Chronic amiodarone effects on epicardial conduction and repolarization in the isolated porcine heart

Amiodarone is a potent antiarrhythmic agent with complex chronic effects, n otably on repolarization and conduction, that are not fully understood. Its low arrhythmogenic potential has been related to a lack of increase in rep olarization dispersion. Since its effects are not documented in pigs we con ducted a mapping study of activation and repolarization in isolated perfuse d porcine hearts. Amio20 female pigs (n = 7) received amiodarone 20 mg/kg p er 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 cl inical studies. Then, activation patterns and activation-to-recovery interv als (ARI) were mapped epicardially from 128 unipolar electrograms in isolat ed perfused hearts in corroboration of epicardial action potential recordin gs. 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 smoo th gradients. In Amio50 experiments, mean ARI was further prolonged (390 +/ - 10 ms at 1,500 ms) with an exaggerated reverse rate dependence concomitan t with a depressant effect on the plateau of the action potential. Again, A RI dispersion did not differ from controls. Finally, the drug depressed the maximal rate of depolarization (Vmax) and slowed conduction in a rate depe ndent and concentration dependent fashion. In conclusion, chronic amiodaron e induces Class I and Class III antiarrhythmic effects in ventricular porci ne epicardium that are concentration dependent but does not affect dispersi on of repolarization. This may partly explain its low arrhythmogenic potent ial.