coeur de Montreal, Montreal (Quebec) H4J 1C5, Canada. FAU - Potse, Mark AU - Potse M FAU - Coronel, Ruben AU - Coronel R FAU - Opthof, Tobias AU - Opthof T FAU - Vinet, Alain AU - Vinet A LA - eng PT - Journal Article PL - United States TA - Conf Proc IEEE Eng Med Biol Soc JT - Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference JID - 101243413 SB - IM MH - Computer Simulation MH - *Electrocardiography MH - Heart/*physiology MH - Humans MH - *Models, Biological MH - Myocytes, Cardiac/physiology EDAT- 2007/11/16 09:00 MHDA- 2008/04/09 09:00 CRDT- 2007/11/16 09:00 AID - 10.1109/IEMBS.2007.4353883 [doi] PST - ppublish SO - Conf Proc IEEE Eng Med Biol Soc. 2007;2007:6644-7. PMID- 17954406 OWN - NLM STAT- MEDLINE DA - 20071023 DCOM- 20080208 LR - 20091027 IS - 1547-5271 (Print) IS - 1547-5271 (Linking) VI - 4 IP - 11 DP - 2007 Nov TI - Dietary fish oil reduces the incidence of triggered arrhythmias in pig ventricular myocytes. PG - 1452-60 AB - BACKGROUND: Fish oil reduces the incidence of sudden cardiac death in postmyocardial infarction patients. Triggered activity is the principal mechanism of arrhythmogenesis under these conditions. OBJECTIVE: The purpose of this study was to test whether dietary fish oil in pigs inhibits Ca2+ overload-induced triggered activity. METHODS: Pigs were fed a diet of fish oil or sunflower oil for 8 weeks. Ventricular myocytes (omega3: fish oil, n = 11; control: sunflower oil, n = 8) were isolated by enzymatic dissociation and used for patch clamp studies and intracellular Ca2+ recordings. Triggered activity was induced by rapid pacing in the presence of norepinephrine. RESULTS: Dietary fish oil reduced the incidence of triggered action potentials and delayed afterdepolarizations compared to control (9.1% in omega3 and 84.6% in control, P <.05), concomitant with a reduction in spontaneous Ca2+ release. Dietary fish oil prevented Ca2+ overload and reduced action potential prolongation in response to norepinephrine (DeltaAPD(90): 23.2 +/- 8.5 ms in omega3 and 107.4 +/- 15.9 in control, P <.05). omega3 myocytes displayed decreased sarcoplasmic reticulum Ca2+ content, reduced L-type Ca2+ current (I(Ca,L)), and less recruitment of the Na+/Ca2+ exchange current (I(NCX)) in response to norepinephrine compared to control. In the absence of norepinephrine, the slow component of the delayed rectifier current (I(Ks)) was larger in omega3 myocytes. In the presence of norepinephrine, I(Ks) increased to the same level in omega3 and control myocytes. CONCLUSION: Dietary fish oil reduces the incidence of triggered activity and prevents Ca2+ overload and AP prolongation in response to norepinephrine. Fish oil may prevent arrhythmias in patients with heart failure. AD - Experimental Cardiology Group (ECG), Center for Heart Failure Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. FAU - Berecki, Geza AU - Berecki G FAU - Den Ruijter, Hester M AU - Den Ruijter HM FAU - Verkerk, Arie O AU - Verkerk AO FAU - Schumacher, Cees A AU - Schumacher CA FAU - Baartscheer, Antonius AU - Baartscheer A FAU - Bakker, Diane AU - Bakker D FAU - Boukens, Bastiaan J AU - Boukens BJ FAU - van Ginneken, Antoni C G AU - van Ginneken AC FAU - Fiolet, Jan W T AU - Fiolet JW FAU - Opthof, Tobias AU - Opthof T FAU - Coronel, Ruben AU - Coronel R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070717 PL - United States TA - Heart Rhythm JT - Heart rhythm : the official journal of the Heart Rhythm Society JID - 101200317 RN - 0 (Calcium Channels) RN - 0 (Dust) RN - 0 (Fish Oils) RN - 0 (Phospholipids) SB - IM MH - *Action Potentials MH - Animals MH - Arrhythmias, Cardiac/*prevention & control MH - Calcium Channels/drug effects MH - Death, Sudden, Cardiac/*prevention & control MH - *Dust MH - Fish Oils/*pharmacology MH - Heart Ventricles/*drug effects MH - Incidence MH - Male MH - Membrane Potentials/drug effects MH - Muscle Cells/*drug effects MH - *Nutritional Status MH - Phospholipids MH - Risk Factors MH - Swine MH - Time Factors EDAT- 2007/10/24 09:00 MHDA- 2008/02/09 09:00 CRDT- 2007/10/24 09:00 PHST- 2007/06/05 [received] PHST- 2007/07/10 [accepted] PHST- 2007/07/17 [aheadofprint] AID - S1547-5271(07)00727-8 [pii] AID - 10.1016/j.hrthm.2007.07.015 [doi] PST - ppublish SO - Heart Rhythm. 2007 Nov;4(11):1452-60. Epub 2007 Jul 17. PMID- 17584714 OWN - NLM STAT- MEDLINE DA - 20070622 DCOM- 20070914 LR - 20071115 IS - 1302-8723 (Print) IS - 1302-8723 (Linking) VI - 7 Suppl 1 DP - 2007 Jul TI - The positive T wave. PG - 164-7 AB - OBJECTIVE: The instant of maximum slope (Tup) of the T wave in the unipolar electrogram is a well-established measure of repolarisation time (TR). Nevertheless, recent observations on positive T waves have caused a renewed debate. The purpose of this study was to elucidate the mechanism that leads to positive and negative T waves and to investigate which electrogram feature best predicts TR. METHODS: We simulated propagating action potentials (AP) and electrograms with a bidomain reaction-diffusion model of the human heart including heterogeneous ion-channel properties. To explain positive T waves we compared results with those of a much simpler model, which predicts T waves from local and remote AP. RESULTS: Repolarisation time was defined as the instant of steepest downstroke of the AP. T wave polarity was mostly determined by TR. Positive T waves occurred at early-repolarising sites. Correlation between Tup and TR was >0.99, in both negative and positive T waves. T wave area and peak value also correlated highly with TR. CONCLUSION: The polarity of the T wave is primarily determined by TR. Positive T waves occur at early-repolarising sites. Local TR is best estimated by Tup, also in positive T waves. AD - Department of Physiology, Institute of Biomedical Engineering, Universite de Montreal, Montreal, Quebec, Canada. mark@potse.nl FAU - Potse, Mark AU - Potse M FAU - Coronel, Ruben AU - Coronel R FAU - Opthof, Tobias AU - Opthof T FAU - Vinet, Alain AU - Vinet A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Turkey TA - Anadolu Kardiyol Derg JT - Anadolu kardiyoloji dergisi : AKD = the Anatolian journal of cardiology JID - 101095069 SB - IM MH - Action Potentials MH - Arrhythmias, Cardiac/*physiopathology MH - *Computer Simulation MH - *Electrocardiography MH - Humans EDAT- 2007/08/01 09:00 MHDA- 2007/09/15 09:00 CRDT- 2007/08/01 09:00 PST - ppublish SO - Anadolu Kardiyol Derg. 2007 Jul;7 Suppl 1:164-7. PMID- 17654014 OWN - NLM STAT- MEDLINE DA - 20070726 DCOM- 20080104 IS - 1042-5179 (Print) IS - 1026-7913 (Linking) VI - 18 IP - 5 DP - 2007 Oct TI - Cloning, sequence analysis and phylogeny of connexin43 isolated from American black bear heart. PG - 380-4 AB - Conduction in the heart requires gap junctions. In mammalian ventricular myocytes these consist of connexin43 (Cx43). Hearts of non-hibernating species display conduction disturbances at reduced temperatures. These may exacerbate into lethal arrhythmias. Hibernating species are protected against these arrhythmias by a non-resolved mechanism. To analyze whether the amino acid composition of Cx43 from the hibernating American black bear displays specific features, we cloned the full coding sequence of Ursus americanus Cx43 and compared with that of other (non)hibernating species. UaCx43 displays 99.7% identity to rabbit Cx43 at the amino acid level. No specific features were observed in UaCx43 when compared to previously cloned Cx43 from hibernating and non-hibernating mammals. Phylogenetic tree reconstruction of this and other published full-length Cx43 sequences reveals a very high level of conservation from fish to men. Finally, one of the previously identified six mammalian characteristic amino acids, is not conserved in the black bear. AD - Department of Medical Physiology, Heart Lung Center Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands. m.a.g.vanderheyden@umcutrecht.nl FAU - Van Der Heyden, Marcel A G AU - Van Der Heyden MA FAU - Kok, Bart AU - Kok B FAU - Kouwenhoven, Evelyn N AU - Kouwenhoven EN FAU - Toien, Oivind AU - Toien O FAU - Barnes, Brian M AU - Barnes BM FAU - Fedorov, Vadim G AU - Fedorov VG FAU - Efimov, Igor R AU - Efimov IR FAU - Opthof, Tobias AU - Opthof T LA - eng SI - GENBANK/DQ833440 PT - Comparative Study PT - Journal Article PL - England TA - DNA Seq JT - DNA sequence : the journal of DNA sequencing and mapping JID - 9107800 RN - 0 (Connexin 43) RN - 0 (DNA, Complementary) RN - 0 (Protein Isoforms) SB - IM MH - Americas MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Body Temperature MH - *Cloning, Molecular MH - Connexin 43/*genetics/*isolation & purification MH - Conserved Sequence MH - DNA, Complementary MH - Heart Ventricles MH - Hibernation MH - Male MH - Molecular Sequence Data MH - Myocardium/*metabolism MH - *Phylogeny MH - Protein Isoforms MH - Sequence Analysis, DNA MH - Sequence Homology, Amino Acid MH - Ursidae EDAT- 2007/07/27 09:00 MHDA- 2008/01/05 09:00 CRDT- 2007/07/27 09:00 AID - 778406105 [pii] AID - 10.1080/10425170701400589 [doi] PST - ppublish SO - DNA Seq. 2007 Oct;18(5):380-4. PMID- 17644563 OWN - NLM STAT- MEDLINE DA - 20071108 DCOM- 20080107 LR - 20081121 IS - 0363-6135 (Print) IS - 0363-6135 (Linking) VI - 293 IP - 5 DP - 2007 Nov TI - Aldosterone modulates I(f) current through gene expression in cultured neonatal rat ventricular myocytes. PG - H2710-8 AB - Mineralocorticoid receptor (MR) antagonists decrease the incidence of sudden cardiac death in patients with heart failure, as has been reported in two clinical trials (Randomized Aldactone Evaluation Study and Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study). Aldosterone has been shown to increase the propensity to arrhythmias by changing the expression or function of various ion channels. In this study, we investigate the effect of aldosterone on the expression of hyperpolarization-activated current (I(f)) channels in cultured neonatal rat ventricular myocytes, using the whole cell patch-clamp technique, real-time PCR, and Western blotting. Incubation with 10 nM aldosterone for 17-24 h significantly accelerates the rate of spontaneous beating by increasing diastolic depolarization. I(f) current elicited by hyperpolarization from -50 to -130 mV significantly increases aldosterone by 10 nM (by 1.9-fold). Exposure to aldosterone for 1.5 h increases hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 mRNA by 26.3% and HCN4 mRNA by 47.2%, whereas HCN1 mRNA expression remains unaffected. Aldosterone (24-h incubation) increases the expression of HCN2 protein (by 60.0%) and HCN4 protein (by 84.8%), but not HCN1 protein. MR antagonists (1 microM eplerenone or 0.1 microM spironolactone) abolish the increase of I(f) channel expression (currents, mRNA, and protein levels) by 10 nM aldosterone. In contrast, 1 microM aldosterone downregulated I(f) channel gene expression. Glucocorticoid receptor antagonist (100 nM RU-38486) did not affect the increase of I(f) current by 10 nM aldosterone. These findings suggest that aldosterone in physiological concentrations upregulates I(f) channel gene expression by MR activation in cardiac myocytes and may increase excitability, which may have a potential proarrhythmic bearing under pathophysiological conditions. AD - Research Institute of Environmental Medicine, Department of Bio-Information Analysis, Nagoya University, Nagoya 464-8601, Japan. FAU - Muto, Takao AU - Muto T FAU - Ueda, Norihiro AU - Ueda N FAU - Opthof, Tobias AU - Opthof T FAU - Ohkusa, Tomoko AU - Ohkusa T FAU - Nagata, Kohzo AU - Nagata K FAU - Suzuki, Shinsuke AU - Suzuki S FAU - Tsuji, Yukiomi AU - Tsuji Y FAU - Horiba, Mitsuru AU - Horiba M FAU - Lee, Jong-Kook AU - Lee JK FAU - Honjo, Haruo AU - Honjo H FAU - Kamiya, Kaichiro AU - Kamiya K FAU - Kodama, Itsuo AU - Kodama I FAU - Yasui, Kenji AU - Yasui K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070720 PL - United States TA - Am J Physiol Heart Circ Physiol JT - American journal of physiology. Heart and circulatory physiology JID - 100901228 RN - 0 (Cyclic Nucleotide-Gated Cation Channels) RN - 52-39-1 (Aldosterone) SB - IM MH - Aldosterone/*administration & dosage MH - Animals MH - Animals, Newborn MH - Cells, Cultured MH - Cyclic Nucleotide-Gated Cation Channels/*physiology MH - Dose-Response Relationship, Drug MH - Gene Expression Regulation, Developmental/drug effects MH - Heart Ventricles/cytology/drug effects MH - Ion Channel Gating/drug effects/*physiology MH - Myocytes, Cardiac/drug effects/*physiology MH - Rats MH - Rats, Wistar MH - Ventricular Function EDAT- 2007/07/24 09:00 MHDA- 2008/01/08 09:00 CRDT- 2007/07/24 09:00 PHST- 2007/07/20 [aheadofprint] AID - 01399.2006 [pii] AID - 10.1152/ajpheart.01399.2006 [doi] PST - ppublish SO - Am J Physiol Heart Circ Physiol. 2007 Nov;293(5):H2710-8. Epub 2007 Jul 20. PMID- 17526999 OWN - NLM STAT- MEDLINE DA - 20070528 DCOM- 20071212 LR - 20110722 IS - 1346-9843 (Print) IS - 1346-9843 (Linking) VI - 71 IP - 6 DP - 2007 Jun TI - Beta-, not alpha-adrenergic stimulation enhances conduction velocity in cultures of neonatal cardiomyocytes. PG - 973-81 AB - BACKGROUND: During both cardiac maturation and myopathy, elevated levels of circulating catecholamines coincide with alterations in impulse propagation. An in vitro model of cultured cardiomyocytes was used to study the effects of adrenergic stimulation on the conduction characteristics of immature heart cells. METHODS AND RESULTS: Neonatal rat cardiomyocytes were cultured on preparations designed to measure conduction velocity (CV). CV was measured on the same preparation twice at t=0 and at t=24 h. Under control conditions (n=7), CV at t=0 (30.9+/-1.9 cm/s) and t=24 (32.4+/-4.4 cm/s) was similar (p=0.70). Immunohistochemistry revealed expression of the gap junction proteins connexin (Cx) 40, Cx43 and Cx45, with Cx43 being highly predominant. Stimulation for 24 h with the beta-adrenergic agonist isoproterenol (ISO) significantly increased CV from 28.0 +/-2.0 cm/s at t=0 to 34.8+/-2.2 cm/s at t=24 (p=0.002, n=5). Microelectrode recordings showed a faster upstroke of the action potential (AP) of ISO-treated cells. Reverse transcribed-polymerase chain reactions (RT-PCR) showed that ISO increased expression of SCN5A and alpha(1c) (alpha-subunit of the cardiac sodium and L-type calcium channel, respectively). Stimulation of cells with ISO did not induce alterations in distribution or expression of Cx40, Cx43 and Cx45 (both mRNA and protein), but slightly increased the phosphorylation of Cx43. Stimulation for 24 h with the alpha-adrenergic agonist phenylephrine did neither affect CV nor the expression of the connexin isoforms, SCN5A and alpha(1c). CONCLUSIONS: Alpha- and beta-adrenergic stimulation differently affect propagation of the electric impulse, which is primarily not caused by a differential effect on intercellular coupling. RT-PCR analysis and an enhanced AP upstroke velocity indicate a higher functional expression level of alpha(1c) and SCN5A in beta-adrenergic stimulated cells, which may explain the observed increase in CV. AD - Department of Medical Physiology, Heart Lung Center Utrecht, Yalelaan 50, 3584 CM Utrecht, The Netherlands. FAU - de Boer, Teun P AU - de Boer TP FAU - van Rijen, Harold V M AU - van Rijen HV FAU - Van der Heyden, Marcel A G AU - Van der Heyden MA FAU - Kok, Bart AU - Kok B FAU - Opthof, Tobias AU - Opthof T FAU - Vos, Marc A AU - Vos MA FAU - Jongsma, Habo J AU - Jongsma HJ FAU - de Bakker, Jacques M T AU - de Bakker JM FAU - van Veen, Toon A B AU - van Veen TA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Japan TA - Circ J JT - Circulation journal : official journal of the Japanese Circulation Society JID - 101137683 RN - 0 (Adrenergic alpha-Agonists) RN - 0 (Adrenergic beta-Agonists) RN - 0 (Connexins) RN - 0 (Sodium Channels) RN - 0 (sodium channel protein type 5 subunit alpha) RN - 59-42-7 (Phenylephrine) RN - 7683-59-2 (Isoproterenol) SB - IM MH - Action Potentials/drug effects MH - Adrenergic alpha-Agonists/*pharmacology MH - Adrenergic beta-Agonists/*pharmacology MH - Animals MH - Animals, Newborn MH - Cardiomyopathies/*metabolism/pathology MH - Cells, Cultured MH - Connexins/metabolism MH - *Electric Conductivity MH - Heart/growth & development MH - Isoproterenol/*pharmacology MH - Models, Biological MH - Myocytes, Cardiac/*metabolism/pathology MH - Phenylephrine/*pharmacology MH - Phosphorylation/drug effects MH - Protein Processing, Post-Translational/drug effects MH - Rats MH - Rats, Wistar MH - Sodium Channels/biosynthesis EDAT- 2007/05/29 09:00 MHDA- 2007/12/13 09:00 CRDT- 2007/05/29 09:00 AID - JST.JSTAGE/circj/71.973 [pii] PST - ppublish SO - Circ J. 2007 Jun;71(6):973-81. PMID- 17391659 OWN - NLM STAT- MEDLINE DA - 20070514 DCOM- 20070917 LR - 20071203 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 74 IP - 3 DP - 2007 Jun 1 TI - Long-term cardiac memory in canine heart is associated with the evolution of a transmural repolarization gradient. PG - 416-25 AB - OBJECTIVE: The contribution of regional electrophysiologic heterogeneity to the T-wave changes of long-term cardiac memory (CM) is not known. We mapped activation and repolarization in dogs after induction of CM and in sham animals. METHODS AND RESULTS: CM was induced by three weeks of AV-sequential pacing at the anterior free wall of the left ventricle (LV), midway between apex and base in 5 dogs. In 4 sham controls a pacemaker was implanted but ventricular pacing was not performed. At 3 weeks, unipolar electrograms were recorded (98 epicardial, 120 intramural and endocardial electrodes) during atrial stimulation (cycle length 450 ms). Activation times (AT) and repolarization times (RT) were measured and activation recovery intervals (ARIs) calculated. CM was associated with 1) deeper T waves on ECG, with no change in QT interval; 2) longer activation time at the site of stimulation in CM (29.7+/-1.0, X+/-SEM) than sham (23.9+/-1.3 ms p<0.01); 3) an LV transmural gradient in repolarization time such that repolarization at the epicardium terminated 12.4+/-2.4 ms later than at the endocardium p<0.01), in contrast to no gradient in shams (2.7+/-4.2 ms); in memory dogs, the repolarization time gradient was greatest at sites around the pacing electrode varying from 13.1+/-2.3 ms to 25.5+/-3.8 ms; 4) more negative left ventricular potentials at the peak of the body surface T wave (-4.9+/-0.8 vs -2.2+/-0.4 mV; p<0.05) but no altered right ventricular epicardial T-wave potentials. ARIs did not differ between groups. Right ventricular activation was delayed but was not associated with altered repolarization because of compensatory shortening of the right ventricular ARIs. CONCLUSION: CM-induced T-wave changes are caused by evolution of transmural repolarization gradients manifested during atrial stimulation that are maximal near the site of ventricular pacing. AD - Experimental Cardiology Group, Academic Medical Center, University of Amsterdam, The Netherlands. r.coronel@amc.uva.nl FAU - Coronel, Ruben AU - Coronel R FAU - Opthof, Tobias AU - Opthof T FAU - Plotnikov, Alexei N AU - Plotnikov AN FAU - Wilms-Schopman, Francien J G AU - Wilms-Schopman FJ FAU - Shlapakova, Iryna N AU - Shlapakova IN FAU - Danilo, Peter Jr AU - Danilo P Jr FAU - Sosunov, Eugene A AU - Sosunov EA FAU - Anyukhovsky, Evgeny P AU - Anyukhovsky EP FAU - Janse, Michiel J AU - Janse MJ FAU - Rosen, Michael R AU - Rosen MR LA - eng GR - HL-67101/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20070228 PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM MH - Action Potentials MH - Animals MH - *Cardiac Pacing, Artificial MH - Dogs MH - *Electrocardiography MH - Endocardium/physiology MH - Heart Conduction System/*physiology MH - Male MH - Pericardium/physiology MH - Time Factors MH - Ventricular Function EDAT- 2007/03/30 09:00 MHDA- 2007/09/18 09:00 CRDT- 2007/03/30 09:00 PHST- 2006/10/05 [received] PHST- 2007/02/20 [revised] PHST- 2007/02/22 [accepted] PHST- 2007/02/28 [aheadofprint] AID - S0008-6363(07)00098-3 [pii] AID - 10.1016/j.cardiores.2007.02.024 [doi] PST - ppublish SO - Cardiovasc Res. 2007 Jun 1;74(3):416-25. Epub 2007 Feb 28. PMID- 17341400 OWN - NLM STAT- MEDLINE DA - 20070307 DCOM- 20070807 LR - 20091027 IS - 1547-5271 (Print) IS - 1547-5271 (Linking) VI - 4 IP - 3 DP - 2007 Mar TI - Dispersion of repolarization in canine ventricle and the electrocardiographic T wave: Tp-e interval does not reflect transmural dispersion. PG - 341-8 AB - BACKGROUND: The concept that the interval between the peak (T(peak)) and the end (T(end)) of the T wave (T(p-e)) is a measure of transmural dispersion of repolarization time is widely accepted but has not been tested rigorously by transmural mapping of the intact heart. OBJECTIVES: The purpose of this study was to test the relationship of T(p-e) to transmural dispersion of repolarization by correlating local repolarization times at endocardial, midmural, and epicardial sites in the left and right ventricles with the T wave of the ECG. METHODS: Local activation times, activation-recovery intervals, and repolarization times were measured at 98 epicardial sites and up to 120 midmural and endocardial sites in eight open-chest dogs. In four of the dogs, long-term cardiac memory was induced by 3 weeks of ventricular pacing at 130 bpm because previous data suggest that, in this setting, delayed epicardial repolarization increases transmural dispersion. The other four dogs were sham operated. RESULTS: In sham dogs, T(p-e) was 41 +/- 2.2 ms (X +/- SEM), whereas the transmural dispersion of repolarization time was 2.7 +/- 4.2 ms (not significant between endocardium and epicardium). Cardiac memory was associated with evolution of a transmural gradient of 14.5 +/- 1.9 ms (P <.02), with epicardium repolarizing later than endocardium. The corresponding T(p-e) was 43 +/- 2.3 ms (not different from sham). In combined sham and memory dogs, T(p-e) intervals did not correlate with transmural dispersion of repolarization times. In contrast, dispersion of repolarization of the whole heart (measured as the difference between the earliest and the latest moment of repolarization from all left and right ventricular, endocardial, intramural, and epicardial recording sites) did correlate with T(p-e) (P <.0005, r = 0.98), although the latter underestimated total repolarization time by approximately 35%. The explanation for this finding is that parts of the heart fully repolarize before the moment of T(peak). CONCLUSION: T(p-e) does not correlate with transmural dispersion of repolarization but is an index of total dispersion of repolarization. AD - Department of Experimental Cardiology, Experimental and Molecular Cardiology Groups, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. t.opthof@med.uu.nl FAU - Opthof, Tobias AU - Opthof T FAU - Coronel, Ruben AU - Coronel R FAU - Wilms-Schopman, Francien J G AU - Wilms-Schopman FJ FAU - Plotnikov, Alexei N AU - Plotnikov AN FAU - Shlapakova, Iryna N AU - Shlapakova IN FAU - Danilo, Peter Jr AU - Danilo P Jr FAU - Rosen, Michael R AU - Rosen MR FAU - Janse, Michiel J AU - Janse MJ LA - eng GR - HL-67101/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20061129 PL - United States TA - Heart Rhythm JT - Heart rhythm : the official journal of the Heart Rhythm Society JID - 101200317 SB - IM CIN - Heart Rhythm. 2007 Mar;4(3):349-50. PMID: 17341401 CIN - Heart Rhythm. 2007 Aug;4(8):1114-6; author reply 1116-9. PMID: 17675094 MH - Action Potentials MH - Analysis of Variance MH - Animals MH - Cardiac Pacing, Artificial MH - Dogs MH - *Electrocardiography MH - Electrodes, Implanted MH - Electrophysiologic Techniques, Cardiac MH - Endocardium/physiology MH - Female MH - Heart Conduction System/*physiology MH - Image Processing, Computer-Assisted MH - Linear Models MH - Male MH - Models, Animal MH - Models, Cardiovascular MH - Pericardium/physiology MH - Research Design MH - Ventricular Function EDAT- 2007/03/08 09:00 MHDA- 2007/08/08 09:00 CRDT- 2007/03/08 09:00 PHST- 2006/09/12 [received] PHST- 2006/11/17 [accepted] PHST- 2006/11/29 [aheadofprint] AID - S1547-5271(06)02217-X [pii] AID - 10.1016/j.hrthm.2006.11.022 [doi] PST - ppublish SO - Heart Rhythm. 2007 Mar;4(3):341-8. Epub 2006 Nov 29. PMID- 17203321 OWN - NLM STAT- MEDLINE DA - 20070716 DCOM- 20070810 IS - 0140-0118 (Print) IS - 0140-0118 (Linking) VI - 45 IP - 2 DP - 2007 Feb TI - Embryological development of pacemaker hierarchy and membrane currents related to the function of the adult sinus node: implications for autonomic modulation of biopacemakers. PG - 119-32 AB - The sinus node is an inhomogeneous structure. In the embryonic heart all myocytes have sinus node type pacemaker channels (I (f)) in their sarcolemma. Shortly before birth, these channels disappear from the ventricular myocytes. The response of the adult sinus node to changes in the interstitium, in particular to (neuro)transmitters, results from the interplay between the responses of all of its constituent cells. The response of the whole sinus node cannot be simply deduced from these cellular responses, because all cells have different responses to specific agonists. A biological pacemaker will be more homogeneous. Therefore it can be anticipated that tuning of cycle length may be problematic. It is discussed that efforts to create a biological pacemaker responsive to vagal stimulation, may be counterproductive, because it may have the potential risk of 'standstill' of the biological pacemaker. A normal sinus node remains spontaneously active at high concentrations of acetylcholine, because it has areas that are unresponsive to acetylcholine. The same is pertinent to other substances with a negative chronotropic effect. Such functional inhomogeneity is lacking in biological pacemakers. AD - Experimental and Molecular Cardiology Group, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. t.opthof@med.uu.nl FAU - Opthof, Tobias AU - Opthof T LA - eng PT - Journal Article PT - Review DEP - 20070103 PL - United States TA - Med Biol Eng Comput JT - Medical & biological engineering & computing JID - 7704869 RN - 0 (Ion Channels) SB - IM MH - Adult MH - Animals MH - Autonomic Nervous System/embryology/*physiology MH - Embryonic Stem Cells/*physiology MH - Fetal Development/physiology MH - Gene Therapy/methods MH - Humans MH - Ion Channels/*metabolism MH - Myocardial Contraction/physiology MH - Myocytes, Cardiac/physiology MH - Sinoatrial Node/embryology/*physiology MH - Stem Cell Transplantation RF - 69 EDAT- 2007/01/05 09:00 MHDA- 2007/08/11 09:00 CRDT- 2007/01/05 09:00 PHST- 2006/05/01 [received] PHST- 2006/11/22 [accepted] PHST- 2007/01/03 [aheadofprint] AID - 10.1007/s11517-006-0138-x [doi] PST - ppublish SO - Med Biol Eng Comput. 2007 Feb;45(2):119-32. Epub 2007 Jan 3. PMID- 17179951 OWN - NLM STAT- MEDLINE DA - 20070205 DCOM- 20070424 LR - 20091118 IS - 0007-1188 (Print) IS - 0007-1188 (Linking) VI - 150 IP - 3 DP - 2007 Feb TI - Omega-3 polyunsaturated fatty acids (PUFAs or fish oils) and atrial fibrillation. PG - 258-60 AD - Department of Experimental and Clinical Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. t.opthof@med.uu.nl FAU - Opthof, T AU - Opthof T FAU - Den Ruijter, H M AU - Den Ruijter HM LA - eng PT - Comment PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061218 PL - England TA - Br J Pharmacol JT - British journal of pharmacology JID - 7502536 RN - 0 (Fatty Acids, Omega-3) RN - 0 (Fish Oils) SB - IM CON - Br J Pharmacol. 2007 Feb;150(3):281-5. PMID: 17179952 MH - Animals MH - Atrial Fibrillation/*drug therapy MH - Dogs MH - Electrophysiology MH - Fatty Acids, Omega-3/*therapeutic use MH - Fish Oils/*therapeutic use MH - Research Design PMC - PMC2013891 OID - NLM: PMC2013891 EDAT- 2006/12/21 09:00 MHDA- 2007/04/25 09:00 CRDT- 2006/12/21 09:00 PHST- 2006/12/18 [aheadofprint] AID - 0706978 [pii] AID - 10.1038/sj.bjp.0706978 [doi] PST - ppublish SO - Br J Pharmacol. 2007 Feb;150(3):258-60. Epub 2006 Dec 18. PMID- 17116294 OWN - NLM STAT- MEDLINE DA - 20061225 DCOM- 20070402 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 73 IP - 2 DP - 2007 Jan 15 TI - Dietary n-3 fatty acids promote arrhythmias during acute regional myocardial ischemia in isolated pig hearts. PG - 386-94 AB - OBJECTIVE: Dietary supplementation with fish oil-derived n-3 fatty acids reduces mortality in patients with myocardial infarction, but may have adverse effects in angina patients. The underlying electrophysiologic mechanisms are poorly understood. We studied the arrhythmias and the electrophysiologic changes during regional ischemia in hearts from pigs fed a diet rich in fish oil. METHODS: Pigs received diets rich in fish oil, in sunflower oil, or a control diet for 8 weeks. Hearts were isolated and perfused. Ischemia was created by occluding the left anterior descending artery. Diastolic stimulation threshold, refractory period, conduction velocity, activation recovery intervals and the maximum downstroke velocity of 176 electrograms were measured in the ischemic zone. Spontaneous arrhythmias during 75 min of regional ischemia were counted. RESULTS: More episodes of spontaneous ischemia-induced sustained ventricular tachycardia and ventricular fibrillation occurred in the fish oil and sunflower oil group than in the control group. More inexcitable myocardium was present in the ischemic zone in the group fed fish oil or sunflower oil than in the control group after 20 min of ischemia. After 40 min of ischemia, more block occurred in the control group than in the other groups. The downstroke velocity of the electrograms in the ischemic border zone was lower in the fish oil group and sunflower oil group than in the control after 20 min. CONCLUSIONS: A diet rich in fish oil results in proarrhythmia compared to a control diet during regional ischemia in pigs. Myocardial excitability is reduced in the fish oil and sunflower oil group during the early phase of arrhythmogenesis. In the late phase of arrhythmogenesis, excitability is more reduced in the control group than in the fish oil and sunflower oil group. AD - Department of Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands. r.coronel@amc.uva.nl FAU - Coronel, Ruben AU - Coronel R FAU - Wilms-Schopman, Francien J G AU - Wilms-Schopman FJ FAU - Den Ruijter, Hester M AU - Den Ruijter HM FAU - Belterman, Charly N AU - Belterman CN FAU - Schumacher, Cees A AU - Schumacher CA FAU - Opthof, Tobias AU - Opthof T FAU - Hovenier, Robert AU - Hovenier R FAU - Lemmens, Arnoldina G AU - Lemmens AG FAU - Terpstra, Antonius H M AU - Terpstra AH FAU - Katan, Martijn B AU - Katan MB FAU - Zock, Peter AU - Zock P LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061013 PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Fatty Acids, Omega-3) RN - 0 (Plant Oils) RN - 1553-41-9 (Eicosapentaenoic Acid) RN - 25167-62-8 (Docosahexaenoic Acids) RN - 8001-21-6 (sunflower seed oil) SB - IM MH - Animals MH - Arrhythmias, Cardiac/*chemically induced/physiopathology MH - Dietary Supplements MH - Docosahexaenoic Acids/analysis/blood MH - Eicosapentaenoic Acid/analysis/blood MH - Electrocardiography MH - Fatty Acids, Omega-3/*administration & dosage MH - Heart/physiopathology MH - Male MH - Myocardial Ischemia/metabolism/physiopathology MH - Perfusion MH - Plant Oils/administration & dosage MH - Swine EDAT- 2006/11/23 09:00 MHDA- 2007/04/03 09:00 CRDT- 2006/11/23 09:00 PHST- 2006/04/28 [received] PHST- 2006/09/20 [revised] PHST- 2006/10/09 [accepted] PHST- 2006/10/13 [aheadofprint] AID - S0008-6363(06)00454-8 [pii] AID - 10.1016/j.cardiores.2006.10.006 [doi] PST - ppublish SO - Cardiovasc Res. 2007 Jan 15;73(2):386-94. Epub 2006 Oct 13. PMID- 17026972 OWN - NLM STAT- MEDLINE DA - 20061106 DCOM- 20070709 LR - 20110722 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 72 IP - 3 DP - 2006 Dec 1 TI - Why the Brugada syndrome is not yet a disease: syndromes, diseases, and genetic causality. PG - 361-3 FAU - Coronel, Ruben AU - Coronel R FAU - Berecki, Geza AU - Berecki G FAU - Opthof, Tobias AU - Opthof T LA - eng PT - Editorial DEP - 20060916 PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Sodium Channels) RN - 0 (sodium channel protein type 5 subunit alpha) SB - IM MH - Brugada Syndrome/*classification/genetics/pathology MH - Humans MH - Long QT Syndrome/genetics/pathology MH - Mutation MH - Myocardium/pathology MH - Sodium Channels/genetics EDAT- 2006/10/10 09:00 MHDA- 2007/07/10 09:00 CRDT- 2006/10/10 09:00 PHST- 2006/06/27 [received] PHST- 2006/08/15 [revised] PHST- 2006/09/12 [accepted] PHST- 2006/09/16 [aheadofprint] AID - S0008-6363(06)00403-2 [pii] AID - 10.1016/j.cardiores.2006.09.004 [doi] PST - ppublish SO - Cardiovasc Res. 2006 Dec 1;72(3):361-3. Epub 2006 Sep 16. PMID- 16945799 OWN - NLM STAT- MEDLINE DA - 20060901 DCOM- 20061220 LR - 20091027 IS - 1547-5271 (Print) IS - 1547-5271 (Linking) VI - 3 IP - 9 DP - 2006 Sep TI - Monophasic action potentials and activation recovery intervals as measures of ventricular action potential duration: experimental evidence to resolve some controversies. PG - 1043-50 AB - BACKGROUND: Activation recovery intervals (ARIs) and monophasic action potential (MAP) duration are used as measures of action potential duration in beating hearts. However, controversies exist concerning the correct way to record MAPs or calculate ARIs. We have addressed these issues experimentally. OBJECTIVES: To experimentally address the controversies concerning the correct way to record MAPs or calculate ARIs. METHODS: Left ventricular local electrograms were recorded in isolated pig hearts with an exploring electrode grid, with a KCl reference electrode on the left ventricular myocardium, the aortic root, or the left atrium. Local activation was determined from calculated Laplacian electrograms. RESULTS: With the KCl electrode on the aortic root, local electrograms represented local activation. However, with the KCl electrode on the myocardium remote from the exploring electrode, a combined electrogram emerged consisting of local activation recorded from the grid and remote activation recorded from the reference electrode. The remote, inverted monophasic component did not show propagation and did not correlate with the Laplacian complex. When the KCl electrode was placed on the atrium during AV block, remote atrial monophasic components were completely dissociated from local, ventricular deflections. At left ventricular sites with a positive T wave, the Laplacian signal showed that the end of the T wave was caused by remote repolarization. During cooling-induced regional action potential prolongation, the T wave became negative, whereby the positive flank of the T wave remained correlated with repolarization (recorded with a MAP at the same site). CONCLUSIONS: MAPs are recorded from the depolarizing electrode. In both negative and positive T waves, the moment of maximum dV/dt corresponds to local repolarization. AD - Department of Experimental Cardiology, Academic Medical Center Amsterdam, Amsterdam, The Netherlands. r.coronel@amc.uva.nl FAU - Coronel, Ruben AU - Coronel R FAU - de Bakker, Jacques M T AU - de Bakker JM FAU - Wilms-Schopman, Francien J G AU - Wilms-Schopman FJ FAU - Opthof, Tobias AU - Opthof T FAU - Linnenbank, Andre C AU - Linnenbank AC FAU - Belterman, Charly N AU - Belterman CN FAU - Janse, Michiel J AU - Janse MJ LA - eng PT - Journal Article DEP - 20060615 PL - United States TA - Heart Rhythm JT - Heart rhythm : the official journal of the Heart Rhythm Society JID - 101200317 SB - IM CIN - Heart Rhythm. 2007 Jan;4(1):119-20. PMID: 17199005 CIN - Heart Rhythm. 2006 Sep;3(9):1051-2. PMID: 16945800 CIN - Heart Rhythm. 2007 Jan;4(1):120-1; author reply 121. PMID: 17199007 MH - Action Potentials/*physiology MH - Animals MH - Arrhythmias, Cardiac/*physiopathology MH - Electrophysiologic Techniques, Cardiac MH - Female MH - Heart Conduction System/*physiology MH - Male MH - Refractory Period, Electrophysiological/physiology MH - Swine MH - *Ventricular Function EDAT- 2006/09/02 09:00 MHDA- 2006/12/21 09:00 CRDT- 2006/09/02 09:00 PHST- 2006/03/28 [received] PHST- 2006/05/30 [accepted] PHST- 2006/06/15 [aheadofprint] AID - S1547-5271(06)01601-8 [pii] AID - 10.1016/j.hrthm.2006.05.027 [doi] PST - ppublish SO - Heart Rhythm. 