Anti-arrhythmic effects of amiodarone and desethylamiodarone on malignant ventricular arrhythmias arising as a consequence of ischaemia and reperfusion in the anaesthetised rat.

Abstract

The effects of amiodarone and its metabolite desethylamiodarone on arrhythmias induced by ischaemia and reperfusion were studied in vivo in the anaesthetised rat with transient regional ischaemia (7 min of left coronary artery occlusion) and reperfusion (10 min). Amiodarone or desethylamiodarone were administered intravenously either 10 min prior to ischaemia or 2 min prior to reperfusion. Control rats received an equivalent volume of vehicle. Administration of 5.0 mg.kg-1 amiodarone or desethylamiodarone prior to ischaemia reduced the incidence of ventricular tachycardia during the ischaemic period from 67% to 20% (p less than 0.02) and 47% respectively. During reperfusion, mortality was reduced from 53% to 7% and 7% (p less than 0.02) respectively, and reperfusion induced ventricular fibrillation from 73% to 20% (p less than 0.01) and 47% respectively. When the drugs were given prior to ischaemia, the plasma concentrations of amiodarone and desethylamiodarone were 1.03 (SEM 0.18) and 0.22(0.02) micrograms.ml-1 and the myocardial concentrations were 23.43(2.78) and 30.41(1.87) micrograms.g-1 respectively. Similar concentrations were found in plasma and myocardium with drugs given prior to reperfusion. No significant differences in plasma or myocardial concentrations of amiodarone or desethylamiodarone were observed between animals which developed ventricular fibrillation and those which did not. In conclusion, this study demonstrates that desethylamiodarone can, like its parent compound, protect the heart against malignant ventricular arrhythmias arising as a consequence of regional myocardial ischaemia and reperfusion.