Long-term pretreatment with desethylamiodarone (DEA) or amiodarone (AMIO) protects against coronary artery occlusion induced ventricular arrhythmias in conscious rats

Abstract

The aim of this investigation was to compare the effectiveness of long-term pretreatment with amiodarone (AMIO) and its active metabolite desethylamiodarone (DEA) on arrhythmias induced by acute myocardial infarction in rats. Acute myocardial infarction was induced in conscious, male, Sprague–Dawley rats by pulling a previously inserted loose silk loop around the left main coronary artery. Long-term oral pretreatment with AMIO (30 or 100 mg·(kg body mass)−1·day−1, loading dose 100 or 300 mg·kg−1 for 3 days) or DEA (15 or 50 mg·kg−1·day−1, loading dose 100 or 300 mg·kg−1 for 3 days), was applied for 1 month before the coronary artery occlusion. Chronic oral treatment with DEA (50 mg·kg−1·day−1) resulted in a similar myocardial DEA concentration as chronic AMIO treatment (100 mg·kg−1·day−1) in rats (7.4 ± 0.7 μg·g−1 and 8.9 ± 2.2 μg·g−1). Both pretreatments in the larger doses significantly improved the survival rate during the acute phase of experimental myocardial infarction (82% and 64% by AMIO and DEA, respectively, vs. 31% in controls). Our results demonstrate that chronic oral treatment with DEA resulted in similar cardiac tissue levels to that of chronic AMIO treatment, and offered an equivalent degree of antiarrhythmic effect against acute coronary artery ligation induced ventricular arrhythmias in conscious rats.