2006 Sep;3(9):1043-50. Epub 2006 Jun 15. PMID- 16859661 OWN - NLM STAT- MEDLINE DA - 20061225 DCOM- 20070402 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 73 IP - 2 DP - 2007 Jan 15 TI - Pro- and antiarrhythmic properties of a diet rich in fish oil. PG - 316-25 AB - Increased consumption of fish rich in omega-3 polyunsaturated fatty acids (omega3-PUFAs) is associated with decreased incidence of sudden cardiac death in post-myocardial infarction patients, but is also related to increased incidence of sudden death and arrhythmias in patients with acute myocardial ischemia. This review discusses the possible pro- and antiarrhythmic mechanisms of omega3-PUFAs in relation to various cardiac pathologies. Differences between circulating and incorporated omega3-PUFAs with respect to electrophysiology are emphasized. We conclude that omega3-PUFAs alter cardiac electrophysiology and thereby may be pro- or antiarrhythmic, dependent on the mechanism of arrhythmia. As omega3-PUFAs may be antiarrhythmic under conditions that favour triggered activity, they may facilitate re-entrant arrhythmias. This may explain the contradictory outcomes of increased intake of fish oil on sudden death and arrhythmias in clinical trials. Advice to increase intake of omega3-PUFA supplements or fatty fish should be tailored to individual patients with respect to the arrhythmogenic mechanisms associated with the underlying pathology. AD - Experimental and Molecular Cardiology Group, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. h.m.denruijter@amc.uva.nl FAU - Den Ruijter, Hester M AU - Den Ruijter HM FAU - Berecki, Geza AU - Berecki G FAU - Opthof, Tobias AU - Opthof T FAU - Verkerk, Arie O AU - Verkerk AO FAU - Zock, Peter L AU - Zock PL FAU - Coronel, Ruben AU - Coronel R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20060616 PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Fish Oils) RN - 0 (Ion Channels) SB - IM MH - Action Potentials/physiology MH - Animals MH - Arrhythmias, Cardiac/*etiology/*prevention & control MH - *Diet MH - Dietary Supplements MH - Electrocardiography MH - *Fish Oils MH - Humans MH - Ion Channels/metabolism RF - 70 EDAT- 2006/07/25 09:00 MHDA- 2007/04/03 09:00 CRDT- 2006/07/25 09:00 PHST- 2006/05/03 [received] PHST- 2006/06/06 [revised] PHST- 2006/06/08 [accepted] PHST- 2006/06/16 [aheadofprint] AID - S0008-6363(06)00269-0 [pii] AID - 10.1016/j.cardiores.2006.06.014 [doi] PST - ppublish SO - Cardiovasc Res. 2007 Jan 15;73(2):316-25. Epub 2006 Jun 16. PMID- 16762331 OWN - NLM STAT- MEDLINE DA - 20060731 DCOM- 20061006 LR - 20091119 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 71 IP - 3 DP - 2006 Aug 1 TI - Molecular aspects of adrenergic modulation of the transient outward current. PG - 430-42 AB - Transient outward channels have a different impact on action potential configuration in small mammals compared to large mammals. Small mammals depend primarily on Ito1 for repolarization, while in larger animals Ito1 only indirectly determines action potential duration by setting the level of the plateau. Transient outward channel expression and distribution also differ between animal species. Nevertheless, the primary protein sequence of the underlying Kv1.4, Kv4.2 and Kv4.3 alpha1-subunits displays remarkably high levels of amino acid identity. Transient outward channels are subject to alpha- and beta-adrenergic regulation, mainly decreasing Ito1. However, adrenergic stimulation is also an important determinant of transient outward channel downregulation in cardiac disease. Adrenergic stimulation of PKA as well as PKC leads to an inhibition of Ito1, which has been correlated with phosphorylation of the Kv1.4, Kv4.2 and Kv4.3 alpha1-subunits. Calmodulin-dependent kinase II, on the other hand, has been shown to be involved in an increase of Ito1. Comparison of Kv1.4, Kv4.2 and Kv4.3 primary amino acid sequences demonstrates a strong conservation of (potential) phosphorylation sites between different species, despite the fact that Ito1 has a different effect on action potential configuration in mammalian species. AD - Department of Medical Physiology, University Medical Center Utrecht, The Netherlands. m.a.g.vanderheyden@med.uu.nl FAU - van der Heyden, Marcel A G AU - van der Heyden MA FAU - Wijnhoven, Tessa J M AU - Wijnhoven TJ FAU - Opthof, Tobias AU - Opthof T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20060427 PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Adrenergic Agents) RN - 0 (Kv1.4 Potassium Channel) RN - 0 (Shal Potassium Channels) RN - EC 2.7.- (Protein Kinases) SB - IM MH - Action Potentials/drug effects MH - Adrenergic Agents/*pharmacology MH - Amino Acid Sequence MH - Animals MH - Heart Diseases/physiopathology MH - Kv1.4 Potassium Channel/*drug effects/genetics MH - Molecular Sequence Data MH - Phosphorylation MH - Protein Kinases/physiology MH - Sequence Alignment MH - Shal Potassium Channels/*drug effects/genetics MH - Species Specificity RF - 128 EDAT- 2006/06/10 09:00 MHDA- 2006/10/07 09:00 CRDT- 2006/06/10 09:00 PHST- 2005/09/16 [received] PHST- 2006/04/05 [revised] PHST- 2006/04/20 [accepted] PHST- 2006/04/27 [aheadofprint] AID - S0008-6363(06)00177-5 [pii] AID - 10.1016/j.cardiores.2006.04.012 [doi] PST - ppublish SO - Cardiovasc Res. 2006 Aug 1;71(3):430-42. Epub 2006 Apr 27. PMID- 16564514 OWN - NLM STAT- MEDLINE DA - 20060522 DCOM- 20070402 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 70 IP - 3 DP - 2006 Jun 1 TI - Incorporated sarcolemmal fish oil fatty acids shorten pig ventricular action potentials. PG - 509-20 AB - BACKGROUND: Omega-3 polyunsaturated fatty acids (omega3-PUFAs) from fish oil reduce the risk of sudden death presumably by preventing life-threatening arrhythmias. Acutely administered omega3-PUFAs modulate the activity of several cardiac ion channels, but the chronic effects of a diet enriched with fish oil leading to omega3-PUFA-incorporation into the sarcolemma on membrane currents are unknown. METHODS: Pigs received a diet either rich in omega3-PUFAs or in omega9-fatty acids for 8 weeks. Ventricular myocytes (VMs) were isolated and used for patch-clamp studies. RESULTS: omega3-VMs contained higher amounts of omega3-PUFAs and had a shorter action potential (AP) with a more negative plateau than control VM. In omega3 VMs, L-type Ca(2+) current (I(Ca,L)) and Na(+)-Ca(2+) exchange current (I(NCX)) were reduced by approximately 20% and 60%, respectively, and inward rectifier K(+) current (I(K1)) and slow delayed rectifier K(+) current (I(Ks)) were increased by approximately 50% and 70%, respectively, compared to control. Densities of rapid delayed rectifier K(+) current, Ca(2+)-activated Cl(-) current, and Na(+) current (I(Na)) were unchanged, although voltage-dependence of I(Na) inactivation was more negative in omega3 VMs. CONCLUSIONS: A fish oil diet increases omega3-PUFA content in the ventricular sarcolemma, decreases I(Ca,L) and I(NCX), and increases I(K1) and I(Ks), resulting in AP shortening. Incorporation of omega3-PUFAs in the sarcolemma may have consequences for arrhythmias independent of circulating omega3-PUFAs. AD - Experimental and Molecular Cardiology Group, Academic Medical Center, University of Amsterdam, The Netherlands. FAU - Verkerk, Arie O AU - Verkerk AO FAU - van Ginneken, Antoni C G AU - van Ginneken AC FAU - Berecki, Geza AU - Berecki G FAU - den Ruijter, Hester M AU - den Ruijter HM FAU - Schumacher, Cees A AU - Schumacher CA FAU - Veldkamp, Marieke W AU - Veldkamp MW FAU - Baartscheer, Antonius AU - Baartscheer A FAU - Casini, Simona AU - Casini S FAU - Opthof, Tobias AU - Opthof T FAU - Hovenier, Robert AU - Hovenier R FAU - Fiolet, Jan W T AU - Fiolet JW FAU - Zock, Peter L AU - Zock PL FAU - Coronel, Ruben AU - Coronel R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060228 PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Antioxidants) RN - 0 (Calcium Channel Blockers) RN - 0 (Calcium Channels) RN - 0 (Chromans) RN - 0 (Fatty Acids, Omega-3) RN - 0 (Fish Oils) RN - 0 (Sodium Channels) RN - 0 (Sodium-Calcium Exchanger) RN - 21829-25-4 (Nifedipine) RN - 53005-05-3 (4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid) RN - 950-99-2 (2,2,5,7,8-pentamethyl-1-hydroxychroman) SB - IM MH - 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid MH - Action Potentials/*physiology MH - Animals MH - Antioxidants/pharmacology MH - Arrhythmias, Cardiac/metabolism MH - Calcium Channel Blockers/pharmacology MH - Calcium Channels/metabolism MH - Chromans/pharmacology MH - *Diet MH - Fatty Acids, Omega-3/*administration & dosage MH - *Fish Oils MH - Heart Ventricles MH - Male MH - Membrane Potentials/physiology MH - Myocytes, Cardiac/metabolism/*physiology MH - Nifedipine/pharmacology MH - Patch-Clamp Techniques MH - Sarcolemma/metabolism/*physiology MH - Sodium Channels/metabolism MH - Sodium-Calcium Exchanger/physiology MH - Swine MH - Time Factors EDAT- 2006/03/28 09:00 MHDA- 2007/04/03 09:00 CRDT- 2006/03/28 09:00 PHST- 2005/09/13 [received] PHST- 2006/02/10 [revised] PHST- 2006/02/21 [accepted] PHST- 2006/02/28 [aheadofprint] AID - S0008-6363(06)00083-6 [pii] AID - 10.1016/j.cardiores.2006.02.022 [doi] PST - ppublish SO - Cardiovasc Res. 2006 Jun 1;70(3):509-20. Epub 2006 Feb 28. PMID- 16461816 OWN - NLM STAT- MEDLINE DA - 20060214 DCOM- 20060310 LR - 20071115 IS - 1524-4539 (Electronic) IS - 0009-7322 (Linking) VI - 113 IP - 6 DP - 2006 Feb 14 TI - Larger cell size in rabbits with heart failure increases myocardial conduction velocity and QRS duration. PG - 806-13 AB - BACKGROUND: Patients with heart failure (HF) have an increased QRS duration, usually attributed to decreased conduction velocity (CV) due to ionic remodeling but which may alternatively result from increased heart size or cellular uncoupling. We investigated the relationship between QRS width, heart size, intercellular coupling, and CV in a rabbit model of moderate HF and in computer simulations. METHODS AND RESULTS: HF was induced by pressure-volume overload. Heart weight (21.1+/-0.5 versus 10.2+/-0.4 g, mean+/-SEM; P<0.01) and QRS duration (58+/-1 versus 50+/-1 ms; P<0.01) were increased in HF versus control. Longitudinal CV (thetaL; 79+/-2 versus 67+/-4 cm/s; P<0.01) and transversal subepicardial CV (thetaT; 43+/-2 versus 37+/-2 cm/s; P<0.05) were higher in HF than in controls. Transmural CV (thetaTM) was unchanged (25+/-2 versus 24+/-1 cm/s; P=NS). Patch-clamp experiments demonstrated that sodium current was unchanged in HF versus control. Immunohistochemical experiments revealed that connexin43 content was reduced in midmyocardium but unchanged in subepicardium. Myocyte dimensions were increased in HF by approximately 30%. Simulated strands of mammalian ventricular cells (Luo-Rudy dynamic model) revealed increased thetaL and thetaT with increased myocyte size; however, increased CV could not compensate for increased strand size of longitudinally coupled cells, and consequently, total activation time was longer. CONCLUSIONS: Increased myocyte size combined with the observed expression pattern of connexin43 yields increased thetaL and thetaT and unchanged thetaTM in our nonischemic model of HF. A hypertrophied left ventricle together with insufficiently increased thetaL and unaltered thetaTM results in a prolonged QRS duration. AD - Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. R.F.Wiegerinck@amc.uva.nl FAU - Wiegerinck, Rob F AU - Wiegerinck RF FAU - Verkerk, Arie O AU - Verkerk AO FAU - Belterman, Charly N AU - Belterman CN FAU - van Veen, Toon A B AU - van Veen TA FAU - Baartscheer, Antonius AU - Baartscheer A FAU - Opthof, Tobias AU - Opthof T FAU - Wilders, Ronald AU - Wilders R FAU - de Bakker, Jacques M T AU - de Bakker JM FAU - Coronel, Ruben AU - Coronel R LA - eng PT - In Vitro PT - Journal Article DEP - 20060206 PL - United States TA - Circulation JT - Circulation JID - 0147763 RN - 0 (Connexin 43) SB - AIM SB - IM MH - Animals MH - Cardiomegaly/pathology/*physiopathology MH - Cell Communication MH - Cell Size MH - Computer Simulation MH - Connexin 43/analysis MH - Electrocardiography MH - Heart Conduction System/pathology/*physiopathology MH - Heart Failure/*pathology/physiopathology MH - Hypertrophy, Left Ventricular MH - Muscle Cells/pathology MH - Rabbits EDAT- 2006/02/08 09:00 MHDA- 2006/03/11 09:00 CRDT- 2006/02/08 09:00 PHST- 2006/02/06 [aheadofprint] AID - CIRCULATIONAHA.105.565804 [pii] AID - 10.1161/CIRCULATIONAHA.105.565804 [doi] PST - ppublish SO - Circulation. 2006 Feb 14;113(6):806-13. Epub 2006 Feb 6. PMID- 16373596 OWN - NLM STAT- MEDLINE DA - 20051223 DCOM- 20060123 LR - 20071115 IS - 0363-6135 (Print) IS - 0363-6135 (Linking) VI - 290 IP - 1 DP - 2006 Jan TI - In vivo dispersion in repolarization and arrhythmias in the human heart. PG - H77-8 FAU - Opthof, Tobias AU - Opthof T LA - eng PT - Comment PT - Editorial PL - United States TA - Am J Physiol Heart Circ Physiol JT - American journal of physiology. Heart and circulatory physiology JID - 100901228 SB - IM CON - Am J Physiol Heart Circ Physiol. 2006 Jan;290(1):H79-86. PMID: 16113076 MH - Arrhythmias, Cardiac/*physiopathology MH - Electrocardiography MH - Heart Conduction System/physiopathology MH - Humans MH - Ventricular Dysfunction/physiopathology EDAT- 2005/12/24 09:00 MHDA- 2006/01/24 09:00 CRDT- 2005/12/24 09:00 AID - 290/1/H77 [pii] AID - 10.1152/ajpheart.00954.2005 [doi] PST - ppublish SO - Am J Physiol Heart Circ Physiol. 2006 Jan;290(1):H77-8. PMID- 16272790 OWN - NLM STAT- MEDLINE DA - 20051118 DCOM- 20051228 IS - 1347-8613 (Print) IS - 1347-8613 (Linking) VI - 99 IP - 3 DP - 2005 Nov TI - Pathophysiological significance of T-type Ca2+ channels: expression of T-type Ca2+ channels in fetal and diseased heart. PG - 205-10 AB - Re-expression of fetal genes has been considered to underlie ionic remodeling in diseased heart. T-type Ca(2+) channels have been reported to be functionally expressed in embryonic hearts. In this review, we summarize developmental changes of T-type Ca(2+) channels in mouse ventricles from 9.5 days postcoitum (dpc) to adulthood, using patch clamp and quantitative PCR. In addition, we introduced T-type Ca(2+) channel expression in hypertrophied ventricles caused by myocardial infarction (MI) and aortic banding (AOB). Substantial T-type Ca(2+) channel current was recorded at both 9.5 and 18 dpc. The currents were inhibited by Ni(2+) at low concentrations. The current was not detectable in the adult stage. Ca(v)3.2 (alpha(1H)) mRNA is expressed dominantly at both 9.5 and 18 dpc. Ca(v)3.1 (alpha(1G)) increases from 9.5 to 18 dpc, but remains at low level compared with Ca(v)3.2. In contrast, Ca(v)3.1 is greater than Ca(v)3.2 at the adult stage. In MI, Ca(v)3.1 mRNA correlates negatively with brain natriuretic peptide (BNP) mRNA, whereas Ca(v)3.2 mRNA correlates positively with BNP mRNA. In AOB, these correlations are weak. We also analyzed the neuron-restrictive silencer factor (NRSF) in these hearts because it is the suppressor of transcription of the fetal cardiac gene program. The negative correlation between NRSF and BNP was stronger in MI than in AOB. Our findings show that Ca(v)3.2 underlies the functional T-type Ca(2+) channel in embryonic heart and suggest that NRSF may regulate Ca(v)3.2 expression in diseased hearts. AD - Department of Bioinformation Analysis, Research Institute of Environmental Medicine, Nagoya University, Japan. kenji@riem.nagoya-u.ac.jp FAU - Yasui, Kenji AU - Yasui K FAU - Niwa, Noriko AU - Niwa N FAU - Takemura, Haruki AU - Takemura H FAU - Opthof, Tobias AU - Opthof T FAU - Muto, Takao AU - Muto T FAU - Horiba, Mitsuru AU - Horiba M FAU - Shimizu, Atsuya AU - Shimizu A FAU - Lee, Jong-Kook AU - Lee JK FAU - Honjo, Haruo AU - Honjo H FAU - Kamiya, Kaichiro AU - Kamiya K FAU - Kodama, Itsuo AU - Kodama I LA - eng PT - Journal Article PT - Review DEP - 20051101 PL - Japan TA - J Pharmacol Sci JT - Journal of pharmacological sciences JID - 101167001 RN - 0 (Calcium Channels, T-Type) SB - IM MH - Animals MH - Calcium Channels, T-Type/analysis/*physiology MH - Fetal Heart/*metabolism MH - Humans MH - Myocardial Infarction/*metabolism MH - Myocardium/*metabolism RF - 35 EDAT- 2005/11/08 09:00 MHDA- 2005/12/29 09:00 CRDT- 2005/11/08 09:00 PHST- 2005/11/01 [aheadofprint] AID - JST.JSTAGE/jphs/FMJ05002X3 [pii] PST - ppublish SO - J Pharmacol Sci. 2005 Nov;99(3):205-10. Epub 2005 Nov 1. PMID- 16247219 OWN - NLM STAT- MEDLINE DA - 20051025 DCOM- 20060323 LR - 20061115 IS - 1346-9843 (Print) IS - 1346-9843 (Linking) VI - 69 IP - 11 DP - 2005 Nov TI - Subtype switching of L-Type Ca 2+ channel from Cav1.3 to Cav1.2 in embryonic murine ventricle. PG - 1405-11 AB - BACKGROUND: Embryonic hearts exhibit spontaneous electrical activity, which depends on Ca2+ influx through L-type Ca2+ channels. In this study the expression of the L-type Ca2+ channel alpha1 subunit gene in the developing mouse heart was investigated. METHODS AND RESULTS: Mouse cardiac ventricles 9.5 days post coitum (dpc), 18 dpc and adult were used. At 9.5 dpc the level of Cav1.3 mRNA was higher than that of Cav1.2 mRNA. With development, Cav1.2 mRNA increased and Cav1.3 mRNA decreased. Analysis of Cav1.3 splicing variants showed that Cav1.3(1b) mRNA was expressed at a higher density than Cav1.3(1a) mRNA. Cav1.3 protein was detected only at 9.5 dpc, whereas Cav1.2 protein was expressed from 9.5 dpc and its expression increased with development. L-type Ca2+ currents were prominent at 9.5 dpc. The Ca2+ current amplitude at 9.5 dpc was comparable to that at 18 dpc, and was larger in adults than at the embryonic stage. L-type Ca2+ current at 9.5 dpc was activated and/or inactivated at more negative membrane potentials than at 18 dpc or adult. L-type Ca2+ channels at 9.5 dpc were less sensitive to inhibition by nisoldipine than at adult. CONCLUSIONS: The Cav1.3 channel is functionally expressed in early embryonic mouse ventricular myocytes and potentially underlies ventricular automaticity. AD - Department of Cardio-Thoracic Surgery, Nagoya University Graduate School of Medicine, Nagoya University, Japan. FAU - Takemura, Haruki AU - Takemura H FAU - Yasui, Kenji AU - Yasui K FAU - Opthof, Tobias AU - Opthof T FAU - Niwa, Noriko AU - Niwa N FAU - Horiba, Mitsuru AU - Horiba M FAU - Shimizu, Atsuya AU - Shimizu A FAU - Lee, Jong-Kook AU - Lee JK FAU - Honjo, Haruo AU - Honjo H FAU - Kamiya, Kaichiro AU - Kamiya K FAU - Ueda, Yuichi AU - Ueda Y FAU - Kodama, Itsuo AU - Kodama I LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Japan TA - Circ J JT - Circulation journal : official journal of the Japanese Circulation Society JID - 101137683 RN - 0 (Cacna1d protein, mouse) RN - 0 (Calcium Channel Blockers) RN - 0 (Calcium Channels, L-Type) RN - 0 (L-type calcium channel alpha(1C)) RN - 0 (RNA, Messenger) RN - 63675-72-9 (Nisoldipine) RN - 7440-70-2 (Calcium) SB - IM MH - Animals MH - Calcium/metabolism MH - Calcium Channel Blockers/pharmacology MH - Calcium Channels, L-Type/*biosynthesis MH - Electric Conductivity MH - Female MH - Gene Expression Regulation, Developmental/*physiology MH - Heart Ventricles/embryology/enzymology MH - Ion Transport/drug effects MH - Male MH - Membrane Potentials/drug effects MH - Mice MH - Nisoldipine/pharmacology MH - Organ Culture Techniques MH - RNA, Messenger/biosynthesis EDAT- 2005/10/26 09:00 MHDA- 2006/03/24 09:00 CRDT- 2005/10/26 09:00 AID - JST.JSTAGE/circj/69.1405 [pii] PST - ppublish SO - Circ J. 2005 Nov;69(11):1405-11. PMID- 16203908 OWN - NLM STAT- MEDLINE DA - 20051011 DCOM- 20060302 LR - 20081121 IS - 1524-4539 (Electronic) IS - 0009-7322 (Linking) VI - 112 IP - 15 DP - 2005 Oct 11 TI - Discontinuous conduction in mouse bundle branches is caused by bundle-branch architecture. PG - 2235-44 AB - BACKGROUND: Recordings of the electrical activity of mouse bundle branches (BBs) suggest reduced conduction velocity (CV) in the midseptal compared with the proximal part of the BB. The present study was performed to elucidate the mechanism responsible for this slowing of conduction. METHODS AND RESULTS: Hearts of 16 mice were isolated and Langendorff perfused. After the right and left ventricular free walls were removed, the extracellular activity of the BB was mapped with a 247-point electrode. Premature stimulation was used to estimate CV restitution in the BBs. Expression/distribution of connexin40 (Cx40), Cx43, and Cx45 was determined. Morphology of the conduction system was assessed by whole-mount acetylcholine esterase staining and in Cx40(+/KI-GFP) hearts. Effective CV in the midseptal part of the left and right BBs was reduced by 50% compared with the proximal BB. CV restitution in the proximal and midseptal parts of the BBs was similar. Myocytes labeled positive for Cx40 and Cx45 in the entire BB. Cx43 colocalized with Cx40 and Cx45 only in the very distal BB. Subcellular distribution of gap junctions differed between proximal and distal BBs. Geometry of the midseptal and distal BBs revealed on both sides a profuse network of interlacing fibers, whereas the proximal BB consisted of a single (right BB) or multiple (left BB) parallel fibers. CONCLUSIONS: Comparison of connexin expression/distribution, geometry of the BBs, and CV characteristics suggests that increased path length for activation resulting from BB geometry is responsible for the apparently reduced CV in the midseptal BB of the mouse heart. AD - Department of Medical Physiology, University Medical Center Utrecht, Utrecht, The Netherlands. A.A.B.vanVeen@med.uu.nl FAU - van Veen, Toon A B AU - van Veen TA FAU - van Rijen, Harold V M AU - van Rijen HV FAU - van Kempen, Marjan J A AU - van Kempen MJ FAU - Miquerol, Lucile AU - Miquerol L FAU - Opthof, Tobias AU - Opthof T FAU - Gros, Daniel AU - Gros D FAU - Vos, Marc A AU - Vos MA FAU - Jongsma, Habo J AU - Jongsma HJ FAU - de Bakker, Jacques M T AU - de Bakker JM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20051003 PL - United States TA - Circulation JT - Circulation JID - 0147763 RN - 0 (Connexins) RN - 0 (connexin 40) SB - AIM SB - IM MH - Animals MH - Bundle of His/*physiology/physiopathology MH - Bundle-Branch Block/*etiology/pathology/physiopathology MH - Connexins/genetics MH - Disease Models, Animal MH - Electrophysiology/methods MH - Heart Conduction System/*physiology MH - Immunohistochemistry MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Neural Conduction/*physiology MH - Promoter Regions, Genetic EDAT- 2005/10/06 09:00 MHDA- 2006/03/03 09:00 CRDT- 2005/10/06 09:00 PHST- 2005/10/03 [aheadofprint] AID - CIRCULATIONAHA.105.547893 [pii] AID - 10.1161/CIRCULATIONAHA.105.547893 [doi] PST - ppublish SO - Circulation. 2005 Oct 11;112(15):2235-44. Epub 2005 Oct 3. PMID- 16171753 OWN - NLM STAT- MEDLINE DA - 20050920 DCOM- 20060606 LR - 20100526 IS - 1547-5271 (Print) IS - 1547-5271 (Linking) VI - 2 IP - 9 DP - 2005 Sep TI - The hidden secrets of the hibernator's heart may protect against arrhythmias. PG - 976-8 FAU - van der Heyden, Marcel A G AU - van der Heyden MA FAU - Opthof, Tobias AU - Opthof T LA - eng PT - Comment PT - Editorial PL - United States TA - Heart Rhythm JT - Heart rhythm : the official journal of the Heart Rhythm Society JID - 101200317 RN - 0 (Connexin 43) RN - 0 (Connexins) RN - 0 (connexin 45) SB - IM CON - Heart Rhythm. 2005 Sep;2(9):966-75. PMID: 16171752 MH - Animals MH - Blood Flow Velocity MH - Connexin 43/metabolism MH - Connexins/metabolism MH - Heart Arrest, Induced MH - Heart Block/prevention & control MH - Heart Conduction System/*metabolism/physiopathology MH - Heart Rate MH - Humans MH - *Hypothermia, Induced MH - Myocardial Contraction MH - Tachycardia/*metabolism/physiopathology/*prevention & control MH - Up-Regulation EDAT- 2005/09/21 09:00 MHDA- 2006/06/07 09:00 CRDT- 2005/09/21 09:00 PHST- 2005/06/27 [received] AID - S1547-5271(05)01778-9 [pii] AID - 10.1016/j.hrthm.2005.06.028 [doi] PST - ppublish SO - Heart Rhythm. 2005 Sep;2(9):976-8. PMID- 16157774 OWN - NLM STAT- MEDLINE DA - 20050920 DCOM- 20060309 LR - 20071114 IS - 1524-4539 (Electronic) IS - 0009-7322 (Linking) VI - 112 IP - 12 DP - 2005 Sep 20 TI - Repolarization gradients in the canine left ventricle before and after induction of short-term cardiac memory. PG - 1711-8 AB - BACKGROUND: Questions remain about the contributions of transmural versus apicobasal repolarization gradients to the configuration of the T wave in control settings and after the induction of short-term cardiac memory. METHODS AND RESULTS: Short-term cardiac memory is seen as T-wave changes induced by altered ventricular activation that persists after restoration of sinus rhythm. We studied cardiac memory in anesthetized, open-chest dogs paced from the ventricle for 2 hours. Unipolar electrograms were recorded from as many as 98 epicardial and 144 intramural sites, and activation times and activation-recovery intervals (ARIs) were measured. In separate experiments, epicardial monophasic action potentials were recorded. We found no appreciable left ventricular intramural gradients in repolarization times (activation time+ARI) in either control conditions or after the induction of memory. In controls, there was a left ventricular apicobasal gradient, with the shortest repolarization times in anterobasal regions and longest repolarization times posteroapically. After induction of memory, repolarization times shortened uniformly throughout the ventricular wall. Monophasic action potential duration at 90% repolarization decreased by approximately 10 ms after induction of memory. CONCLUSIONS: In the intact canine left ventricle at physiological rates, there is no transmural gradient in repolarization. Apicobasal gradients in repolarization time, with shortest repolarization times in anterobasal areas and longest repolarization times in posteroapical regions, are important in the genesis of the T wave. Repolarization times and monophasic action potentials at the 90% repolarization level shorten after the induction of memory. The deeper T wave in the ECG after induction of memory may be explained by the more rapid phase 3 of the action potential. AD - Center for Molecular Therapeutics, Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, USA. m.j.janse@amc.uva.nl FAU - Janse, Michiel J AU - Janse MJ FAU - Sosunov, Eugene A AU - Sosunov EA FAU - Coronel, Ruben AU - Coronel R FAU - Opthof, Tobias AU - Opthof T FAU - Anyukhovsky, Evgeny P AU - Anyukhovsky EP FAU - de Bakker, Jacques M T AU - de Bakker JM FAU - Plotnikov, Alexei N AU - Plotnikov AN FAU - Shlapakova, Iryna N AU - Shlapakova IN FAU - Danilo, Peter Jr AU - Danilo P Jr FAU - Tijssen, Jan G P AU - Tijssen JG FAU - Rosen, Michael R AU - Rosen MR LA - eng GR - HL-67101/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20050912 PL - United States TA - Circulation JT - Circulation JID - 0147763 SB - AIM SB - IM MH - Action Potentials/*physiology MH - Animals MH - Blood Pressure MH - Dogs MH - Electrocardiography MH - Electroshock MH - Heart Conduction System/*physiology MH - Male MH - Membrane Potentials/physiology MH - Models, Animal MH - Ventricular Function, Left/*physiology EDAT- 2005/09/15 09:00 MHDA- 2006/03/10 09:00 CRDT- 2005/09/15 09:00 PHST- 2005/09/12 [aheadofprint] AID - CIRCULATIONAHA.104.516583 [pii] AID - 10.1161/CIRCULATIONAHA.104.516583 [doi] PST - ppublish SO - Circulation. 2005 Sep 20;112(12):1711-8. Epub 2005 Sep 12. PMID- 16054611 OWN - NLM STAT- MEDLINE DA - 20051014 DCOM- 20060310 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 68 IP - 2 DP - 2005 Nov 1 TI - Transmural dispersion in LQT3 and arrhythmogenesis. PG - 336-7; author reply 338-9 FAU - Opthof, Tobias AU - Opthof T FAU - Coronel, Ruben AU - Coronel R LA - eng PT - Letter DEP - 20050728 PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Sodium Channels) RN - 71-62-5 (Veratridine) SB - IM MH - Action Potentials/drug effects MH - Animals MH - Arrhythmias, Cardiac/*etiology MH - Electrocardiography/drug effects MH - Humans MH - Long QT Syndrome/*metabolism MH - Models, Animal MH - Rabbits MH - Sodium Channels/*drug effects MH - Veratridine/*pharmacology EDAT- 2005/08/02 09:00 MHDA- 2006/03/11 09:00 CRDT- 2005/08/02 09:00 PHST- 2005/02/02 [received] PHST- 2005/07/08 [accepted] PHST- 2005/07/28 [aheadofprint] AID - S0008-6363(05)00371-8 [pii] AID - 10.1016/j.cardiores.2005.07.006 [doi] PST - ppublish SO - Cardiovasc Res. 2005 Nov 1;68(2):336-7; author reply 338-9. Epub 2005 Jul 28. PMID- 16023179 OWN - NLM STAT- MEDLINE DA - 20060807 DCOM- 20061128 LR - 20081121 IS - 0079-6107 (Print) IS - 0079-6107 (Linking) VI - 92 IP - 3 DP - 2006 Nov TI - Ventricular repolarization: an overview of (patho)physiology, sympathetic effects and genetic aspects. PG - 269-307 AB - Most textbook knowledge on ventricular repolarization is based on animal data rather than on data from the in vivo human heart. Yet, these data have been extrapolated to the human heart, often without an appropriate caveat. Here, we review multiple aspects of repolarization, from basic membrane currents to cellular aspects including extrinsic factors such as the effects of the sympathetic nervous system. We critically discuss some mechanistic aspects of the genesis of the T-wave of the ECG in the human heart. Obviously, the T-wave results from the summation of repolarization all over the heart. The T-wave in a local electrogram ideally reflects local repolarization. The repolarization moment is composed of the moment of local activation plus local action potential duration (APD) at 90% repolarization (APD90). The duration of the latter largely depends on the balance between L-type Ca2+ current and the delayed rectifier currents. Generally speaking, there is an inverse relationship between local activation time and local APD90, leading to less dispersion in repolarization moments than in activation moments or in APD90. In transmural direction, the time needed for activation from endocardium toward epicardium has been considered to be overcompensated by shorter APD90 at the epicardium, leading to the earliest repolarization at the subepicardium. In addition, mid-myocardial cells would display the latest repolarization moments. The sparse human data available, however, do not show any transmural dispersion in repolarization moment. Also, the effect of adrenergic stimulation on APD90 has been studied mainly in animals. Again, sparse human data suggest that the effect of adrenergic stimulation is different in the human heart compared to many other mammalian hearts. Finally, aspects of the long QT syndrome are discussed, because this intrinsic genetic disease results from repolarization disorders with extrinsic aspects. AD - Department of Cardiology, University Medical Center, Utrecht, The Netherlands. c.e.conrath@med.uu.nl FAU - Conrath, Chantal E AU - Conrath CE FAU - Opthof, Tobias AU - Opthof T LA - eng PT - Journal Article PT - Review DEP - 20050617 PL - England TA - Prog Biophys Mol Biol JT - Progress in biophysics and molecular biology JID - 0401233 RN - 0 (Adrenergic beta-Antagonists) RN - 0 (Calcium Channels, L-Type) SB - IM MH - Action Potentials/physiology MH - Adrenergic beta-Antagonists/pharmacology MH - Animals MH - Calcium Channels, L-Type/physiology MH - *Electrocardiography MH - *Electrophysiology MH - Heart/*physiology MH - Heart Conduction System/*physiology MH - Humans MH - Long QT Syndrome/genetics/pathology MH - Myocardium/cytology/metabolism MH - Sympathetic Nervous System/*physiology MH - *Ventricular Function RF - 149 EDAT- 2005/07/19 09:00 MHDA- 2006/12/09 09:00 CRDT- 2005/07/19 09:00 PHST- 2005/06/17 [aheadofprint] AID - S0079-6107(05)00033-7 [pii] AID - 10.1016/j.pbiomolbio.2005.05.009 [doi] PST - ppublish SO - Prog Biophys Mol Biol. 2006 Nov;92(3):269-307. Epub 2005 Jun 17. PMID- 15979600 OWN - NLM STAT- MEDLINE DA - 20050711 DCOM- 20060113 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 67 IP - 2 DP - 2005 Aug 1 TI - The hills and valleys of an impact factor. PG - 175 FAU - Piper, Hans Michael AU - Piper HM FAU - Martinson, Elizabeth A AU - Martinson EA FAU - Opthof, Tobias AU - Opthof T LA - eng PT - Editorial PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM MH - Bibliometrics MH - *Cardiology MH - Humans MH - *Information Dissemination MH - *Periodicals as Topic MH - Research EDAT- 2005/06/28 09:00 MHDA- 2006/01/18 09:00 CRDT- 2005/06/28 09:00 AID - S0008-6363(05)00286-5 [pii] AID - 10.1016/j.cardiores.2005.06.001 [doi] PST - ppublish SO - Cardiovasc Res. 2005 Aug 1;67(2):175. PMID- 15979057 OWN - NLM STAT- MEDLINE DA - 20050711 DCOM- 20060113 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 67 IP - 2 DP - 2005 Aug 1 TI - The patient U wave. PG - 184-6 FAU - Conrath, Chantal E AU - Conrath CE FAU - Opthof, Tobias AU - Opthof T LA - eng PT - Editorial PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM MH - *Computer Simulation MH - Diastole MH - *Electrocardiography MH - Heart/*physiopathology MH - Heart Diseases/*physiopathology MH - Humans MH - *Models, Cardiovascular MH - Myocardial Contraction EDAT- 2005/06/28 09:00 MHDA- 2006/01/18 09:00 CRDT- 2005/06/28 09:00 PHST- 2005/05/23 [received] PHST- 2005/05/31 [accepted] AID - S0008-6363(05)00281-6 [pii] AID - 10.1016/j.cardiores.2005.05.027 [doi] PST - ppublish SO - Cardiovasc Res. 2005 Aug 1;67(2):184-6. PMID- 15910881 OWN - NLM STAT- MEDLINE DA - 20050524 DCOM- 20050914 LR - 20110722 IS - 0022-2828 (Print) IS - 0022-2828 (Linking) VI - 38 IP - 6 DP - 2005 Jun TI - A mutation in the human cardiac sodium channel (E161K) contributes to sick sinus syndrome, conduction disease and Brugada syndrome in two families. PG - 969-81 AB - BACKGROUND: Mutations in the gene encoding the human cardiac sodium channel (SCN5A) have been associated with three distinct cardiac arrhythmia disorders: the long QT syndrome, the Brugada syndrome and cardiac conduction disease. Here we report the biophysical features of a novel sodium channel mutation, E161K, which we identified in individuals of two non-related families with symptoms of bradycardia, sinus node dysfunction, generalized conduction disease and Brugada syndrome, or combinations thereof. METHODS AND RESULTS: Wild-type (WT) or E161K sodium channel alpha-subunit and beta-subunit were cotransfected into tsA201 cells to study the functional consequences of mutant sodium channels. Characterization of whole-cell sodium current (I(Na)) using the whole cell patch-clamp technique revealed that the E161K mutation caused an almost threefold reduction in current density (P < 0.001), and an 11.9 mV positive shift of the voltage-dependence of activation (P < 0.0001). The inactivation properties of mutant and WT sodium channels were similar. These results suggest an overall reduction of E161K I(Na). Incorporation of the experimental findings into computational models demonstrate atrial and ventricular conduction slowing as well as a reduction in sinus rate by slowing of the diastolic depolarization rate and upstroke velocity of the sinus node action potential. This reduction in sinus rate was aggravated by application of acetylcholine, simulating the dominant vagal tone during night. CONCLUSION: Our experimental and computational analysis of the E161K mutation suggests that a loss of sodium channel function is not only associated with Brugada syndrome and conduction disease, but may also cause sinus node dysfunction in carriers of this mutation. AD - Experimental and Molecular Cardiology Group, Academic Medical Center, University of Amsterdam, The Netherlands. FAU - Smits, Jeroen P P AU - Smits JP FAU - Koopmann, Tamara T AU - Koopmann TT FAU - Wilders, Ronald AU - Wilders R FAU - Veldkamp, Marieke W AU - Veldkamp MW FAU - Opthof, Tobias AU - Opthof T FAU - Bhuiyan, Zahir A AU - Bhuiyan ZA FAU - Mannens, Marcel M A M AU - Mannens MM FAU - Balser, Jeffrey R AU - Balser JR FAU - Tan, Hanno L AU - Tan HL FAU - Bezzina, Connie R AU - Bezzina CR FAU - Wilde, Arthur A M AU - Wilde AA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050401 PL - England TA - J Mol Cell Cardiol JT - Journal of molecular and cellular cardiology JID - 0262322 RN - 0 (Sodium Channels) RN - 0 (sodium channel protein type 5 subunit alpha) RN - 51-84-3 (Acetylcholine) SB - IM CIN - J Mol Cell Cardiol. 2005 Jun;38(6):965-8. PMID: 15878172 MH - Acetylcholine/metabolism MH - Adult MH - Arrhythmias, Cardiac/genetics MH - Computer Simulation MH - DNA Mutational Analysis MH - Electrocardiography MH - Electrophysiology MH - Family Health MH - Female MH - Genotype MH - Haplotypes MH - Heart Conduction System MH - Humans MH - Long QT Syndrome/genetics MH - Male MH - Middle Aged MH - Mutation MH - Patch-Clamp Techniques MH - Pedigree MH - Phenotype MH - Sick Sinus Syndrome/*genetics MH - Sodium Channels/*genetics/*physiology MH - Syndrome MH - Time Factors MH - Transfection EDAT- 2005/05/25 09:00 MHDA- 2005/09/15 09:00 CRDT- 2005/05/25 09:00 PHST- 2004/08/05 [received] PHST- 2005/02/04 [revised] PHST- 2005/02/08 [accepted] PHST- 2005/04/01 [aheadofprint] AID - S0022-2828(05)00061-1 [pii] AID - 10.1016/j.yjmcc.2005.02.024 [doi] PST - ppublish SO - J Mol Cell Cardiol. 2005 Jun;38(6):969-81. Epub 2005 Apr 1. PMID- 15851345 OWN - NLM STAT- MEDLINE DA - 20050426 DCOM- 20050613 LR - 20091027 IS - 1547-5271 (Print) IS - 1547-5271 (Linking) VI - 2 IP - 4 DP - 2005 Apr TI - Prediction of atrial fibrillation: Role of the atrial gradient. PG - 411-2 AD - Experimental and Molecular Cardiology Groups, Academic Medical Center, Amsterdam, The Netherlands and Department of Medical Physiology, University Medical Center Utrecht, Utrecht, The Netherlands. t.opthof@med.uu.nl FAU - Opthof, Tobias AU - Opthof T LA - eng PT - Comment PT - Editorial PL - United States TA - Heart Rhythm JT - Heart rhythm : the official journal of the Heart Rhythm Society JID - 101200317 SB - IM CON - Heart Rhythm. 2005 Apr;2(4):404-10. PMID: 15851344 MH - Animals MH - Atrial Fibrillation/*physiopathology MH - Cardiac Pacing, Artificial MH - *Electrophysiologic Techniques, Cardiac MH - Humans EDAT- 2005/04/27 09:00 MHDA- 2005/07/29 09:00 CRDT- 2005/04/27 09:00 AID - S1547-5271(05)00097-4 [pii] AID - 10.1016/j.hrthm.2005.01.014 [doi] PST - ppublish SO - Heart Rhythm. 