The antiarrhythmic actions of intravenous and oral UM424 in postinfarction canine myocardium.

Abstract

The electrophysiologic and antiarrhythmic effects of oral and intravenous UM424 were studied in canine models of acute and chronic myocardial injury. In the first phase of this study, reentrant ventricular tachyarrhythmias and/or ventricular fibrillation were initiated by programmed electrical stimulation techniques in seven dogs 48-120 h after myocardial infarction. The cycle length of these reentrant ventricular beats was 176 +/- 16 ms, and they were accompanied by fractionated asynchronous epicardial electrical activity in the injured region that bridged the diastolic interval, i.e., 143 +/- 37 ms. When this prolonged, diastolic electrical activity ceased, the ventricular tachyarrhythmias ceased. UM424 5 mg/kg i.v. increased the effective refractory period of the normal myocardium by 21 ms (p less than 0.05), depressed cardiac conduction in the injured, infarcted myocardium and suppressed these reentrant tachyarrhythmias. Ventricular fibrillation could not be initiated after UM424. In the second phase of this study, a canine model of coronary artery thrombosis was used to produce spontaneous ventricular arrhythmias. UM424 60 mg/kg p.o. converted these ventricular arrhythmias to normal sinus rhythm. This pharmacologic action was not associated with deleterious hemodynamic side effects and lasted for 3 h, the duration of each experiment. These results demonstrate that after oral or intravenous administration, UM424 possess antiarrhythmic and antifibrillatory actions in canine models of acute and chronic myocardial injury.