© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Effects of chronic treatment by amiodarone on transmural heterogeneity of canine ventricular repolarization in vivo: interactions with acute sotalol
aLaboratoire de Physiopathologie & Pharmacologie Cellulaires & Moléculaires, INSERM CJF 96-01, Nantes, France
bLaboratoire de Médecine, Ecole Vétérinaire de Nantes, Nantes, France
cService Central de Médecine Nucléaire et Biophysique, Hôpital Saint-Antoine, Paris, France
dService de Pharmacologie, Faculté de Médecine Saint-Antoine, Paris, France
* Corresponding author. Tel.: +33-140-01-1438; fax: +33-140-01-1404 weissenb{at}b3e.jussieu.fr
Objective: The present study was designed to examine the effects of chronic amiodarone on the different ventricular cell subtypes in situ and to evaluate its interactions with sotalol. Methods: Three groups of dogs were studied. Group I (n=8) received no treatment. Group II (n=7) and group III (n=8) received, respectively, 100 and 200 mg amiodarone orally twice a day for 6 weeks to 8 months. In vivo studies were performed under halothane anesthesia 14 h after the last administration of amiodarone. Three leads ECG, femoral blood pressure and left ventricular intramural monophasic action potentials (MAP) were continuously recorded. Bradycardia was obtained by clamping the sinus node and β-blockade and the heart was driven by atrial pacing. Three weeks before the in vivo experiments, the cellular electrophysiologic properties of right ventricular tissues obtained by cardiac biopsy in six treated and six control dogs were studied with standard microelectrodes. Results: Amiodarone produced a dose-dependent decrease in plasma levels of triiodothyronine (T3; 5.9±0.4 pM in control dogs, 3.1±0.2 pM in group III, P<0.001) without affecting thyroxine (T4). Under anesthesia, the QT interval was 14% larger in group III compared to group I at a paced cycle length (PCL) of 1500 ms (P<0.05). This is consistent with the 10% increase in endocardial MAP duration in group III at the same PCL (P<0.05). There was no significant increase in transmural dispersion of MAP duration. In group I, sotalol induced a significant reverse use-dependent increase in MAP duration. This effect was reduced in group II and completely suppressed in group III. Amiodarone prevented the sotalol-induced increase in transmural dispersion of ventricular repolarization which was 69±12 ms in untreated dogs, 41±8 ms in group II (P<0.05) and 34±8 ms (P<0.05) in group III at PCL=1500 ms. Amiodarone also prevented the sotalol-induced ventricular tachyarrhythmias. In vitro, the action potential duration was longer in amiodarone-treated dogs that in control ones (208±5 ms versus 188±9 ms at PCL=1000 ms, P<0.05).The sotalol-induced prolongation of repolarization was reduced in amiodarone-treated dogs. Conclusion: Chronic treatment of dogs with amiodarone induced a moderate prolongation of the QT interval and MAP duration without affecting transmural dispersion of repolarization and inhibited the effects of acute sotalol, including the prolongation of repolarization, the increase in transmural dispersion of repolarization and the induction of arrhythmias.
KEYWORDS ECG, electrocardiogram; i.v., Intravenous; MAP, monophasic action potentials; NS, not significant; RR, Ventricular cycle length; VF, Ventricular fibrillation; VT, Ventricular tachycardia
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Morita, D. P. Zipes, J. Lopshire, S. T. Morita, and J. Wu T wave alternans in an in vitro canine tissue model of Brugada syndrome Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H421 - H428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ueda, D. P. Zipes, and J. Wu Coronary occlusion and reperfusion promote early afterdepolarizations and ventricular tachycardia in a canine tissue model of type 3 long QT syndrome Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H607 - H612. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ueda, D. P. Zipes, and J. Wu Functional and transmural modulation of M cell behavior in canine ventricular wall Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2569 - H2575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Stilli, R. Berni, L. Bocchi, M. Zaniboni, F. Cacciani, A. Sgoifo, and E. Musso Vulnerability to ventricular arrhthmias and heterogeneity of action potential duration in normal rats Exp Physiol, July 1, 2004; 89(4): 387 - 396. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ueda, D. P Zipes, and J. Wu Prior ischemia enhances arrhythmogenicity in isolated canine ventricular wedge model of long QT 3 Cardiovasc Res, July 1, 2004; 63(1): 69 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Antzelevitch, L. Belardinelli, L. Wu, H. Fraser, A. C. Zygmunt, A. Burashnikov, J. M. Di Diego, J. M. Fish, J. M. Cordeiro, R. J. Goodrow Jr, et al. Electrophysiologic Properties and Antiarrhythmic Actions of a Novel Antianginal Agent Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2004; 9(1_suppl): S65 - S83. [Abstract] [PDF]
|
|
|
|
|
|
J. Wu and D. P. Zipes Transmural reentry triggered by epicardial stimulation during acute ischemia in canine ventricular muscle Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H2004 - H2011. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Huang, J. L. Skinner, J. M. Rogers, W. M. Smith, W. L. Holman, and R. E. Ideker The effects of acute and chronic amiodarone on activation patterns and defibrillation threshold during ventricular fibrillation in dogs J. Am. Coll. Cardiol., July 17, 2002; 40(2): 375 - 383. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. van Opstal, M. Schoenmakers, S. C. Verduyn, S.H. M. de Groot, J. D.M. Leunissen, F. F. van der Hulst, M. M.C. Molenschot, H. J.J. Wellens, and M. A. Vos Chronic Amiodarone Evokes No Torsade de Pointes Arrhythmias Despite QT Lengthening in an Animal Model of Acquired Long-QT Syndrome Circulation, November 27, 2001; 104(22): 2722 - 2727. [Abstract] [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 proarrhythmia by non-antiarrhythmic drugs: clinical and regulatory implications. Report on a Policy Conference of the European Society of Cardiology Eur. Heart J., August 1, 2000; 21(15): 1216 - 1231. [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]
|
|