2005 Apr;2(4):411-2. PMID- 15791049 OWN - NLM STAT- MEDLINE DA - 20050325 DCOM- 20051018 LR - 20071115 IS - 1346-9843 (Print) IS - 1346-9843 (Linking) VI - 69 IP - 4 DP - 2005 Apr TI - Decreased vagal control over heart rate in rats with right-sided congestive heart failure: downregulation of neuronal nitric oxide synthase. PG - 493-9 AB - BACKGROUND: Parasympathetic drive is attenuated in heart failure, and resulting autonomic imbalance may increase the risk of sudden cardiac death. The anatomic site(s) and molecular mechanisms underlying this parasympathetic withdrawal are unknown. METHODS AND RESULTS: We examined the effects of pre- and post-ganglionic vagal nerve stimulation (VS) and acetylcholine (ACh) application on the heart rate of rats with right-sided congestive heart failure (CHF) induced by monocrotaline. Heart rate reduction in response to pre-ganglionic VS in CHF rats in vivo was significantly less than in controls. The suppression of spontaneous beating of isolated right atria including the whole sinoatrial (SA) node in response to post-ganglionic VS was significantly attenuated in CHF rats as well. In contrast, ACh application to the right atria resulted in a significantly larger suppression of spontaneous beating in CHF rats than controls. Proteins of neuronal nitric oxide synthase (nNOS) in the right atria were significantly decreased, whereas muscarinic (M2) receptor was significantly increased in CHF rats compared with controls. CONCLUSIONS: Both pre-and post-ganglionic vagal nerve functions are diminished in CHF rats, whereas M2 receptor-mediated regulation of the SA node is upregulated. Downregulation of nNOS may be involved in this parasympathetic withdrawal. AD - Department of Circulation and Humoral Regulation, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan. FAU - Nihei, Motoki AU - Nihei M FAU - Lee, Jong-Kook AU - Lee JK FAU - Honjo, Haruo AU - Honjo H FAU - Yasui, Kenji AU - Yasui K FAU - Uzzaman, Mahmud AU - Uzzaman M FAU - Kamiya, Kaichiro AU - Kamiya K FAU - Opthof, Tobias AU - Opthof T FAU - Kodama, Itsuo AU - Kodama I LA - eng PT - In Vitro PT - Journal Article PL - Japan TA - Circ J JT - Circulation journal : official journal of the Japanese Circulation Society JID - 101137683 RN - 0 (Nerve Tissue Proteins) RN - 0 (Receptor, Muscarinic M2) RN - 315-22-0 (Monocrotaline) RN - 51-84-3 (Acetylcholine) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type I) RN - EC 1.14.13.39 (Nos1 protein, rat) SB - IM MH - Acetylcholine/pharmacology MH - Animals MH - Atrial Function, Right MH - Down-Regulation MH - Heart Atria/chemistry/enzymology MH - Heart Failure/chemically induced/*physiopathology MH - Heart Rate/*physiology MH - Male MH - Monocrotaline/pharmacology MH - Nerve Tissue Proteins/analysis/*genetics/physiology MH - Nitric Oxide Synthase/analysis/*genetics/physiology MH - Nitric Oxide Synthase Type I MH - Rats MH - Rats, Wistar MH - Receptor, Muscarinic M2/analysis/physiology MH - Sinoatrial Node MH - Vagus Nerve/*physiology EDAT- 2005/03/26 09:00 MHDA- 2005/10/19 09:00 CRDT- 2005/03/26 09:00 AID - JST.JSTAGE/circj/69.493 [pii] PST - ppublish SO - Circ J. 2005 Apr;69(4):493-9. PMID- 15621036 OWN - NLM STAT- MEDLINE DA - 20041228 DCOM- 20050302 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 65 IP - 1 DP - 2005 Jan 1 TI - Chronic inhibition of Na+/H+-exchanger attenuates cardiac hypertrophy and prevents cellular remodeling in heart failure. PG - 83-92 AB - OBJECTIVE: In patients with heart disease, the transition from compensatory hypertrophy to heart failure (HF) is associated with altered calcium handling. Up-regulated Na(+)/H(+)-exchanger (NHE-1) activity underlies increased [Na(+)](i) and disturbance of cellular calcium handling in HF. We hypothesize that chronic inhibition of NHE-1 activity prevents the hypertrophic response, cellular remodeling, and development of HF. METHODS: Rabbits received a control or cariporide (inhibitor of NHE-1) diet for 3 months, starting after induction of combined volume and pressure overload. Age-matched animals served as control. Development of HF was examined echocardiographically and electrocardiographically after 3 months. [Na(+)](i), [Ca(2+)](i), pH(i), and action potentials were measured in left ventricular midmural myocytes with SBFI, indo-1, SNARF, and di-4-anepps. Sarcoplasmic reticulum calcium content was calculated from the response of [Ca(2+)](i) to rapid cooling. Calcium after-transients were elicited by cessation of rapid stimulation (3 Hz) in the presence of 100 nmol/l noradrenalin. RESULTS: Chronic treatment of rabbits with the specific Na(+)/H(+)-exchanger activity inhibitor cariporide greatly attenuated development of hypertrophy and entirely abolished development of HF; the heart/body weight ratio increased only little, no change in lung weight occurred, left ventricular dimensions and fractional shortening changed mildly, ascites was not present, QT duration did not increase, and sudden death did not occur. Chronic cariporide treatment also prevented cellular electrical and ionic remodeling. Myocyte dimensions were unaltered, action potentials were not prolonged, cytoplasmic sodium and NHE-1 activity did not increase, cytoplasmic and SR calcium handling remained undisturbed, and no increase of the incidence of calcium after-transient dependent delayed after depolarizations (DADs) occurred. CONCLUSION: We conclude that enhanced activity of NHE-1 underlies cardiac cellular electrical and ionic remodeling in experimental heart failure, and that chronic dietary treatment with cariporide attenuates hypertrophy, development of HF, and cellular remodeling. AD - Experimental Cardiology, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. a.Baartscheer@AMC.UVA.NL FAU - Baartscheer, Antonius AU - Baartscheer A FAU - Schumacher, Cees A AU - Schumacher CA FAU - van Borren, Marcel M G J AU - van Borren MM FAU - Belterman, Charly N W AU - Belterman CN FAU - Coronel, Ruben AU - Coronel R FAU - Opthof, Tobias AU - Opthof T FAU - Fiolet, Jan W T AU - Fiolet JW LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Guanidines) RN - 0 (Sodium-Hydrogen Antiporter) RN - 0 (Sulfones) RN - 0 (cariporide) RN - 0 (growth factor-activatable Na-H exchanger NHE-1) RN - 7440-70-2 (Calcium) SB - IM CIN - Cardiovasc Res. 2005 Jan 1;65(1):10-2. PMID: 15621028 MH - Action Potentials MH - Animals MH - Calcium/metabolism MH - Cardiomegaly/diagnosis/metabolism/*prevention & control MH - Cytoplasm/metabolism MH - Echocardiography MH - Electrocardiography MH - Guanidines/*therapeutic use MH - Heart Failure/diagnosis/*drug therapy/metabolism MH - Male MH - Rabbits MH - Sarcoplasmic Reticulum/metabolism MH - Sodium-Hydrogen Antiporter/*antagonists & inhibitors/metabolism MH - Sulfones/*therapeutic use MH - Ventricular Remodeling EDAT- 2004/12/29 09:00 MHDA- 2005/03/03 09:00 CRDT- 2004/12/29 09:00 PHST- 2004/05/14 [received] PHST- 2004/08/26 [revised] PHST- 2004/09/23 [accepted] AID - S0008-6363(04)00427-4 [pii] AID - 10.1016/j.cardiores.2004.09.024 [doi] PST - ppublish SO - Cardiovasc Res. 2005 Jan 1;65(1):83-92. PMID- 15621031 OWN - NLM STAT- MEDLINE DA - 20041228 DCOM- 20050302 LR - 20091119 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 65 IP - 1 DP - 2005 Jan 1 TI - Molecular aspects of adrenergic modulation of cardiac L-type Ca2+ channels. PG - 28-39 AB - L-type Ca(2+) channels are predominantly regulated by beta-adrenergic stimulation, enhancing L-type Ca(2+) current by increasing the mean channel open time and/or the opening probability of functional Ca(2+) channels. Stimulation of beta-adrenergic receptors (ARs) results in an increased cyclic adenosine monophosphate (cAMP) production by adenylate cyclase (AC) and consequently activation of protein kinase (PK) A and phosphorylation of L-type Ca(2+) channels by this enzyme. Beta(1)-Adrenergic receptors couple exclusively to the G protein Gs, producing a widespread increase in cAMP levels in the cell, whereas beta(2)-adrenergic receptors couple to both Gs and Gi, producing a more localized activation of L-type Ca(2+) channels. Other signaling intermediates (protein kinase C, protein kinase G or protein tyrosine kinase (PTK)) either have negative effects on L-type Ca(2+) current, or they interact with the stimulatory effect of the protein kinase A pathway. AD - Department of Medical Physiology, University Medical Center Utrecht, P.O. Box 85060, 3508 AB Utrecht, The Netherlands. m.a.g.vanderheyden@med.uu.nl FAU - van der Heyden, Marcel A G AU - van der Heyden MA FAU - Wijnhoven, Tessa J M AU - Wijnhoven TJ FAU - Opthof, Tobias AU - Opthof T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Adrenergic Agents) RN - 0 (Calcium Channels, L-Type) RN - 0 (Receptors, Adrenergic) RN - 7440-70-2 (Calcium) RN - EC 2.7.- (Protein Kinases) SB - IM MH - Adrenergic Agents/*pharmacology MH - Amino Acid Sequence MH - Animals MH - Calcium/metabolism MH - Calcium Channels, L-Type/drug effects/genetics/*metabolism MH - Humans MH - *Ion Channel Gating MH - Molecular Sequence Data MH - Myocardium/*metabolism MH - Protein Kinases/metabolism MH - Receptors, Adrenergic/*metabolism MH - Sequence Alignment RF - 89 EDAT- 2004/12/29 09:00 MHDA- 2005/03/03 09:00 CRDT- 2004/12/29 09:00 PHST- 2004/07/28 [received] PHST- 2004/09/22 [revised] PHST- 2004/09/29 [accepted] AID - S0008-6363(04)00431-6 [pii] AID - 10.1016/j.cardiores.2004.09.028 [doi] PST - ppublish SO - Cardiovasc Res. 2005 Jan 1;65(1):28-39. PMID- 15094360 OWN - NLM STAT- MEDLINE DA - 20040419 DCOM- 20040920 LR - 20041117 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 62 IP - 2 DP - 2004 May 1 TI - Intercellular coupling through gap junctions masks M cells in the human heart. PG - 407-14 AB - OBJECTIVES: M cells have been described in many mammalian species. They are thought to be relevant for the genesis of long QT intervals, afterdepolarizations and for dispersion in action potential duration and in repolarization time. Their role in the human heart is subject to debate. METHODS: We simulated action potential propagation in a strand of transversally oriented myocytes running from endocardium towards epicardium through the left ventricular free wall. The characteristics of the myocytes were either based on the Priebe-Beuckelmann ventricular cell model or on the Luo-Rudy ventricular cell model. The former model is based on the latter and includes adaptations in order to mimic the human ventricular myocyte. The amount and location of M cells as well as the intercellular coupling through gap junctions were varied. Also, we assessed action potential duration in a Langendorff-perfused explanted human heart and in a wedge preparation obtained from such a heart. RESULTS: At low, but physiological intercellular coupling conductance, the inclusion of M cells leads to a much longer 'QT interval' in the simulations than in the in vivo or isolated human heart. Dispersion in repolarization time becomes unphysiologically large when M cells are included in the strand and is also substantially larger than in the in vivo or isolated human heart. At stronger intercellular coupling this effect disappears. CONCLUSIONS: The manifestation of M cells is absent in the human heart, probably by effective intercellular coupling, turning them functionally "invisible". AD - Department of Medical Physiology, University Medical Center, Utrecht, The Netherlands. c.e.conrath@med.uu.nl FAU - Conrath, Chantal E AU - Conrath CE FAU - Wilders, Ronald AU - Wilders R FAU - Coronel, Ruben AU - Coronel R FAU - de Bakker, Jacques M T AU - de Bakker JM FAU - Taggart, Peter AU - Taggart P FAU - de Groot, Joris R AU - de Groot JR FAU - Opthof, Tobias AU - Opthof T LA - eng PT - Journal Article PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM MH - Action Potentials/*physiology MH - Cell Communication MH - *Computer Simulation MH - Gap Junctions/*physiology MH - Humans MH - *Models, Cardiovascular MH - Myocytes, Cardiac/*physiology MH - Perfusion EDAT- 2004/04/20 05:00 MHDA- 2004/09/21 05:00 CRDT- 2004/04/20 05:00 PHST- 2003/09/11 [received] PHST- 2004/02/05 [revised] PHST- 2004/02/20 [accepted] AID - 10.1016/j.cardiores.2004.02.016 [doi] AID - S0008636304001130 [pii] PST - ppublish SO - Cardiovasc Res. 2004 May 1;62(2):407-14. PMID- 15083360 OWN - NLM STAT- MEDLINE DA - 20040517 DCOM- 20050128 LR - 20061115 IS - 0949-944X (Print) IS - 0949-944X (Linking) VI - 214 IP - 5 DP - 2004 May TI - Connexin43 orthologues in vertebrates: phylogeny from fish to man. PG - 261-6 AB - The gap junction protein connexin43 (Cx43) is widely expressed in all vertebrate species; however, in ventricular myocardium, Cx43 expression is restricted to mammalian species only, where it provides the molecular correlate for both electrical conduction and synchronization of the repolarization process. The evolutionarily "late" appearance of Cx43 in the heart suggests physiological adaptation to euthermia with its concomitant demands related to increased cardiovascular output. We tested to what extent mammalian Cx43 differs from that of non-mammalian vertebrates and whether Cx43 from hibernating species contains specific sequence characteristics which could be attributed to their non-isothermal life cycle. We cloned the complete coding region of Cx43 from the African green monkey, European hedgehog (hibernator), Russian dwarf hamster, rabbit, European ground squirrel (hibernator) and pig. After sequencing, these were compared to 12 full-length Cx43 sequences present in GenBank (3 fish, 2 frogs, chicken and 6 mammals amongst which there was one other hibernator). Overall identity ranged from 68.7% to 97.7% at the nucleotide level and from 71.6% to 99.7% at the amino acid level. The phylogeny of Cx43 mirrors the general phylogenetic histories of the investigated species to a large extent. From 382 amino acids there were only 6 specific for mammals. There were no substitutions specific for hibernators. In conclusion, mammalian Cx43 is characterized by 6 specific amino acids, and no obvious differences between non-hibernating and hibernating mammals were observed. AD - Department of Medical Physiology, University Medical Center Utrecht, PO Box 85060, 3508 AB, The Netherlands. m.a.g.vanderheyden@med.uu.nl FAU - van der Heyden, Marcel A G AU - van der Heyden MA FAU - van Eijk, Marleen AU - van Eijk M FAU - Wilders, Ronald AU - Wilders R FAU - de Bakker, Jacques M T AU - de Bakker JM FAU - Opthof, Tobias AU - Opthof T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20040409 PL - Germany TA - Dev Genes Evol JT - Development genes and evolution JID - 9613264 RN - 0 (Connexin 43) SB - IM MH - Amino Acid Sequence MH - Animals MH - Connexin 43/genetics/*metabolism MH - Evolution, Molecular MH - Fishes/*genetics/metabolism MH - Gene Expression Regulation MH - Humans MH - Molecular Sequence Data MH - Phylogeny EDAT- 2004/04/15 05:00 MHDA- 2005/01/29 09:00 CRDT- 2004/04/15 05:00 PHST- 2004/02/05 [received] PHST- 2004/03/07 [accepted] PHST- 2004/04/09 [aheadofprint] AID - 10.1007/s00427-004-0403-7 [doi] PST - ppublish SO - Dev Genes Evol. 2004 May;214(5):261-6. Epub 2004 Apr 9. PMID- 14988077 OWN - NLM STAT- MEDLINE DA - 20040518 DCOM- 20040628 LR - 20061115 IS - 0363-6135 (Print) IS - 0363-6135 (Linking) VI - 286 IP - 6 DP - 2004 Jun TI - Cav3.2 subunit underlies the functional T-type Ca2+ channel in murine hearts during the embryonic period. PG - H2257-63 AB - T-type Ca2+ channels are implicated in cardiac automaticity, cell growth, and cardiovascular remodeling. Two voltage-gated Ca2+ subtypes (Ca(v)3.1 and Ca(v)3.2) have been cloned for the pore-forming alpha(1)-subunit of the T-type Ca2+ channel in cardiac muscle, but their differential roles remain to be clarified. The aim of this study was to elucidate the relative contribution of the two subtypes in the normal development of mouse hearts. A whole cell patch clamp was used to record ionic currents from ventricular myocytes isolated from mice of early (E9.5) and late embryonic days (E18) and from adult 10-wk-old mice. Large T-type Ca2+ current (I(Ca,T)) was observed at both E9.5 and E18, displaying similar voltage-dependence and kinetics of activation and inactivation. The current was inhibited by Ni2+ at relatively low concentrations (IC(50) 26-31 microM). I(Ca,T) was undetectable in adult myocytes. Quantitative PCR analysis revealed that Ca(v)3.2 mRNA is the predominant subtype encoding T-type Ca2+ channels at both E9.5 and E18. Ca(v)3.1 mRNA increased from E9.5 to E18, but remained low compared with Ca(v)3.2 mRNA during the whole embryonic period. In the adulthood, in contrast, Ca(v)3.1 mRNA is greater than Ca(v)3.2 mRNA. These results indicate that Ca(v)3.2 underlies the functional T-type Ca2+ channels in the embryonic murine heart, and there is a subtype switching of transcripts from Ca(v)3.2 to Ca(v)3.1 in the perinatal period. AD - Department of Circulation, Division of Regulation of Organ Function, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan. FAU - Niwa, Noriko AU - Niwa N FAU - Yasui, Kenji AU - Yasui K FAU - Opthof, Tobias AU - Opthof T FAU - Takemura, Haruki AU - Takemura H FAU - Shimizu, Atsuya AU - Shimizu A FAU - Horiba, Mitsuru AU - Horiba M FAU - Lee, Jong-Kook AU - Lee JK FAU - Honjo, Haruo AU - Honjo H FAU - Kamiya, Kaichiro AU - Kamiya K FAU - Kodama, Itsuo AU - Kodama I LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20040226 PL - United States TA - Am J Physiol Heart Circ Physiol JT - American journal of physiology. Heart and circulatory physiology JID - 100901228 RN - 0 (CACNA1G protein, human) RN - 0 (CACNA1H protein, human) RN - 0 (Calcium Channels, T-Type) RN - 0 (RNA, Messenger) RN - 7440-02-0 (Nickel) RN - 7440-70-2 (Calcium) SB - IM MH - Animals MH - Calcium/metabolism MH - Calcium Channels, T-Type/*genetics/metabolism MH - Female MH - Gene Expression Regulation, Developmental MH - Heart/*embryology/*physiology MH - Membrane Potentials/drug effects/physiology MH - Mice MH - Mice, Inbred ICR MH - Myocytes, Cardiac/physiology MH - Nickel/pharmacology MH - Pregnancy MH - RNA, Messenger/analysis EDAT- 2004/02/28 05:00 MHDA- 2004/06/29 05:00 CRDT- 2004/02/28 05:00 PHST- 2004/02/26 [aheadofprint] AID - 10.1152/ajpheart.01043.2003 [doi] AID - 01043.2003 [pii] PST - ppublish SO - Am J Physiol Heart Circ Physiol. 2004 Jun;286(6):H2257-63. Epub 2004 Feb 26. PMID- 14967725 OWN - NLM STAT- MEDLINE DA - 20040302 DCOM- 20040601 LR - 20061115 IS - 1524-4539 (Electronic) IS - 0009-7322 (Linking) VI - 109 IP - 8 DP - 2004 Mar 2 TI - Slow conduction and enhanced anisotropy increase the propensity for ventricular tachyarrhythmias in adult mice with induced deletion of connexin43. PG - 1048-55 AB - BACKGROUND: Connexin 43 (Cx43) is a major determinant of conduction in the ventricular working myocardium of mammals. We investigated the effect of decreased Cx43 expression on conduction velocity and arrhythmogenesis using adult mice with inducible deletion of Cx43. METHODS AND RESULTS: Cx43Cre-ER(T)/+ mice, in which 1 coding region of the Cx43 gene was replaced by Cre-ER(T), were mated to Cx43fl/fl mice, generating Cx43Cre-ER(T)/fl mice. Application of 4-hydroxytamoxifen (4-OHT) induced Cre-ER(T)-mediated deletion of the floxed Cx43 allele. Epicardial ventricular mapping using a 13x19 multiterminal electrode grid (300-microm spacing) was performed on Langendorff-perfused hearts from Cx43fl/fl plus carrier (n=10), Cx43fl/fl plus 4-OHT (n=10), Cx43 Cre-ER(T)/fl plus carrier (n=9), and Cx43Cre-ER(T)/fl plus 4-OHT (n=10). Cx43 protein amount in group 3 hearts was decreased by 50% compared with group 1. 4-OHT did not affect cardiac protein amounts in group 2 but decreased Cx43 expression up to 95% in group 4 compared with group 3. Epicardial activation of both left ventricle (LV) and right ventricle (RV) during sinus rhythm was similar in all groups. Conduction velocity (CV) changed only in group 4 animals. For RV (LV), longitudinal CV decreased from 38 (35) to 31.6 (33.6) and transverse CV from 24.4 (16.8) to 10.1 (11.3) cm/s. Dispersion of conduction in RV (LV) was increased by 91% (38%). Programmed stimulation resulted in ventricular arrhythmias in group 4 (7 of 10 mice) but never in groups 1 through 3. CONCLUSIONS: Heterozygous expression of Cx43 did not affect ventricular conduction velocity. Up to 95% decrease of Cx43 protein in 4-OHT-treated Cx43(Cre-ER(T)/fl) mice reduced conduction velocity and increased dispersion of conduction and propensity for ventricular arrhythmias. AD - Department of Medical Physiology, University Medical Center Utrecht, PO Box 80043, 3508TA Utrecht, The Netherlands. H.V.M.vanRijen@med.uu.nl FAU - van Rijen, Harold V M AU - van Rijen HV FAU - Eckardt, Dominik AU - Eckardt D FAU - Degen, Joachim AU - Degen J FAU - Theis, Martin AU - Theis M FAU - Ott, Thomas AU - Ott T FAU - Willecke, Klaus AU - Willecke K FAU - Jongsma, Habo J AU - Jongsma HJ FAU - Opthof, Tobias AU - Opthof T FAU - de Bakker, Jacques M T AU - de Bakker JM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20040216 PL - United States TA - Circulation JT - Circulation JID - 0147763 RN - 0 (Connexin 43) RN - 9007-34-5 (Collagen) SB - AIM SB - IM MH - Animals MH - Anisotropy MH - Collagen/metabolism MH - Connexin 43/*deficiency/genetics/physiology MH - Genotype MH - Heart Conduction System/*physiopathology MH - Mice MH - Mice, Knockout MH - Neural Conduction MH - Tachycardia, Ventricular/*etiology/genetics/physiopathology MH - Ventricular Premature Complexes/*etiology/genetics/physiopathology EDAT- 2004/02/18 05:00 MHDA- 2004/06/02 05:00 CRDT- 2004/02/18 05:00 PHST- 2004/02/16 [aheadofprint] AID - 10.1161/01.CIR.0000117402.70689.75 [doi] AID - 01.CIR.0000117402.70689.75 [pii] PST - ppublish SO - Circulation. 2004 Mar 2;109(8):1048-55. Epub 2004 Feb 16. PMID- 14736534 OWN - NLM STAT- MEDLINE DA - 20040122 DCOM- 20040520 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 61 IP - 2 DP - 2004 Feb 1 TI - Impact factors: no totum pro parte by skewness of citation. PG - 201-3 FAU - Opthof, Tobias AU - Opthof T FAU - Coronel, Ruben AU - Coronel R FAU - Piper, Hans Michael AU - Piper HM LA - eng PT - Editorial PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM MH - Bibliometrics MH - *Cardiology MH - Humans MH - *Information Dissemination MH - Peer Review, Research MH - Periodicals as Topic MH - *Publishing EDAT- 2004/01/23 05:00 MHDA- 2004/05/21 05:00 CRDT- 2004/01/23 05:00 AID - S0008636303007326 [pii] PST - ppublish SO - Cardiovasc Res. 2004 Feb 1;61(2):201-3. PMID- 14586170 OWN - NLM STAT- MEDLINE DA - 20031030 DCOM- 20040727 LR - 20071115 IS - 1015-8987 (Print) IS - 1015-8987 (Linking) VI - 13 IP - 5 DP - 2003 TI - Expression of the electrophysiological system during murine embryonic stem cell cardiac differentiation. PG - 263-70 AB - BACKGROUND: Stem cell based replacement therapy is envisioned as a method to repair failing hearts suffering from cardiomyocyte loss. To prevent potentially lethal arrhythmias, the donor cellular electrophysiological make-up should match with the acceptor tissue. To engineer the desired electrophysiological phenotype, the underlying molecular regulation of ion channels and gap-junction proteins should be clarified first. METHODS: We established the expression of seven main cardiac ion channel a-subunits and four b-subunits using semiquantitive RT-PCR and two major cardiac gap-junction proteins by immunohistochemistry during the differentiation process of murine ES cells into cardiomyocytes. RESULTS: Ion channel mRNA expression profiles display sequential upregulation. Connexin-40 and -43 expression is low in early cardiomyocytes, increased expression rates were found in subsequent differentiation phases. CONCLUSION: Cardiac differentiation of mouse embryonic stem cells is characterized by a sequential upregulation of the main cardiac ion channels and connexins. CI - Copyright 2003 S. Karger AG, Basel AD - Department of Medical Physiology, University Medical Center Utrecht, The Netherlands. FAU - van Kempen, Marjan AU - van Kempen M FAU - van Ginneken, Antoni AU - van Ginneken A FAU - de Grijs, Ingrid AU - de Grijs I FAU - Mutsaers, Nancy AU - Mutsaers N FAU - Opthof, Tobias AU - Opthof T FAU - Jongsma, Habo AU - Jongsma H FAU - van der Heyden, Marcel AU - van der Heyden M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Switzerland TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (Connexin 43) RN - 0 (Ion Channels) SB - IM MH - Action Potentials MH - Animals MH - Base Sequence MH - Cell Differentiation MH - Connexin 43/metabolism MH - Embryo, Mammalian/*cytology MH - Ion Channels/*metabolism MH - Mice MH - Molecular Sequence Data MH - Myocardium/metabolism MH - Myocytes, Cardiac/cytology/*physiology MH - Stem Cells/*cytology MH - Time Factors EDAT- 2003/10/31 05:00 MHDA- 2004/07/28 05:00 CRDT- 2003/10/31 05:00 PHST- 2003/04/30 [accepted] AID - 10.1159/000074541 [doi] AID - 74541 [pii] PST - ppublish SO - Cell Physiol Biochem. 2003;13(5):263-70. PMID- 12757875 OWN - NLM STAT- MEDLINE DA - 20030521 DCOM- 20030721 LR - 20110722 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 58 IP - 2 DP - 2003 May 1 TI - P19 embryonal carcinoma cells: a suitable model system for cardiac electrophysiological differentiation at the molecular and functional level. PG - 410-22 AB - OBJECTIVE: Murine P19 embryonal carcinoma (EC) cells can differentiate into spontaneously beating cardiomyocytes in vitro and have revealed important insight into the early molecular processes of cardiomyocyte differentiation. We assessed the suitability of the P19 cell model for studying cardiac ion channel regulation at the molecular and functional level. METHODS: P19 cells were induced to differentiate towards cardiomyocytes. mRNAs for cardiac markers and ion channels were determined by RT-PCR at six timepoints during the differentiation process. Action potentials and individual ion currents were measured by whole cell patch clamp. RESULTS: Ion channel mRNA expression of several channels is temporally regulated during differentiation, while others show little or no regulation. L-type calcium and transient outward channels are expressed from very early on, while sodium and delayed and inward rectifier channels are upregulated at somewhat later stages during differentiation, which mirrors the in vivo murine cardiomyocyte differentiation during embryogenesis. Spontaneous cardiomyocyte action potentials exhibit a low upstroke velocity, which often can be enhanced by hyperpolarizing the cells, hence activating thusfar dormant ion channels to contribute to the action potential upstroke. Action potential duration decreases considerably during the differentiation of spontaneously beating cells. In late stages, non-beating myocytes can be found which only generate action potentials upon electrical stimulation. Their shape is comparable to neonatal/juvenile ventricular mouse myocytes in culture. Finally, we show that P19-derived cardiomyocytes display a very complete set of functional ion channels. CONCLUSION: P19 cells represent a powerful model to study the regulation of myocardial electrophysiological differentiation at the molecular and functional level. AD - Department of Medical Physiology, University Medical Center Utrecht, P.O. Box 85060, 3508 AB, Utrecht, The Netherlands. m.a.g.vanderheyden@med.uu.nl FAU - van der Heyden, Marcel A G AU - van der Heyden MA FAU - van Kempen, Marjan J A AU - van Kempen MJ FAU - Tsuji, Yukiomi AU - Tsuji Y FAU - Rook, Martin B AU - Rook MB FAU - Jongsma, Habo J AU - Jongsma HJ FAU - Opthof, Tobias AU - Opthof T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Calcium Channels, L-Type) RN - 0 (Connexin 43) RN - 0 (Ion Channels) RN - 0 (KCNQ Potassium Channels) RN - 0 (L-type calcium channel alpha(1C)) RN - 0 (Potassium Channels) RN - 0 (Potassium Channels, Voltage-Gated) RN - 0 (Sodium Channels) RN - 0 (Troponin T) RN - 0 (Tubulin) RN - 0 (sodium channel protein type 5 subunit alpha) RN - 11003-00-2 (Actinin) SB - IM MH - Actinin/analysis MH - Action Potentials/physiology MH - Animals MH - Calcium Channels, L-Type/genetics MH - Carcinoma, Embryonal/*pathology MH - Cell Culture Techniques/methods MH - Cell Differentiation/physiology MH - Connexin 43/analysis MH - Embryonal Carcinoma Stem Cells MH - Ion Channels/physiology MH - KCNQ Potassium Channels MH - Mice MH - Models, Animal MH - Myocytes, Cardiac/*physiology MH - Neoplastic Stem Cells/*pathology MH - Potassium Channels/genetics MH - *Potassium Channels, Voltage-Gated MH - Reverse Transcriptase Polymerase Chain Reaction MH - Sodium Channels/genetics MH - Troponin T/analysis MH - Tubulin/genetics MH - Tumor Cells, Cultured EDAT- 2003/05/22 05:00 MHDA- 2003/07/23 05:00 CRDT- 2003/05/22 05:00 AID - S0008636303002475 [pii] PST - ppublish SO - Cardiovasc Res. 2003 May 1;58(2):410-22. PMID- 12742992 OWN - NLM STAT- MEDLINE DA - 20030603 DCOM- 20030617 LR - 20061115 IS - 1524-4539 (Electronic) IS - 0009-7322 (Linking) VI - 107 IP - 21 DP - 2003 Jun 3 TI - Differentiation of human embryonic stem cells to cardiomyocytes: role of coculture with visceral endoderm-like cells. PG - 2733-40 AB - BACKGROUND: Cardiomyocytes derived from human embryonic stem (hES) cells could be useful in restoring heart function after myocardial infarction or in heart failure. Here, we induced cardiomyocyte differentiation of hES cells by a novel method and compared their electrophysiological properties and coupling with those of primary human fetal cardiomyocytes. METHODS AND RESULTS: hES cells were cocultured with visceral-endoderm (VE)-like cells from the mouse. This initiated differentiation to beating muscle. Sarcomeric marker proteins, chronotropic responses, and ion channel expression and function were typical of cardiomyocytes. Electrophysiology demonstrated that most cells resembled human fetal ventricular cells. Real-time intracellular calcium measurements, Lucifer yellow injection, and connexin 43 expression demonstrated that fetal and hES-derived cardiomyocytes are coupled by gap junctions in culture. Inhibition of electrical responses by verapamil demonstrated the presence of functional alpha1c-calcium ion channels. CONCLUSIONS: This is the first demonstration of induction of cardiomyocyte differentiation in hES cells that do not undergo spontaneous cardiogenesis. It provides a model for the study of human cardiomyocytes in culture and could be a step forward in the development of cardiomyocyte transplantation therapies. AD - Hubrecht Laboratory, University Medical Center Utrecht, Utrecht, The Netherlands. christin@niob.knaw.nl FAU - Mummery, Christine AU - Mummery C FAU - Ward-van Oostwaard, Dorien AU - Ward-van Oostwaard D FAU - Doevendans, Pieter AU - Doevendans P FAU - Spijker, Rene AU - Spijker R FAU - van den Brink, Stieneke AU - van den Brink S FAU - Hassink, Rutger AU - Hassink R FAU - van der Heyden, Marcel AU - van der Heyden M FAU - Opthof, Tobias AU - Opthof T FAU - Pera, Martin AU - Pera M FAU - de la Riviere, Aart Brutel AU - de la Riviere AB FAU - Passier, Robert AU - Passier R FAU - Tertoolen, Leon AU - Tertoolen L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20030512 PL - United States TA - Circulation JT - Circulation JID - 0147763 RN - 0 (Antigens, Differentiation) RN - 0 (Fluorescent Dyes) RN - 0 (Ion Channels) SB - AIM SB - IM CIN - Circulation. 2003 Jun 3;107(21):2638-9. PMID: 12782614 MH - Action Potentials/physiology MH - Animals MH - Antigens, Differentiation/biosynthesis MH - Calcium Signaling/physiology MH - Cell Communication MH - Cell Differentiation/*physiology MH - Cell Line MH - Cell Lineage MH - Coculture Techniques MH - Endoderm/*cytology MH - Fluorescent Dyes MH - Heart/embryology MH - Humans MH - Ion Channels/biosynthesis MH - Mice MH - Myocardium/cytology MH - Myocytes, Cardiac/*cytology/physiology MH - Patch-Clamp Techniques MH - Stem Cells/*cytology MH - Viscera/*cytology EDAT- 2003/05/14 05:00 MHDA- 2003/06/18 05:00 CRDT- 2003/05/14 05:00 PHST- 2003/05/12 [aheadofprint] AID - 10.1161/01.CIR.0000068356.38592.68 [doi] AID - 01.CIR.0000068356.38592.68 [pii] PST - ppublish SO - Circulation. 2003 Jun 3;107(21):2733-40. Epub 2003 May 12. PMID- 12732283 OWN - NLM STAT- MEDLINE DA - 20030506 DCOM- 20030711 LR - 20081121 IS - 0079-6107 (Print) IS - 0079-6107 (Linking) VI - 82 IP - 1-3 DP - 2003 May-Jul TI - Electrotonic cancellation of transmural electrical gradients in the left ventricle in man. PG - 243-54 AB - Myocardial cells isolated from different depths of the ventricular wall show substantial differences in action potential duration. Whether these electrophysiological differences are present in vivo when the cells are well coupled is a subject of ongoing controversy. This article provides a brief review and includes experimental evidence derived from patients undergoing cardiac surgery. AD - Department of Cardiology and Cardiothoracic Surgery, The Hatter Institute for Cardiovascular Studies, University College Hospital, Grafton Way, WC1 6DB, London, UK. peter.taggart@uclh.org FAU - Taggart, Peter AU - Taggart P FAU - Sutton, Peter AU - Sutton P FAU - Opthof, Tobias AU - Opthof T FAU - Coronel, Ruben AU - Coronel R FAU - Kallis, Panny AU - Kallis P LA - eng PT - Journal Article PT - Review PL - England TA - Prog Biophys Mol Biol JT - Progress in biophysics and molecular biology JID - 0401233 SB - IM MH - Action Potentials MH - Animals MH - Dogs MH - Electrophysiology MH - Endocardium/pathology MH - Heart Ventricles/*pathology MH - Humans MH - Myocardial Contraction MH - Myocardial Ischemia MH - Myocardium/pathology MH - Pericardium/physiology MH - Time Factors MH - *Ventricular Function MH - Ventricular Function, Left RF - 35 EDAT- 2003/05/07 05:00 MHDA- 2003/07/12 05:00 CRDT- 2003/05/07 05:00 AID - S0079610703000257 [pii] PST - ppublish SO - Prog Biophys Mol Biol. 2003 May-Jul;82(1-3):243-54. PMID- 12504639 OWN - NLM STAT- MEDLINE DA - 20021230 DCOM- 20030506 LR - 20041117 IS - 1099-5129 (Print) IS - 1099-5129 (Linking) VI - 5 IP - 1 DP - 2003 Jan TI - Right atrial modification of maze surgery does not affect refractoriness and conduction patterns of human lone atrial fibrillation. PG - 39-46 AB - BACKGROUND: Tissue mass and structure are relevant for initiation and persistence of fibrillation. Modification of the right atrium during maze surgery may change the arrhythmogenic substrate of atrial fibrillation (AF). METHODS AND RESULTS: Epicardial mapping was performed in 9 patients undergoing unmodified maze III surgery for lone paroxysmal AF. Simultaneous recording of AF on the right and left atrium was carried out with two spoon-electrodes each harbouring 64 terminals. Activation maps of AF were made to study AF wavelet organization. The recording position on right and left atria was outside the surgical field and remained unchanged before and after surgery. Before surgery, mean right and left fibrillatory intervals were 174+/-23 ms, and 175+/-26 ms, respectively, and did not differ. After completed right atrial surgery, these fibrillary intervals remained unchanged. Mean right and left atrial dispersion of refractoriness (expressed as the coefficient of variation) were 4.2+/-0.8 and 5.2+/-3.8 ms. Only right atrial dispersion of refractoriness increased significantly after right-sided surgery. Prior to surgery, activation patterns of the left atrium were more complex than that of the right atrium. The left activation patterns became less complex afterwards; the right atrial activation patterns did not change. CONCLUSION: The right atrial modification of maze III surgery neither affects atrial refractoriness during human lone AF nor changes AF wavelet organization. Thus, right atrial surgery does not modify the arrhythmogenic substrate of AF. These findings may imply that maze surgery can be restricted to the left atrium. CI - Copyright 2003 The European Society of Cardiology. AD - Departments of Cardiology and Cardio-Thoracic Surgery, St Antonius Hospital, Nieuwegein, The Netherlands. FAU - Jessurun, E R AU - Jessurun ER FAU - de Bakker, J M T AU - de Bakker JM FAU - van Hemel, N M AU - van Hemel NM FAU - Opthof, T AU - Opthof T FAU - Linnenbank, A C AU - Linnenbank AC FAU - van Dessel, P F H M AU - van Dessel PF FAU - Defauw, J J A M T AU - Defauw JJ FAU - de la Riviere, A B AU - de la Riviere AB LA - eng PT - Journal Article PL - England TA - Europace JT - Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology JID - 100883649 SB - IM MH - Atrial Fibrillation/physiopathology/*surgery MH - Heart Atria/physiopathology/*surgery MH - Heart Conduction System/*physiopathology MH - Humans MH - Male MH - Middle Aged EDAT- 2002/12/31 04:00 MHDA- 2003/05/07 05:00 CRDT- 2002/12/31 04:00 AID - S1099512902902825 [pii] PST - ppublish SO - Europace. 2003 Jan;5(1):39-46. PMID- 12445875 OWN - NLM STAT- MEDLINE DA - 20021126 DCOM- 20030108 LR - 20101118 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 56 IP - 3 DP - 2002 Dec TI - beta3-Adrenoceptors in the heart. PG - 353-6 FAU - Conrath, Chantal E AU - Conrath CE FAU - Opthof, Tobias AU - Opthof T LA - eng PT - Comment PT - Editorial PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Adrenergic beta-Antagonists) RN - 0 (Receptors, Adrenergic, beta-3) SB - IM CON - Cardiovasc Res. 2002 Dec;56(3):393-403. PMID: 12445880 MH - Adrenergic beta-Antagonists/therapeutic use MH - Animals MH - Biological Evolution MH - Guinea Pigs MH - Heart/*physiology MH - Heart Failure/drug therapy MH - Humans MH - Membrane Potentials/physiology MH - Myocytes, Cardiac/physiology MH - Receptors, Adrenergic, beta-3/*physiology EDAT- 2002/11/26 04:00 MHDA- 2003/01/09 04:00 CRDT- 2002/11/26 04:00 AID - S000863630200706X [pii] PST - ppublish SO - Cardiovasc Res. 2002 Dec;56(3):353-6. PMID- 12445872 OWN - NLM STAT- MEDLINE DA - 20021126 DCOM- 20030108 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 56 IP - 3 DP - 2002 Dec TI - The significance of the peer review process against the background of bias: priority ratings of reviewers and editors and the prediction of citation, the role of geographical bias. PG - 339-46 FAU - Opthof, Tobias AU - Opthof T FAU - Coronel, Ruben AU - Coronel R FAU - Janse, Michiel J AU - Janse MJ LA - eng PT - Editorial PT - Research Support, Non-U.S. Gov't PT - Review PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM MH - Bibliometrics MH - *Peer Review, Research MH - Periodicals as Topic/*statistics & numerical data MH - Publication Bias/*statistics & numerical data MH - Publishing RF - 17 EDAT- 2002/11/26 04:00 MHDA- 2003/01/09 04:00 CRDT- 2002/11/26 04:00 AID - S0008636302007125 [pii] PST - ppublish SO - Cardiovasc Res. 2002 Dec;56(3):339-46. PMID- 12393085 OWN - NLM STAT- MEDLINE DA - 20021023 DCOM- 20021216 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 56 IP - 2 DP - 2002 Nov TI - Productivity in science: more more and more? PG - 175-7 FAU - Opthof, Tobias AU - Opthof T FAU - Coronel, Ruben AU - Coronel R LA - eng PT - Editorial PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM MH - *Bibliometrics MH - Efficiency MH - Periodicals as Topic/*trends MH - Publishing/trends MH - Science/*trends EDAT- 2002/10/24 04:00 MHDA- 2002/12/18 04:00 CRDT- 2002/10/24 04:00 AID - S000863630200651X [pii] PST - ppublish SO - Cardiovasc Res. 2002 Nov;56(2):175-7. PMID- 12393001 OWN - NLM STAT- MEDLINE DA - 20021023 DCOM- 20031030 LR - 20061115 IS - 0022-2828 (Print) IS - 0022-2828 (Linking) VI - 34 IP - 10 DP - 2002 Oct TI - Remodeling of gap junctions in mouse hearts hypertrophied by forced retinoic acid signaling. PG - 1411-23 AB - BACKGROUND: Beta-MHC-hRARalpha transgenic mice express a constitutively active (truncated) form of the human retinoic acid receptor which triggers development of dilated cardiomyopathy. In those hearts, we studied expression of gap junction proteins in relation to electrical impulse propagation. METHODS AND RESULTS: As compared to wildtype mice, hearts of 4-6 month old mice with 7-12 inserted hRARalpha copies are marked by an increased heart weight/body weight- and heart weight/tibia length ratio. 