Chronic amiodarone effects on epicardial conduction and repolarization in the isolated porcine heart.
Amiodarone is a potent antiarrhythmic agent with complex chronic effects, notably on repolarization and conduction, that are not fully understood. Its low arrhythmogenic potential has been related to a lack of increase in repolarization dispersion. Since its effects are not documented in pigs we conducted a mapping study of activation and repolarization in isolated perfused porcine hearts. Amio20 female pigs (n = 7) received amiodarone 20 mg/kg per day over 4 weeks while Amio50 female pigs (n = 7) received 50 mg/kg per day over 4 weeks. Concentrations of the drug encompassed values found in clinical studies. Then, activation patterns and activation-to-recovery intervals (ARI) were mapped epicardially from 128 unipolar electrograms in isolated perfused hearts in corroboration of epicardial action potential recordings. Mean ARI was longer in Amio20 experiments compared to the seven control hearts (325 +/- 11 ms vs 288 +/- 5 ms at 1,000 ms), whereas ARI dispersion was not different, being comprised between 7 and 11 ms and generating smooth gradients. In Amio50 experiments, mean ARI was further prolonged (390 +/- 10 ms at 1,500 ms) with an exaggerated reverse rate dependence concomitant with a depressant effect on the plateau of the action potential. Again, ARI dispersion did not differ from controls. Finally, the drug depressed the maximal rate of depolarization (Vmax) and slowed conduction in a rate dependent and concentration dependent fashion. In conclusion, chronic amiodarone induces Class I and Class III antiarrhythmic effects in ventricular porcine epicardium that are concentration dependent but does not affect dispersion of repolarization. This may partly explain its low arrhythmogenic potential.
Department of Cardiology, University of Lille, France. dlacroix@chru-lille.fr
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Adamantidis
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Grandmougin
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D000200:Action Potentials; D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D010477:Perfusion; D010496:Pericardium / Q000187:drug effects* / Q000502:physiology; D013552:Swine; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D000638:Amiodarone