© 1994 by European Society of Cardiology
Copyright © 1994, European Society of Cardiology
Triggered activity and automaticity in ventricular trabeculae of failing human and rabbit hearts
Academic Medical Centre, University of Amsterdam, Department of Clinical and Experimental Cardiology, PO Box 22700, 1100 DE Amsterdam, The Netherlands: J T Vermeulen, M A McGuire, T Opthof, R Coronel, J M T de Bakker, C Klöpping, M J Janse. Correspondence to Dr Vermeulen.
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 µM). 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 3=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.
Cardiovascular Research 1994;28:1547-1554
KEYWORDS heart failure; triggered activity; automaticity; action potential duration
The authors wish to thank Dr A Bril, Dr B Gout, and Laurent Landais of SmithKline Beecham Research laboratories, Rennes, France, for assisting them with the development of the model of heart failure in the rabbits. We gratefully acknowledge the heart transplantation team from the Academic Medical Hospital in Utrecht for providing us with the human hearts. We thank Han Rademaker and Muchtiar Khan for excellent help with experiments and Charly Belterman for technical assistance.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. S. Hoeker, R. P. Katra, L. D. Wilson, B. N. Plummer, and K. R. Laurita Spontaneous calcium release in tissue from the failing canine heart Am J Physiol Heart Circ Physiol, October 1, 2009; 297(4): H1235 - H1242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Boyden The failing ventricle: what initiates the complex ventricular arrhythmias? Am J Physiol Heart Circ Physiol, October 1, 2009; 297(4): H1198 - H1199. [Full Text] [PDF]
|
|
|
|
 |
|
 O. Ziv, E. Morales, Y.-k. Song, X. Peng, K. E. Odening, A. E. Buxton, A. Karma, G. Koren, and B.-R. Choi Origin of complex behaviour of spatially discordant alternans in a transgenic rabbit model of type 2 long QT syndrome J. Physiol., October 1, 2009; 587(19): 4661 - 4680. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Casini, A. O. Verkerk, M. M.G.J. van Borren, A. C.G. van Ginneken, M. W. Veldkamp, J. M.T. de Bakker, and H. L. Tan Intracellular calcium modulation of voltage-gated sodium channels in ventricular myocytes Cardiovasc Res, January 1, 2009; 81(1): 72 - 81. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. M. Den Ruijter, G. Berecki, A. O. Verkerk, D. Bakker, A. Baartscheer, C. A. Schumacher, C. N.W. Belterman, N. de Jonge, J. W.T. Fiolet, I. A. Brouwer, et al. Acute Administration of Fish Oil Inhibits Triggered Activity in Isolated Myocytes From Rabbits and Patients With Heart Failure Circulation, January 29, 2008; 117(4): 536 - 544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Coronel, F. J.G. Wilms-Schopman, H. M. Den Ruijter, C. N. Belterman, C. A. Schumacher, T. Opthof, R. Hovenier, A. G. Lemmens, A. H.M. Terpstra, M. B. Katan, et al. Dietary n-3 fatty acids promote arrhythmias during acute regional myocardial ischemia in isolated pig hearts Cardiovasc Res, January 15, 2007; 73(2): 386 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A.G. van der Heyden, T. J.M. Wijnhoven, and T. Opthof Molecular aspects of adrenergic modulation of the transient outward current Cardiovasc Res, August 1, 2006; 71(3): 430 - 442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Baartscheer, C. A. Schumacher, M. M.G.J. van Borren, C. N.W. Belterman, R. Coronel, T. Opthof, and J. W.T. Fiolet Chronic inhibition of Na+/H+-exchanger attenuates cardiac hypertrophy and prevents cellular remodeling in heart failure Cardiovasc Res, January 1, 2005; 65(1): 83 - 92. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J Janse Electrophysiological changes in heart failure and their relationship to arrhythmogenesis Cardiovasc Res, February 1, 2004; 61(2): 208 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nap, C. N. Belterman, M.-J. Mathy, J. C Balt, M. Pfaffendorf, and P. A van Zwieten Impaired neuronal and vascular responses to angiotensin II in a rabbit congestive heart failure model Journal of Renin-Angiotensin-Aldosterone System, December 1, 2003; 4(4): 220 - 227. [Abstract] [PDF]
|
|
|
|
|
|
J. R de Groot, C. A Schumacher, A. O Verkerk, A. Baartscheer, J. W.T Fiolet, and R. Coronel Intrinsic heterogeneity in repolarization is increased in isolated failing rabbit cardiomyocytes during simulated ischemia Cardiovasc Res, September 1, 2003; 59(3): 705 - 714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. K. Reddy, S. Wasson, S. K.G. Koshy, and R. Komatireddy Structural correlates of electrical remodeling in ventricular hypertrophy Cardiovasc Res, June 1, 2003; 58(3): 495 - 497. [Full Text] [PDF]