3-extremity lead ECGs revealed prolongation of the Q-j interval suggesting delayed ventricular activation. Mapping of electrical activity of epi- and endocardial left ventricular free wall revealed activation delay, increased heterogeneity in conduction and regional conduction block. Ventricular tachycardias did not occur spontaneously nor could be induced by ventricular pacing. Immunohistochemical analysis showed profound and heterogeneous redistribution and down-regulation of the gap junction protein connexin43 (Cx43) in the left ventricular free wall. Here, hRARalpha expression induced re-expression of the hypertrophic markers alpha-skeletal actin and beta-MHC, and in 3 out of 10 severely affected mice, re-expression of Cx40. Concomitant with changes in expression/distribution of Cx43, changes in expression and distribution of beta-catenin and N-cadherin (two other intercalated disk associated proteins) were observed. CONCLUSIONS: Beta-MHC-hRARalpha transgenic hearts show heterogeneous re-expression of (early) sarcomeric genes while expression of connexin43, N-cadherin and beta-catenin is down-regulated. We postulate that the resulting aberrant ventricular activation does not trigger development of lethal arrhythmias due to the small size of remaining healthy ventricular tissue where the transgene is not expressed. AD - Department of Medical Physiology, University Medical Center Utrecht, PO Box 85060, 3508 AB Utrecht, The Netherlands. A.A.B.vanVeen@med.uu.nl FAU - van Veen, Toon A B AU - van Veen TA FAU - van Rijen, Harold V M AU - van Rijen HV FAU - Wiegerinck, Rob F AU - Wiegerinck RF FAU - Opthof, Tobias AU - Opthof T FAU - Colbert, Melissa C AU - Colbert MC FAU - Clement, Sophie AU - Clement S FAU - de Bakker, Jacques M T AU - de Bakker JM FAU - Jongsma, Habo J AU - Jongsma HJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Mol Cell Cardiol JT - Journal of molecular and cellular cardiology JID - 0262322 RN - 0 (Actins) RN - 0 (Biological Markers) RN - 0 (Cadherins) RN - 0 (Catnb protein, mouse) RN - 0 (Connexin 43) RN - 0 (Cytoskeletal Proteins) RN - 0 (Receptors, Retinoic Acid) RN - 0 (Trans-Activators) RN - 0 (beta Catenin) RN - 302-79-4 (Tretinoin) SB - IM MH - Actins/metabolism MH - Animals MH - Biological Markers/analysis MH - Blotting, Western MH - Body Weight MH - Cadherins/metabolism MH - Cardiomegaly/*pathology MH - Connexin 43/metabolism MH - Cytoskeletal Proteins/metabolism MH - Down-Regulation MH - Electric Stimulation MH - Electrocardiography MH - Gap Junctions/*metabolism MH - Mice MH - Mice, Transgenic MH - Myocardium/*pathology MH - Organ Size MH - Receptors, Retinoic Acid/genetics/metabolism MH - *Signal Transduction MH - Trans-Activators/metabolism MH - Tretinoin/*metabolism MH - beta Catenin EDAT- 2002/10/24 04:00 MHDA- 2003/10/31 05:00 CRDT- 2002/10/24 04:00 AID - S0022282802921024 [pii] PST - ppublish SO - J Mol Cell Cardiol. 2002 Oct;34(10):1411-23. PMID- 12370228 OWN - NLM STAT- MEDLINE DA - 20021008 DCOM- 20021024 LR - 20051117 IS - 1524-4539 (Electronic) IS - 0009-7322 (Linking) VI - 106 IP - 15 DP - 2002 Oct 8 TI - Ionic mechanisms of acquired QT prolongation and torsades de pointes in rabbits with chronic complete atrioventricular block. PG - 2012-8 AB - BACKGROUND: The ionic basis of acquired QT prolongation and torsade de pointes (TdP) unrelated to drugs is not fully understood. METHODS AND RESULTS: We created a rabbit model with chronic complete atrioventricular block (AVB) (n=34), which showed prominent QT prolongation (by 120%), high incidence of spontaneous TdP (71%), and cardiac hypertrophy. Patch-clamp experiments were performed in left ventricular myocytes from 9 rabbits (8 with TdP, 1 without TdP) at approximately 21 days of AVB and from 8 sham-operated controls with sinus rhythm. Action potential duration was prolonged in AVB myocytes compared with control (+61% at 0.5 Hz, +21% at 3 Hz). Both rapidly and slowly activating components of the delayed rectifier K(+) current (I(Kr) and I(Ks)) in AVB myocytes were significantly smaller than in control by 50% and 55%, respectively. There was no significant difference in Ca(2+)-independent transient outward current (I(to1)). L-type Ca(2+) current (I(Ca,L)) in control and AVB myocytes was similar in peak amplitude, but the half voltage for activation was shifted to the negative direction (5.9 mV) in AVB myocytes. Voltage dependence of I(Ca,L) inactivation was not different in control and AVB myocytes. The inward rectifier K(+) current (I(K1)) significantly increased in AVB myocytes compared with control. CONCLUSIONS: In the rabbit, chronic AVB leads to prominent QT prolongation and high incidence of spontaneous TdP. Downregulation of both I(Kr) and I(Ks) in association with altered I(Ca,L) activation kinetics may underlie the arrhythmogenic ventricular remodeling. AD - Department of Circulation, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan. y-tsuji@hh.iij4u.or.jp FAU - Tsuji, Yukiomi AU - Tsuji Y FAU - Opthof, Tobias AU - Opthof T FAU - Yasui, Kenji AU - Yasui K FAU - Inden, Yasuya AU - Inden Y FAU - Takemura, Haruki AU - Takemura H FAU - Niwa, Noriko AU - Niwa N FAU - Lu, Zhibo AU - Lu Z FAU - Lee, Jong-Kook AU - Lee JK FAU - Honjo, Haruo AU - Honjo H FAU - Kamiya, Kaichiro AU - Kamiya K FAU - Kodama, Itsuo AU - Kodama I LA - eng PT - Journal Article PL - United States TA - Circulation JT - Circulation JID - 0147763 RN - 0 (Calcium Channels, L-Type) RN - 0 (Delayed Rectifier Potassium Channels) RN - 0 (Potassium Channels) RN - 0 (Potassium Channels, Inwardly Rectifying) RN - 0 (Potassium Channels, Voltage-Gated) SB - AIM SB - IM MH - Action Potentials MH - Animals MH - Calcium Channels, L-Type/physiology MH - Chronic Disease MH - Delayed Rectifier Potassium Channels MH - Down-Regulation MH - Echocardiography MH - Electric Conductivity MH - Electrocardiography MH - Heart/physiopathology MH - Heart Block/*complications/diagnosis/mortality MH - Incidence MH - Kinetics MH - Long QT Syndrome/*etiology/physiopathology MH - Models, Cardiovascular MH - Potassium Channels/physiology MH - Potassium Channels, Inwardly Rectifying/physiology MH - *Potassium Channels, Voltage-Gated MH - Rabbits MH - Survival Analysis MH - Torsades de Pointes/epidemiology/*etiology/physiopathology EDAT- 2002/10/09 04:00 MHDA- 2002/10/31 04:00 CRDT- 2002/10/09 04:00 PST - ppublish SO - Circulation. 2002 Oct 8;106(15):2012-8. PMID- 12123756 OWN - NLM STAT- MEDLINE DA - 20020718 DCOM- 20021009 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 55 IP - 2 DP - 2002 Aug 1 TI - Submissions, impact factor, reviewer's recommendations and geographical bias within the peer review system (1997-2002): focus on Germany. PG - 215-9 FAU - Opthof, Tobias AU - Opthof T FAU - Coronel, Ruben AU - Coronel R FAU - Janse, Michiel J AU - Janse MJ CN - Editorial Team LA - eng PT - Journal Article PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM MH - Bibliometrics MH - Cardiology MH - Germany MH - *Peer Review, Research MH - Periodicals as Topic/*statistics & numerical data MH - *Publication Bias EDAT- 2002/07/19 10:00 MHDA- 2002/10/10 04:00 CRDT- 2002/07/19 10:00 AID - S000863630200500X [pii] PST - ppublish SO - Cardiovasc Res. 2002 Aug 1;55(2):215-9. PMID- 12106593 OWN - NLM STAT- MEDLINE DA - 20020710 DCOM- 20020918 LR - 20101118 IS - 0024-3205 (Print) IS - 0024-3205 (Linking) VI - 71 IP - 11 DP - 2002 Aug 2 TI - Developmental changes of Ca(2+) handling in mouse ventricular cells from early embryo to adulthood. PG - 1279-92 AB - Transplant of immature cardiomyocytes is recently attracting a great deal of interest as a new experimental strategy for the treatment of failing hearts. Full understanding of normal cardiomyogenesis is essential to make this regenerative therapy feasible. We analyzed the molecular and functional changes of Ca(2+) handling proteins during development of the mouse heart from early embryo at 9.5 days postcoitum (dpc) through adulthood. From the early to the late (18 dpc) embryonic stage, mRNAs estimated by the real time PCR for ryanodine receptor (type 2, RyR2), sarcoplasmic reticulum (SR) Ca(2+) pump (type 2, SERCA2) and phospholamban (PLB) increased by 3-15 fold in the values normalized to GAPDH mRNA, although Na(+)/Ca(2+) exchanger (type 1, NCX1) mRNA was unchanged. After birth, there was a further increase in the mRNAs for RyR2, SERCA2 and PLB by 18-33 fold, but a 50% decrease in NCX1 mRNA. The protein levels of RyR2, SERCA2, PLB and NCX1, which were normalized to total protein, showed qualitatively parallel developmental changes. L-type Ca(2+) channel currents (I(Ca-L)) were increased during the development (1.3-fold at 18 dpc, 2.2-fold at adult stage, vs. 9.5 dpc). At 9.5 dpc, the Ca(2+) transient was, unlike adulthood, unaffected by the SR blockers, ryanodine (5 microM) and thapsigargin (2 microM), and also by a blocker of the Ca(2+) entry via Na(+)/Ca(2+) exchanger, KB-R 7943 (1 microM). The Ca(2+) transient was abolished after application of nisoldipine (5 microM). These results indicate that activator Ca(2+) for contraction in the early embryonic stage depends almost entirely on I(Ca-L). AD - Department of Circulation, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan. FAU - Liu, Weiran AU - Liu W FAU - Yasui, Kenji AU - Yasui K FAU - Opthof, Tobias AU - Opthof T FAU - Ishiki, Ryoji AU - Ishiki R FAU - Lee, Jong-Kook AU - Lee JK FAU - Kamiya, Kaichiro AU - Kamiya K FAU - Yokota, Mitsuhiro AU - Yokota M FAU - Kodama, Itsuo AU - Kodama I LA - eng PT - Journal Article PL - England TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate) RN - 0 (Anti-Arrhythmia Agents) RN - 0 (Calcium Channel Blockers) RN - 0 (Calcium-Binding Proteins) RN - 0 (Enzyme Inhibitors) RN - 0 (Ryanodine Receptor Calcium Release Channel) RN - 0 (Sodium-Calcium Exchanger) RN - 0 (phospholamban) RN - 0 (sodium-calcium exchanger 1) RN - 62-56-6 (Thiourea) RN - 63675-72-9 (Nisoldipine) RN - 67526-95-8 (Thapsigargin) RN - 7440-70-2 (Calcium) RN - EC 3.6.3.8 (Atp2a2 protein, mouse) RN - EC 3.6.3.8 (Calcium-Transporting ATPases) RN - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases) SB - IM MH - Aging/physiology MH - Animals MH - Anti-Arrhythmia Agents/pharmacology MH - Calcium/*metabolism MH - Calcium Channel Blockers/pharmacology MH - Calcium-Binding Proteins/genetics/metabolism MH - Calcium-Transporting ATPases/genetics/metabolism MH - Enzyme Inhibitors/pharmacology MH - Female MH - Heart Ventricles/cytology/*embryology/*growth & development/metabolism MH - Mice MH - Myocardium/cytology/*metabolism MH - Nisoldipine/pharmacology MH - Patch-Clamp Techniques MH - Pregnancy MH - Ryanodine Receptor Calcium Release Channel/genetics/metabolism MH - Sarcoplasmic Reticulum/drug effects/metabolism MH - Sarcoplasmic Reticulum Calcium-Transporting ATPases MH - Sodium-Calcium Exchanger/antagonists & inhibitors/genetics/metabolism MH - Thapsigargin/pharmacology MH - Thiourea/*analogs & derivatives/pharmacology EDAT- 2002/07/11 10:00 MHDA- 2002/09/19 10:01 CRDT- 2002/07/11 10:00 AID - S002432050201826X [pii] PST - ppublish SO - Life Sci. 2002 Aug 2;71(11):1279-92. PMID- 12033727 OWN - NLM STAT- MEDLINE DA - 20020529 DCOM- 20020712 LR - 20091118 IS - 0021-8782 (Print) IS - 0021-8782 (Linking) VI - 200 IP - Pt 3 DP - 2002 Mar TI - Cardiomyocyte differentiation of mouse and human embryonic stem cells. PG - 233-42 AB - Ischaemic heart disease is the leading cause of morbidity and mortality in the western world. Cardiac ischaemia caused by oxygen deprivation and subsequent oxygen reperfusion initiates irreversible cell damage, eventually leading to widespread cell death and loss of function. Strategies to regenerate damaged cardiac tissue by cardiomyocyte transplantation may prevent or limit post-infarction cardiac failure. We are searching for methods for inducing pluripotent stem cells to differentiate into transplantable cardiomyocytes. We have already shown that an endoderm-like cell line induced the differentiation of embryonal carcinoma cells into immature cardiomyocytes. Preliminary results show that human and mouse embryonic stem cells respond in a similar manner. This study presents initial characterization of these cardiomyocytes and the mouse myocardial infarction model in which we will test their ability to restore cardiac function. AD - Hubrecht Laboratory, Utrecht, The Netherland. christin@niob.knaw.nl FAU - Mummery, C AU - Mummery C FAU - Ward, D AU - Ward D FAU - van den Brink, C E AU - van den Brink CE FAU - Bird, S D AU - Bird SD FAU - Doevendans, P A AU - Doevendans PA FAU - Opthof, T AU - Opthof T FAU - Brutel de la Riviere, A AU - Brutel de la Riviere A FAU - Tertoolen, L AU - Tertoolen L FAU - van der Heyden, M AU - van der Heyden M FAU - Pera, M AU - Pera M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Anat JT - Journal of anatomy JID - 0137162 RN - 0 (Ion Channels) SB - IM MH - Adult MH - Animals MH - Cell Differentiation MH - Cell Line MH - *Cell Transplantation MH - Coculture Techniques MH - Disease Models, Animal MH - Electrophysiology MH - Embryo, Mammalian/*cytology MH - Humans MH - Ion Channels/metabolism MH - Mice MH - Myocardial Infarction/physiopathology/*therapy MH - Myocardium/*cytology MH - Patch-Clamp Techniques MH - Reverse Transcriptase Polymerase Chain Reaction MH - Stem Cells/*cytology MH - Ventricular Function, Left PMC - PMC1570681 OID - NLM: PMC1570681 EDAT- 2002/05/30 10:00 MHDA- 2002/07/13 10:01 CRDT- 2002/05/30 10:00 PST - ppublish SO - J Anat. 2002 Mar;200(Pt 3):233-42. PMID- 11890673 OWN - NLM STAT- MEDLINE DA - 20020313 DCOM- 20020430 LR - 20081121 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 292 IP - 1 DP - 2002 Mar 22 TI - Sp1 and Sp3 activate the rat connexin40 proximal promoter. PG - 71-8 AB - The rat gap junction protein connexin40 (rCx40) has a characteristic developmental and regional expression pattern, for which the exact regulatory mechanisms are not known. To identify the molecular factors controlling Cx40 expression, its proximal promoter was characterized. The proximal rCx40 promoter is the most conserved noncoding region within the Cx40-gene known thus far and contains five potential binding sites for Sp-family transcription factors. The binding of both Sp1 and Sp3 to each of these DNA elements was demonstrated by EMSA. Luciferase assays of the natural rCx40 proximal promoter or mutated derivatives in Cx40-expressing (NCM, primary rat neonatal cardiomyocytes and A7r5, rat smooth muscle embryonic thoracic aorta cells) and -nonexpressing cells (N2A, mouse neuroblastoma cells) revealed that all sites are contributing to basal promoter activity. Trans-activation assays in Drosophila Schneider line 2 cells demonstrated that Sp1 and Sp3 activate the rCx40 proximal promoter in a dose-dependent and additive manner. CI - (C)2002 Elsevier Science (USA). AD - Department of Medical Physiology, University Medical Center Utrecht, 3508 AB Utrecht, The Netherlands. B.E.J.Teunissen@med.uu.nl FAU - Teunissen, Birgit E J AU - Teunissen BE FAU - van Amersfoorth, Shirley C M AU - van Amersfoorth SC FAU - Opthof, Tobias AU - Opthof T FAU - Jongsma, Habo J AU - Jongsma HJ FAU - Bierhuizen, Marti F A AU - Bierhuizen MF LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Connexins) RN - 0 (DNA-Binding Proteins) RN - 0 (SP3 protein, human) RN - 0 (Sp1 Transcription Factor) RN - 0 (Sp3 protein, mouse) RN - 0 (Sp3 protein, rat) RN - 0 (Transcription Factors) RN - 0 (connexin 40) RN - 148710-94-5 (Sp3 Transcription Factor) SB - IM MH - Animals MH - Base Sequence MH - Binding Sites MH - Cell Line MH - Cells, Cultured MH - Connexins/*genetics MH - DNA-Binding Proteins/*metabolism MH - Electrophoretic Mobility Shift Assay MH - Humans MH - Male MH - Mice MH - Molecular Sequence Data MH - *Promoter Regions, Genetic MH - Rats MH - Rats, Wistar MH - Response Elements MH - Sequence Alignment MH - Sp1 Transcription Factor/*metabolism MH - Sp3 Transcription Factor MH - Transcription Factors/*metabolism MH - *Transcriptional Activation EDAT- 2002/03/14 10:00 MHDA- 2002/05/01 10:01 CRDT- 2002/03/14 10:00 AID - S0006291X02966210 [pii] PST - ppublish SO - Biochem Biophys Res Commun. 2002 Mar 22;292(1):71-8. PMID- 11862110 OWN - NLM STAT- MEDLINE DA - 20020225 DCOM- 20020813 LR - 20081121 IS - 0160-2446 (Print) IS - 0160-2446 (Linking) VI - 39 IP - 3 DP - 2002 Mar TI - Is the apico-basal gradient larger than the transmural gradient? PG - 328-31 FAU - de Bakker, Jacques M T AU - de Bakker JM FAU - OptHof, Tobias AU - OptHof T LA - eng PT - Comment PT - Editorial PL - United States TA - J Cardiovasc Pharmacol JT - Journal of cardiovascular pharmacology JID - 7902492 RN - 0 (Chromans) RN - 0 (Phenethylamines) RN - 0 (Potassium Channel Blockers) RN - 0 (Potassium Channels, Inwardly Rectifying) RN - 0 (Sulfonamides) RN - 115256-11-6 (dofetilide) RN - 163163-23-3 (6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane) SB - IM CON - J Cardiovasc Pharmacol. 2002 Mar;39(3):460-7. PMID: 11862126 MH - Action Potentials/drug effects/physiology MH - Animals MH - Chromans/pharmacology MH - Dogs MH - Heart/*physiology MH - Myocardial Contraction/drug effects/physiology MH - Phenethylamines/pharmacology MH - Potassium Channel Blockers/pharmacology MH - Potassium Channels, Inwardly Rectifying/antagonists & inhibitors MH - Sulfonamides/pharmacology MH - Ventricular Function EDAT- 2002/02/28 10:00 MHDA- 2002/08/14 10:01 CRDT- 2002/02/28 10:00 PST - ppublish SO - J Cardiovasc Pharmacol. 2002 Mar;39(3):328-31. PMID- 11861047 OWN - NLM STAT- MEDLINE DA - 20020307 DCOM- 20020429 LR - 20061115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 53 IP - 3 DP - 2002 Feb 15 TI - Gender differences in the long QT syndrome: effects of beta-adrenoceptor blockade. PG - 770-6 AB - BACKGROUND: Gender differences have been reported in patients with the congenital long QT syndrome (LQTS). We analyzed whether electrocardiographic differences existed in females, males, girls and boys in response to beta-adrenoceptor blockade. METHODS: 12-lead ECGs before and during beta-adrenoceptor blockade were collected in 87 genotyped LQTS patients (48 women, 14 men, 12 girls and 13 boys). Up to three QTc intervals were determined in each lead of the ECG. V4 was used for QT/QTc analysis. Difference between longest and shortest QT interval was taken as a measure for dispersion of QT intervals. RESULTS: (1) Adult males had the greatest shortening of the QTc interval upon treatment with beta-adrenoceptor blockade. During treatment, adult males with LQTS(1) (mutation in the KCNQ1 gene, affecting I(Ks) current) were found to have shorter QTc intervals than adult females; this difference did not exist in LQTS(2) patients (mutation in the HERG gene, affecting I(Kr) current). (2) Female LQTS(2) patients had a 50% larger dispersion than female LQTS(1) patients both before and during treatment. (3) Adult male LQTS(1) patients constitute the only patient group with a marked decrease in QTc intervals and dispersion associated with a 100% efficacy of treatment in response to beta-adrenoceptor blockade. CONCLUSIONS: These findings indicate that, in addition to underlying differences in repolarization between men and women, cardiac electrophysiological responses to beta-adrenoceptor blockade can be modulated by gender-related factors. AD - Department of Cardiology, University Medical Center, Utrecht, The Netherlands FAU - Conrath, Chantal E AU - Conrath CE FAU - Wilde, Arthur A M AU - Wilde AA FAU - Jongbloed, Rosalie J E AU - Jongbloed RJ FAU - Alders, Marielle AU - Alders M FAU - van Langen, Irene M AU - van Langen IM FAU - van Tintelen, J Peter AU - van Tintelen JP FAU - Doevendans, Pieter A AU - Doevendans PA FAU - Opthof, Tobias AU - Opthof T LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Adrenergic beta-Antagonists) RN - 0 (KCNQ Potassium Channels) RN - 0 (KCNQ1 Potassium Channel) RN - 0 (KCNQ1 protein, human) RN - 0 (Potassium Channels) RN - 0 (Potassium Channels, Voltage-Gated) SB - IM MH - Adrenergic beta-Antagonists/*therapeutic use MH - Adult MH - Analysis of Variance MH - Child MH - Electrocardiography MH - Female MH - Genotype MH - Humans MH - KCNQ Potassium Channels MH - KCNQ1 Potassium Channel MH - Long QT Syndrome/drug therapy/*genetics/*physiopathology MH - Male MH - Mutation MH - Mutation, Missense MH - Potassium Channels/genetics MH - *Potassium Channels, Voltage-Gated MH - *Sex EDAT- 2002/02/28 10:00 MHDA- 2002/05/01 10:01 CRDT- 2002/02/28 10:00 AID - S0008636301004771 [pii] PST - ppublish SO - Cardiovasc Res. 2002 Feb 15;53(3):770-6. PMID- 11744016 OWN - NLM STAT- MEDLINE DA - 20011217 DCOM- 20020530 LR - 20100526 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 53 IP - 1 DP - 2002 Jan TI - Heterogeneous expression of connexins in rabbit sinoatrial node cells: correlation between connexin isotype and cell size. PG - 89-96 AB - OBJECTIVE: Intercellular coupling through gap junctions allows the morphologically and functionally heterogeneous sinoatrial node to synchronize and drive the atrial muscle. The purpose of this study was to identify the connexin isotypes expressed by sinoatrial node cells and to analyse the density of connexins in relation to cell size. METHODS: Labeling for the different connexins using isotype-specific antibodies was assessed in cells isolated from the rabbit sinoatrial node by immunoconfocal microscopy. RESULTS: Sinoatrial node cells with a cell projection area smaller than 800 microm(2) were devoid of immunolabeling for connexin43. Such small cells showed high levels of connexin45 labeling (compared to that in large cells) and low levels of connexin40 labeling. Sinoatrial node cells with a projection area between 800 and 1200 microm(2) had a lower amount of connexin45 label and again a small amount of connexin40 but an increased amount of connexin43 label. In the larger sinoatrial node cells, some colocalization of connexin45 and connexin43 immunolabeled spots was observed. CONCLUSIONS: Rabbit sinoatrial node cells are heterogeneous in terms of connexin expression, and there is a clear cell size-dependence in pattern of connexin expression. Small (putative central) cells express connexin45 but not connexin43, whereas larger (putative peripheral) cells express both connexin45 and connexin43. The co-localization of connexin43 and connexin45 in larger cells raises the possibility that heterotypic or heteromeric connexin43/connexin45 channels could be present in gap junctions at the periphery of the sinoatrial node. AD - Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan. honjo@riem.nagoya-u.ac.jp FAU - Honjo, Haruo AU - Honjo H FAU - Boyett, Mark R AU - Boyett MR FAU - Coppen, Steven R AU - Coppen SR FAU - Takagishi, Yoshiko AU - Takagishi Y FAU - Opthof, Tobias AU - Opthof T FAU - Severs, Nicholas J AU - Severs NJ FAU - Kodama, Itsuo AU - Kodama I LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Connexin 43) RN - 0 (Connexins) RN - 0 (Protein Isoforms) RN - 0 (connexin 40) RN - 0 (connexin 45) SB - IM MH - Animals MH - Cell Size MH - Cells, Cultured MH - Connexin 43/analysis MH - Connexins/*analysis MH - Immunohistochemistry/methods MH - Microscopy, Confocal MH - Protein Isoforms/metabolism MH - Rabbits MH - Sinoatrial Node/*metabolism EDAT- 2001/12/18 10:00 MHDA- 2002/05/31 10:01 CRDT- 2001/12/18 10:00 AID - S0008636301004217 [pii] PST - ppublish SO - Cardiovasc Res. 2002 Jan;53(1):89-96. PMID- 11557227 OWN - NLM STAT- MEDLINE DA - 20010914 DCOM- 20011207 LR - 20041117 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 52 IP - 1 DP - 2001 Oct TI - Function and structure of the mouse sinus node: nothing you can see that isn't shown. PG - 1-4 FAU - Opthof, T AU - Opthof T LA - eng PT - Comment PT - Editorial PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Connexins) RN - 0 (Ion Channels) SB - IM CON - Cardiovasc Res. 2001 Oct;52(1):51-64. PMID: 11557233 CON - Cardiovasc Res. 2001 Oct;52(1):40-50. PMID: 11557232 MH - Action Potentials/*physiology MH - Animals MH - Body Weight MH - Cats MH - Connexins/physiology MH - Dogs MH - Guinea Pigs MH - Haplorhini MH - Humans MH - Ion Channels/physiology MH - Membrane Potentials/physiology MH - Muridae/*physiology MH - Rabbits MH - Sinoatrial Node/*physiology MH - Species Specificity MH - Swine EDAT- 2001/09/15 10:00 MHDA- 2002/01/05 10:01 CRDT- 2001/09/15 10:00 AID - S0008636301004175 [pii] PST - ppublish SO - Cardiovasc Res. 2001 Oct;52(1):1-4. PMID- 11514385 OWN - NLM STAT- MEDLINE DA - 20010821 DCOM- 20010913 LR - 20051117 IS - 1524-4539 (Electronic) IS - 0009-7322 (Linking) VI - 104 IP - 8 DP - 2001 Aug 21 TI - Density and kinetics of I(Kr) and I(Ks) in guinea pig and rabbit ventricular myocytes explain different efficacy of I(Ks) blockade at high heart rate in guinea pig and rabbit: implications for arrhythmogenesis in humans. PG - 951-6 AB - BACKGROUND: Class III antiarrhythmic agents commonly exhibit reverse frequency-dependent prolongation of the action potential duration (APD). This is undesirable because of the danger of bradycardia-related arrhythmias and the limited protection against ventricular tachyarrhythmias. The effects of blockade of separate components of delayed rectifier K(+) current (I(K)) may help to develop agents effective at high heart rate. METHODS AND RESULTS: We assessed the density and kinetics of the 2 components of the delayed rectifier K(+) current, I(Kr) and I(Ks), in rabbit and guinea pig ventricular myocytes. The effects of their specific blockers (chromanol 293B for I(Ks) and E-4031 for I(Kr)) on the action potential was studied at different heart rates by use of whole-cell patch-clamp techniques. In guinea pig ventricular myocytes only, blockade of I(Ks) causes APD prolongation in a frequency-independent manner, whereas blockade of I(Ks) in rabbit ventricular myocytes shows reverse frequency dependence, as does blockade of I(Kr) in both species. This result can be explained primarily by the higher density of I(Ks) in guinea pig ventricle and by its slow deactivation kinetics, which allows I(Ks) to accumulate at high heart rate because little time is available for complete deactivation of it during diastole. CONCLUSIONS: Density and kinetics of components of I(K) explain why blockade of I(Ks) is more effective at high heart rate in the guinea pig ventricle than in the rabbit ventricle, without adverse effects at low heart rate. AD - Department of Circulation, Division of Regulation of Organ Function, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan. FAU - Lu, Z AU - Lu Z FAU - Kamiya, K AU - Kamiya K FAU - Opthof, T AU - Opthof T FAU - Yasui, K AU - Yasui K FAU - Kodama, I AU - Kodama I LA - eng PT - Journal Article PL - United States TA - Circulation JT - Circulation JID - 0147763 RN - 0 (Anti-Arrhythmia Agents) RN - 0 (Chromans) RN - 0 (Delayed Rectifier Potassium Channels) RN - 0 (Piperidines) RN - 0 (Potassium Channel Blockers) RN - 0 (Potassium Channels) RN - 0 (Potassium Channels, Voltage-Gated) RN - 0 (Pyridines) RN - 0 (Sulfonamides) RN - 113558-89-7 (E 4031) RN - 163163-23-3 (6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane) SB - AIM SB - IM MH - Action Potentials/drug effects MH - Animals MH - Anti-Arrhythmia Agents/pharmacology MH - Cells, Cultured MH - Chromans/pharmacology MH - Delayed Rectifier Potassium Channels MH - Guinea Pigs MH - Heart Rate/drug effects/*physiology MH - Heart Ventricles/cytology/drug effects/*metabolism MH - Humans MH - Myocardium/cytology/*metabolism MH - Patch-Clamp Techniques MH - Piperidines/pharmacology MH - Potassium Channel Blockers MH - Potassium Channels/*metabolism MH - *Potassium Channels, Voltage-Gated MH - Pyridines/pharmacology MH - Rabbits MH - Sulfonamides/pharmacology EDAT- 2001/08/22 10:00 MHDA- 2001/09/14 10:01 CRDT- 2001/08/22 10:00 PST - ppublish SO - Circulation. 2001 Aug 21;104(8):951-6. PMID- 11470461 OWN - NLM STAT- MEDLINE DA - 20010725 DCOM- 20010927 LR - 20100526 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 51 IP - 2 DP - 2001 Aug 1 TI - Cardiac gap junction channels: modulation of expression and channel properties. PG - 217-29 AB - In the heart, intercellular gap junction channels constructed from connexin molecules are crucial for conduction of the electric impulse. Cardiomyocytes can be interconnected by channels composed of three types of connexin proteins: Cx40, Cx43 or Cx45. In mammalian hearts, these three isoforms are regionally differently expressed and even between the species differences exist. Each of these channel-types possesses specific properties and are susceptible to modulation by various mechanisms. In this paper we compare the differences in properties of these channels as deduced from studies on transfected cells and isolated cardiomyocytes and discuss the factors involved in modulation of channel properties. Next, we evaluate the consequences of alterations in expression and modulation of channel properties for cardiac function. Therefore, we have compared reports on genetically engineered animals and discuss this information in relation to various pathophysiological disorders. AD - Department of Medical Physiology, University Medical Center Utrecht, Utrecht, The Netherlands. FAU - van Veen, A A AU - van Veen AA FAU - van Rijen, H V AU - van Rijen HV FAU - Opthof, T AU - Opthof T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Connexin 43) RN - 0 (Connexins) RN - 0 (Ion Channels) RN - 0 (connexin 40) RN - 0 (connexin 45) SB - IM MH - Animals MH - Cardiovascular Diseases/*metabolism MH - Connexin 43/metabolism MH - Connexins/metabolism MH - Gap Junctions/*metabolism MH - Humans MH - Ion Channels/*metabolism MH - Mammals/*metabolism MH - Mice MH - Mice, Knockout MH - Models, Animal MH - Myocardium/*metabolism RF - 159 EDAT- 2001/07/27 10:00 MHDA- 2001/09/28 10:01 CRDT- 2001/07/27 10:00 AID - S0008636301003248 [pii] PST - ppublish SO - Cardiovasc Res. 2001 Aug 1;51(2):217-29. PMID- 11470459 OWN - NLM STAT- MEDLINE DA - 20010725 DCOM- 20010927 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 51 IP - 2 DP - 2001 Aug 1 TI - Submissions and impact factor 1997-2001: focus on Sweden. PG - 202-4 FAU - Opthof, T AU - Opthof T FAU - Coronel, R AU - Coronel R FAU - Janse, M J AU - Janse MJ LA - eng PT - Editorial PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM MH - Bibliometrics MH - *Cardiology MH - *Cardiovascular Diseases MH - Humans MH - *Information Services MH - Peer Review, Research MH - *Periodicals as Topic MH - Sweden EDAT- 2001/07/27 10:00 MHDA- 2001/09/28 10:01 CRDT- 2001/07/27 10:00 AID - S0008636301003558 [pii] PST - ppublish SO - Cardiovasc Res. 2001 Aug 1;51(2):202-4. PMID- 11428819 OWN - NLM STAT- MEDLINE DA - 20010628 DCOM- 20010816 LR - 20071115 IS - 0195-668X (Print) IS - 0195-668X (Linking) VI - 22 IP - 11 DP - 2001 Jun TI - Norepinephrine induces action potential prolongation and early afterdepolarizations in ventricular myocytes isolated from human end-stage failing hearts. PG - 955-63 AB - AIMS: Congestive heart failure is characterized by high levels of norepinephrine which is considered to be arrhythmogenic. It is unclear whether increased norepinephrine is only a marker of the severity of heart failure or whether it directly triggers ventricular arrhythmias. METHODS AND RESULTS: Ventricular myocytes were isolated from eight explanted hearts of patients with end-stage heart failure (ischaemic or dilated cardiomyopathy). With the whole-cell configuration of the patch-clamp technique the effect of 1 micromol x l(-1)norepinephrine on action potentials and membrane currents was studied. The cells had a membrane capacitance of 256 +/- 25 pF (n = 26) and action potential duration (APD90) during control conditions was 620 +/- 45 ms at 1 Hz (n = 14). Norepinephrine induced action potential prolongation in all cells and early afterdepolarizations in 50% of them. Norepinephrine significantly increased the calcium current but had no effect on the delayed rectifier current, the inward rectifier current or the transient outward current. Norepinephrine also significantly increased the steady-state calcium window-current measured between -40 and 0 mV. CONCLUSIONS: In contrast to many animal species, norepinephrine induces action potential prolongation in ventricular myocytes from human failing hearts, as well as early afterdepolarization, by an increase in both the calcium peak current and window current. Thus norepinephrine seems to be an important arrhythmogenic factor in congestive heart failure. AD - Experimental and Molecular Cardiology Group, Cardiovascular Research Institute Amsterdam, Academic Medical Center, Amsterdam, the Netherlands. FAU - Veldkamp, M W AU - Veldkamp MW FAU - Verkerk, A O AU - Verkerk AO FAU - van Ginneken, A C AU - van Ginneken AC FAU - Baartscheer, A AU - Baartscheer A FAU - Schumacher, C AU - Schumacher C FAU - de Jonge, N AU - de Jonge N FAU - de Bakker, J M AU - de Bakker JM FAU - Opthof, T AU - Opthof T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (Adrenergic alpha-Agonists) RN - 0 (Calcium Channels) RN - 0 (Delayed-Action Preparations) RN - 0 (Ion Channels) RN - 51-41-2 (Norepinephrine) SB - IM MH - Action Potentials/*drug effects/*physiology MH - Adrenergic alpha-Agonists/*pharmacology MH - Calcium Channels/drug effects MH - Delayed-Action Preparations MH - Heart Failure/*blood MH - Heart Ventricles/cytology MH - Humans MH - Ion Channels/drug effects MH - Myocardium/*cytology MH - Norepinephrine EDAT- 2001/06/29 10:00 MHDA- 2001/08/17 10:01 CRDT- 2001/06/29 10:00 AID - 10.1053/euhj.2000.2499 [doi] AID - S0195668X00924990 [pii] PST - ppublish SO - Eur Heart J. 2001 Jun;22(11):955-63. PMID- 11376621 OWN - NLM STAT- MEDLINE DA - 20010529 DCOM- 20010621 LR - 20061115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 50 IP - 3 DP - 2001 Jun TI - Transmural repolarisation in the left ventricle in humans during normoxia and ischaemia. PG - 454-62 AB - BACKGROUND: Studies in isolated tissues and myocytes show different repolarisation properties in subepicardium, midmyocardium and subendocardium. Whether these differences are present in vivo and are relevant to humans has been the subject of controversy. Our objectives were (1) to ascertain whether transmural repolarisation gradients are present in humans, (2) to determine whether the greater sensitivity of subepicardial cells to ischaemia in vitro is manifest during early ischaemia in humans in vivo. METHODS AND RESULTS: We studied 21 patients during routine coronary artery surgery. Unipolar activation recovery intervals (ARI) were recorded from five transmural locations between subepicardium and subendocardium in the left ventricular wall. A pacing protocol spanned a range of cycle lengths from a cycle length of 300 ms to the maximum permitted by the intrinsic atrial activity. Following the onset of cardiopulmonary bypass recordings were obtained before (control) and during a 3-min period of global ischaemia. During control transmural ARIs were homogeneous between 300 and 1500 ms (ventricular pacing) and 750 and 1500 ms (atrial spontaneous beats). During ischaemia, ARIs shortened similarly at all transmural electrode sites and transmural homogeneity was maintained. CONCLUSIONS: Transmural repolarisation differences within the ventricular wall of the human heart were absent at cycle lengths within the physiological range but also during prolonged cycles. During early (global) ischaemia repolarisation changed equally in subepicardial and subendocardial regions and transmural homogeneity of repolarisation was preserved. AD - Department of Cardiology,The Middlesex Hospital, London, and Hatter Institute for Cardiovascular Studies, University College Hospital, Grafton Way, WC1E 6DB, London, UK. peter.sutton@ucl.ac.uk FAU - Taggart, P AU - Taggart P FAU - Sutton, P M AU - Sutton PM FAU - Opthof, T AU - Opthof T FAU - Coronel, R AU - Coronel R FAU - Trimlett, R AU - Trimlett R FAU - Pugsley, W AU - Pugsley W FAU - Kallis, P AU - Kallis P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM CIN - Cardiovasc Res. 2001 Jun;50(3):426-31. PMID: 11376617 CIN - Cardiovasc Res. 2001 Jun;50(3):423-5. PMID: 11376616 MH - Adult MH - Aged MH - Aged, 80 and over MH - Coronary Artery Bypass MH - *Electrocardiography MH - Endocardium/physiopathology MH - Female MH - Humans MH - Male MH - Middle Aged MH - Myocardial Ischemia/*physiopathology MH - Pericardium/physiopathology MH - Ventricular Function, Left/*physiology EDAT- 2001/05/30 10:00 MHDA- 2001/06/22 10:01 CRDT- 2001/05/30 10:00 AID - S0008-6363(01)00223-1 [pii] PST - ppublish SO - Cardiovasc Res. 2001 Jun;50(3):454-62. PMID- 11334840 OWN - NLM STAT- MEDLINE DA - 20010503 DCOM- 20010607 LR - 20041117 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 50 IP - 2 DP - 2001 May TI - Late ventricular arrhythmias during acute regional ischemia in the isolated blood perfused pig heart. Role of electrical cellular coupling. PG - 362-72 AB - OBJECTIVE: Acute ischemia comes with two phases of life-threatening arrhythmias, early (within 10 minutes, 1A) and late (after about 15 minutes, 1B). The mechanism of the latter is unknown and in this paper, we test the hypothesis that a phase of intermediate coupling between surviving epicardium and inexcitable midmyocardium underlies 1B arrhythmias. METHODS: Pig hearts (n=26) were retrogradely perfused with a blood Tyrode's mixture. The left anterior descending