Antiarrhythmic effects of desethylamiodarone in dogs with subacute myocardial infarction and inducible ventricular arrhythmias

To determine if desethylamiodarone (DA), the principal metabolite of amiodarone, has antiarrhythmic activity, DA was administered intravenously (i.v.) as a 5 mg/kg bolus followed by a 2-h infusion of 8 mg/kg/h to 12 dogs with 5-7-day-old myocardial infarction and reproducibly inducible sustained ventricular arrhythmias. Programmed electrical stimulation of the right ventricle was repeated, and plasma DA concentration was determined at 15-min intervals during DA administration. At the end of the infusion, the animals were killed and DA concentration in infarcted and noninfarcted myocardium was measured. Grading and statistical analysis of induced arrhythmias revealed significant amelioration during DA infusion, with partial or complete suppression in 9 of the 12 dogs. Apparent steady-state plasma DA concentration (range 0.8-1.0 micrograms/ml) was achieved and maintained during the final 105 min of infusion. DA concentration in noninfarcted myocardium (62.6 +/- 22.0 micrograms/g) was significantly higher (p less than 0.01) than DA concentration in infarcted myocardium (25.6 +/- 18.6 micrograms/g). We conclude that DA administered i.v. has antiarrhythmic activity in dogs with subacute myocardial infarction and reproducibly inducible sustained ventricular arrhythmias.