Prevention of postischaemic ventricular fibrillation by long term beta adrenoceptor blockade with acebutolol in the anaesthetised dog

Abstract

Acute occlusions of the proximal left circumflex coronary arteriovenous pedicle were performed in open chest anaesthetised dogs. Twenty eight dogs were randomly allocated to receive acebutolol (3 mg·kg⁻¹ twice daily) or placebo given blindly by mouth for five days; a control group of 14 dogs without any pretreatment underwent the same procedure. Coronary ligations in the randomised study were performed during seven consecutive days, and four dogs were operated on each day. This schedule was chosen in order to measure acebutolol plasma concentrations just before ligation from 60 to 540 min after the last dose of the drug. Long term oral treatment with acebutolol protected against postischaemic ventricular fibrillation and significantly reduced the incidence of both early phase (0-10 min postocclusion) ventricular arrhythmias and ventricular fibrillation. As a result the outcome was significantly improved after 60 min of ischaemia in acebutolol compared with placebo treated animals. The results in the control animals were similar to those in the placebo treated dogs. The protective effect of long term oral treatment with acebutolol lasted for nine hours and was apparently independent of the plasma concentrations of the drug. These data show that improved outcome in this canine model is due to the prevention of ischaemia induced ventricular fibrillation by long term beta adrenoceptor blockade, which is able to overcome the effect, if any, of partial agonist activity of acebutolol. A direct myocardial anti-ischaemic effect might explain the effectiveness of long term oral treatment, which is independent of plasma concentrations of the drug.