artery was occluded. We investigated (1) inducibility of ventricular fibrillation (VF) with programmed stimulation, (2) tissue impedance (Rt) heterogeneity within the ischemic zone, (3) multiple subepicardial and midmyocardial electrograms, (4) subepicardial lactate dehydrogenase (LDH) and glycogen content. RESULTS: In nine of ten hearts, one--three premature stimuli caused VF between 14 and 53 min of ischemia. This typically happened when the Rt of the ischemic zone had increased up to 40% of its final value. More uncoupling terminated the period of VF inducibility. The excitability of the surviving subepicardial layer was depressed during the same period with partial uncoupling, but recovered when the uncoupling from the midmyocardium had progressed further. CONCLUSIONS: We show that 1B-VF can be induced within a distinct time window and coincides with a distinct range of Rt rise. Subepicardium is electrically depressed, presumably through coupling with midmyocardium, complete uncoupling causes subepicardial recovery and terminates the substrate for 1B-VF. Hence, we suggest that the substrate for 1B-VF consists of intermediate coupling of subepicardium and midmyocardium. AD - Experimental and Molecular Cardiology Group, Academic Medical Center, Amsterdam, The Netherlands. j.r.degroot@amc.uva.nl FAU - de Groot, J R AU - de Groot JR FAU - Wilms-Schopman, F J AU - Wilms-Schopman FJ FAU - Opthof, T AU - Opthof T FAU - Remme, C A AU - Remme CA FAU - Coronel, R AU - Coronel R LA - eng PT - Journal Article PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 9005-79-2 (Glycogen) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) SB - IM MH - Animals MH - Cell Communication/physiology MH - Death, Sudden, Cardiac/etiology MH - Electrocardiography MH - Female MH - Glycogen/metabolism MH - Heart Conduction System/physiopathology MH - L-Lactate Dehydrogenase/metabolism MH - Male MH - Myocardial Ischemia/*complications MH - Myocardium/metabolism MH - Organ Culture Techniques MH - Swine MH - Tachycardia, Ventricular/*etiology/metabolism EDAT- 2001/05/04 10:00 MHDA- 2001/06/08 10:01 CRDT- 2001/05/04 10:00 AID - S000863630100222X [pii] PST - ppublish SO - Cardiovasc Res. 2001 May;50(2):362-72. PMID- 11334835 OWN - NLM STAT- MEDLINE DA - 20010503 DCOM- 20010607 LR - 20061115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 50 IP - 2 DP - 2001 May TI - Transgenic mice overexpressing human KvLQT1 dominant-negative isoform. Part I: Phenotypic characterisation. PG - 314-27 AB - OBJECTIVES: The KCNQ1 gene encodes the KvLQT1 potassium channel, which generates in the human heart the slow component of the cardiac delayed rectifier current, I(Ks). Mutations in KCNQ1 are the most frequent cause of the congenital long QT syndrome. We have previously cloned a cardiac KCNQ1 human isoform, which exerts a strong dominant-negative effect on KvLQT1 channels. We took advantage of this dominant-negative isoform to engineer an in vivo model of KvLQT1 disruption, obtained by overexpressing the dominant-negative subunit under the control of the alpha-myosin heavy chain promoter. RESULTS: Three different transgenic lines demonstrated a phenotype with increasing severity. Functional suppression of KvLQT1 in transgenic mice led to a markedly prolonged QT interval associated with sinus node dysfunction. Transgenic mice also demonstrated atrio-ventricular block leading to occasional Wenckebach phenomenon. The atrio-ventricular block was associated with prolonged AH but normal HV interval in His recordings. Prolonged QT interval correlated with prolonged action potential duration and with reduced K(+) current density in patch-clamp experiments. RNase protection assay revealed remodeling of K(+) channel expression in transgenic mice. CONCLUSIONS: Our transgenic mouse model suggests a role for KvLQT1 channels not only in the mouse cardiac repolarisation but also in the sinus node automaticity and in the propagation of the impulse through the AV node. AD - INSERM U533, Laboratoire de Physiopathologie et de Pharmacologie Cellulaires et Moleculaires G & R Laennec, Faculte de Medecine, 1 rue Gaston Veil, 44035 Nantes cedex 01, France. FAU - Demolombe, S AU - Demolombe S FAU - Lande, G AU - Lande G FAU - Charpentier, F AU - Charpentier F FAU - van Roon, M A AU - van Roon MA FAU - van den Hoff, M J AU - van den Hoff MJ FAU - Toumaniantz, G AU - Toumaniantz G FAU - Baro, I AU - Baro I FAU - Guihard, G AU - Guihard G FAU - Le Berre, N AU - Le Berre N FAU - Corbier, A AU - Corbier A FAU - de Bakker, J AU - de Bakker J FAU - Opthof, T AU - Opthof T FAU - Wilde, A AU - Wilde A FAU - Moorman, A F AU - Moorman AF FAU - Escande, D AU - Escande D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (KCNQ Potassium Channels) RN - 0 (KCNQ1 Potassium Channel) RN - 0 (KCNQ1 protein, human) RN - 0 (Kcnq1 protein, mouse) RN - 0 (Potassium Channels) RN - 0 (Potassium Channels, Voltage-Gated) SB - IM MH - Action Potentials/physiology MH - Animals MH - Electrocardiography MH - Humans MH - KCNQ Potassium Channels MH - KCNQ1 Potassium Channel MH - Long QT Syndrome/genetics/*metabolism/physiopathology MH - Mice MH - Mice, Transgenic MH - Patch-Clamp Techniques MH - Phenotype MH - Potassium Channels/*metabolism MH - *Potassium Channels, Voltage-Gated EDAT- 2001/05/04 10:00 MHDA- 2001/06/08 10:01 CRDT- 2001/05/04 10:00 AID - S0008636301002310 [pii] PST - ppublish SO - Cardiovasc Res. 2001 May;50(2):314-27. PMID- 11332576 OWN - NLM STAT- MEDLINE DA - 20010502 DCOM- 20010913 LR - 20051116 IS - 1045-3873 (Print) IS - 1045-3873 (Linking) VI - 12 IP - 4 DP - 2001 Apr TI - Arrhythmogenesis in heart failure. PG - 496-9 AB - In a rabbit model of heart failure produced by combined pressure and volume overload, nonsustained ventricular tachycardias developed in 15 of 23 failing rabbits. Sinus rate was increased in rabbits dying suddenly, but was decreased in survivors. This also was true in isolated preparations. Microelectrode recordings from ventricular trabeculae both from patients with end-stage failure and from failing rabbits showed that in half of the preparations, delayed afterdepolarizations and triggered activity occurred, but only in the presence of norepinephrine and a lowered extracellular K+ concentration of 3 mM. This was due to spontaneous release of Ca2+ from the sarcoplasmic reticulum. AD - Cardiovascular Research, Academic Medical Center, University of Amsterdam, The Netherlands. M.J.Janse@amc.uva.nl FAU - Janse, M J AU - Janse MJ FAU - Vermeulen, J T AU - Vermeulen JT FAU - Opthof, T AU - Opthof T FAU - Coronel, R AU - Coronel R FAU - Wilms-Schopman, F J AU - Wilms-Schopman FJ FAU - Rademaker, H M AU - Rademaker HM FAU - Baartscheer, A AU - Baartscheer A FAU - Dekker, L R AU - Dekker LR LA - eng PT - Journal Article PT - Review PL - United States TA - J Cardiovasc Electrophysiol JT - Journal of cardiovascular electrophysiology JID - 9010756 SB - IM MH - Animals MH - Cardiac Output, Low/*complications/etiology/physiopathology MH - Electrocardiography MH - Electrophysiology MH - Heart Rate MH - Humans MH - Myocardial Ischemia/complications MH - Sinoatrial Node/physiopathology MH - Tachycardia, Ventricular/*etiology/physiopathology RF - 34 EDAT- 2001/05/03 10:00 MHDA- 2001/09/14 10:01 CRDT- 2001/05/03 10:00 PST - ppublish SO - J Cardiovasc Electrophysiol. 2001 Apr;12(4):496-9. PMID- 11282071 OWN - NLM STAT- MEDLINE DA - 20010403 DCOM- 20010607 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 50 IP - 1 DP - 2001 Apr TI - Impact factor of Cardiovascular Research in 2000: all time high! PG - 1-2 FAU - Opthof, T AU - Opthof T FAU - Coronel, R AU - Coronel R FAU - Janse, M J AU - Janse MJ CN - Editorial Team LA - eng PT - Editorial PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM MH - Bibliometrics MH - *Cardiology MH - Documentation/statistics & numerical data MH - Great Britain MH - Humans MH - Peer Review, Research MH - Periodicals as Topic/*statistics & numerical data EDAT- 2001/04/03 10:00 MHDA- 2001/06/19 10:01 CRDT- 2001/04/03 10:00 AID - S000863630100219X [pii] PST - ppublish SO - Cardiovasc Res. 2001 Apr;50(1):1-2. PMID- 11257090 OWN - NLM STAT- MEDLINE DA - 20010321 DCOM- 20010426 LR - 20061115 IS - 1524-4539 (Electronic) IS - 0009-7322 (Linking) VI - 103 IP - 11 DP - 2001 Mar 20 TI - Impaired conduction in the bundle branches of mouse hearts lacking the gap junction protein connexin40. PG - 1591-8 AB - BACKGROUND: Connexin (Cx)40 and Cx45 are the major protein subunits of gap junction channels in the conduction system of mammals. To determine the role of Cx40, we correlated cardiac activation with Connexin distribution in normal and Cx40-deficient mice hearts. METHODS AND RESULTS: Epicardial and septal activation was recorded in Langendorff-perfused adult mice hearts with a 247-point compound electrode (interelectrode distance, 0.3 mm). After electrophysiological measurements, hearts were prepared for immunohistochemistry and histology to determine Connexin distribution and fibrosis. In both wild-type and Cx40-deficient animals, epicardial activation patterns were similar. The right and left ventricular septum was invariably activated from base to apex. Histology revealed a continuity of myocytes from the common bundle to the septal myocardium. Within this continuity, colocalization was found of Cx43 and Cx45 but not of Cx40 and Cx43. Both animals showed similar His-bundle activation. In Cx40-deficient mice, the proximal bundle branches expressed Cx45 only. The absence of Cx40 in the proximal bundles correlated with right bundle-branch block. Conduction in the left bundle branch was impaired as compared with wild-type animals. CONCLUSIONS: Our data show that (1) in mice, a continuity exists between the common bundle and the septum, and (2) Cx40 deficiency results in right bundle-branch block and impaired left bundle-branch conduction. AD - Department of Medical Physiology, Utrecht, The Netherlands. H.V.M.vanRijen@med.uu.nl FAU - van Rijen, H V AU - van Rijen HV FAU - van Veen, T A AU - van Veen TA FAU - van Kempen, M J AU - van Kempen MJ FAU - Wilms-Schopman, F J AU - Wilms-Schopman FJ FAU - Potse, M AU - Potse M FAU - Krueger, O AU - Krueger O FAU - Willecke, K AU - Willecke K FAU - Opthof, T AU - Opthof T FAU - Jongsma, H J AU - Jongsma HJ FAU - de Bakker, J M AU - de Bakker JM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Circulation JT - Circulation JID - 0147763 RN - 0 (Connexins) RN - 0 (connexin 40) SB - IM MH - Animals MH - Bundle-Branch Block/*metabolism/physiopathology MH - Connexins/deficiency/*metabolism MH - Heart Conduction System MH - Heart Septum/metabolism/pathology MH - Mice MH - Mice, Inbred C57BL MH - Pericardium/metabolism MH - Tissue Distribution EDAT- 2001/03/21 10:00 MHDA- 2001/05/11 10:01 CRDT- 2001/03/21 10:00 PST - ppublish SO - Circulation. 2001 Mar 20;103(11):1591-8. PMID- 11249878 OWN - NLM STAT- MEDLINE DA - 20010316 DCOM- 20010517 LR - 20081121 IS - 1524-4571 (Electronic) IS - 0009-7330 (Linking) VI - 88 IP - 5 DP - 2001 Mar 16 TI - I(f) current and spontaneous activity in mouse embryonic ventricular myocytes. PG - 536-42 AB - Knowledge of the initiation of electrical and contractile activity in the embryonic heart relies to a large extent on data obtained in chicken. In recent years, molecular biological techniques have raised an interest in mouse physiology, including early embryonic development. We studied action potentials and the occurrence of one of the pacemaker currents, I(f), by the whole-cell voltage and current-clamp technique at the earliest stage at which a regular heartbeat is established (9.5 days postcoitum) and at 1 day before birth. We show, first, that at the early stage there is a prominent I(f) in mouse embryonic ventricles, which decreases by 82% before birth in concert with the loss of regular spontaneous activity of ventricular cells. Second, the decrease in I(f) current is associated with a slight change in channel gating kinetics and a decrease in total mRNA expression of the genes encoding for I(f) current. Third, the most prevalent mRNA subtype is switched from HCN4 to HCN2 during the second half of embryonic development. Fourth, the I(f) current may be modulated by the beta-adrenergic cascade, although the coupling to the beta-adrenoceptor in the sarcolemma itself is not yet mature. We conclude that I(f) current of the sinus node type is present in early embryonic mouse ventricular cells. In association with a loss of I(f) current, the ventricle tends to lose pacemaker potency during the second half of embryonic development. AD - Department of Circulation, Division of Regulation of Organ Function, Research Institute of Environmental Medicine, Nagoya University, Japan. kenji@riem.nagoya-u.ac.jp FAU - Yasui, K AU - Yasui K FAU - Liu, W AU - Liu W FAU - Opthof, T AU - Opthof T FAU - Kada, K AU - Kada K FAU - Lee, J K AU - Lee JK FAU - Kamiya, K AU - Kamiya K FAU - Kodama, I AU - Kodama I LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Circ Res JT - Circulation research JID - 0047103 RN - 0 (Adrenergic beta-Agonists) RN - 0 (Ion Channels) RN - 0 (RNA, Messenger) RN - 66428-89-5 (Forskolin) RN - 7683-59-2 (Isoproterenol) SB - IM MH - Action Potentials/drug effects/physiology MH - Adrenergic beta-Agonists/pharmacology MH - Animals MH - Brain/metabolism MH - Cells, Cultured MH - Female MH - Forskolin/pharmacology MH - Gene Expression Regulation, Developmental MH - Heart Ventricles/cytology/embryology MH - Ion Channels/drug effects/genetics/*physiology MH - Isoproterenol/pharmacology MH - Membrane Potentials/drug effects/*physiology MH - Mice MH - Myocardium/cytology/metabolism MH - Pregnancy MH - RNA, Messenger/genetics/metabolism MH - Time Factors MH - *Ventricular Function EDAT- 2001/03/16 10:00 MHDA- 2001/05/22 10:01 CRDT- 2001/03/16 10:00 PST - ppublish SO - Circ Res. 2001 Mar 16;88(5):536-42. PMID- 11054476 OWN - NLM STAT- MEDLINE DA - 20010808 DCOM- 20010927 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 48 IP - 2 DP - 2000 Nov TI - Pacing-induced heart failure causes a reduction of delayed rectifier potassium currents along with decreases in calcium and transient outward currents in rabbit ventricle. PG - 300-9 AB - OBJECTIVE: Heart failure in patients and in animal models is associated with action potential prolongation of the ventricular myocytes. Changes in several membrane currents have been already demonstrated to underlie this prolongation. However, information on the two components (I(Kr) and I(Ks)) of the delayed rectifier potassium current (I(K)) in rapid pacing induced heart failure is lacking. METHODS AND RESULTS: Action potentials and whole-cell currents, I(K), I(to1), I(K1), and I(Ca-L) were recorded in apical myocytes of left ventricle from 10 rabbits subjected to left ventricular pacing at 350-380 beats/min for 3-4 weeks and 10 controls with sham operation. Action potential duration at 90% repolarization (APD(90)) was prolonged in myocytes from failing hearts compared to controls at both cycle lengths of 333 and 1000 ms. Both E-4031-sensitive and -resistant components of I(K) (I(Kr), I(Ks)) in myocytes from failing hearts were significantly less than those of control hearts; tail current densities of I(Kr) and I(Ks) following depolarization to +50 mV were 0.62+/-0.05 vs. 0.96+/-0.12 pA/pF (P<0.05), and 0.27+/-0.08 vs. 0.52+/-0.08 pA/pF (P<0.05), respectively. There was no significant difference between control and failing myocytes in the voltage- and time-dependence of activation of total I(K), I(Kr) and I(Ks). The peak of L-type Ca(2+) current (I(Ca-L)) was significantly reduced in myocytes from failing hearts (at +10 mV, -9.29+/-0.52 vs. -12.28+/-1.63 pA/pF, P<0.05), as was the Ca(2+)-independent transient outward current (I(to1); at +40 mV, 4.8+/-0.9 vs. 9.6+/-1.3 pA/pF, P<0.05). Steady state I-V curve for I(K1) was similar in myocytes from failing and control hearts. CONCLUSIONS: Decrease of I(K) (both I(Kr) and I(Ks)) in addition to reduced I(to1), may underly action potential prolongation at physiological cycle length and thereby contribute to arrhythmogenesis in heart failure. AD - Department of Circulation, Division of Regulation of Organ Function, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan. FAU - Tsuji, Y AU - Tsuji Y FAU - Opthof, T AU - Opthof T FAU - Kamiya, K AU - Kamiya K FAU - Yasui, K AU - Yasui K FAU - Liu, W AU - Liu W FAU - Lu, Z AU - Lu Z FAU - Kodama, I AU - Kodama I LA - eng PT - Journal Article PL - Netherlands TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Anti-Arrhythmia Agents) RN - 0 (Calcium Channels, L-Type) RN - 0 (Piperidines) RN - 0 (Potassium Channels) RN - 0 (Pyridines) RN - 113558-89-7 (E 4031) SB - IM CIN - Cardiovasc Res. 2000 Nov;48(2):188-90. PMID: 11054465 MH - *Action Potentials MH - Animals MH - Anti-Arrhythmia Agents/pharmacology MH - Calcium Channels, L-Type/*metabolism MH - *Cardiac Pacing, Artificial MH - Heart Failure/*metabolism MH - Myocardium/*metabolism MH - Patch-Clamp Techniques MH - Piperidines/pharmacology MH - Potassium Channels/drug effects/*metabolism MH - Pyridines/pharmacology MH - Rabbits EDAT- 2000/10/31 MHDA- 2001/09/28 10:01 CRDT- 2000/10/31 00:00 AID - S0008-6363(00)00180-2 [pii] PST - ppublish SO - Cardiovasc Res. 2000 Nov;48(2):300-9. PMID- 11033109 OWN - NLM STAT- MEDLINE DA - 20001120 DCOM- 20001120 LR - 20061115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 48 IP - 1 DP - 2000 Oct TI - Cell-to-cell interaction prevents cell death in cultured neonatal rat ventricular myocytes. PG - 68-76 AB - OBJECTIVES: Loss of cardiac cells and the anatomical or functional remodeling of intercellular coupling occur under several pathological conditions. We have assessed the significance of intercellular coupling for cell death. METHODS AND RESULTS: Ventricular cells obtained from 1 day old Wistar rats were cultured. Apoptosis was detected by nick-end labeling. Cells were plated at low and high cell density (3x10(4)/ml and 12x10(4)/ml, respectively). Cultured myocytes died spontaneously by apoptosis in a time dependent manner. The increase of the apoptotic cell population in a culture with high cell density on day 4 (1+/-1.2%, n=4) was significantly lower than that in a culture with low cell density (20+/-5.5%, n=4). The progression of apoptosis in the culture of low cell density was prevented in part after application of the medium extract from the culture of high cell density; the apoptotic cell population on day 6 decreased from 57+/-8.0% (n=4) to 36+/-3.8% (n=4). Treatment of the cultured myocytes at high cell density with antisense oligonucleotide for connexin43 (Cx43) for 24 h on day 2 resulted in a significant decrease in Cx43 expression as judged by Western blot, dye transfer and immunocytochemistry using mouse monoclonal antibody for Cx43. In association with the down-regulation of Cx43, the progress of apoptosis was accelerated; the apoptotic cell population on day 5 in the antisense-treated cultures (27+/-5.7%, n=4) was significantly higher than the sense-treated cultures (5+/-1.1%, n=4). The effect of Cx43 antisense treatment to promote apoptosis was not reversed by application of high cell-density culture medium. CONCLUSIONS: These findings suggest that cell-cell communication through gap junction formation and some humoral factors play important roles in the survival of cultured myocytes. AD - Department of Circulation, Division of Organ Function, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan. FAU - Yasui, K AU - Yasui K FAU - Kada, K AU - Kada K FAU - Hojo, M AU - Hojo M FAU - Lee, J K AU - Lee JK FAU - Kamiya, K AU - Kamiya K FAU - Toyama, J AU - Toyama J FAU - Opthof, T AU - Opthof T FAU - Kodama, I AU - Kodama I LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - NETHERLANDS TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Connexin 43) RN - 0 (Oligonucleotides, Antisense) RN - 11003-00-2 (Actinin) SB - IM CIN - Cardiovasc Res. 2000 Oct;48(1):8-10. PMID: 11033102 MH - Actinin/analysis MH - Animals MH - Animals, Newborn MH - Apoptosis/*physiology MH - Blotting, Western MH - Cell Communication MH - Cells, Cultured MH - Connexin 43/analysis MH - Gap Junctions/*physiology MH - Immunohistochemistry MH - In Situ Nick-End Labeling MH - Mice MH - Myocardium/cytology/*metabolism MH - Oligonucleotides, Antisense/pharmacology MH - Rats MH - Rats, Wistar MH - Time Factors EDAT- 2000/10/18 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/10/18 11:00 AID - S0008-6363(00)00145-0 [pii] PST - ppublish SO - Cardiovasc Res. 2000 Oct;48(1):68-76. PMID- 11033100 OWN - NLM STAT- MEDLINE DA - 20001120 DCOM- 20001120 LR - 20041117 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 48 IP - 1 DP - 2000 Oct TI - Reviewer's recommendations predict impact: why you have to send us your very best work. PG - 1-3 FAU - Opthof, T AU - Opthof T FAU - Coronel, R AU - Coronel R FAU - Janse, M J AU - Janse MJ LA - eng PT - Editorial PL - NETHERLANDS TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM MH - Cardiology/*standards MH - Humans MH - *Peer Review MH - Publishing/*standards/statistics & numerical data MH - Research/*standards EDAT- 2000/10/18 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/10/18 11:00 AID - S0008636300001905 [pii] PST - ppublish SO - Cardiovasc Res. 2000 Oct;48(1):1-3. PMID- 10995401 OWN - NLM STAT- MEDLINE DA - 20001012 DCOM- 20001012 LR - 20091118 IS - 1468-201X (Electronic) IS - 1355-6037 (Linking) VI - 84 IP - 4 DP - 2000 Oct TI - Repolarisation and refractoriness during early ischaemia in humans. PG - 365-9 AB - OBJECTIVES: To determine whether effective refractory period (ERP) shortens or lengthens in the first minutes of ischaemia in humans, and the relation between ERP changes and action potential duration (APD). METHODS: ERP and monophasic action potential duration (MAPD) were measured from a single left ventricular epicardial site in 26 patients undergoing coronary artery surgery. Cardiopulmonary bypass was instituted and normothermia maintained. Refractory period was determined by the extrastimulus technique at a basic cycle length of 500 ms, at four times (group 1, 15 patients) or two times (group 2, 11 patients) the preischaemic diastolic threshold. A three minute period of ischaemia was instituted by aortic cross clamping between the input from the pump oxygenator and the heart. RESULTS: After three minutes of ischaemia, mean (SEM) ERP lengthened from 232 (5) ms (control) to 246 (7) ms (p < 0.005) in group 1, and from 256 (10) ms (control) to 348 (25) ms (p < 0.005) in group 2. In the same time MAPD shortened from 256 (5) ms (control) to 189 (9) ms (p < 0.001) with no difference between groups. Thus postrepolarisation refractoriness developed during ischaemia. Before ischaemia, ERP showed a good correlation with APD (R(2) = 0.64) but by one minute of ischaemia the correlation was poor (R(2) = 0.29). CONCLUSIONS: These results show that during the first three minutes of global ischaemia in patients with coronary artery disease: (1) ERP lengthened in response to both a low and a high stimulus strength; and (2) there was a good correlation between ERP and APD before ischaemia, which was lost by one minute as APD decreased and ERP increased. These findings may have important implications in arrhythmogenesis. AD - The Hatter Institute, Department of Cardiology, University College London Hospitals, Grafton Way, London WC1E 6DB, UK. peter.sutton@ucl.ac.uk FAU - Sutton, P M AU - Sutton PM FAU - Taggart, P AU - Taggart P FAU - Opthof, T AU - Opthof T FAU - Coronel, R AU - Coronel R FAU - Trimlett, R AU - Trimlett R FAU - Pugsley, W AU - Pugsley W FAU - Kallis, P AU - Kallis P LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - ENGLAND TA - Heart JT - Heart (British Cardiac Society) JID - 9602087 SB - IM CIN - Heart. 2000 Oct;84(4):363-4. PMID: 10995399 MH - *Action Potentials MH - Adult MH - Aged MH - Cardiac Pacing, Artificial MH - Cardiopulmonary Bypass MH - Coronary Disease/surgery MH - Female MH - Humans MH - Male MH - Middle Aged MH - Myocardial Ischemia/*physiopathology/therapy MH - Time Factors MH - Ventricular Dysfunction, Left/*physiopathology/therapy PMC - PMC1729435 OID - NLM: PMC1729435 EDAT- 2000/09/20 MHDA- 2000/10/14 CRDT- 2000/09/20 00:00 PST - ppublish SO - Heart. 2000 Oct;84(4):365-9. PMID- 10946055 OWN - NLM STAT- MEDLINE DA - 20000929 DCOM- 20000929 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 47 IP - 2 DP - 2000 Aug TI - Submissions, editorial process and impact factor 1992-2000: focus on Europe. PG - 203-6 FAU - Opthof, T AU - Opthof T FAU - Coronel, R AU - Coronel R FAU - Janse, M J AU - Janse MJ LA - eng PT - Journal Article PL - NETHERLANDS TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM MH - Bibliometrics MH - *Cardiology MH - Europe MH - Humans MH - *Information Services MH - *Periodicals as Topic MH - *Publishing MH - *Societies, Medical EDAT- 2000/08/18 11:00 MHDA- 2000/10/07 11:01 CRDT- 2000/08/18 11:00 AID - S0008-6363(00)00132-2 [pii] PST - ppublish SO - Cardiovasc Res. 2000 Aug;47(2):203-6. PMID- 10924305 OWN - NLM STAT- MEDLINE DA - 20000915 DCOM- 20000915 LR - 20071115 IS - 0195-668X (Print) IS - 0195-668X (Linking) VI - 21 IP - 15 DP - 2000 Aug TI - Impact factor of the European Heart Journal. PG - 1202-3 FAU - Opthof, T AU - Opthof T FAU - Fox, K AU - Fox K LA - eng PT - Editorial PL - ENGLAND TA - Eur Heart J JT - European heart journal JID - 8006263 SB - IM MH - Bibliometrics MH - *Cardiology MH - Europe MH - Humans MH - Periodicals as Topic/standards/statistics & numerical data/*trends EDAT- 2000/08/05 11:00 MHDA- 2000/09/23 11:01 CRDT- 2000/08/05 11:00 AID - 10.1053/euhj.2000.2258 [doi] AID - S0195668X00922589 [pii] PST - ppublish SO - Eur Heart J. 2000 Aug;21(15):1202-3. PMID- 10869524 OWN - NLM STAT- MEDLINE DA - 20000929 DCOM- 20000929 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 47 IP - 1 DP - 2000 Jul TI - The hibernators heart. Nature's response to arrhythmogenesis? PG - 6-8 AD - Department of Medical Physiology, University Medical Center, PO Box 80043, 3508 TA, Utrecht, The Netherlands. FAU - Opthof, T AU - Opthof T FAU - Rook, M B AU - Rook MB LA - eng PT - Comment PT - Editorial PL - NETHERLANDS TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Connexin 43) SB - IM SB - S CON - Cardiovasc Res. 2000 Jul;47(1):108-15. PMID: 10869536 MH - Animals MH - Arrhythmias, Cardiac/physiopathology MH - Connexin 43/*metabolism MH - Cricetinae MH - Electrophysiology MH - Gap Junctions/physiology MH - Heart Conduction System/physiology MH - Hibernation/*physiology MH - Myocardium/*metabolism EDAT- 2000/06/28 11:00 MHDA- 2000/10/07 11:01 CRDT- 2000/06/28 11:00 AID - S0008-6363(00)00080-8 [pii] PST - ppublish SO - Cardiovasc Res. 2000 Jul;47(1):6-8. PMID- 10869272 OWN - NLM STAT- MEDLINE DA - 20000719 DCOM- 20000719 LR - 20071115 IS - 1524-4539 (Electronic) IS - 0009-7322 (Linking) VI - 101 IP - 25 DP - 2000 Jun 27 TI - Changes in sinus node function in a rabbit model of heart failure with ventricular arrhythmias and sudden death. PG - 2975-80 AB - BACKGROUND: Heart failure is associated with profound changes in the balance of the autonomic nervous system, such as vagal withdrawal and increased catecholamine levels. It is not known whether the intrinsic sinus node function changes during the progression of heart failure. METHODS AND RESULTS: We implanted transmitters for Holter recording in an established rabbit model of heart failure (n=9) and observed changes in sinus cycle length and the occurrence of arrhythmias during the progression of heart failure. The in vitro sinus cycle length and the responses to acetylcholine and norepinephrine in the isolated right atria were analyzed in 12 rabbits with heart failure and in 6 control rabbits. In vivo cycle length increased in some animals and decreased in others. Sudden death occurred in 3 of 9 rabbits. These rabbits had developed a shorter cycle length than the surviving rabbits. Ventricular tachycardias developed in all but 1 rabbit. The in vitro sinus cycle length increased in heart failure. The response to acetylcholine also increased in heart failure, whereas the response to norepinephrine was unchanged. CONCLUSIONS: Changes in intrinsic sinus node function during the progression of heart failure cannot explain the observed decreases in heart rate variability and/or baroreflex sensitivity in this disease, because increased responsiveness to acetylcholine would be expected to cause the opposite. AD - Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands. t.opthof@med.uu.nl FAU - Opthof, T AU - Opthof T FAU - Coronel, R AU - Coronel R FAU - Rademaker, H M AU - Rademaker HM FAU - Vermeulen, J T AU - Vermeulen JT FAU - Wilms-Schopman, F J AU - Wilms-Schopman FJ FAU - Janse, M J AU - Janse MJ LA - eng PT - In Vitro PT - Journal Article PL - UNITED STATES TA - Circulation JT - Circulation JID - 0147763 SB - AIM SB - IM MH - Animals MH - Arrhythmias, Cardiac/*etiology/*physiopathology MH - Cardiac Output, Low/*complications/*physiopathology MH - Death, Sudden, Cardiac MH - Disease Progression MH - Electrocardiography MH - Male MH - Rabbits MH - Sinoatrial Node/*physiopathology MH - Ventricular Dysfunction/*etiology/physiopathology EDAT- 2000/06/28 MHDA- 2000/07/25 CRDT- 2000/06/28 00:00 PST - ppublish SO - Circulation. 2000 Jun 27;101(25):2975-80. PMID- 10841627 OWN - NLM STAT- MEDLINE DA - 20000523 DCOM- 20000523 LR - 20051116 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 45 IP - 1 DP - 2000 Jan 1 TI - The normal range and determinants of the intrinsic heart rate in man. PG - 177-84 AD - Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands. t.opthof@amc.uva.nl FAU - Opthof, T AU - Opthof T LA - eng PT - Comment PT - Journal Article PT - Review PL - NETHERLANDS TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM CON - Cardiovasc Res. 2000 Jan 1;45(1):173-6. PMID: 10728332 MH - Aging MH - Animals MH - Diagnostic Techniques, Cardiovascular MH - Female MH - Heart/growth & development/*physiology MH - *Heart Rate MH - Humans MH - Male MH - Reference Values RF - 89 EDAT- 2000/06/08 MHDA- 2000/06/08 00:01 CRDT- 2000/06/08 00:00 AID - S0008-6363(99)00322-3 [pii] PST - ppublish SO - Cardiovasc Res. 2000 Jan 1;45(1):177-84. PMID- 10756118 OWN - NLM STAT- MEDLINE DA - 20000613 DCOM- 20000613 LR - 20061115 IS - 0022-2828 (Print) IS - 0022-2828 (Linking) VI - 32 IP - 4 DP - 2000 Apr TI - Inhomogeneous transmural conduction during early ischaemia in patients with coronary artery disease. PG - 621-30 AB - Electrical inhomogeneity and conduction slowing are critical factors in the initiation and maintenance of ventricular arrhythmias during early ischaemia. Studies in animal models have shown delay in epicardial activation compared to endocardial activation. Epicardial activation delay has been attributed to either enhanced sensitivity of epicardium to ischaemia or to mid-myocardial conduction delay. No information is available in humans and in particular in patients with chronic ischaemia due to coronary artery disease who may have altered electrophysiological properties. Twenty-three patients undergoing routine coronary surgery were studied. All had severe two or three vessel coronary artery disease and a documented history of angina for a mean of 2.4 years. On cardiopulmonary bypass a 3 min period of ischaemia was created by cross clamping the aorta between the input from the pump oxygenator and the coronary arteries. During atrial pacing (normal endocardial to epicardial activation) intramyocardial activation time within the left ventricular free wall between subendocardial and subepicardial plunge electrode terminals, increased from 12.7+/-1.5 ms (control) to 28.2+/-3.2 ms after 3 min ischaemia at the base. At the apex, the activation time increase (over the same distance) was less (19.5+/-2 ms at 3 min ischaemia). This difference in increase in activation time at the base and apex was significant (P<0.05). At the apex the ischaemia induced activation delay occurred primarily over the endocardial half of the wall, whereas the opposite was observed at the base of the heart. Using an epicardial electrode array stimulation along the long axis of the epicardial fibres showed minimal conduction delay during ischaemia whereas stimulation transverse to the epicardial fibres resulted in substantial conduction time prolongation, as was the case with intramural conduction. Intramural conduction during ischaemia was similar in non-infarcted regions of infarcted hearts compared to hearts with no previous MI. To conclude, in patients with coronary artery disease epicardial activation delay early during ischaemia is caused primarily by intramural delay and not by delay along the epicardium. Moreover, the ischaemia-induced transmural activation delay is inhomogeneous. CI - Copyright 2000 Academic Press. AD - Departments of Cardiology and Cardiothoracic Surgery, The Middlesex Hospital, London, UK. FAU - Taggart, P AU - Taggart P FAU - Sutton, P M AU - Sutton PM FAU - Opthof, T AU - Opthof T FAU - Coronel, R AU - Coronel R FAU - Trimlett, R AU - Trimlett R FAU - Pugsley, W AU - Pugsley W FAU - Kallis, P AU - Kallis P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - ENGLAND TA - J Mol Cell Cardiol JT - Journal of molecular and cellular cardiology JID - 0262322 SB - IM MH - Aged MH - Blood Circulation Time MH - Coronary Disease/*complications/physiopathology MH - Electrophysiology MH - Female MH - Humans MH - Male MH - Middle Aged MH - Myocardial Infarction/physiopathology MH - Myocardial Ischemia/*physiopathology MH - Ventricular Dysfunction, Left/physiopathology EDAT- 2000/04/11 09:00 MHDA- 2000/06/17 09:00 CRDT- 2000/04/11 09:00 AID - 10.1006/jmcc.2000.1105 [doi] AID - S0022-2828(00)91105-2 [pii] PST - ppublish SO - J Mol Cell Cardiol. 