(Circulation. 2000;102:2145.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Contractile Adaptations Preserving Cardiac Output Predispose the Hypertrophied Canine Heart to Delayed Afterdepolarization–Dependent Ventricular Arrhythmias
From the Department of Cardiology, Cardiovascular Research Institute Maastricht, Academic Hospital Maastricht, Netherlands.
Correspondence to M.A. Vos, PhD, Department of Cardiology, Cardiovascular Research Institute Maastricht, Academic Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, Netherlands. E-mail m.vos{at}cardio.azm.nl
Background—In dogs, chronic complete atrioventricular block (CAVB) results in structural (biventricular hypertrophy) and electrical (delayed repolarization) remodeling, which predisposes the heart to torsade de pointes arrhythmias. We assessed the contractile alterations in the CAVB dog and tested the hypothesis that these adaptations increase delayed afterdepolarization (DAD)–dependent triggered arrhythmias.
Methods and Results—Steady-state and dynamic (fast pacing: 1 to 68 stimuli) left and right ventricular systolic and diastolic parameters were determined by positive and negative inotropic interventions at acute AVB and CAVB. Concomitantly, left and right ventricular endocardial monophasic action potentials were registered. In CAVB, all systolic contractile parameters were markedly increased, resulting in preserved cardiac output. The increase was most pronounced at low heart rates, altering the force-frequency response. At both acute AVB and CAVB, the degree of potentiation of cardiac function with pacing was dependent on the number of stimuli and showed a maximum at 8 to 13 stimuli. With CAVB, this potentiation curve was shifted upward, and it was only then that pacing resulted in DADs (in 8 of 10 dogs) and ectopic beats (EBs, in 6 of 10 dogs). The incidence of EBs in relation to the number of stimuli also had a maximum at 8 to 13 stimuli. Ouabain increased the incidence of DADs and EBs, whereas the negative inotropic interventions prevented them completely.
Conclusions—The alterations responsible for improvement in systolic contractile function in CAVB dogs predispose the hypertrophied heart to DAD-dependent triggered arrhythmias during positive inotropic interventions.
Key Words: tachycardia • hypertrophy • contractility • electrophysiology
This article has been cited by other articles:
 |
|
 |
|
  T. P. Nguyen, D. W. Wang, T. H. Rhodes, and A. L. George Jr Divergent Biophysical Defects Caused by Mutant Sodium Channels in Dilated Cardiomyopathy With Arrhythmia Circ. Res., February 15, 2008; 102(3): 364 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Bito, F. R. Heinzel, L. Biesmans, G. Antoons, and K. R. Sipido Crosstalk between L-type Ca2+ channels and the sarcoplasmic reticulum: alterations during cardiac remodelling Cardiovasc Res, January 15, 2008; 77(2): 315 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K.G. Winckels, M. B. Thomsen, P. Oosterhoff, A. Oros, J. D.M. Beekman, N. J.M. Attevelt, L. Kretzers, and M. A. Vos High-Septal Pacing Reduces Ventricular Electrical Remodeling and Proarrhythmia in Chronic Atrioventricular Block Dogs J. Am. Coll. Cardiol., August 28, 2007; 50(9): 906 - 913. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gizurarson, M. Lorentzon, T. Ramunddal, F. Waagstein, L. Bergfeldt, and E. Omerovic Effects of complete heart block on myocardial function, morphology, and energy metabolism in the rat Europace, June 1, 2007; 9(6): 411 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Antoons, P. G. A. Volders, T. Stankovicova, V. Bito, M. Stengl, M. A. Vos, and K. R. Sipido Window Ca2+ current and its modulation by Ca2+ release in hypertrophied cardiac myocytes from dogs with chronic atrioventricular block J. Physiol., February 15, 2007; 579(1): 147 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Thomsen, A. Oros, M. Schoenmakers, J. M. van Opstal, J. N. Maas, J. D.M. Beekman, and M. A. Vos Proarrhythmic electrical remodelling is associated with increased beat-to-beat variability of repolarisation Cardiovasc Res, February 1, 2007; 73(3): 521 - 530. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Peschar, K. Vernooy, R. N Cornelussen, X. A.A.M Verbeek, R. S Reneman, M. A Vos, and F. W Prinzen Structural, electrical and mechanical remodeling of the canine heart in AV-block and LBBB Eur. Heart J. Suppl., August 1, 2004; 6(suppl_D): D61 - D65. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Thomsen, P. G. A. Volders, M. Stengl, R. L. H. M. G. Spaatjens, J. D. M. Beekman, U. Bischoff, M. A. Kall, K. Frederiksen, J. Matz, and M. A. Vos Electrophysiological Safety of Sertindole in Dogs with Normal and Remodeled Hearts J. Pharmacol. Exp. Ther., November 1, 2003; 307(2): 776 - 784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Schoenmakers, C. Ramakers, J. M. van Opstal, J. D.M. Leunissen, C. Londono, and M. A. Vos Asynchronous development of electrical remodeling and cardiac hypertrophy in the complete AV block dog Cardiovasc Res, August 1, 2003; 59(2): 351 - 359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Peschar, K. Vernooy, W. Y.R Vanagt, R. S Reneman, M. A Vos, and F. W Prinzen Absence of reverse electrical remodeling during regression of volume overload hypertrophy in canine ventricles Cardiovasc Res, June 1, 2003; 58(3): 510 - 517. [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]
|
|
|
|
|
|
F. Verdonck, P. G.A Volders, M. A Vos, and K. R Sipido Increased Na+ concentration and altered Na/K pump activity in hypertrophied canine ventricular cells Cardiovasc Res, March 15, 2003; 57(4): 1035 - 1043. [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]
|
|
|
|
 |
|
 S. C. Verduyn, C. Ramakers, G. Snoep, J. D. M. Leunissen, H. J. J. Wellens, and M. A. Vos Time course of structural adaptations in chronic AV block dogs: evidence for differential ventricular remodeling Am J Physiol Heart Circ Physiol, June 1, 2001; 280(6): H2882 - H2890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Babuty and M. J Lab Mechanoelectric contributions to sudden cardiac death Cardiovasc Res, May 1, 2001; 50(2): 270 - 279. [Full Text] [PDF]
|
|
|
|
|
|
J.M van Opstal, S.C Verduyn, H.D.M Leunissen, S.H.M de Groot, H.J.J Wellens, and M.A Vos Electrophysiological parameters indicative of sudden cardiac death in the dog with chronic complete AV-block Cardiovasc Res, May 1, 2001; 50(2): 354 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Verduyn, J. M. v. Opstal, J. D. Leunissen, and M. A. Vos Assessment of the Pro-Arrhythmic Potential of Anti-Arrhythmic Drugs: An Experimental Approach Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2001; 6(1): 89 - 97. [PDF]
|
|