Antifibrillatory efficacy of concomitant beta adrenergic receptor blockade with dilevalol, the R,R-isomer of labetalol, and muscarinic receptor blockade with methylscopolamine

Abstract

The antiarrhythmic and antifibrillatory actions of dilevalol, the R,R-isomer of labetalol, were evaluated in conscious dogs 4 to 6 days after anterior myocardial infarction. The administration of dilevalol in a lower dose of 0.3 mg/kg i.v. q 8 hr or a higher dose of 3.0 mg/kg i.v. q 8 hr over a period of 24 hr failed to alter electrophysiologic parameters or significantly suppress the induction of ventricular tachycardia by programmed ventricular stimulation (incidence of ventricular tachycardia suppression: 4 of 25 [16%] dilevalol vs. 1 of 14 [7%] vehicle). Pretreatment with dilevalol failed to reduce arrhythmic death in response to the subsequent development of ischemia at a site distant to the area of previous infarction (mortality: 8 of 10 [80%] dilevalol vs. 14 of 14 [100%] vehicle), but did alter the nature of the lethal ischemic arrhythmia from ventricular fibrillation (incidence of ventricular fibrillation: 14 of 14 [100%] vehicle vs. 2 of 8 [25%] dilevalol, P less than .05) to bradyarrhythmia with eventual sinoatrial arrest (6 of 8 [75%] dilevalol). The administration of methylscopolamine, 0.01 mg/kg both i.v. and i.m., to postinfarction animals pretreated with dilevalol, 3.0 mg/kg i.v. q 8 hr for 24 hr, reduced significantly mortality in response to subsequent posterolateral ischemia (mortality: 4 of 10 [40%] dilevalol plus methylscopolamine vs. 14 of 14 [100%] vehicle, P less than .05). However, methylscopolamine alone failed to suppress the development of ischemic ventricular fibrillation in 5 of 6 (83%) postinfarction dogs.(ABSTRACT TRUNCATED AT 250 WORDS)