2000 Apr;32(4):621-30. PMID- 10728343 OWN - NLM STAT- MEDLINE DA - 20000523 DCOM- 20000523 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 45 IP - 1 DP - 2000 Jan 1 TI - Regrets or no regrets? No regrets! The fate of rejected manuscripts. PG - 255-8 AD - Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands. t.opthof@amc.uva.nl FAU - Opthof, T AU - Opthof T FAU - Furstner, F AU - Furstner F FAU - van Geer, M AU - van Geer M FAU - Coronel, R AU - Coronel R LA - eng PT - Journal Article PL - NETHERLANDS TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM MH - *Bibliometrics MH - *Cardiovascular System MH - Manuscripts as Topic MH - Periodicals as Topic/*statistics & numerical data MH - Publishing/*statistics & numerical data EDAT- 2000/03/23 09:00 MHDA- 2000/06/08 09:00 CRDT- 2000/03/23 09:00 AID - S0008-6363(99)00339-9 [pii] PST - ppublish SO - Cardiovasc Res. 2000 Jan 1;45(1):255-8. PMID- 10728339 OWN - NLM STAT- MEDLINE DA - 20000523 DCOM- 20000523 LR - 20041117 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 45 IP - 1 DP - 2000 Jan 1 TI - Electrocardiogram of the normal mouse, Mus musculus: general considerations and genetic aspects. PG - 227-30 AD - Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands. t.opthof@amc.uva.nl FAU - Opthof, T AU - Opthof T FAU - Coronel, R AU - Coronel R LA - eng PT - Biography PT - Historical Article PT - Journal Article PL - NETHERLANDS TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM SB - Q CIN - Cardiovasc Res. 2000 Jan 1;45(1):231-7. PMID: 10728340 MH - Animals MH - Bibliometrics MH - Electrocardiography/*history MH - History, 20th Century MH - Mice MH - Mice, Inbred C57BL/physiology MH - Mice, Inbred Strains/genetics/*physiology MH - Publishing/history MH - Reference Values EDAT- 2000/03/23 09:00 MHDA- 2000/06/08 09:00 CRDT- 2000/03/23 09:00 PST - ppublish SO - Cardiovasc Res. 2000 Jan 1;45(1):227-30. PMID- 10728332 OWN - NLM STAT- MEDLINE DA - 20000523 DCOM- 20000523 LR - 20041117 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 45 IP - 1 DP - 2000 Jan 1 TI - The normal range and determinants of the intrinsic heart rate in man. PG - 173-6 AB - Jose and Collison published a study on the normal range and the determinants of intrinsic heart rate in man in Cardiovascular Research in 1970 [Jose AD, Collison D. The normal range and determinants of the intrinsic heart rate in man. Cardiovasc Res 1970; 4: 160-167)]. The intrinsic heart rate is the heart rate under complete pharmacological blockade. They showed that (i) the resting heart rate is lower than the intrinsic heart rate and that (ii) the intrinsic heart rate declines with age. They also established that the variability in intrinsic heart rate between individuals of the same age is of the same order as the effect of ageing at the population level. This update discusses the relevance of these data with emphasis on sinus node function and autonomic balance. The paper of Jose and Collison was cited more than 200 times. The frequency of citation started to increase more than 10 years after publication. AD - Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands. t.opthof@amc.uva.nl FAU - Opthof, T AU - Opthof T LA - eng PT - Biography PT - Historical Article PT - Journal Article PL - NETHERLANDS TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM SB - Q CIN - Cardiovasc Res. 2000 Jan 1;45(1):177-84. PMID: 10841627 MH - Bibliometrics MH - Diagnostic Techniques, Cardiovascular MH - *Heart Rate MH - History, 20th Century MH - Humans MH - Publishing/history MH - Reference Values PS - Jose AD FPS - Jose, A D PS - Collison D FPS - Collison, D EDAT- 2000/03/23 09:00 MHDA- 2000/06/08 09:00 CRDT- 2000/03/23 09:00 PST - ppublish SO - Cardiovasc Res. 2000 Jan 1;45(1):173-6. PMID- 10728305 OWN - NLM STAT- MEDLINE DA - 20000523 DCOM- 20000523 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 45 IP - 1 DP - 2000 Jan 1 TI - The most frequently cited papers of Cardiovascular Research (1967-1998): 'the Millennium Minutes'. The Editorial Team. PG - 3-5 AD - Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands. t.opthof@amc.uva.nl FAU - Opthof, T AU - Opthof T FAU - Coronel, R AU - Coronel R LA - eng PT - Historical Article PT - Journal Article PL - NETHERLANDS TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM SB - Q MH - *Bibliometrics MH - Cardiovascular System MH - History, 20th Century MH - Periodicals as Topic/*history MH - Publishing/*history EDAT- 2000/03/23 09:00 MHDA- 2000/06/08 09:00 CRDT- 2000/03/23 09:00 AID - S0008636399003417 [pii] PST - ppublish SO - Cardiovasc Res. 2000 Jan 1;45(1):3-5. PMID- 10727646 OWN - NLM STAT- MEDLINE DA - 20000807 DCOM- 20000807 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 46 IP - 1 DP - 2000 Apr TI - Where do our reviewers come from? PG - 1-13 FAU - Opthof, T AU - Opthof T FAU - Coronel, R AU - Coronel R FAU - Janse, M J AU - Janse MJ LA - eng PT - Editorial PL - NETHERLANDS TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM MH - Humans MH - *Peer Review, Research MH - *Periodicals as Topic MH - *Publishing EDAT- 2000/03/23 09:00 MHDA- 2000/08/12 11:00 CRDT- 2000/03/23 09:00 AID - S0008-6363(00)00016-X [pii] PST - ppublish SO - Cardiovasc Res. 2000 Apr;46(1):1-13. PMID- 10728331 OWN - NLM STAT- Publisher DA - 20000322 IS - 1755-3245 (Electronic) IS - 0008-6363 (Linking) VI - 45 IP - 1 DP - 2000 Jan 1 TI - The normal range and determinants of the intrinsic heart rate in man PG - 175-6 AD - Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands. t.opthof@amc.uva.nl AU - Opthof T AU - Coronel R LA - Eng PT - JOURNAL ARTICLE PL - NETHERLANDS TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 EDAT- 2000/03/23 MHDA- 2000/03/23 CRDT- 2000/03/23 00:00 AID - S0008636399003211 [pii] PST - ppublish SO - Cardiovasc Res. 2000 Jan 1;45(1):175-6. PMID- 10615394 OWN - NLM STAT- MEDLINE DA - 20000114 DCOM- 20000114 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 44 IP - 1 DP - 1999 Oct TI - Intracellular Ca2+ and delay of ischemia-induced electrical uncoupling in preconditioned rabbit ventricular myocardium. PG - 101-12 AB - OBJECTIVE: Short periods of ischemia and reperfusion alter myocardial Ca2+ handling and temporarily induce a mild increase of [Ca2+]i. We hypothesized that these alterations are involved in the cardioprotective mechanism of ischemic preconditioning, possibly via a Ca(2+)-dependent activation of protein kinase C (PKC). METHODS AND RESULTS: In arterially perfused rabbit papillary muscles, we determined Ca2+ transients (indo 1) and indicators of the onset of irreversible ischemic damage, including [Ca2+]i rise, electrical uncoupling and contracture. We tested three protocols of ischemic preconditioning (1-3). In addition, the effects of infusion of staurosporine, a blocker of PKC (4), or glibenclamide, a blocker of K+ATP channels (5) were analyzed. Furthermore, pretreatment with phorbol 12-myrisate 13-acetate (PMA), an activator of PKC (6), or cyclopiazonic acid (CPA), an inhibitor of the SR Ca2+ pump (7) was tested. During periods of reperfusion in the preconditioning protocols, the duration of the Ca2+ transient and the diastolic Ca2+ level temporarily increased. Only if sustained ischemia was induced during these changes of the transients, cardioprotection was present. Similar alterations of the Ca2+ transient concurring with cardioprotection were induced by pretreatment with PMA as well as CPA. Staurosporine and glibenclamide antagonized the reperfusion-induced changes of the Ca2+ transients as well as cardioprotection. If reperfusion was extended until the Ca2+ transient had normalized, cardioprotection was also absent. Under all conditions tested, the diastolic Ca2+ elevation or the Ca2+ transient prolongation prior to sustained ischemia correlated with the postponement of ischemic injury. CONCLUSIONS: A pre-ischemic mild increase of [Ca2-]i presents a common effector of preconditioning. Our data suggest that activation of PKC or opening of K+ATP channels may initiate the pathway leading to an alteration of Ca2+ metabolism and a protected status of the myocardium. AD - Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands. L.R.Dekker@AMC.UVA.NL FAU - Dekker, L R AU - Dekker LR FAU - Coronel, R AU - Coronel R FAU - VanBavel, E AU - VanBavel E FAU - Spaan, J A AU - Spaan JA FAU - Opthof, T AU - Opthof T LA - eng PT - In Vitro PT - Journal Article PL - NETHERLANDS TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Calcium Channel Blockers) RN - 0 (Enzyme Inhibitors) RN - 0 (Indoles) RN - 0 (Potassium Channels) RN - 10238-21-8 (Glyburide) RN - 16561-29-8 (Tetradecanoylphorbol Acetate) RN - 18172-33-3 (cyclopiazonic acid) RN - 56-65-5 (Adenosine Triphosphate) RN - 62996-74-1 (Staurosporine) RN - 7440-70-2 (Calcium) RN - EC 2.7.11.13 (Protein Kinase C) SB - IM MH - Adenosine Triphosphate/metabolism MH - Animals MH - Calcium/*metabolism MH - Calcium Channel Blockers/pharmacology MH - *Enzyme Activation MH - Enzyme Inhibitors/pharmacology MH - Female MH - Glyburide/pharmacology MH - Indoles/pharmacology MH - Intracellular Fluid/*metabolism MH - *Ischemic Preconditioning, Myocardial MH - Male MH - Myocardial Ischemia/physiopathology/prevention & control MH - Myocardium/*metabolism MH - Papillary Muscles/drug effects/physiopathology MH - Potassium Channels/drug effects/metabolism MH - Protein Kinase C/antagonists & inhibitors/*metabolism MH - Rabbits MH - Staurosporine/pharmacology MH - Tetradecanoylphorbol Acetate/pharmacology EDAT- 2000/01/01 MHDA- 2000/01/01 00:01 CRDT- 2000/01/01 00:00 AID - S0008-6363(99)00179-0 [pii] PST - ppublish SO - Cardiovasc Res. 1999 Oct;44(1):101-12. PMID- 9764198 OWN - NLM STAT- MEDLINE DA - 19981023 DCOM- 19981023 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 39 IP - 1 DP - 1998 Jul TI - Animal models of cardiac arrhythmias. PG - 165-77 AD - Department of Clinical and Experimental Cardiology, Academic Medical Centre, University of Amsterdam, Netherlands. FAU - Janse, M J AU - Janse MJ FAU - Opthof, T AU - Opthof T FAU - Kleber, A G AU - Kleber AG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - NETHERLANDS TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Anti-Arrhythmia Agents) SB - IM MH - Action Potentials/drug effects MH - Animals MH - Anti-Arrhythmia Agents/therapeutic use MH - *Arrhythmias, Cardiac/drug therapy MH - Cats MH - *Disease Models, Animal MH - Dogs MH - Guinea Pigs MH - Humans MH - Myocardial Infarction MH - Rabbits MH - Rats MH - Swine RF - 163 EDAT- 1998/10/09 MHDA- 1998/10/09 00:01 CRDT- 1998/10/09 00:00 AID - S0008-6363(97)00313-1 [pii] PST - ppublish SO - Cardiovasc Res. 1998 Jul;39(1):165-77. PMID- 9747423 OWN - NLM STAT- MEDLINE DA - 19981015 DCOM- 19981015 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 38 IP - 3 DP - 1998 Jun TI - The membrane current (I(f)) in human atrial cells: implications for atrial arrhythmias. PG - 537-40 FAU - Opthof, T AU - Opthof T LA - eng PT - Editorial PT - Review PL - NETHERLANDS TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Ion Channels) RN - 0 (Potassium Channels) SB - IM MH - Arrhythmias, Cardiac/*physiopathology MH - Heart Atria MH - Heart Conduction System/*physiopathology MH - Heart Failure/*metabolism MH - Heart Ventricles MH - Humans MH - Ion Channels/*physiology MH - Potassium Channels/physiology RF - 31 EDAT- 1998/09/25 MHDA- 1998/09/25 00:01 CRDT- 1998/09/25 00:00 AID - S0008636398000893 [pii] PST - ppublish SO - Cardiovasc Res. 1998 Jun;38(3):537-40. PMID- 9593568 OWN - NLM STAT- MEDLINE DA - 19980604 DCOM- 19980604 LR - 20061115 IS - 0009-7322 (Print) IS - 0009-7322 (Linking) VI - 97 IP - 16 DP - 1998 Apr 28 TI - Distribution of atrial and nodal cells within the rabbit sinoatrial node: models of sinoatrial transition. PG - 1623-31 AB - BACKGROUND: In the sinoatrial node (SAN) the course of the action potential gradually changes from the primary pacemaker region toward the atrium. It is not known whether this gradient results from different intrinsic characteristics of the nodal cells, from an increasing electrotonic interaction with the atrium, or from both. Therefore we have characterized the immunohistochemical, morphological, and electrophysiological correlates of this functional gradient. METHODS AND RESULTS: The distribution of rabbit nodal myocytes in the SAN has been studied by immunohistochemistry. After cell isolation, the electrophysiological characteristics of different nodal cell types were measured. (1) The staining pattern of a neurofilament protein coincides with the electrophysiologically mapped pacemaker region in the SAN. (2) Enzymatic digestion of the SAN reveals three morphologically different nodal cell types and one atrial type. Of each nodal cell type, neurofilament-positive as well as neurofilament-negative myocytes are found. Atrial cells are all neurofilament-negative. (3) In contrast to previous findings, we observed atrial cells in the very center of the SAN. The relative number of atrial cells gradually increases from the central pacemaker area toward the atrium. (4) Differences in electrophysiological characteristics between individual nodal cells are not associated with differences in cell type. CONCLUSIONS: (1) The expression of neurofilaments can be used to delineate the nodal area in the intact SAN but is not sufficiently sensitive for characterizing all individual isolated nodal cells. (2) A fundamentally different organization of the SAN is presented: The gradual increase in density of atrial cells from the dominant area toward the crista terminalis in the SAN causes a gradual increase of atrial electrotonic influence that may be an important cause of the gradual transition of the nodal to the atrial type of action potential. AD - Department of Physiology, Academic Medical Center, University of Amsterdam, The Netherlands. e.verheijck@amc.uva.nl FAU - Verheijck, E E AU - Verheijck EE FAU - Wessels, A AU - Wessels A FAU - van Ginneken, A C AU - van Ginneken AC FAU - Bourier, J AU - Bourier J FAU - Markman, M W AU - Markman MW FAU - Vermeulen, J L AU - Vermeulen JL FAU - de Bakker, J M AU - de Bakker JM FAU - Lamers, W H AU - Lamers WH FAU - Opthof, T AU - Opthof T FAU - Bouman, L N AU - Bouman LN LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - UNITED STATES TA - Circulation JT - Circulation JID - 0147763 RN - 0 (Neurofilament Proteins) SB - AIM SB - IM CIN - Circulation. 1999 Aug 31;100(9):1011-2. PMID: 10469429 MH - Action Potentials MH - Animals MH - *Atrial Function MH - Cell Differentiation/physiology MH - Heart Atria/*cytology MH - Neurofilament Proteins/physiology MH - Rabbits MH - Sinoatrial Node/*cytology/*physiology EDAT- 1998/05/21 MHDA- 1998/05/21 00:01 CRDT- 1998/05/21 00:00 PST - ppublish SO - Circulation. 1998 Apr 28;97(16):1623-31. PMID- 9591767 OWN - NLM STAT- MEDLINE DA - 19980528 DCOM- 19980528 LR - 20071115 IS - 0009-7322 (Print) IS - 0009-7322 (Linking) VI - 97 IP - 17 DP - 1998 May 5 TI - Cellular uncoupling during ischemia in hypertrophied and failing rabbit ventricular myocardium: effects of preconditioning. PG - 1724-30 AB - BACKGROUND: Patients with heart failure show a very high incidence of arrhythmias and sudden death that is often preceded by ischemia; however, data on electrophysiological changes during ischemia in failing myocardium are sparse. We studied electrical uncoupling during ischemia in normal and failing myocardium. METHODS AND RESULTS: Tissue resistance, intracellular Ca2+ concentration (Indo-1 fluorescence ratio), and mechanical activity were simultaneously determined in arterially perfused right ventricular papillary muscles from 11 normal and 15 failing rabbits. Heart failure was induced by combined volume and pressure overload. Before sustained ischemia, muscles were subjected to control perfusion (non-PC) or ischemic preconditioning (PC). The onset of uncoupling during ischemia was equal in non-PC normal (13.6+/-0.9 minutes of ischemia) and non-PC failing hearts (13.3+/-0.7 minutes of ischemia). PC postponed uncoupling in normal hearts by 10 minutes. In failing hearts, however, PC caused a large variability in the onset of uncoupling during ischemia (mean, 12.2+/-2.1; range, 5 to 22 minutes of ischemia). The duration of uncoupling process was prolonged in failing hearts (12.9+/-0.9 minutes) compared with normal hearts (7.8+/-0.4 minutes). The degree of heart failure and relative heart weight of the failing hearts significantly correlated with the earlier uncoupling after PC and the duration of uncoupling. In every experiment, the start of Ca2+ rise and contracture preceded uncoupling during ischemia. CONCLUSIONS: The duration of the process of ischemia-induced electrical uncoupling in failing hearts is prolonged compared with that in normal hearts. Ischemic PC has detrimental effects in severely failing papillary muscles because it advances the moment of irreversible ischemic damage. AD - Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands. LRDekker@AMC.UVA.NL FAU - Dekker, L R AU - Dekker LR FAU - Rademaker, H AU - Rademaker H FAU - Vermeulen, J T AU - Vermeulen JT FAU - Opthof, T AU - Opthof T FAU - Coronel, R AU - Coronel R FAU - Spaan, J A AU - Spaan JA FAU - Janse, M J AU - Janse MJ LA - eng PT - Journal Article PL - UNITED STATES TA - Circulation JT - Circulation JID - 0147763 RN - 7440-70-2 (Calcium) SB - AIM SB - IM MH - Animals MH - Arrhythmias, Cardiac/etiology MH - Calcium/metabolism MH - Cardiomegaly/*physiopathology MH - Heart Failure/*physiopathology MH - *Ischemic Preconditioning, Myocardial MH - Myocardial Ischemia/*physiopathology MH - Rabbits MH - Time Factors EDAT- 1998/05/20 MHDA- 1998/05/20 00:01 CRDT- 1998/05/20 00:00 PST - ppublish SO - Circulation. 1998 May 5;97(17):1724-30. PMID- 9093520 OWN - NLM STAT- MEDLINE DA - 19970609 DCOM- 19970609 LR - 20061115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 33 IP - 3 DP - 1997 Mar TI - Differential electrophysiology of repolarisation from clone to clinic. PG - 503-17 AD - Department of Experimental Cardiology, Academic Medical Centre, Amsterdam, Netherlands. r.coronel@amc.uva.nl FAU - Coronel, R AU - Coronel R FAU - Opthof, T AU - Opthof T FAU - Taggart, P AU - Taggart P FAU - Tytgat, J AU - Tytgat J FAU - Veldkamp, M AU - Veldkamp M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - NETHERLANDS TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Ion Channels) SB - IM MH - Animals MH - Clone Cells MH - Disease Models, Animal MH - Electrophysiology MH - Humans MH - Ion Channels/*metabolism MH - Myocardial Ischemia/*metabolism MH - Patch-Clamp Techniques MH - *Research RF - 30 EDAT- 1997/03/01 MHDA- 1997/03/01 00:01 CRDT- 1997/03/01 00:00 AID - S0008636396002714 [pii] PST - ppublish SO - Cardiovasc Res. 1997 Mar;33(3):503-17. PMID- 9059521 OWN - NLM STAT- MEDLINE DA - 19970328 DCOM- 19970328 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 33 IP - 1 DP - 1997 Jan TI - Sense and nonsense about the impact factor. PG - 1-7 AB - The impact factor is based on citations of papers published by a scientific journal. It has been published since 1961 by the Institute for Scientific Information. It may be regarded as an estimate of the citation rate of a journal's papers, and the higher its value, the higher the scientific esteem of the journal. Although the impact factor was originally meant for comparison of journals, it is also used for assessment of the quality of individual papers, scientists and departments. For the latter a scientific basis is lacking, as we will demonstrate in this contribution. AD - Department of Clinical and Experimental Cardiology, University of Amsterdam, Netherlands. t.opthof@amc.uva.nl FAU - Opthof, T AU - Opthof T LA - eng PT - Journal Article PL - NETHERLANDS TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM MH - Bibliometrics MH - Information Management MH - *Periodicals as Topic MH - *Quality Control MH - *Research EDAT- 1997/01/01 MHDA- 1997/01/01 00:01 CRDT- 1997/01/01 00:00 AID - S0008-6363(96)00215-5 [pii] PST - ppublish SO - Cardiovasc Res. 1997 Jan;33(1):1-7. PMID- 8899555 OWN - NLM STAT- MEDLINE DA - 19970522 DCOM- 19970522 LR - 20061115 IS - 0022-2828 (Print) IS - 0022-2828 (Linking) VI - 28 IP - 9 DP - 1996 Sep TI - The origin of increased cytoplasmic calcium upon reversal of the Na+/Ca(2+)-exchanger in isolated rat ventricular myocytes. PG - 1963-73 AB - Reversal of the driving force of the Na+/Ca(2+)-exchanger (delta Gexch) by a sufficiently large change of the transsarcolemmal electrochemical potential of sodium and calcium causes a transient increase of cytoplasmic calcium ([Ca2+]i). The objective of this study was to investigate the origin of this transient increase of calcium. In isolated quiescent rat ventricular myocytes delta Gexch was abruptly changed by reduction of extracellular sodium ([Na+]o), with or without a simultaneous increase of potassium ([K+]o) or calcium ([Ca2+]i). [Ca2+]i was measured with indo-1. A particular change of delta Gexch induced either by reduction of [Na+]o alone or in combination with increase of [Ca2+]o, produced a transient increase of [Ca2+]i of the same magnitude with a maximum after around 30s. The response of [Ca2+]i was insensitive to verapamil, but was greatly reduced by ryanodine, thapsigargin and caffeine, indicating a large contribution originating from the sarcoplasmic reticulum (SR). The magnitude of the response of [Ca2+]i and also the contribution from SR increased with increasing change of delta Gexch. A particular change of delta Gexch. Induced by a reduction of [Na+]o in combination with membrane depolarization (increase of [K+]o) increased the response of [Ca2+]i, compared that induced by reduction of [Na+]o alone at the same change of delta Gexch. This effect increased with the degree of depolarization, and was completely abolished by verapamil. Also in depolarized cells the response of [Ca2+]i was reduced by ryanodine. However, the contribution from SR to the response did not depend on the degree of depolarization, but only on the magnitude of the change of delta Gexch. Inhibition of the Na+/Ca(2+)-exchanger by Ni2+ almost completely abolished the response of [Ca2+]i to reduction of [Na+]o. Restitution of [Na+]o during the course of the calcium response greatly accelerated the rate of decay of [Ca2+]i. It is concluded that in quiescent rat ventricular myocytes, a large part of the transient increase of cytoplasmic calcium associated with reversal of the driving force of the Na+/Ca(2+)-exchanger originates from SR. Reversal of the exchanger combined with sustained depolarization increased the transient of [Ca2+]i, but the extra influx of calcium associated with depolarization did not affect the contribution from SR. AD - Department of Clinical and Experimental Cardiology, University of Amsterdam, The Netherlands. FAU - Baartscheer, A AU - Baartscheer A FAU - Schumacher, C A AU - Schumacher CA FAU - Opthof, T AU - Opthof T FAU - Fiolet, J W AU - Fiolet JW LA - eng PT - In Vitro PT - Journal Article PL - ENGLAND TA - J Mol Cell Cardiol JT - Journal of molecular and cellular cardiology JID - 0262322 RN - 0 (Carrier Proteins) RN - 0 (Sodium-Calcium Exchanger) RN - 15662-33-6 (Ryanodine) RN - 52-53-9 (Verapamil) RN - 58-08-2 (Caffeine) RN - 67526-95-8 (Thapsigargin) RN - 7440-09-7 (Potassium) RN - 7440-70-2 (Calcium) SB - IM MH - Animals MH - Caffeine/pharmacology MH - Calcium/*metabolism MH - Carrier Proteins/*metabolism MH - Cytoplasm/metabolism MH - Heart Ventricles/*chemistry/drug effects MH - Ion Transport/drug effects/physiology MH - Male MH - Osmolar Concentration MH - Potassium/metabolism MH - Rats MH - Rats, Wistar MH - Ryanodine/pharmacology MH - Sarcoplasmic Reticulum/drug effects MH - Sodium-Calcium Exchanger MH - Thapsigargin/pharmacology MH - Verapamil/pharmacology EDAT- 1996/09/01 MHDA- 1996/09/01 00:01 CRDT- 1996/09/01 00:00 AID - S0022-2828(96)90189-3 [pii] AID - 10.1006/jmcc.1996.0189 [doi] PST - ppublish SO - J Mol Cell Cardiol. 1996 Sep;28(9):1963-73. PMID- 8756000 OWN - NLM STAT- MEDLINE DA - 19961212 DCOM- 19961212 LR - 20031114 IS - 0009-7330 (Print) IS - 0009-7330 (Linking) VI - 79 IP - 2 DP - 1996 Aug TI - Intracellular Ca2+, intercellular electrical coupling, and mechanical activity in ischemic rabbit papillary muscle. Effects of preconditioning and metabolic blockade. PG - 237-46 AB - During myocardial ischemia, electrical uncoupling and contracture herald irreversible damage. In the present study, we tested the hypothesis that an increase of intracellular Ca2+ is an important factor initiating these events. Therefore, we simultaneously determined tissue resistance, mechanical activity, pH(0), and intracellular Ca2+ (with the fluorescent indicator indo 1, Molecular Probes, Inc) in arterially perfused rabbit papillary muscles. Sustained ischemia was induced in three experimental groups: (1) control, (2) preparations preconditioned with two 5-minute periods of ischemia followed by reperfusion, and (3) preparations pretreated with 1 mmol/L iodoacetate to block anaerobic metabolism and minimize acidification during ischemia. In a fourth experimental group, intracellular Ca2+ was increased under nonischemic conditions by perfusing with 0.1 mmol/L ionomycin and 0.1 mumol/L gramicidin. Ca2+ transients and contractions rapidly disappeared after the induction of ischemia. In the control group, diastolic Ca2+ began to rise after 12.6 +/- 1.3 minutes of ischemia; uncoupling, after 14.5 +/- 1.2 minutes of ischemia; and contracture, after 12.6 +/- 1.5 minutes of ischemia (mean +/- SEM). Preconditioning significantly postponed Ca2+ rise, uncoupling, and contracture (21.5 +/- 4.0, 24.0 +/- 4.1, and 23.0 +/- 5.3 minutes of ischemia, respectively). Pretreatment with iodoacetate significantly advanced these events (1.9 +/- 0.7, 3.6 +/- 0.9, and 1.9 +/- 0.2 minutes of ischemia, respectively). In all groups, the onset of uncoupling always followed the start of Ca2+ rise, whereas the start of contracture was not different from the rise in Ca2+. Perfusion with ionomycin and gramicidin permitted estimation of a threshold [Ca2+] for electrical uncoupling of 685 +/- 85 nmol/L. In conclusion, the rise in intracellular Ca2+ is the main trigger for cellular uncoupling during ischemia. Contracture is closely associated with the increase of intracellular Ca2+ during ischemia. AD - Department of Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands. FAU - Dekker, L R AU - Dekker LR FAU - Fiolet, J W AU - Fiolet JW FAU - VanBavel, E AU - VanBavel E FAU - Coronel, R AU - Coronel R FAU - Opthof, T AU - Opthof T FAU - Spaan, J A AU - Spaan JA FAU - Janse, M J AU - Janse MJ LA - eng PT - Journal Article PL - UNITED STATES TA - Circ Res JT - Circulation research JID - 0047103 RN - 0 (Fluorescent Dyes) RN - 0 (Indoles) RN - 0 (Iodoacetates) RN - 64-69-7 (Iodoacetic Acid) RN - 7440-70-2 (Calcium) RN - 96314-96-4 (indo-1) SB - IM MH - Animals MH - Biomechanics MH - Calcium/*metabolism MH - Electric Conductivity MH - Female MH - Fluorescent Dyes MH - Hydrogen-Ion Concentration MH - Indoles MH - Intracellular Membranes/metabolism/*physiology MH - Iodoacetates/pharmacology MH - Iodoacetic Acid MH - Male MH - Myocardial Contraction MH - Myocardial Ischemia/metabolism/*physiopathology MH - *Myocardial Reperfusion MH - Papillary Muscles/drug effects/metabolism/*physiopathology MH - Rabbits MH - Time Factors EDAT- 1996/08/01 MHDA- 1996/08/01 00:01 CRDT- 1996/08/01 00:00 PST - ppublish SO - Circ Res. 1996 Aug;79(2):237-46. PMID- 8745220 OWN - NLM STAT- MEDLINE DA - 19961011 DCOM- 19961011 LR - 20061115 IS - 0022-2828 (Print) IS - 0022-2828 (Linking) VI - 28 IP - 1 DP - 1996 Jan TI - Electrophysiologic and extracellular ionic changes during acute ischemia in failing and normal rabbit myocardium. PG - 123-31 AB - The incidence of ventricular arrhythmias is higher in failing hearts than in control hearts, especially during acute ischemia. Electrophysiological and extracellular ionic changes during acute ischemia in normal and failing rabbit myocardium were assessed. Heart failure was induced in rabbits by combined volume and pressure overload. In perfused papillary muscles, the onset of electrical uncoupling and changes in action potential duration and conduction velocity during acute ischemia were determined. In Langendorff-perfused rabbit hearts the changes in extracellular potassium concentration ([K+]o) and pH during acute global ischemia were studied. In perfused papillary muscles, during the first 10 min of ischemia, action potential duration at 80% of repolarization decreased more in preparations from failing than from control hearts (from 174 to 104 ms and from 156 to 119 ms respectively (P < 0.001)). Conduction velocity was significantly lower in failing hearts during ischemia (P < 0.005). The onset of electrical uncoupling was similar in failing and control hearts (mean +/- S.E.M., 17 +/- 1 and 15 +/- 1 min respectively, n.s.). Langendorff-perfused hearts [K+]o, after 10 min of ischemia, was 11.0 +/- 0.4 mM in failing and 9.5 +/- 0.3 mM in control hearts (P < 0.01), while the change in pH was the same. After pretreatment with glibenclamide, an ATP sensitive K+ channel blocker, [K+]o reached lower values after 10 min of ischemia in both failing (8.8 +/- 0.5 mM) and control hearts (7.2 +/- 0.4 mM). During ischemia, action potential duration shortening is more pronounced and conduction velocity is lower in failing myocardium than in control myocardium. [K+]o reaches higher values during acute ischemia in failing compared with normal myocardium. These changes are not caused by an earlier activation of IK.ATP. Increased spatial dispersion in electrophysiological parameters and [K+]o over the ischemic border in failing hearts may explain the higher propensity for reentrant arrhythmias during acute regional ischemia in failing hearts. AD - Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, Netherlands. FAU - Vermeulen, J T AU - Vermeulen JT FAU - Tan, H L AU - Tan HL FAU - Rademaker, H AU - Rademaker H FAU - Schumacher, C A AU - Schumacher CA FAU - Loh, P AU - Loh P FAU - Opthof, T AU - Opthof T FAU - Coronel, R AU - Coronel R FAU - Janse, M J AU - Janse MJ LA - eng PT - Comparative Study PT - In Vitro PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - ENGLAND TA - J Mol Cell Cardiol JT - Journal of molecular and cellular cardiology JID - 0262322 RN - 0 (Potassium Channels) RN - 10238-21-8 (Glyburide) RN - 7440-09-7 (Potassium) SB - IM MH - Action Potentials MH - Analysis of Variance MH - Animals MH - Electric Stimulation MH - Glyburide/pharmacology MH - Heart/drug effects/*physiology/*physiopathology MH - Lung/anatomy & histology MH - Myocardial Ischemia/metabolism/*physiopathology MH - Myocardium/*metabolism MH - Organ Size MH - Papillary Muscles/physiology/physiopathology MH - Perfusion MH - Potassium/metabolism/pharmacology MH - Potassium Channels/drug effects/physiology MH - Rabbits MH - Reference Values EDAT- 1996/01/01 MHDA- 1996/01/01 00:01 CRDT- 1996/01/01 00:00 AID - S0022-2828(96)90012-7 [pii] AID - 10.1006/jmcc.1996.0012 [doi] PST - ppublish SO - J Mol Cell Cardiol. 1996 Jan;28(1):123-31. PMID- 8521572 OWN - NLM STAT- MEDLINE DA - 19960123 DCOM- 19960123 LR - 20041117 IS - 0009-7322 (Print) IS - 0009-7322 (Linking) VI - 92 IP - 12 DP - 1995 Dec 15 TI - Delayed rectifier channels in human ventricular myocytes. PG - 3497-504 AB - BACKGROUND: Previous studies have shown that in heart there are two kinetically distinct components of delayed rectifier current: a rapidly activating component (IKr) and a more slowly activating component (IKs). The presence of IKr and/or IKs appears to be species dependent. We studied the nature of the delayed rectifier current in human ventricle in whole-cell and single-channel experiments. METHODS AND RESULTS: Ventricular myocytes were obtained from hearts of patients with ischemic or dilated cardiomyopathy. Single-channel currents and whole-cell tail currents were recorded at negative potentials directly after return from a depolarizing step. Single-channel currents were measured in the cell-attached patch configuration with 140 mmol/L K+ in the pipette. In the present study, we identified a voltage-dependent channel with a single-channel conductance of 12.9 +/- 0.8 pS (mean +/- SEM, n = 5) and a reversal potential near to the K+ equilibrium potential, suggesting that the channel is selective to K+ ions. Channel activity was observed only after a depolarizing step and increased with the duration and amplitude of the depolarization, indicating time- and voltage-dependent activation. Activation at +30 mV was complete within 300 milliseconds, and the time constant of activation, determined in the whole-cell configuration, was 101 +/- 25 milliseconds (mean +/- SEM, n = 4). The voltage dependence of activation could be described by a Boltzmann equation with a half-activation potential of -29.9 mV and a slope factor of 9.5 mV. The addition of the class III antiarrhythmic drug E-4031 completely blocked channel activity in one patch. No indications for the presence of IKs were found in these experiments. CONCLUSIONS: The conformity between the properties of IKr and those of the K+ channel in the present study strongly suggests that IKr is present in human ventricle. AD - Department of Physiology, University of Amsterdam, The Netherlands. FAU - Veldkamp, M W AU - Veldkamp MW FAU - van Ginneken, A C AU - van Ginneken AC FAU - Opthof, T AU - Opthof T FAU - Bouman, L N AU - Bouman LN LA - eng PT - Journal Article PL - UNITED STATES TA - Circulation JT - Circulation JID - 0147763 RN - 0 (Anti-Arrhythmia Agents) RN - 0 (Piperidines) RN - 0 (Potassium Channels) RN - 0 (Pyridines) RN - 113558-89-7 (E 4031) SB - AIM SB - IM MH - Action Potentials MH - Anti-Arrhythmia Agents/pharmacology MH - Cardiomyopathy, Dilated/pathology MH - Cells, Cultured MH - Heart Ventricles MH - Humans MH - Myocardial Ischemia/pathology MH - Myocardium/*cytology/metabolism MH - Piperidines/pharmacology MH - Potassium Channels/drug effects/*physiology MH - Pyridines/pharmacology EDAT- 1995/12/15 MHDA- 1995/12/15 00:01 CRDT- 1995/12/15 00:00 PST - ppublish SO - Circulation. 1995 Dec 15;92(12):3497-504. PMID- 8523466 OWN - NLM STAT- MEDLINE DA - 19960125 DCOM- 19960125 LR - 20071114 IS - 0022-2828 (Print) IS - 0022-2828 (Linking) VI - 27 IP - 9 DP - 1995 Sep TI - The relation between extracellular potassium concentration and pH in the border zone during regional ischemia in isolated porcine hearts. PG - 2069-73 AB - During regional ischemia gradients of extracellular potassium concentration ([K+]o) and extracellular pH (pHo) exist. In globally ischemic papillary muscles increased PCO2 causes a rise in [K+]o. We studied whether pHo and [K+]o are causally related during acute regional ischemia in the isolated blood-perfused pig heart. Multiple pH- or K(+)-sensitive electrodes were inserted in the left ventricular midmyocardium. Local electrograms and ionic data were simultaneously acquired. Regional ischemia was produced by interrupting left anterior descending (LAD) artery flow (10 min). Up to 5 mm from the electrophysiological border the pH-K relation deviated from that in the central ischemic zone. Respiratory acidosis (pH about 7.10) of the perfusate in the presence of LAD-ischemia caused acidification of the ischemic border zone without a local change in [K+]o. We conclude that pHo changes are not related to changes of intramural [K+]o in the lateral border zone during regional ischemia. AD - Department of Experimental Cardiology, Academic Medical Centre, Amsterdam, The Netherlands. FAU - Coronel, R AU - Coronel R FAU - Wilms-Schopman, F J AU - Wilms-Schopman FJ FAU - Fiolet, J W AU - Fiolet JW FAU - Opthof, T AU - Opthof T FAU - Janse, M J AU - Janse MJ LA - eng GR - 2 PO1 HL27430/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - ENGLAND TA - J Mol Cell Cardiol JT - Journal of molecular and cellular cardiology JID - 0262322 RN - 7440-09-7 (Potassium) SB - IM MH - Animals MH - Extracellular Space/metabolism MH - Hydrogen-Ion Concentration MH - Myocardial Ischemia/*metabolism MH - Potassium/*metabolism MH - Swine EDAT- 1995/09/01 MHDA- 1995/09/01 00:01 CRDT- 1995/09/01 00:00 AID - 0022-2828(95)90028-4 [pii] PST - ppublish SO - J Mol Cell Cardiol. 1995 Sep;27(9):2069-73. PMID- 7743618 OWN - NLM STAT- MEDLINE DA - 19950615 DCOM- 19950615 LR - 20061115 IS - 0009-7322 (Print) IS - 0009-7322 (Linking) VI - 91 IP - 10 DP - 1995 May 15 TI - Dispersion of 'refractoriness' in noninfarcted myocardium of patients with ventricular tachycardia or ventricular fibrillation after myocardial infarction. PG - 2566-72 AB - BACKGROUND: Postinfarction ventricular tachycardias (VTs) may degenerate into ventricular fibrillation (VF), but this does not happen in all patients. The underlying mechanism is not exactly known, but dispersion of refractory periods is considered a major factor in both induction and persistence of reentrant arrhythmias in general. Hypertrophied, noninfarcted myocardium has altered electrophysiological characteristics. We hypothesized that noninfarcted ventricular tissue may provide the heterogeneities that cause the transition from VT into VF. Local fibrillation intervals, ie, the average interval between local activations during VF, have previously been shown to correlate well with local refractoriness in human and canine atrium and in porcine and canine ventricle and may therefore be used as an index of local refractoriness. This technique permits simultaneous assessment of refractoriness at multiple sites. METHODS AND RESULTS: We measured local fibrillation intervals at 32 to 64 sites in the noninfarcted part of the left ventricle in patients undergoing antiarrhythmic surgery for symptomatic, drug-refractory, postinfarction ventricular tachyarrhythmias. The grid of electrodes (interelectrode distance, 7 mm) was attached to the epicardium of the left ventricle remote from the infarcted tissue. Group 1 consisted of 7 patients with hemodynamically tolerable sustained VT (VT group). Group 2 consisted of 7 patients with cardiac arrest and documented VF (VF group). With the patients on cardiopulmonary bypass, VF was induced by multiple premature stimulation. The VF interval was not significantly different in the two study groups (VT group, 136 +/- 5.5 ms; VF group, 129 +/- 3.4 ms, mean +/- SEM). However, spatial dispersion of the VF intervals (remote from the infarcted area) expressed as the coefficient of variation of VF intervals (SD x 100/mean VF interval in each heart) was significantly larger in the VF group. It was 3.63 +/- 0.56 in the VF group and 1.55 +/- 0.40 in the VT group (mean +/- SEM; P < .01). Differences between the shortest and longest VF intervals in one and the same heart and the largest difference between two adjacent sites were also larger in the VF group (P < .02 and P < .05, respectively). CONCLUSIONS: This study shows larger dispersion in VF intervals and therefore suggests larger dispersion of refractory periods in parts of the myocardium remote from the infarction in patients with postinfarction VF than in patients with postinfarction VT. AD - Academic Medical Center, University of Amsterdam, Department of Clinical and Experimental Cardiology, The Netherlands. FAU - Misier, A R AU - Misier AR FAU - Opthof, T AU - Opthof T FAU - van Hemel, N M AU - van Hemel NM FAU - Vermeulen, J T AU - Vermeulen JT FAU - de Bakker, J M AU - de Bakker JM FAU - Defauw, J J AU - Defauw JJ FAU - van Capelle, F J AU - van Capelle FJ FAU - Janse, M J AU - Janse MJ LA - eng PT - Comparative Study PT - Journal Article PL - UNITED STATES TA - Circulation JT - Circulation JID - 0147763 SB - AIM SB - IM CIN - Circulation. 1997 Jan 21;95(2):531-2. PMID: 9008475 MH - Aged MH - Electrophysiology MH - Female MH - Heart Conduction System/*physiopathology MH - Humans MH - Male MH - Middle Aged MH - Myocardial Infarction/*complications MH - *Refractory Period, Electrophysiological MH - Tachycardia, Ventricular/etiology/*physiopathology/surgery MH - Ventricular Fibrillation/etiology/*physiopathology/surgery EDAT- 1995/05/15 MHDA- 1995/05/15 00:01 CRDT- 1995/05/15 00:00 PST - ppublish SO - Circulation. 