Comparative effects of acute vs. chronic oral amiodarone treatment during acute myocardial infarction in rats

Abstract

Aims: This study investigated whether chronic and acute amiodarone treatment has differential effects on ventricular arrhythmogenesis during acute myocardial infarction in rats. Methods and results: Forty-six rats were randomly allocated into vehicle, chronic oral amiodarone (30 mg/kg daily for 2 weeks), or acute amiodarone (a single dose, 100 mg/kg). Five additional rats were sham-operated. Myocardial infarction was generated by left coronary artery ligation 2 weeks after chronic treatment. Amiodarone was administered acutely 5 min post-ligation. The electrocardiogram was recorded for 24 h, using an implanted telemetry transmitter. Episodes of ventricular tachyarrhythmias and mortality rates were analysed. Serum catecholamines and infarct size were measured 24 h post-ligation. No differences were found in infarct size. Compared with controls (22.7 ± 10.9), there was a similar reduction in the number of tachyarrhythmia episodes after either chronic (2.6 ± 1.6, P = 0.0011) or acute (3.6 ± 1.7, P = 0.031) amiodarone administration. Norepinephrine levels were lower only after chronic treatment. Mortality in both amiodarone treatment arms was exclusively due to bradyarrhythmia secondary to cardiac failure, whereas mortality in controls was mainly attributed to tachyarrhythmic death. Conclusions: A rapid antiarrhythmic effect was observed after acute amiodarone administration in the rat. Norepinephrine levels decreased after chronic treatment and may be associated with bradyarrhythmic mortality. © The European Society of Cardiology 2007. All rights reserved.