Acute electrophysiologic effects and antiarrhythmic/antifibrillatory activity of intravenous amiodarone in a chronic feline infarction model

In animal studies, amiodarone has substantial and immediate antiarrhythmic/antifibrillatory action during acute myocardial ischemia. The magnitude of this effect is discordant with the minor degree of prolongation of ventricular action potential duration (APD) and refractoriness which occurs immediately after acute drug administration. However, amiodarone's early onset of antiadrenergic activity and inhibition of inward slow calcium channel currents may be important when arrhythmogenesis is dependent on increased sympathetic tone. Because ventricular arrhythmia substrate may differ in acute and chronic ischemic heart disease, we investigated the acute electrophysiologic and antiarrhythmic/antifibrillatory effects of intravenously (i.v.) administered amiodarone in nine chronically infarcted cats. Amiodarone caused significant decreases (-17%) in mean heart rate (HR) and increases (+10%) in mean ventricular effective refractory period (ERP), which occurred promptly after drug administration. Increases in mean ventricular fibrillation (VF) threshold also occurred (11 +/- 3.4 and 12.5 +/- 2.4 mA for right and left ventricular sites before drug as compared with 45.5 +/- 13.2 and 42 +/- 13.9 mA after drug). Despite these changes, no significant reduction in the incidence of malignant ventricular arrhythmias induced by programmed stimulation was noted (63% of animals with arrhythmia induced before drug were still inducible after drug). In addition, no change in the increased degree of mean dispersion of refractoriness between infarcted and normal myocardial sites occurred following amiodarone (22.8 +/- 3.9 ms before vs. 30.2 +/- 2.5 ms after drug). In chronic myocardial infarction without superimposed acute ischemia, early onset of amiodarone's antiadrenergic and calcium channel blocking activities may play only a minor role in preventing ventricular arrhythmias inducible by programmed stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)