1995 May 15;91(10):2566-72. PMID- 8001044 OWN - NLM STAT- MEDLINE DA - 19950126 DCOM- 19950126 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 28 IP - 10 DP - 1994 Oct TI - Triggered activity and automaticity in ventricular trabeculae of failing human and rabbit hearts. PG - 1547-54 AB - OBJECTIVE: The aim of the study was to assess the occurrence of triggered activity and automaticity in ventricular trabeculae from failing human hearts and normal and failing rabbit hearts during exposure to a normal and altered extracellular environment. METHODS: Ventricular trabeculae were harvested from failing human hearts (from patients undergoing cardiac transplantation) and from normal and failing rabbit hearts (combined volume and pressure overload). Trabeculae were superfused with normal Tyrode solution followed by a modified Tyrode solution, which mimicked the extracellular milieu in patients with severe heart failure. Modified Tyrode solution contained low potassium (3.0 mM), low magnesium (0.4 mM), and noradrenaline (1 microM). RESULTS: During superfusion with normal Tyrode solution, early afterdepolarisations, delayed afterdepolarisations, and automaticity were not observed in trabeculae from failing hearts. In the modified Tyrode solution, early afterdepolarisations could be induced in 26% of control rabbit and 30% of failing rabbit trabeculae, but never in human trabeculae. During superfusion with the modified solution delayed afterdepolarisations or triggered activity could be induced in 50% of the human failing trabeculae, in 43% of the failing rabbit trabeculae, and in 9% of the normal rabbit trabeculae (p < 0.01); automaticity was observed in 44% of the human trabeculae, and in 7% of the failing rabbit trabeculae, but in none of the control rabbit trabeculae. In failing rabbit myocardium action potential duration was prolonged at cycle lengths > or = 350 ms, but not at shorter cycle lengths. CONCLUSIONS: Delayed afterdepolarisations and automaticity, but not early afterdepolarisations, occur more frequently in myocardium from failing hearts, but only during superfusion with a modified Tyrode solution. This emphasises that the extracellular environment is important with respect to arrhythmogenesis in heart failure, apart from the fixed cellular defect due to heart failure per se. Prolongation of the action potential in failing hearts does not occur at physiological and higher heart rates and therefore cannot be regarded as a protective factor in the prevention of reentrant arrhythmias. The rate of triggered and automatic rhythms was slow. Therefore these mechanisms cannot be responsible for clinical ventricular tachycardias or fibrillation, but may serve as triggers for reentrant arrhythmias. AD - University of Amsterdam, Department of Clinical and Experimental Cardiology, The Netherlands. FAU - Vermeulen, J T AU - Vermeulen JT FAU - McGuire, M A AU - McGuire MA FAU - Opthof, T AU - Opthof T FAU - Coronel, R AU - Coronel R FAU - de Bakker, J M AU - de Bakker JM FAU - Klopping, C AU - Klopping C FAU - Janse, M J AU - Janse MJ LA - eng PT - Journal Article PL - ENGLAND TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 51-41-2 (Norepinephrine) RN - 7439-95-4 (Magnesium) RN - 7440-09-7 (Potassium) SB - IM MH - Animals MH - Arrhythmias, Cardiac/metabolism/*physiopathology MH - Electrophysiology MH - Extracellular Space/metabolism MH - Heart/*physiopathology MH - Heart Conduction System/*physiopathology MH - Heart Failure/metabolism/*physiopathology MH - Humans MH - Magnesium/metabolism MH - Norepinephrine/pharmacology MH - Perfusion MH - Potassium/metabolism MH - Rabbits EDAT- 1994/10/01 MHDA- 1994/10/01 00:01 CRDT- 1994/10/01 00:00 AID - 0008-6363(94)90201-1 [pii] PST - ppublish SO - Cardiovasc Res. 1994 Oct;28(10):1547-54. PMID- 7923290 OWN - NLM STAT- MEDLINE DA - 19941024 DCOM- 19941024 LR - 20031114 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 28 IP - 6 DP - 1994 Jun TI - Phentolamine blocks ATP sensitive potassium channels in cardiac ventricular cells. PG - 847-50 AB - OBJECTIVE: The alpha adrenoceptor antagonist phentolamine prevents ischaemia related arrhythmias in rat, guinea pig, and cat heart. This effect has been related to the attenuation of ischaemia induced shortening of the action potential and has been ascribed to its alpha adrenoceptor antagonist properties. The aim of this study was to examine the effect of phentolamine on the ATP sensitive potassium channel (KATP), because this channel seems to be involved in action potential shortening during ischaemia. METHODS: Single channel experiments were performed on inside-out and outside-out patches of isolated rabbit ventricular cells at room temperature. Cells were isolated with conventional isolation techniques. Pipette and bath solution contained (in mmol.litre-1): K-gluconate 140, KCl 10, and HEPES-KOH 10 (pH 7.4). RESULTS: Excision of the patch always resulted in KATP channel activity [single channel conductance 60(SD 2.8) pS n = 4], which could be completely blocked by 5 mM ATP. In 22 of 26 patches the addition of 5 microM phentolamine to the intracellular side of the membrane reduced KATP channel activity. In 17 of these patches the effect was reversible. In four patches no effect was observed. Open probability decreased by 94% (n = 12). Addition of 50 microM phentolamine resulted in the disappearance of channel activity in six of eight patches which was reversible in four patches. In outside-out patches 5 microM phentolamine was only effective in 50% of the patches, reducing open probability by 98 to 100%. CONCLUSIONS: Phentolamine blocks ATP sensitive potassium channels in rabbit ventricular cells independently of the alpha adrenoceptor. This blocking effect probably occurs at the intracellular side of the membrane. The antiarrhythmic effect of phentolamine may at least partially be explained by blockade of KATP channels and may thus partly be independent of its effects on the alpha adrenoceptor. AD - University of Amsterdam, Academic Medical Centre, The Netherlands. FAU - Wilde, A A AU - Wilde AA FAU - Veldkamp, M W AU - Veldkamp MW FAU - van Ginneken, A C AU - van Ginneken AC FAU - Opthof, T AU - Opthof T LA - eng PT - Journal Article PL - ENGLAND TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Potassium Channels) RN - 50-60-2 (Phentolamine) RN - 56-65-5 (Adenosine Triphosphate) SB - IM MH - Action Potentials/drug effects MH - Adenosine Triphosphate/*metabolism MH - Animals MH - Cell Membrane/metabolism MH - Cells, Cultured MH - Ion Channel Gating/*drug effects MH - Membrane Potentials/physiology MH - Myocardium/cytology/*metabolism MH - Phentolamine/*pharmacology MH - Potassium Channels/*drug effects MH - Rabbits EDAT- 1994/06/01 MHDA- 1994/06/01 00:01 CRDT- 1994/06/01 00:00 AID - 0008-6363(94)90399-9 [pii] PST - ppublish SO - Cardiovasc Res. 1994 Jun;28(6):847-50. PMID- 8181161 OWN - NLM STAT- MEDLINE DA - 19940614 DCOM- 19940614 LR - 20031114 IS - 0009-7322 (Print) IS - 0009-7322 (Linking) VI - 89 IP - 5 DP - 1994 May TI - Origin and significance of double potentials near the atrioventricular node. Correlation of extracellular potentials, intracellular potentials, and histology. PG - 2351-60 AB - BACKGROUND: Atrioventricular junctional (AV nodal) reentrant tachycardia can be cured by catheter ablation of the slow pathway, which is part of the reentrant circuit. Previous work has suggested that extracellular double potentials may help identify the site of the slow pathway, but the origin and significance of these potentials are controversial. The aim of this study was to identify the source of these potentials. METHODS AND RESULTS: Studies were performed in isolated, blood-perfused porcine (n = 8) and canine (n = 4) hearts. Several methods were used to identify the origin of potentials: microelectrode recording, extracellular mapping, pacing from multiple sites, and light microscopy. Two types of double potentials, similar to those found in humans, were found in all hearts. LH potentials consisted of a low-frequency deflection followed by a high-frequency deflection during sinus rhythm or anterior septal pacing. HL potentials consisted of a high-frequency deflection followed by a low-frequency deflection. LH potentials were found close to the coronary sinus orifice. They were caused by asynchronous activation of the sinus septum and the region between the coronary sinus orifice and tricuspid annulus. HL double potentials were found along the tricuspid annulus. They were caused by asynchronous activation of two cell layers. The high-frequency component was caused by depolarization of atrial-type cells in the deep subendocardial layer. The low-frequency component was caused by depolarization of cells with nodal characteristics close to the endocardium. These cells were present around the entire tricuspid annulus, were not part of the compact AV node, and could be dissociated from the bulk of the atria by rapid atrial pacing. CONCLUSIONS: LH potentials are caused by asynchronous activation of muscle bundles above and below the coronary sinus orifice. Their proximity to the site of the slow pathway is probably serendipity. HL double potentials are caused by asynchronous activation of atrial cells and a band of nodal-type cells close to the tricuspid annulus. The band of nodal-type cells is not part of the compact AV node and may represent the substrate of the slow AV nodal pathway. AD - Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands. FAU - McGuire, M A AU - McGuire MA FAU - de Bakker, J M AU - de Bakker JM FAU - Vermeulen, J T AU - Vermeulen JT FAU - Opthof, T AU - Opthof T FAU - Becker, A E AU - Becker AE FAU - Janse, M J AU - Janse MJ LA - eng PT - Journal Article PL - UNITED STATES TA - Circulation JT - Circulation JID - 0147763 SB - AIM SB - IM MH - Action Potentials/physiology MH - Animals MH - Atrioventricular Node/pathology/*physiopathology MH - Cardiac Pacing, Artificial MH - Catheter Ablation MH - Dogs MH - Electrodes, Implanted MH - Female MH - Heart Conduction System/pathology/physiopathology MH - Male MH - Myocardium/*pathology MH - Swine MH - Tachycardia, Atrioventricular Nodal Reentry/pathology/*physiopathology/surgery EDAT- 1994/05/01 MHDA- 1994/05/01 00:01 CRDT- 1994/05/01 00:00 PST - ppublish SO - Circulation. 1994 May;89(5):2351-60. PMID- 8174164 OWN - NLM STAT- MEDLINE DA - 19940608 DCOM- 19940608 LR - 20071115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 28 IP - 3 DP - 1994 Mar TI - IK1 blockade is unlikely to be a useful antiarrhythmic mechanism. PG - 420 AD - Laboratorium Experimentele Cardiologie, Universiteit van Amsterdam, The Netherlands. FAU - Opthof, T AU - Opthof T LA - eng PT - Journal Article PL - ENGLAND TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Potassium Channels) SB - IM CIN - Cardiovasc Res. 1994 Mar;28(3):421. PMID: 8068088 CIN - Cardiovasc Res. 1994 May;28(5):720. PMID: 8068130 MH - Animals MH - Arrhythmias, Cardiac/metabolism/*prevention & control MH - *Ion Channel Gating MH - Mice MH - Myocardium/metabolism MH - Potassium Channels/*drug effects/physiology EDAT- 1994/03/01 MHDA- 1994/03/01 00:01 CRDT- 1994/03/01 00:00 AID - 0008-6363(94)90143-0 [pii] PST - ppublish SO - Cardiovasc Res. 1994 Mar;28(3):420. PMID- 8113556 OWN - NLM STAT- MEDLINE DA - 19940331 DCOM- 19940331 LR - 20100324 IS - 0735-1097 (Print) IS - 0735-1097 (Linking) VI - 23 IP - 3 DP - 1994 Mar 1 TI - Slow potentials in the atrioventricular junctional area of patients operated on for atrioventricular node tachycardias and in isolated porcine hearts. PG - 709-15 AB - OBJECTIVES: The purpose of this study was to 1) investigate extracellular electrograms in the atrioventricular (AV) junctional area of patients with AV node reentrant tachycardia, 2) compare them with recordings made in isolated porcine hearts, and 3) study their origin. BACKGROUND: Electrograms with slow components have been used to target the delivery of radiofrequency energy for the cure of AV node reentrant tachycardia. The origin of these electrograms is unknown. METHODS: In 12 human and 19 porcine hearts, extracellular recordings were made simultaneously from 64 sites. In five other porcine hearts, intracellular recordings were made at sites at which extracellular electrograms revealed slow potentials. Histologic investigations were carried out in four of these hearts. RESULTS: Electrograms with slow components were recorded in five human and eight porcine hearts. These signals were found at sites up to 12 mm from the His bundle. Characteristics of the electrograms did not differ significantly among human and porcine hearts. Electrophysiologic evidence for multiple pathways was present in four hearts. Superficial impalements with microelectrodes at sites with slow potentials showed action potentials with AV node characteristics. In the majority of these recordings, the upstroke coincided with the downstroke of slow potentials. Histologic investigations of the sites of impalement revealed transitional cells directly underneath the endocardium. CONCLUSIONS: Slow potentials were recorded in both human and porcine hearts in similar measure. They arise from transitional cells and have action potentials similar to N cells. AD - Interuniversity Cardiology Institute of The Netherlands, Amsterdam. FAU - de Bakker, J M AU - de Bakker JM FAU - Coronel, R AU - Coronel R FAU - McGuire, M A AU - McGuire MA FAU - Vermeulen, J T AU - Vermeulen JT FAU - Opthof, T AU - Opthof T FAU - Tasseron, S AU - Tasseron S FAU - van Hemel, N M AU - van Hemel NM FAU - Defauw, J J AU - Defauw JJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - UNITED STATES TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 SB - AIM SB - IM MH - Animals MH - Atrioventricular Node/*physiopathology MH - Cardiac Pacing, Artificial MH - Catheter Ablation MH - Electrocardiography/methods MH - Female MH - Heart MH - Heart Conduction System/*physiopathology MH - Humans MH - Male MH - Middle Aged MH - Perfusion MH - Swine MH - Tachycardia, Atrioventricular Nodal Reentry/*physiopathology/surgery EDAT- 1994/03/01 MHDA- 1994/03/01 00:01 CRDT- 1994/03/01 00:00 PST - ppublish SO - J Am Coll Cardiol. 1994 Mar 1;23(3):709-15. PMID- 8186883 OWN - NLM STAT- MEDLINE DA - 19940617 DCOM- 19940617 LR - 20051116 IS - 1045-3873 (Print) IS - 1045-3873 (Linking) VI - 5 IP - 2 DP - 1994 Feb TI - Gap junctions in the sinoatrial node: immunohistochemical localization and correlation with activation pattern. PG - 138-43 AD - Department of Clinical and Experimental Cardiology, University of Amsterdam, The Netherlands. FAU - Opthof, T AU - Opthof T LA - eng PT - Journal Article PT - Review PL - UNITED STATES TA - J Cardiovasc Electrophysiol JT - Journal of cardiovascular electrophysiology JID - 9010756 RN - 0 (GAP-43 Protein) RN - 0 (Membrane Glycoproteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Phosphoproteins) SB - IM MH - Animals MH - GAP-43 Protein MH - Humans MH - Immunohistochemistry MH - Membrane Glycoproteins/metabolism/physiology MH - Nerve Tissue Proteins/metabolism/physiology MH - Neuromuscular Junction/physiology/*ultrastructure MH - Phosphoproteins/metabolism/physiology MH - Sinoatrial Node/metabolism/physiology/*ultrastructure RF - 52 EDAT- 1994/02/01 MHDA- 1994/02/01 00:01 CRDT- 1994/02/01 00:00 PST - ppublish SO - J Cardiovasc Electrophysiol. 1994 Feb;5(2):138-43. PMID- 8287403 OWN - NLM STAT- MEDLINE DA - 19940224 DCOM- 19940224 LR - 20061115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 27 IP - 11 DP - 1993 Nov TI - Dispersion of refractoriness in normal and ischaemic canine ventricle: effects of sympathetic stimulation. PG - 1954-60 AB - OBJECTIVE: Dispersion in refractoriness is considered a major factor in induction and persistence of cardiac arrhythmias. The sympathetic nervous system is known to modulate refractoriness. An index of refractoriness has therefore been assessed in normal and ischaemic myocardium simultaneously at multiple sites, with and without sympathetic stimulation. METHODS: In six dogs on total cardiopulmonary bypass the average interval between local activations was measured during artificially induced ventricular fibrillation from extracellular electrograms simultaneously recorded from 32 ventricular sites. These local ventricular fibrillation intervals may be used as an index of local refractoriness. RESULTS: During regional ischaemia, ventricular fibrillation intervals of ischaemic sites could prolong by up to 60% after 3 min following coronary occlusion. Left stellate ganglion stimulation during ischaemia produced either no response or prolonged the ventricular fibrillation intervals even further at ischaemic sites, whereas ventricular fibrillation intervals at non-ischaemic sites shortened. Dispersion in refractoriness across the ischaemic border increased by 14-59% in individual hearts following sympathetic stimulation during acute, regional ischaemia. CONCLUSIONS: Due to opposite effects on normal and ischaemic myocardium, sympathetic stimulation increases the difference in refractoriness over the ischaemic border. This may enhance the chance for regional conduction block and the propensity to re-entrant arrhythmias. AD - Department of Clinical and Experimental Cardiology, University of Amsterdam, The Netherlands. FAU - Opthof, T AU - Opthof T FAU - Coronel, R AU - Coronel R FAU - Vermeulen, J T AU - Vermeulen JT FAU - Verberne, H J AU - Verberne HJ FAU - van Capelle, F J AU - van Capelle FJ FAU - Janse, M J AU - Janse MJ LA - eng PT - Comparative Study PT - Journal Article PL - ENGLAND TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM MH - Acute Disease MH - Animals MH - Cardiopulmonary Bypass MH - Dogs MH - Electric Stimulation MH - Heart/*physiopathology MH - Myocardial Ischemia/*physiopathology MH - Sympathetic Nervous System/*physiopathology MH - Ventricular Fibrillation/physiopathology EDAT- 1993/11/01 MHDA- 1993/11/01 00:01 CRDT- 1993/11/01 00:00 PST - ppublish SO - Cardiovasc Res. 1993 Nov;27(11):1954-60. PMID- 8283469 OWN - NLM STAT- MEDLINE DA - 19940215 DCOM- 19940215 LR - 20061115 IS - 0022-2828 (Print) IS - 0022-2828 (Linking) VI - 25 IP - 9 DP - 1993 Sep TI - R 56865 delays cellular electrical uncoupling in ischemic rabbit papillary muscle. PG - 1059-66 AB - The compound R56865 protects the heart from irreversible ischemic damage. The proposed mechanism of its action is a reduction of Ca2+ overload secondary to a reduction of intracellular Na+, caused by blockade of the Na(+)-channel. In addition, cardioprotection is ascribed to blockade of the Na(+)-sensitive K(+)-channel (IK-Na). We tested whether R 56865 delays cellular electrical uncoupling, one aspect of irreversible ischemic damage that is due to Ca2+ overload. Also, we studied whether the Na(+)-channel and IK-Na are involved in cardioprotection by relating delay of the onset of cellular electrical uncoupling to changes of conduction velocity and action potential duration (APD80), respectively. Experiments were performed with isolated perfused rabbit papillary muscles that were treated with 1 microM R 56865 for 45 min prior to ischemia. Uncoupling started at 15.0 +/- 0.8 min (mean +/- S.E.M., n = 12) of ischemia in the control group and at 23.4 +/- 1.7 min in the R 56865 group (n = 9, P < 0.005 vs control). R 56865 tended to decrease conduction velocity and to increase APD80 during pre-treatment, but these changes were not statistically significant. During ischemia, conduction velocity was statistically not different between the R 56865 group and the control group. APD80 was significantly longer in the R 56865 than in the control group during the first 7 min of ischemia and similar after that. We conclude that R 56865 delays the onset of cellular uncoupling during ischemia and that this effect is not related to changes of conduction velocity and at most in part to changes of APD80. AD - Department of Clinical and Experimental Cardiology, University of Amsterdam, The Netherlands. FAU - Tan, H L AU - Tan HL FAU - Netea, A O AU - Netea AO FAU - Sleeswijk, M E AU - Sleeswijk ME FAU - Mazon, P AU - Mazon P FAU - Coronel, R AU - Coronel R FAU - Opthof, T AU - Opthof T FAU - Janse, M J AU - Janse MJ LA - eng PT - In Vitro PT - Journal Article PL - ENGLAND TA - J Mol Cell Cardiol JT - Journal of molecular and cellular cardiology JID - 0262322 RN - 0 (Benzothiazoles) RN - 0 (Piperidines) RN - 0 (Thiazoles) RN - 104606-13-5 (R 56865) RN - 7440-70-2 (Calcium) SB - IM MH - Action Potentials/drug effects MH - Animals MH - Benzothiazoles MH - Calcium/metabolism MH - Heart Conduction System/drug effects MH - Myocardial Contraction/*drug effects MH - Myocardial Ischemia/*drug therapy MH - Piperidines/*pharmacology/therapeutic use MH - Rabbits MH - Thiazoles/*pharmacology/therapeutic use EDAT- 1993/09/01 MHDA- 1993/09/01 00:01 CRDT- 1993/09/01 00:00 AID - S0022-2828(83)71118-1 [pii] AID - 10.1006/jmcc.1993.1118 [doi] PST - ppublish SO - J Mol Cell Cardiol. 1993 Sep;25(9):1059-66. PMID- 8348575 OWN - NLM STAT- MEDLINE DA - 19930913 DCOM- 19930913 LR - 20061115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 27 IP - 5 DP - 1993 May TI - Interaction of sympathetic and parasympathetic nervous system on ventricular refractoriness assessed by local fibrillation intervals in the canine heart. PG - 753-9 AB - OBJECTIVE: The aim was to assess the effects of autonomic nerve stimulation on local ventricular refractoriness by measuring local ventricular fibrillation intervals. METHODS: In 10 dogs on cardiopulmonary bypass, ventricular fibrillation intervals were recorded simultaneously at up to 32 sites before and after neural stimulation. In four dogs (group 1) the response to bilateral stellate ganglion stimulation was measured before and after bilateral cervical vagotomy. In three dogs (group 2) bilateral stellate ganglion stimulation, vagal nerve stimulation, and combined vagal and stellate ganglia stimulation were performed. In three dogs (group 3) the same protocol was applied after total decentralisation of the autonomic nervous system. RESULTS: Bilateral stellate ganglion stimulation shortened the ventricular fibrillation interval at 44-50% of myocardial sites before and after vagotomy, whereas prolongation of the interval was observed at 14-18% of the sites. At higher stimulus strength shortening of the interval was measured at 85% of the sites in the intact and decentralised groups. No prolongation was observed. The shortening was largest in the decentralised group (11.1 ms). Dispersion in refractoriness increased in hearts from all groups, but not in each individual heart. Left, right, or bilateral vagal stimulation was without effect at about 75% of the tested sites. The fact that the response to autonomic nerve stimulation varies from site to site warrants our approach of simultaneous recordings at multiple sites. Dispersion in refractoriness was not affected by vagal stimulation. Combined autonomic stimulation had approximately the same effect on dispersion in refractoriness as bilateral stellate ganglion stimulation alone. However, vagal stimulation attenuated the responses to bilateral stellate ganglion stimulation by some 20% in the decentralised group. CONCLUSIONS: Vagal stimulation has minor effects on ventricular refractoriness, but this is not due to sparse innervation, since vagal stimulation is able to mitigate the effects of sympathetic stimulation in decentralised hearts. AD - Department of Clinical and Experimental Cardiology, Academic Medical Centre, University of Amsterdam, The Netherlands. FAU - Opthof, T AU - Opthof T FAU - Dekker, L R AU - Dekker LR FAU - Coronel, R AU - Coronel R FAU - Vermeulen, J T AU - Vermeulen JT FAU - van Capelle, F J AU - van Capelle FJ FAU - Janse, M J AU - Janse MJ LA - eng PT - Comparative Study PT - Journal Article PL - ENGLAND TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 SB - IM MH - Animals MH - Autonomic Nervous System/*physiopathology MH - Cardiopulmonary Bypass MH - Dogs MH - Electric Stimulation MH - Heart/*physiopathology MH - Parasympathetic Nervous System/physiopathology MH - Sympathetic Nervous System/physiopathology MH - Vagotomy MH - Ventricular Fibrillation/*physiopathology EDAT- 1993/05/01 MHDA- 1993/05/01 00:01 CRDT- 1993/05/01 00:00 PST - ppublish SO - Cardiovasc Res. 1993 May;27(5):753-9. PMID- 8324799 OWN - NLM STAT- MEDLINE DA - 19930812 DCOM- 19930812 LR - 20061115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 27 IP - 4 DP - 1993 Apr TI - Ischaemic preconditioning delays ischaemia induced cellular electrical uncoupling in rabbit myocardium by activation of ATP sensitive potassium channels. PG - 644-51 AB - OBJECTIVE: The aim was to examine whether ischaemic preconditioning delays the onset of cellular electrical uncoupling during ischaemia, and whether the effect of preconditioning is mediated by the activation of ATP sensitive K+ channels (IK-ATP). METHODS: Onset of uncoupling, action potential duration (APD80), and conduction velocity were measured in an isolated perfused rabbit papillary muscle. Preconditioning consisted of 10 min occlusion and 10 min reperfusion prior to 40 min sustained ischaemia. Five groups were studied: (1) control (sustained ischaemia only); (2) preconditioning; (3) preconditioning with 20 microM glibenclamide, a blocker of IK-ATP, added for 10 min during the reperfusion period; (4) sustained ischaemia after 15 min perfusion with 20 microM cromakalim (BRL 34915), an opener of IK-ATP; (5) sustained ischaemia after 10 min perfusion with 20 microM glibenclamide without preconditioning. RESULTS: Uncoupling started at 15.0(SEM 0.7) min of ischaemia in the control group and at 22.8(1.5) min after preconditioning (p < 0.001 v control group). Blocking IK-ATP during the preconditioning protocol with glibenclamide abolished the delay of uncoupling: onset was at 14.7(1.2) min. Activation of IK-ATP with cromakalim resulted in uncoupling at 23.3(1.9) min (p < 0.002 v control). Glibenclamide without preconditioning had no effect on uncoupling: onset was at 15.6(1.0) min. APD80 during ischaemia was significantly shorter in the preconditioning and cromakalim groups than in the control group from 5 min of ischaemia onward. In the preconditioning+glibenclamide group and the glibenclamide group APD80 was at no point significantly different from the control group. Conduction velocity during ischaemia decreased to about 70% of baseline after 10 min and was not different between the five groups. CONCLUSIONS: (1) Preconditioning delays the onset of electrical uncoupling; (2) the protective effect of preconditioning may be caused by activation of the IK-ATP channel; (3) the protective effect is associated with reduction of action potential duration, but not with changes of conduction velocity. AD - Department of Clinical and Experimental Cardiology, Academic Medical Centre, University of Amsterdam, The Netherlands. FAU - Tan, H L AU - Tan HL FAU - Mazon, P AU - Mazon P FAU - Verberne, H J AU - Verberne HJ FAU - Sleeswijk, M E AU - Sleeswijk ME FAU - Coronel, R AU - Coronel R FAU - Opthof, T AU - Opthof T FAU - Janse, M J AU - Janse MJ LA - eng PT - Comparative Study PT - Journal Article PL - ENGLAND TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Potassium Channels) RN - 10238-21-8 (Glyburide) RN - 56-65-5 (Adenosine Triphosphate) SB - IM EIN - Cardiovasc Res 1993 Jul;27(7):1385 MH - Action Potentials/physiology MH - Adenosine Triphosphate/*metabolism MH - Animals MH - Culture Techniques MH - Disease Models, Animal MH - Female MH - Glyburide/pharmacology MH - Ion Channel Gating/drug effects/*physiology MH - Male MH - Myocardial Ischemia/*metabolism MH - *Myocardial Reperfusion MH - Papillary Muscles/*metabolism MH - Potassium Channels/drug effects/*metabolism MH - Rabbits EDAT- 1993/04/01 MHDA- 1993/04/01 00:01 CRDT- 1993/04/01 00:00 PST - ppublish SO - Cardiovasc Res. 1993 Apr;27(4):644-51. PMID- 1394875 OWN - NLM STAT- MEDLINE DA - 19921116 DCOM- 19921116 LR - 20071115 IS - 0009-7330 (Print) IS - 0009-7330 (Linking) VI - 71 IP - 5 DP - 1992 Nov TI - Reperfusion arrhythmias in isolated perfused pig hearts. Inhomogeneities in extracellular potassium, ST and TQ potentials, and transmembrane action potentials. PG - 1131-42 AB - We recorded direct current electrograms and local [K+]o at multiple sites and transmembrane potentials at selected sites during reperfusion after 5 minutes and 10 minutes of regional ischemia in isolated perfused pig hearts. After 10 minutes of ischemia, the incidence of ventricular fibrillation (VF) was 38%. At 80-90 seconds after reperfusion, [K+]o was 0.8 mM less than in normal tissue in half of the reperfused tissue, especially in the border zone. This was associated with TQ elevation of +4.5 mV and large peaked T waves. The latter was caused by an abrupt decrease of action potential duration in reperfused tissue, leading to a difference of up to 165 msec with normal tissue. Reperfusion VF started with a closely coupled ventricular premature beat. Activation block between reperfused and normal tissue permitted reentrant activation, leading to VF. Pretreatment with ryanodine (10(-6) M) and reperfusion with elevated [K+] (both of which prevent delayed afterdepolarizations) did not prevent closely coupled ventricular premature beats or VF. Five minutes of ischemia never caused VF. K+ depletion and TQ elevation in the reperfused zone was less frequent and smaller (-0.4 mM and 1.8 mV, respectively). Peaked T waves did not occur, and shortening of the action potential duration was less. We conclude that extracellular K+ depletion and marked action potential duration shortening in the reperfused tissue play a role in the genesis of reperfusion VF, which is caused by reentry. The closely coupled ventricular premature beat that initiates reentry is not caused by delayed afterdepolarizations but most likely by intramural reentry. AD - Department of Experimental Cardiology, Academic Medical Centre, Amsterdam, The Netherlands. FAU - Coronel, R AU - Coronel R FAU - Wilms-Schopman, F J AU - Wilms-Schopman FJ FAU - Opthof, T AU - Opthof T FAU - Cinca, J AU - Cinca J FAU - Fiolet, J W AU - Fiolet JW FAU - Janse, M J AU - Janse MJ LA - eng PT - In Vitro PT - Journal Article PL - UNITED STATES TA - Circ Res JT - Circulation research JID - 0047103 RN - 7440-09-7 (Potassium) SB - IM MH - Action Potentials MH - Animals MH - Arrhythmias, Cardiac/metabolism/*physiopathology MH - *Electrocardiography MH - Extracellular Space/*metabolism MH - Heart/*physiopathology MH - *Myocardial Reperfusion Injury/metabolism/*physiopathology MH - Myocardium/*metabolism MH - Osmolar Concentration MH - Perfusion MH - Potassium/*metabolism MH - Reaction Time MH - Swine MH - Ventricular Fibrillation/physiopathology EDAT- 1992/11/01 MHDA- 1992/11/01 00:01 CRDT- 1992/11/01 00:00 PST - ppublish SO - Circ Res. 1992 Nov;71(5):1131-42. PMID- 1628384 OWN - NLM STAT- MEDLINE DA - 19920817 DCOM- 19920817 LR - 20091119 IS - 0009-7330 (Print) IS - 0009-7330 (Linking) VI - 71 IP - 2 DP - 1992 Aug TI - Persisting zones of slow impulse conduction in developing chicken hearts. PG - 240-50 AB - We performed a correlative electrophysiological and immunohistochemical study of embryonic chicken hearts during the septational period (Hamburger and Hamilton stages 13-31 [2-7 days of incubation]). The analyses yield conclusive evidence for slow conduction, up to 7 days of development, in the outflow tract, in the atrioventricular canal, and in the sinoatrial junction. The conduction velocity remains approximately 1 cm/sec in the outflow tract and increases in the ventricle 20-fold to approximately 20 cm/sec between 2 and 7 days of development. Transmembrane potentials of myocytes in the outflow tract and atrioventricular canal slowly rise (less than 5 V/sec), whereas in the atrium and ventricle, the upstroke velocity is eightfold to 13-fold higher. In the outflow tract, repolarization is completed only after the start of the next cycle. Because of the persistence of slow conduction, the myocardium flanking the developing atria and ventricle is thought to represent segments of persisting "primary" myocardium, whereas the more rapidly conducting "working" myocardium of the ventricle and atria is thought to represent more advanced stages of myocardial differentiation. The persisting primary myocardium was characterized by a continued coexpression of both the atrial and ventricular isoforms of myosin heavy chain. The developing atria and ventricle could be demarcated morphologically from the primary myocardium because the free walls of these segments only express their respective isoforms of myosin heavy chain. The slowly conducting myocardial zones appear to be essential for the function of the embryonic heart because 1) they provide the septating heart with alternating segments of slow and relatively fast conduction necessary for consecutive contraction of the atrial and ventricular segments and 2) their sphincterlike prolonged peristaltic contraction pattern can substitute for the adult type of one-way valves that start to develop at the end of septation. AD - Department of Anatomy and Embryology, University of Amsterdam, The Netherlands. FAU - de Jong, F AU - de Jong F FAU - Opthof, T AU - Opthof T FAU - Wilde, A A AU - Wilde AA FAU - Janse, M J AU - Janse MJ FAU - Charles, R AU - Charles R FAU - Lamers, W H AU - Lamers WH FAU - Moorman, A F AU - Moorman AF LA - eng PT - Comparative Study PT - In Vitro PT - Journal Article PL - UNITED STATES TA - Circ Res JT - Circulation research JID - 0047103 RN - EC 3.6.4.1 (Myosins) SB - IM MH - Animals MH - Chick Embryo MH - Electrophysiology MH - Heart/*embryology/physiology MH - Heart Conduction System/*embryology/physiology MH - Heart Ventricles/embryology MH - Immunohistochemistry MH - Membrane Potentials MH - Myocardium/chemistry MH - Myosins/analysis EDAT- 1992/08/01 MHDA- 1992/08/01 00:01 CRDT- 1992/08/01 00:00 PST - ppublish SO - Circ Res. 1992 Aug;71(2):240-50. PMID- 1423432 OWN - NLM STAT- MEDLINE DA - 19921202 DCOM- 19921202 LR - 20061115 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 26 IP - 7 DP - 1992 Jul TI - Effect of transmural vagal stimulation on electrotonic current spread in the rabbit sinoatrial node. PG - 678-86 AB - OBJECTIVE: The effect of vagal stimulation on the decay of electrotonic potential caused by intracellular current injection and on input resistance was measured in the sinoatrial node of isolated rabbit right atria. METHODS: Studies were performed on New Zealand White rabbits weighing approximately 2-3 kg. Vagal stimulation was achieved by transmural stimulation of intramural nerve fibres in the presence of propranolol. A K+ perfused suction electrode was used to inject hyperpolarising current pulses; input resistance was measured by means of a double barrel microelectrode. RESULTS: Vagal stimulation which caused a 14-20% increase of cycle length diminished electronic potential significantly by a decrease of membrane resistance. The input resistance of the sinoatrial node was not affected. Space constant values calculated by using either a one or a two dimensional model of electrotonic current spread were decreased on average by 13% and 14% respectively. CONCLUSIONS: The results from this study show that vagal stimulation which gave rise to a moderate negative chronotropic effect and marked changes in action potential configuration of nodal fibres affects the electrotonic interaction within the sinoatrial node. This may have consequences for the electrical activity and synchronisation of the sinoatrial nodal fibres. AD - Department of Physiology, University of Amsterdam, The Netherlands. FAU - Duivenvoorden, J J AU - Duivenvoorden JJ FAU - Bouman, L N AU - Bouman LN FAU - Opthof, T AU - Opthof T FAU - Bukauskas, F F AU - Bukauskas FF FAU - Jongsma, H J AU - Jongsma HJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - ENGLAND TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 525-66-6 (Propranolol) SB - IM MH - Action Potentials/drug effects/physiology MH - Animals MH - Electric Conductivity/drug effects/physiology MH - Electric Stimulation/methods MH - Female MH - Male MH - Propranolol/pharmacology MH - Rabbits MH - Sinoatrial Node/*physiology MH - Vagus Nerve/drug effects/*physiology EDAT- 1992/07/01 MHDA- 1992/07/01 00:01 CRDT- 1992/07/01 00:00 PST - ppublish SO - Cardiovasc Res. 1992 Jul;26(7):678-86. PMID- 1593049 OWN - NLM STAT- MEDLINE DA - 19920626 DCOM- 19920626 LR - 20061115 IS - 0735-1097 (Print) IS - 0735-1097 (Linking) VI - 19 IP - 7 DP - 1992 Jun TI - Increased dispersion of "refractoriness" in patients with idiopathic paroxysmal atrial fibrillation. PG - 1531-5 AB - The average interval between local depolarizations during atrial fibrillation, the so-called atrial fibrillation interval, was used as an index for local "refractoriness." This was based on the assumption that during fibrillation, cells are reexcited as soon as their refractory period ends. A very good correlation was found between refractory periods determined with the extrastimulus technique at a basic cycle length of 400 ms and atrial fibrillation intervals measured at the same epicardial sites of the right atrium. This new technique was used to assess dispersion in atrial fibrillation intervals in 10 patients with idiopathic paroxysmal atrial fibrillation and in a control group of 6 patients who were undergoing cardiac surgery. After a routine median sternotomy a multiterminal grid with up to 40 electrodes was placed over the right atrium, and atrial fibrillation was induced by premature stimulation. The average fibrillation interval in the test group, recorded at 247 sites, was 152 +/- 3 ms and that in the control group, recorded at 118 sites, was 176 +/- 8.1 ms (p less than 0.05). Dispersion in atrial fibrillation intervals, defined as the variance of the fibrillation intervals at all the recording sites, was three times larger in the group with paroxysmal atrial fibrillation than in the control group. This study suggests that both a shorter refractory period and a larger dispersion in refractoriness are responsible for the recurrence of atrial fibrillation. AD - Department of Cardiology, St. Antonius Hospital, Nieuwegein, The Netherlands. FAU - Misier, A R AU - Misier AR FAU - Opthof, T AU - Opthof T FAU - van Hemel, N M AU - van Hemel NM FAU - Defauw, J J AU - Defauw JJ FAU - de Bakker, J M AU - de Bakker JM FAU - Janse, M J AU - Janse MJ FAU - van Capelle, F J AU - van Capelle FJ LA - eng PT - Journal Article PL - UNITED STATES TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 SB - AIM SB - IM MH - Atrial Fibrillation/*diagnosis/physiopathology MH - Atrial Function, Right/physiology MH - *Cardiac Pacing, Artificial MH - Electrocardiography/methods MH - Electrophysiology MH - Heart Block/physiopathology MH - Heart Conduction System/*physiopathology MH - Humans MH - Refractory Period, Electrophysiological/physiology MH - Signal Processing, Computer-Assisted EDAT- 1992/06/01 MHDA- 1992/06/01 00:01 CRDT- 1992/06/01 00:00 PST - ppublish SO - J Am Coll Cardiol. 