Acute coronary artery occlusion-reperfusion arrhythmias in pigs: Antiarrhythmic and antifibrillatory evaluation of verapamil, nifedipine, prenylamine and propranolol

Abstract

The antiarrhythmic activity of the calcium entry blockers, verapamil, nifedipine and prenylamine, was assessed against arrhythmias occuring during 20 min of acute occlusion, or upon rapid reperfusion of the left anterior descending coronary artery (LAD) in anesthetized pigs. Propranolol, which may indirectly reduce calcium entry by blocking the facilitory action of catecholamines on slow channel conductance, was also evaluated for antiarrhythmic activity in this acute arrhythmia model. Only verapamil (0.2 mg/kg i.v.) reduced both the number of arrhythmias occuring during LAD occlusion and the incidence of ventricular fibrillation (VF) occurring after occlusion and reperfusion. Although both nifedipine (0.04–0.2 mg/kg i.v.) and propranolol (1–2 mg/kg i.v.) produced a slight but significant (P < 0.05) dose-dependent decrease in the incidence of VF during the occlusion period only, this protection was accompanied by a significant increase in ectopic activity. The increase in ectopic activity produced by propranolol (1.0 mg/kg i.v.) persisted even in combination with verapamil (0.2 mg/kg i.v.) which given alone decreased the ectopic frequency. Prenylamine up to 5 mg/kg was without significant antiarrhythmic or antifibrillatory activity. However, unlike verapamil and nifedipine, this drug produced only slight changes in heart rate or blood pressure which suggested the presence of only minimal calcium entry blocking action on myocardial and vascular tissue at the doses we employed. Because the relative antifibrillatory efficacies of verapamil and nifedipine paralleled the relative efficacies reported for depression of atrioventricular conduction, this may implicate the slow inward current channel in the etiology of VF occurring during acute myocardial ischemia. However, this selective antifibrillatory action of calcium entry blockers may be independent of effects on slow response action potentials, myocardial oxygen consumption, or their reported ability to reduce ischemic damage to the myocardium.