Electrophysiologic effects of bretylium on canine ventricular muscle during acute ischemia and reperfusion.

Electrophysiologic effects of bretylium were assessed on a recently developed animal model for analysis of conduction of premature impulses and excitation threshold. Bretylium was administered intravenously 10 mg/kg over 10 minutes followed by 2 mg/min of infusion immediately after coronary ligation. Conduction of the premature impulse was recorded in the epicardial and endocardial sites both in the base-to-apex and apex-to-base directions, in the normal, in the center, and across the border of ischemic myocardium. Compared to the control group of animals, bretylium did not cause any significant change in the conduction characteristics in the ischemic myocardium; however, it delayed the conduction of premature impulses in the normal myocardium. Thus the disparity in conduction times between the normal and the ischemic myocardium was lessened by bretylium. Further, conduction of impulses from normal tissue across the border of ischemia was also delayed. Bretylium also decreased the excitability threshold in the ischemic myocardium, although the normal myocardial excitation threshold was unaffected. These unique effects of bretylium on conduction and excitability in the normal, in the center, and across the border of ischemic myocardium, when a therapeutic dosage of the drug is used, further validate its antiarrhythmic potential and offer an insight into its mechanism of action in the setting of acute myocardial ischemia.