|
|
|
|
|
|
A. Baartscheer, C. A. Schumacher, C. N.W. Belterman, R. Coronel, and J. W.T. Fiolet SR calcium handling and calcium after-transients in a rabbit model of heart failure Cardiovasc Res, April 1, 2003; 58(1): 99 - 108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M Pogwizd, K. R Sipido, F. Verdonck, and D. M Bers Intracellular Na in animal models of hypertrophy and heart failure: contractile function and arrhythmogenesis Cardiovasc Res, March 15, 2003; 57(4): 887 - 896. [Full Text] [PDF]
|
|
|
|
|
|
A Baartscheer, C.A Schumacher, C.N.W Belterman, R Coronel, and J.W.T Fiolet [Na+]i and the driving force of the Na+/Ca2+-exchanger in heart failure Cardiovasc Res, March 15, 2003; 57(4): 986 - 995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A Baartscheer, C.A Schumacher, M.M.G.J van Borren, C.N.W Belterman, R Coronel, and J.W.T Fiolet Increased Na+/H+-exchange activity is the cause of increased [Na+]i and underlies disturbed calcium handling in the rabbit pressure and volume overload heart failure model Cardiovasc Res, March 15, 2003; 57(4): 1015 - 1024. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kneller, H. Sun, N. Leblanc, and S. Nattel Remodeling of Ca2+-handling by atrial tachycardia: evidence for a role in loss of rate-adaptation Cardiovasc Res, May 1, 2002; 54(2): 416 - 426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Coronel Repolarization abnormalities in heart failure Cardiovasc Res, April 1, 2002; 54(1): 11 - 12. [Full Text] [PDF]
|
|
|
|
|
|
D. Lacroix, P. Gluais, C. Marquie, C. D'Hoinne, M. Adamantidis, and M. Bastide Repolarization abnormalities and their arrhythmogenic consequences in porcine tachycardia-induced cardiomyopathy Cardiovasc Res, April 1, 2002; 54(1): 42 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R Sipido, P. G.A Volders, M. A Vos, and F. Verdonck Altered Na/Ca exchange activity in cardiac hypertrophy and heart failure: a new target for therapy? Cardiovasc Res, March 1, 2002; 53(4): 782 - 805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M.G.J van Borren, A. O Verkerk, S. K Vanharanta, A. Baartscheer, R. Coronel, and J. H Ravesloot Reduced swelling-activated Cl- current densities in hypertrophied ventricular myocytes of rabbits with heart failure Cardiovasc Res, March 1, 2002; 53(4): 869 - 878. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. L Burton and S. M Cobbe Dispersion of ventricular repolarization and refractory period Cardiovasc Res, April 1, 2001; 50(1): 10 - 23. [Full Text] [PDF]
|
|
|
|
|
|
A Baartscheer Adenovirus gene transfer of SERCA in heart failure. A promising therapeutic approach ? Cardiovasc Res, February 1, 2001; 49(2): 249 - 252. [Full Text] [PDF]
|
|
|
|
|
|
W. Haverkamp, G. Breithardt, A.J. Camm, M. J Janse, M. R Rosen, C. Antzelevitch, D. Escande, M. Franz, M. Malik, A. Moss, et al. The potential for QT prolongation and pro-arrhythmia by non-anti-arrhythmic drugs: Clinical and regulatory implications: Report on a Policy Conference of the European Society of Cardiology Cardiovasc Res, August 1, 2000; 47(2): 219 - 233. [Full Text] [PDF]
|
|
|
|
|
|
E. Cerbai, A. Crucitti, L. Sartiani, P. De Paoli, R. Pino, M. L. Rodriguez, G. Gensini, and A. Mugelli Long-term treatment of spontaneously hypertensive rats with losartan and electrophysiological remodeling of cardiac myocytes Cardiovasc Res, January 14, 2000; 45(2): 388 - 396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.A. McIntosh, S.M. Cobbe, and G.L. Smith Heterogeneous changes in action potential and intracellular Ca2+ in left ventricular myocyte sub-types from rabbits with heart failure Cardiovasc Res, January 14, 2000; 45(2): 397 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-J. Du, H. S. Cox, A. M. Dart, and M. D. Esler Sympathetic activation triggers ventricular arrhythmias in rat heart with chronic infarction and failure Cardiovasc Res, September 1, 1999; 43(4): 919 - 929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. F. Tomaselli and E. Marban Electrophysiological remodeling in hypertrophy and heart failure Cardiovasc Res, May 1, 1999; 42(2): 270 - 283. [Full Text] [PDF]
|
|
|
|
|
|
M. J. Janse, T. Opthof, and A. G. Kleber Animal models of cardiac arrhythmias Cardiovasc Res, July 1, 1998; 39(1): 165 - 177. [Full Text] [PDF]
|
|
|
|
|
|
B. Swynghedauw, B. Chevalier, D. Charlemagne, P. Mansier, and F. Carre Cardiac hypertrophy, arrhythmogenicity and the new myocardial phenotype. II. The cellular adaptational process Cardiovasc Res, July 1, 1997; 35(1): 6 - 12. [Abstract] [Full Text] [PDF]
|
|