1992 Jun;19(7):1531-5. PMID- 2018989 OWN - NLM STAT- MEDLINE DA - 19910530 DCOM- 19910530 LR - 20071115 IS - 0009-7330 (Print) IS - 0009-7330 (Linking) VI - 68 IP - 5 DP - 1991 May TI - Injury current and gradients of diastolic stimulation threshold, TQ potential, and extracellular potassium concentration during acute regional ischemia in the isolated perfused pig heart. PG - 1241-9 AB - During acute regional myocardial ischemia, a "current of injury" flows between the ischemic and the normal tissue. Its direction and magnitude change during the cardiac cycle. During diastole, the injury current flows intracellularly from the ischemic cells toward the normal cells and tends to depolarize the latter. The gain insight into the possible role of the injury current in arrhythmogenesis, we simultaneously determined diastolic stimulation threshold, [K+]o and TQ potential at multiple sites closely spaced across the cyanotic border in Langendorff-perfused pig hearts during the first 10 minutes after occlusion of the left anterior descending coronary artery. The position of the electrodes relative to the border was validated by their response to 1) regional ischemia and 2) selective perfusion with a high-K+ perfusate of the left anterior descending coronary artery. A temporary decrease of diastolic stimulation threshold preceded a rapid increase in the central ischemic zone; a lasting reduction (by +/- 20%) without a concomitant increase of [K+]o was observed at seven sites (of 39 sites tested), five of which were less than 2 mm outside the electrophysiological border. Moreover, up to 4 mm inside the electrophysiological border, a similar lasting decrease of diastolic stimulation threshold was accompanied by a moderate increase of [K+]o. We conclude that 1) the injury current causes increased excitability in normal tissue close to the "ischemic" border and 2) increased excitability related to a moderately increased [K+]o may persist up to 10 minutes of ischemia at the ischemic side of the border. Both factors may facilitate the induction of life-threatening arrhythmias in acute myocardial ischemia. AD - Department of Experimental Cardiology, Academic Medical Centre, Amsterdam, The Netherlands. FAU - Coronel, R AU - Coronel R FAU - Wilms-Schopman, F J AU - Wilms-Schopman FJ FAU - Opthof, T AU - Opthof T FAU - van Capelle, F J AU - van Capelle FJ FAU - Janse, M J AU - Janse MJ LA - eng PT - Comparative Study PT - In Vitro PT - Journal Article PL - UNITED STATES TA - Circ Res JT - Circulation research JID - 0047103 RN - 7440-09-7 (Potassium) SB - IM MH - Action Potentials MH - Animals MH - Arrhythmias, Cardiac/etiology MH - *Diastole MH - Electric Stimulation MH - Electrophysiology MH - Myocardial Infarction/metabolism/*physiopathology MH - Myocardium/*metabolism MH - Perfusion MH - Potassium/*metabolism MH - Swine MH - Time Factors EDAT- 1991/05/01 MHDA- 1991/05/01 00:01 CRDT- 1991/05/01 00:00 PST - ppublish SO - Circ Res. 1991 May;68(5):1241-9. PMID- 2018987 OWN - NLM STAT- MEDLINE DA - 19910530 DCOM- 19910530 LR - 20061115 IS - 0009-7330 (Print) IS - 0009-7330 (Linking) VI - 68 IP - 5 DP - 1991 May TI - Dispersion of refractoriness in canine ventricular myocardium. Effects of sympathetic stimulation. PG - 1204-15 AB - In 18 dogs on total cardiopulmonary bypass, the average interval between local activations during artificially induced ventricular fibrillation (VF interval) was measured from extracellular electrograms, simultaneously recorded from up to 32 ventricular sites. VF intervals were used as an index of local refractoriness, based on the assumption that during ventricular fibrillation, cells are reexcited as soon as they have recovered their excitability. In support of this, microelectrode recordings in two hearts during ventricular fibrillation did not show a diastolic interval between successive action potentials. Refractory periods determined at a basic cycle length of 300 msec with the extrastimulus method correlated well with VF intervals measured at the same sites. Thus, this technique allows assessment of spatial dispersion of refractoriness during brief interventions such as sympathetic stimulation. The responses to left, right, and combined stellate ganglion stimulation varied substantially among individual hearts. This was observed both in dogs with an intact (n = 12) and decentralized (n = 6) autonomic nervous system. Individual ventricular sites could show effects of both left and right stellate ganglion stimulation (42% of tested sites) or show effects of left-sided stimulation only (31%) or right-sided stimulation only (14%). In 13% of sites, no effects of stellate stimulation were observed. Apart from these regional effects, the responses could be qualitatively different; that is, within the same heart, the VF interval prolonged at one site but shortened at another in response to the same intervention, although shortening was the general effect and prolongation the exception. Whenever sites responded to stellate ganglion stimulation with a shortening of VF interval, this shortening was approximately 10% for left, right, or combined stimulation, whether the autonomic nervous system was intact or decentralized. In six of 12 hearts in the intact group, there was a distinct regional effect of left stellate ganglion stimulation; in the other six hearts, the effects were distributed homogeneously over the ventricles. In three hearts, the effect of left stellate ganglion stimulation was strongest in the posterior wall, and in the other three hearts, in the anterior wall. The effects of right stellate ganglion stimulation were restricted to the anterior or lateral part of the left ventricle. Dispersion of VF intervals increased after left and combined stellate ganglion stimulation in the intact group and after right stellate ganglion stimulation in the decentralized group, but not significantly in every heart. This points to a marked individual variation with regard to the effects of sympathetic stimulation on electrophysiological properties of the heart. AD - Department of Clinical and Experimental Cardiology, University of Amsterdam, The Netherlands. FAU - Opthof, T AU - Opthof T FAU - Misier, A R AU - Misier AR FAU - Coronel, R AU - Coronel R FAU - Vermeulen, J T AU - Vermeulen JT FAU - Verberne, H J AU - Verberne HJ FAU - Frank, R G AU - Frank RG FAU - Moulijn, A C AU - Moulijn AC FAU - van Capelle, F J AU - van Capelle FJ FAU - Janse, M J AU - Janse MJ LA - eng PT - Comparative Study PT - Journal Article PL - UNITED STATES TA - Circ Res JT - Circulation research JID - 0047103 SB - IM MH - Action Potentials MH - Algorithms MH - Animals MH - Autonomic Nervous System/*physiopathology MH - Dogs MH - Electric Stimulation MH - Electrophysiology MH - Heart/*physiopathology MH - Microelectrodes MH - Refractory Period, Electrophysiological MH - Stellate Ganglion/*physiopathology MH - Ventricular Fibrillation/*physiopathology EDAT- 1991/05/01 MHDA- 1991/05/01 00:01 CRDT- 1991/05/01 00:00 PST - ppublish SO - Circ Res. 1991 May;68(5):1204-15. PMID- 2345240 OWN - NLM STAT- MEDLINE DA - 19900703 DCOM- 19900703 LR - 20061115 IS - 0735-1097 (Print) IS - 0735-1097 (Linking) VI - 15 IP - 7 DP - 1990 Jun TI - Ventricular tachycardia in the infarcted, Langendorff-perfused human heart: role of the arrangement of surviving cardiac fibers. PG - 1594-607 AB - Electrophysiologic and histologic studies were performed on Langendorff-perfused human hearts from patients who underwent heart transplantation because of extensive infarction. In nine hearts, 15 sustained ventricular tachycardias could be induced by programmed stimulation. In all hearts, mapping of epicardial and endocardial electrical activity during tachycardia was carried out. Histologic examination of the infarcted area between the site of latest activation of one cycle and the site of earliest activation of the next cycle revealed zones of viable myocardial tissue. In two hearts in which the time gap between latest and earliest activation was small, surviving myocardial tissue constituted a continuous tract that traversed the infarct. In three other hearts in which the time gap was large, surviving tissue consisted of parallel bundles that coursed separately over a few hundred micrometers, then merged into a single bundle and finally branched again. The direction of the fibers within the bundles was perpendicular to the direction of the activation front in that area. A similar type of inhomogeneous anisotrophy and activation delay was found in an infarcted papillary muscle removed from one of the explanted hearts and studied in a tissue bath during basic stimulation. Histologic examination of this preparation revealed that the delay was caused by a zigzag route of activation over branching and merging bundles of surviving myocytes separated by connective tissue. AD - Department of Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands. FAU - de Bakker, J M AU - de Bakker JM FAU - Coronel, R AU - Coronel R FAU - Tasseron, S AU - Tasseron S FAU - Wilde, A A AU - Wilde AA FAU - Opthof, T AU - Opthof T FAU - Janse, M J AU - Janse MJ FAU - van Capelle, F J AU - van Capelle FJ FAU - Becker, A E AU - Becker AE FAU - Jambroes, G AU - Jambroes G LA - eng PT - In Vitro PT - Journal Article PL - UNITED STATES TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 SB - AIM SB - IM CIN - J Am Coll Cardiol. 1990 Jun;15(7):1608-9. PMID: 2345241 MH - Cardiac Pacing, Artificial MH - Diastole MH - Electrophysiology MH - Endocardium/physiopathology MH - Heart/*physiopathology MH - Heart Transplantation MH - Humans MH - Myocardial Infarction/*complications/therapy MH - Myocardium/*pathology MH - Papillary Muscles/physiopathology MH - Perfusion MH - Tachycardia/etiology/*physiopathology EDAT- 1990/06/01 MHDA- 1990/06/01 00:01 CRDT- 1990/06/01 00:00 PST - ppublish SO - J Am Coll Cardiol. 1990 Jun;15(7):1594-607. PMID- 2388276 OWN - NLM STAT- MEDLINE DA - 19900925 DCOM- 19900925 LR - 20061115 IS - 0022-2828 (Print) IS - 0022-2828 (Linking) VI - 22 IP - 4 DP - 1990 Apr TI - Phase dependency of electrotonic spread of hyperpolarizing current pulses in the rabbit sinoatrial node. PG - 415-27 AB - Electrotonic current spread in the SA node of the rabbit was measured by means of hyperpolarizing current pulses (1 to 10 microA, 60 ms), which were injected intracellularly through a K(+)-perfused suction electrode. The pulses were applied at the beginning, middle or end of the diastolic depolarization phase. The resulting membrane potential change of nodal fibers was measured with microelectrodes. Space constants were calculated by fitting single exponential curves to the data. The input resistance (Rin) of fibers at different sites in the SA node was measured by means of a double barrel microelectrode (current pulses 5.5 to 11 nA, 60 ms) to detect a change in the internal resistance during the diastolic depolarization phase. During diastole the average electrotonic potential increased by 30% (P less than 0.001), the increase of the space constant ranged from 9 to 183% (P less than 0.05). Rin however, did not change during diastole. It is concluded that the electrotonic spread increased phase dependently, due to an increase of membrane resistance; the internal resistance was not phase dependent. AD - Department of Physiology, University of Amsterdam, The Netherlands. FAU - Duivenvoorden, J J AU - Duivenvoorden JJ FAU - Bouman, L N AU - Bouman LN FAU - Bukauskas, F F AU - Bukauskas FF FAU - Opthof, T AU - Opthof T FAU - Jongsma, H J AU - Jongsma HJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - ENGLAND TA - J Mol Cell Cardiol JT - Journal of molecular and cellular cardiology JID - 0262322 SB - IM MH - Animals MH - Diastole MH - Electrophysiology MH - Female MH - Male MH - Membrane Potentials MH - Microelectrodes MH - Rabbits MH - Reproducibility of Results MH - Sinoatrial Node/*physiology MH - Vascular Resistance EDAT- 1990/04/01 MHDA- 1990/04/01 00:01 CRDT- 1990/04/01 00:00 AID - 0022-2828(90)91477-O [pii] PST - ppublish SO - J Mol Cell Cardiol. 1990 Apr;22(4):415-27. PMID- 1691395 OWN - NLM STAT- MEDLINE DA - 19900524 DCOM- 19900524 LR - 20061115 IS - 0160-2446 (Print) IS - 0160-2446 (Linking) VI - 15 IP - 4 DP - 1990 Apr TI - Mechanism of antifibrillatory action of Org 7797 in regionally ischemic pig heart. PG - 633-43 AB - Org 7797 is effective against ventricular fibrillation (VF) induced during ischemia. In Langendorff-perfused pig hearts, application of three premature stimuli to nonischemic myocardium between 3 and 5 min after coronary occlusion always resulted in VF in the absence of drug. In no instance when Org 7797 was present (2-10 microM) could VF be induced, although sustained and nonsustained ventricular tachycardias (VTs) could still be initiated in about two thirds of treated hearts. We determined the effects of Org 7797 on wavelength in normal and ischemic myocardium during regular driving at a cycle length of 350 ms. Wavelength, the algebraic product of conduction velocity and refractory period, is considered a useful parameter in assessing efficacy of antiarrhythmic agents in preventing reentrant arrhythmias. Conduction velocity was obtained by analyzing the spread of activation under 121 unipolar electrodes (1 mm apart) placed around a central stimulus electrode. Refractory periods were determined with premature test stimuli at an intensity of twice diastolic threshold. Both in normal and ischemic myocardium Org 7797 (5-10 microM) produced a marked shortening of wavelength. This should predispose to reentry. However, Org 7797 prolonged the refractory period at the fastest possible driving rate from 154 to 247 ms and attenuated (5 microM) or prevented (10 microM) shortening of the refractory period during application of subsequent premature stimuli. The antifibrillatory effect of the drug may be explained by prolongation of wavelength at very short cycles. AD - Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands. FAU - Janse, M J AU - Janse MJ FAU - Wilms-Schopman, F AU - Wilms-Schopman F FAU - Opthof, T AU - Opthof T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - UNITED STATES TA - J Cardiovasc Pharmacol JT - Journal of cardiovascular pharmacology JID - 7902492 RN - 0 (Anti-Arrhythmia Agents) RN - 0 (Estrenes) RN - 80177-51-1 (Org 7797) SB - IM MH - Animals MH - Anti-Arrhythmia Agents/*therapeutic use MH - Coronary Disease/complications MH - Electric Stimulation MH - Electrocardiography MH - Estrenes/*therapeutic use MH - Female MH - Heart Conduction System/*drug effects MH - Male MH - Swine MH - Ventricular Fibrillation/etiology/*prevention & control EDAT- 1990/04/01 MHDA- 1990/04/01 00:01 CRDT- 1990/04/01 00:00 PST - ppublish SO - J Cardiovasc Pharmacol. 1990 Apr;15(4):633-43. PMID- 2736748 OWN - NLM STAT- MEDLINE DA - 19890804 DCOM- 19890804 LR - 20061115 IS - 0009-7322 (Print) IS - 0009-7322 (Linking) VI - 80 IP - 1 DP - 1989 Jul TI - Distribution of extracellular potassium and electrophysiologic changes during two-stage coronary ligation in the isolated, perfused canine heart. PG - 165-77 AB - We studied the relation between [K+]o and the electrophysiologic changes during a "Harris two-stage ligation," which is an occlusion of a coronary artery, preceded by a 30-minute period of 50% reduction of flow through the artery. This two-stage ligation has been reported to be antiarrhythmic. Local direct current electrograms and [K+]o signals from up to 48 intramural sites were simultaneously recorded in isolated, perfused dog hearts. A second period of one-stage ligation was compared with a consecutive two-stage ligation because reproducibility in [K+]o and electrophysiologic changes are established only after the first period of ischemia. In control experiments, no difference was found between the second and third period of one-stage ligation in the electrophysiologic changes and in increases in [K+]o. After complete occlusion during two-stage ligation, activation block in the ischemic tissue occurred about 6 minutes earlier than during one-stage ligation, but the average potassium concentration at which block occurred was identical. This [K+]o during total ischemia was achieved earlier during two-stage ligation than during one-stage ligation. No indication was found for a large decrease of intracellular potassium content during the period of low flow perfusion. Early activation block may explain the previously reported reduced incidence of ventricular fibrillation during two-stage ligation. AD - Department of Clinical and Experimental Cardiology, Academic Medical Centre, Amsterdam, The Netherlands. FAU - Coronel, R AU - Coronel R FAU - Fiolet, J W AU - Fiolet JW FAU - Wilms-Schopman, J G AU - Wilms-Schopman JG FAU - Opthof, T AU - Opthof T FAU - Schaapherder, A F AU - Schaapherder AF FAU - Janse, M J AU - Janse MJ LA - eng PT - In Vitro PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - UNITED STATES TA - Circulation JT - Circulation JID - 0147763 RN - 7440-09-7 (Potassium) SB - AIM SB - IM MH - Animals MH - Constriction, Pathologic MH - Coronary Circulation MH - Coronary Disease/physiopathology MH - *Coronary Vessels MH - Dogs MH - Electrophysiology MH - Extracellular Space/*metabolism MH - Heart/*physiology MH - Ligation MH - Myocardium/*metabolism MH - Osmolar Concentration MH - Perfusion MH - Potassium/*metabolism MH - Tissue Distribution EDAT- 1989/07/01 MHDA- 1989/07/01 00:01 CRDT- 1989/07/01 00:00 PST - ppublish SO - Circulation. 1989 Jul;80(1):165-77. PMID- 3154325 OWN - NLM STAT- MEDLINE DA - 19910325 DCOM- 19910325 LR - 20041117 IS - 0920-3206 (Print) IS - 0920-3206 (Linking) VI - 1 IP - 6 DP - 1988 Mar TI - The mammalian sinoatrial node. PG - 573-97 AB - The sinoatrial node (SAN) was discovered in 1906 by Keith and Flack. The relation between its ultrastructure and function was first studied by Trautwein and Uchizono in 1963, whereas this relation was definitely established by Taylor and coworkers in 1978. The impulse originates from cells with a relatively low percentage of myofilaments. Earliest discharge is restricted to one site only in rabbit, guinea pig, cat, and pig and presumably also in larger animals. From this primary pacemaker area, the impulse is preferentially conducted towards the crista terminalis. The amount of cells in the primary pacemaker area may vary from a few hundred to a few thousand. In rabbit, guinea pig, cat, and pig, the amount of collagen is considerable. Normal SAN function was observed in the cat although the SAN volume occupied by myocytes was less than 5%. Changes in ionic composition of the perfusion fluid and the addition of autonomic substances may cause pacemaker shifts and altered activation patterns. AD - Department of Physiology, University of Amsterdam, The Netherlands. FAU - Opthof, T AU - Opthof T LA - eng PT - Journal Article PT - Review PL - UNITED STATES TA - Cardiovasc Drugs Ther JT - Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy JID - 8712220 SB - IM MH - Animals MH - Humans MH - Mammals/*physiology MH - Sinoatrial Node/*physiology RF - 175 EDAT- 1988/03/01 MHDA- 1988/03/01 00:01 CRDT- 1988/03/01 00:00 PST - ppublish SO - Cardiovasc Drugs Ther. 1988 Mar;1(6):573-97. PMID- 3451880 OWN - NLM STAT- MEDLINE DA - 19880719 DCOM- 19880719 LR - 20071115 IS - 0195-668X (Print) IS - 0195-668X (Linking) VI - 8 Suppl L DP - 1987 Dec TI - Alinidine as a model of the mode of action of specific bradycardic agents on SA node activity. PG - 25-33 AB - Three different bradycardic agents, alinidine, AQ-A39 and UL-FS49 increase the intrinsic cycle length of the isolated SA node preparation of the rabbit. This increase is mainly caused by a decrease in rate of diastolic depolarization. One of these agents, alinidine, was used to study the underlying ionic mechanism of the decrease in the diastolic depolarization rate in isolated cells and small cell clusters of the rabbit SA node. In these preparations alinidine slowed down the rate of spontaneous activity at higher concentrations (80 microM). At lower concentrations (10 microM) the decrease in rate of spontaneous activity was variable, but injection of a hyperpolarizing current slowed the spontaneous rate more in the presence of alinidine, indicating an increase in membrane resistance. In voltage clamp experiments we found that the main effect of alinidine was a block of the hyperpolarization activated current if. The block was potential dependent and was maximal in the potential range in which diastolic depolarization occurs. These results are discussed in relation to previous findings of others. AD - Department of Physiology, Academic Medical Centre, Amsterdam, The Netherlands. FAU - van Ginneken, A C AU - van Ginneken AC FAU - Bouman, L N AU - Bouman LN FAU - Jongsma, H J AU - Jongsma HJ FAU - Duivenvoorden, J J AU - Duivenvoorden JJ FAU - Opthof, T AU - Opthof T FAU - Giles, W R AU - Giles WR LA - eng PT - In Vitro PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - ENGLAND TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (Anti-Arrhythmia Agents) RN - 0 (Benzazepines) RN - 0 (Isoindoles) RN - 0 (Phthalimides) RN - 33178-86-8 (alinidine) RN - 4205-90-7 (Clonidine) RN - 77862-92-1 (falipamil) RN - 85175-67-3 (zatebradine) SB - IM MH - Animals MH - Anti-Arrhythmia Agents/*pharmacology MH - Benzazepines/pharmacology MH - Clonidine/*analogs & derivatives/pharmacology MH - Female MH - Heart Rate/*drug effects MH - Isoindoles MH - Male MH - Membrane Potentials/drug effects MH - Myocardial Contraction/drug effects MH - Phthalimides/pharmacology MH - Rabbits MH - Sinoatrial Node/cytology/*drug effects EDAT- 1987/12/01 MHDA- 1987/12/01 00:01 CRDT- 1987/12/01 00:00 PST - ppublish SO - Eur Heart J. 1987 Dec;8 Suppl L:25-33. PMID- 2832616 OWN - NLM STAT- MEDLINE DA - 19880504 DCOM- 19880504 LR - 20061115 IS - 0022-2828 (Print) IS - 0022-2828 (Linking) VI - 19 IP - 12 DP - 1987 Dec TI - Functional morphology of the pig sinoatrial node. PG - 1221-36 AB - The porcine sinoatrial node in an isolated right atrium preparation is characterized by unifocal impulse generation. It has a rather elongated shape and the larger part of its volume is taken up by collagen and fibroblasts. The impulse appears to emerge from a site where the percentage of myofilaments is relatively low. The impulse is propagated faster towards the crista terminalis than to the interatrial septum with preference for the oblique-upward direction. A very large zone of cells with low excitability is located at the interatrial septal side of the node. AD - Department of Physiology, University of Amsterdam, The Netherlands. FAU - Opthof, T AU - Opthof T FAU - de Jonge, B AU - de Jonge B FAU - Jongsma, H J AU - Jongsma HJ FAU - Bouman, L N AU - Bouman LN LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - ENGLAND TA - J Mol Cell Cardiol JT - Journal of molecular and cellular cardiology JID - 0262322 RN - 9007-34-5 (Collagen) SB - IM MH - Animals MH - Biological Clocks MH - Collagen/physiology MH - Electrophysiology MH - Microfilaments/ultrastructure MH - Microscopy, Electron MH - Sinoatrial Node/*anatomy & histology/*physiology MH - Swine MH - Synaptic Transmission EDAT- 1987/12/01 MHDA- 1987/12/01 00:01 CRDT- 1987/12/01 00:00 PST - ppublish SO - J Mol Cell Cardiol. 1987 Dec;19(12):1221-36. PMID- 3691562 OWN - NLM STAT- MEDLINE DA - 19880212 DCOM- 19880212 LR - 20061115 IS - 0195-668X (Print) IS - 0195-668X (Linking) VI - 8 IP - 11 DP - 1987 Nov TI - Functional morphology of the mammalian sinuatrial node. PG - 1249-59 AB - The primary pacemaker area is located at the site with lowest percentage of myofilaments and the highest rate of diastolic depolarization in rabbit, guinea-pig, cat and pig. All investigated sinuatrial nodes contained large amounts, 45% or more, of collagen. There was, however, substantially more collagen in the sinuatrial nodes of the cat and the pig than in the rabbit and the guinea-pig. This had, however, no consequences for the sinuatrial conduction time and the regularity of the beat-to-beat cycle length in the different species, because the rabbit and cat had comparable sinuatrial conduction times, although their nodal collagen content was very different and the beat-to-beat cycle length showed a comparable variability in the different species. We conclude that extensive proliferation of collagen and fibroblasts does not necessarily impair intercellular coupling in the sinuatrial node. AD - Department of Physiology, University of Amsterdam, The Netherlands. FAU - Opthof, T AU - Opthof T FAU - de Jonge, B AU - de Jonge B FAU - Jongsma, H J AU - Jongsma HJ FAU - Bouman, L N AU - Bouman LN LA - eng PT - Comparative Study PT - In Vitro PT - Journal Article PL - ENGLAND TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 9007-34-5 (Collagen) SB - IM MH - Action Potentials MH - Animals MH - Cats MH - Collagen/analysis MH - Guinea Pigs MH - Microfilaments/ultrastructure MH - Microscopy, Electron MH - Rabbits MH - Sinoatrial Node/*anatomy & histology/physiology/ultrastructure MH - Species Specificity MH - Swine EDAT- 1987/11/01 MHDA- 1987/11/01 00:01 CRDT- 1987/11/01 00:00 PST - ppublish SO - Eur Heart J. 1987 Nov;8(11):1249-59. PMID- 3430642 OWN - NLM STAT- MEDLINE DA - 19880321 DCOM- 19880321 LR - 20061115 IS - 0022-2828 (Print) IS - 0022-2828 (Linking) VI - 19 IP - 9 DP - 1987 Sep TI - The intrinsic cycle length in small pieces isolated from the rabbit sinoatrial node. PG - 923-34 AB - In this study we show that small pieces of tissue cut from the intact sinoatrial node beat faster, but with the same regularity as the intact sinoatrial node. The pieces with highest diastolic depolarization rate are not isolated from the primary pacemaker area, but from sites closer to the crista terminalis. In pieces cut from the primary pacemaker area, changes in the action potential configuration are restricted to the action potential duration, whereas in pieces cut from sites closer to the crista terminalis, not only the action potential duration has decreased, but also the diastolic depolarization rate has increased. Under the influence of adrenaline or acetylcholine, quiescent pieces are able to generate spontaneous activity. AD - Department of Physiology, University of Amsterdam, The Netherlands. FAU - Opthof, T AU - Opthof T FAU - VanGinneken, A C AU - VanGinneken AC FAU - Bouman, L N AU - Bouman LN FAU - Jongsma, H J AU - Jongsma HJ LA - eng PT - In Vitro PT - Journal Article PL - ENGLAND TA - J Mol Cell Cardiol JT - Journal of molecular and cellular cardiology JID - 0262322 RN - 51-43-4 (Epinephrine) RN - 51-84-3 (Acetylcholine) SB - IM MH - Acetylcholine/pharmacology MH - Action Potentials MH - Animals MH - Biological Clocks MH - Epinephrine/pharmacology MH - Female MH - Male MH - Microelectrodes MH - Rabbits MH - Sinoatrial Node/drug effects/*physiology EDAT- 1987/09/01 MHDA- 1987/09/01 00:01 CRDT- 1987/09/01 00:00 PST - ppublish SO - J Mol Cell Cardiol. 1987 Sep;19(9):923-34. PMID- 3791339 OWN - NLM STAT- MEDLINE DA - 19870205 DCOM- 19870205 LR - 20031114 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 20 IP - 10 DP - 1986 Oct TI - Electrophysiological effects of alinidine (ST 567) on sinoatrial node fibres in the rabbit heart. PG - 727-39 AB - In a study of the electrophysiological effects of alinidine a concentration of 0.7-14.3 mumol X litre-1 decreased the rate of diastolic depolarisation and prolonged especially the terminal part of the action potential in the rabbit sinoatrial node. It did not induce pacemaker shifts since the effects were not restricted to the primary pacemaker or the central nodal area but were evident in the more peripheral nodal region. The substitution of chlorine ions by other anions did not prevent the decrease in the rate of diastolic depolarisation due to alinidine but did prevent the effect on the action potential duration. The decreased chronotropic action of alinidine in low chlorine Tyrode solution was, however, caused by a shift of pacemaker dominance towards an atrial pacemaker. This pacemaker shift concealed the response of the primary pacemaker to alinidine in low chlorine Tyrode. Blockade of the pacemaker current of if by caesium prevented neither the alinidine effect on the diastolic depolarisation completely nor its effect on the action potential duration, but blockade of if probably was one of the determinants of the action of alinidine. It cannot be excluded that alinidine interferes with still another current than if. Alinidine decreased the chronotropic responses to adrenaline and to acetylcholine and also prevented pacemaker shifts due to these substances. FAU - Opthof, T AU - Opthof T FAU - Duivenvoorden, J J AU - Duivenvoorden JJ FAU - Vanginneken, A C AU - Vanginneken AC FAU - Jongsma, H J AU - Jongsma HJ FAU - Bouman, L N AU - Bouman LN LA - eng PT - Journal Article PL - ENGLAND TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 33178-86-8 (alinidine) RN - 4205-90-7 (Clonidine) RN - 51-43-4 (Epinephrine) RN - 51-84-3 (Acetylcholine) RN - 7440-46-2 (Cesium) RN - 7782-50-5 (Chlorine) SB - IM MH - Acetylcholine/pharmacology MH - Action Potentials/drug effects MH - Animals MH - Cesium/pharmacology MH - Chlorine/pharmacology MH - Clonidine/*analogs & derivatives/pharmacology MH - Depression, Chemical MH - Epinephrine/pharmacology MH - Female MH - Heart Rate/drug effects MH - Male MH - Rabbits MH - Sinoatrial Node/*drug effects MH - Time Factors EDAT- 1986/10/01 MHDA- 1986/10/01 00:01 CRDT- 1986/10/01 00:00 PST - ppublish SO - Cardiovasc Res. 1986 Oct;20(10):727-39. PMID- 3783721 OWN - NLM STAT- MEDLINE DA - 19861224 DCOM- 19861224 LR - 20031114 IS - 0022-2828 (Print) IS - 0022-2828 (Linking) VI - 18 IP - 10 DP - 1986 Oct TI - Functional and morphological organization of the cat sinoatrial node. PG - 1015-31 AB - The feline sinoatrial node has a unifocal impulse generation as previously described for rodents. Its main component is collagen. The primary pacemaker consists of at most 2000 cells, but appears to function normally with less than 500 cells. Primary pacemaker cells are found in the area where empty cells are predominant. A negative correlation between myofilament density and diastolic depolarization rate, known to exist in the rabbit and guinea-pig, is absent in the cat. Gap junctions are seen in the center and in the periphery of the nodal region, but they are extremely rare. The electrophysiological characteristics of the primary pacemaker of the cat are quite similar to those of the rabbit, although the nodal morphology is very different. Abrupt transitions from one cell type into another are observed in the feline sinoatrial node. From this morphological point of view the feline sinoatrial node resembles the canine and human sinoatrial nodes more than the lapine sinoatrial node. FAU - Opthof, T AU - Opthof T FAU - de Jonge, B AU - de Jonge B FAU - Masson-Pevet, M AU - Masson-Pevet M FAU - Jongsma, H J AU - Jongsma HJ FAU - Bouman, L N AU - Bouman LN LA - eng PT - Journal Article PL - ENGLAND TA - J Mol Cell Cardiol JT - Journal of molecular and cellular cardiology JID - 0262322 RN - 9007-34-5 (Collagen) SB - IM MH - Animals MH - Cats MH - Collagen/analysis MH - Electrophysiology MH - Female MH - Heart Conduction System/physiology MH - Male MH - Microscopy, Electron MH - Sinoatrial Node/*physiology/ultrastructure EDAT- 1986/10/01 MHDA- 1986/10/01 00:01 CRDT- 1986/10/01 00:00 AID - S0022-2828(86)80290-5 [pii] PST - ppublish SO - J Mol Cell Cardiol. 1986 Oct;18(10):1015-31. PMID- 4020878 OWN - NLM STAT- MEDLINE DA - 19850925 DCOM- 19850925 LR - 20061115 IS - 0022-2828 (Print) IS - 0022-2828 (Linking) VI - 17 IP - 6 DP - 1985 Jun TI - Functional and morphological organization of the guinea-pig sinoatrial node compared with the rabbit sinoatrial node. PG - 549-64 AB - The primary pacemaker, i.e. the group of pacemaker cells discharging the sinoatrial node comprises less than 1000 cells in the guinea-pig and about 5000 cells in the rabbit. These primary pacemaker cells are described as 'central nodal' cells in light microscopy and as 'typical nodal' cells in electron microscopy. The action potential of the leading cells has a higher upstroke velocity in the guinea-pig than in the rabbit (6.2 v. 1.9 V/s). Gap junctions have been observed even in the very center of the node in both species. A zone of double-component action potentials at the septal margin of the node was observed in the rabbit, but not in the guinea-pig. Evidence is presented for abrupt transitions in electrophysiological as well as in ultrastructural characteristics in the guinea-pig sinoatrial node. The differences in intrinsic cycle length between both species but also between individuals of the same species are discussed. FAU - Opthof, T AU - Opthof T FAU - de Jonge, B AU - de Jonge B FAU - Mackaay, A J AU - Mackaay AJ FAU - Bleeker, W K AU - Bleeker WK FAU - Masson-Pevet, M AU - Masson-Pevet M FAU - Jongsma, H J AU - Jongsma HJ FAU - Bouman, L N AU - Bouman LN LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - ENGLAND TA - J Mol Cell Cardiol JT - Journal of molecular and cellular cardiology JID - 0262322 SB - IM MH - Action Potentials MH - Animals MH - Electrophysiology MH - Guinea Pigs MH - Membrane Potentials MH - Microscopy, Electron MH - Periodicity MH - Rabbits MH - Sinoatrial Node/*anatomy & histology/physiology/ultrastructure EDAT- 1985/06/01 MHDA- 1985/06/01 00:01 CRDT- 1985/06/01 00:00 AID - S0022-2828(85)80024-9 [pii] PST - ppublish SO - J Mol Cell Cardiol. 1985 Jun;17(6):549-64. PMID- 6512175 OWN - NLM STAT- MEDLINE DA - 19850219 DCOM- 19850219 LR - 20061115 IS - 0165-1838 (Print) IS - 0165-1838 (Linking) VI - 11 IP - 4 DP - 1984 Dec TI - Cycle length dependence of the chronotropic effects of adrenaline, acetylcholine, Ca2+ and Mg2+ in the Guinea-pig sinoatrial node. PG - 349-66 AB - Ca (1.1-5.5 mM) has a positive chronotropic action on isolated right atria of the guinea-pig. The magnitude of the response depends on the cycle length. Magnitude and cycle length dependence of the Ca response are independent of beta-blockade by propranolol. Mg (0.6-6.0 mM) has a negative chronotropic action. At 6.0 mM it interferes with responses to adrenaline and acetylcholine by preventing pacemaker shifts. Adrenaline has a positive chronotropic action in a cycle length dependent manner. A shift of pacemaker dominance under the influence of adrenaline to an identical site in all preparations (as in the rabbit) was not observed. However, pacemaker shifts in the presence of adrenaline do occur and they are always directed towards the inferior part of the node. Acetylcholine has a negative chronotropic action, independent of cycle length. Acetylcholine also induces pacemaker shifts. Contrary to the pacemaker shifts caused by adrenaline, the new, acetylcholine-induced pacemaker center, has an identical site in all preparations. This was previously observed in the rabbit too. The acetylcholine-induced center is located about 1 mm inferior from the primary center. During exposure to acetylcholine different action potentials may be recorded at the epi- and endocardial side of the preparation, but only close to the Ach-induced center. The acetylcholine-induced center is located at the epicardial side. The response to acetylcholine predominates over the response to adrenaline. All results are discussed in comparison with our previous findings in the rabbit. FAU - Opthof, T AU - Opthof T FAU - de Jonge, B AU - de Jonge B FAU - Schade, B AU - Schade B FAU - Jongsma, H J AU - Jongsma HJ FAU - Bouman, L N AU - Bouman LN LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - NETHERLANDS TA - J Auton Nerv Syst JT - Journal of the autonomic nervous system JID - 8003419 RN - 51-43-4 (Epinephrine) RN - 51-84-3 (Acetylcholine) RN - 7439-95-4 (Magnesium) RN - 7440-70-2 (Calcium) SB - IM MH - Acetylcholine/pharmacology MH - Animals MH - Calcium/pharmacology MH - Epinephrine/pharmacology MH - Guinea Pigs MH - Magnesium/pharmacology MH - Rabbits MH - Sinoatrial Node/*drug effects MH - Stimulation, Chemical EDAT- 1984/12/01 MHDA- 1984/12/01 00:01 CRDT- 1984/12/01 00:00 PST - ppublish SO - J Auton Nerv Syst. 1984 Dec;11(4):349-66. PMID- 6716276 OWN - NLM STAT- MEDLINE DA - 19840618 DCOM- 19840618 LR - 20061115 IS - 0022-3565 (Print) IS - 0022-3565 (Linking) VI - 229 IP - 2 DP - 1984 May TI - Electrophysiological effects of alinidine on nodal and atrial fibers in the guinea-pig heart. PG - 551-6 AB - The effect of alinidine on transmembrane electrical activity of nodal and atrial fibers was studied in the isolated right auricle of the guinea-pig. Alinidine was applied in concentrations between 0.72 and 28.5 X 10(-5) M. In nodal fibers the main effect was a dose-dependent decrease in rate of diastolic depolarization and a delayed repolarization of especially the terminal part of the action potential. In both fiber types alinidine causes a marked delay of the terminal part of repolarization; the increase of the duration of the action potential was related to the alinidine concentration over the whole concentration range used. In addition the amplitude of the action potential and the maximal diastolic potential are increased dose dependently up to a concentration of 2.8 x 10(-5) M. Application of higher concentrations does not increase these parameters. In nodal fibers diastolic depolarization is already depressed considerably at a relatively low concentration. This is particularly so in fibers that normally have a high rate of diastolic depolarization, i.e., the dominant pacemaker fibers. A shifting of the pacemaker seems only to occur at high concentrations (11.4 X 10(-5) M or higher). The strong negative chronotropic effect of alinidine can be attributed to both the depression of diastolic depolarization and the increase in duration of the action potential. At low concentrations the increase of the maximum diastolic potential can also contribute to the slowing of the heart rate. FAU - Bouman, L N AU - Bouman LN FAU - Duivenvoorden, J J AU - Duivenvoorden JJ FAU - Opthof, T AU - Opthof T FAU - Treijtel, B W AU - Treijtel BW LA - eng PT - In Vitro PT - Journal Article PL - UNITED STATES TA - J Pharmacol Exp Ther JT - The Journal of pharmacology and experimental therapeutics JID - 0376362 RN - 0 (Cardiovascular Agents) RN - 33178-86-8 (alinidine) RN - 4205-90-7 (Clonidine) SB - IM MH - Action Potentials/drug effects MH - Animals MH - Cardiovascular Agents/*pharmacology MH - Clonidine/*analogs & derivatives/pharmacology MH - Diastole MH - Female MH - Guinea Pigs MH - Heart/*drug effects/physiology MH - Heart Atria MH - Sinoatrial Node/physiology EDAT- 1984/05/01 MHDA- 1984/05/01 00:01 CRDT- 1984/05/01 00:00 PST - ppublish SO - J Pharmacol Exp Ther. 1984 May;229(2):551-6.