Effects of Amiodarone on Cardiac Electrophysiology and Inducibility of Arrhythmias in Chronically Infarcted Dogs: Late Arrhythmias, Haemodynamics, and Sympatholytic Actions

Abstract

The electrophysiological and antiarrhythmic effects of acute (2 and 10 mg/kg i.v.) and chronic (400 mg/day p.o. for 28 days) amiodarone (AM) treatment were compared in anaesthetised dogs with 5-6-day-old myocardial infarcts. Intravenous AM prolonged the RR interval, sinus node recovery time, the PR interval, and atrial to His conduction time by 36, 33, 25, and 36%, respectively. Corresponding increases after oral amiodarone were 50, 57, 12, and 26%. Atrial and His-Purkinje conduction times were unchanged. Atrial and ventricular refractory periods were increased especially after oral treatment. Oral AM additionally prolonged QRS, QT, and paced QT (by 4, 34, and 19%, respectively). Effects of oral AM on ventricular repolarisation and on the fast inward sodium current were confirmed in vitro. Both modes of AM administration protected against inducible arrhythmias, an effect that was more marked during normal sinus rhythm than during pacing in orally treated dogs. Oral amiodarone failed to protect against spontaneous late arrhythmias 24 h after infarction whilst both modes of administration noncompetitively inhibited isoprenaline-induced tachycardia. Oral AM reduced blood pressure (13%) and LV dP/dt/P (24%) whereas cardiac output was maintained by an increase in stroke volume. It was concluded that oral AM is haemodynamically well tolerated and that prolonged ventricular repolarisation enhanced by bradycardia together with sympatholytic actions may be important mechanisms for antiarrhythmic efficacy, whereas the mechanisms involved in i.v. efficacy are less clear but may depend, at least partly, on sympatholytic actions and perhaps (tentatively) on sodium channel block in Purkinje tissue.