The effect of beta-adrenergic blockade on vulnerability to ventricular fibrillation and inducibility of ventricular arrhythmia in short- and long-term feline infarction models

Abstract

Previous investigation, predominantly in the short-term canine model, has documented a potent antifibrillatory effect of beta-adrenergic blockade. To determine whether the protection afforded by beta blockade is species- and model-specific, we studied 23 chloralose-anesthetized cats. Eight animals were studied over a short term and underwent serial determinations of the ventricular fibrillation (VF) threshold prior to and 1 minute after occlusion of the left anterior descending coronary artery (LAD) and immediately following reperfusion of a 10-minute occlusion. Beta-blocking doses of intravenous propranolol (P) (0.5 mg/kg) attenuated the fall in VF threshold during acute ischemia. Increasing the dose of P to 1 mg/kg did not provide further protection, nor did P protect against reperfusion VF. The other 15 animals underwent a preliminary surgical procedure during which the LAD was completely and irreversibly occluded (nine animals) or in which a sham procedure was performed (six animals). Two weeks later, we measured ventricular refractoriness at several left ventricular sites, ventricular inducibility using programmed electrical stimulation, and VF thresholds both before and after administration of intravenous P (1 mg/kg). Ventricular refractory periods in the infarcted zones were significantly increased compared with normal sites and with values obtained in sham-operated animals. In addition, VF thresholds in the infarcted animals were lower than those obtained in the sham-operated group. Before treatment, a reproducible sustained ventricular tachyarrhythmia was induced by means of programmed stimulation in seven of the nine chronically infarcted animals but in none of the sham-operated animals ( p < 0.02). P increased refractory periods in the normal and infarcted zones proportionately and significantly. After P, sustained ventricular arrhythmia was induced in only one cat in the infarcted group ( p < 0.03). This attenuated inducibility was coincident with a significant increase in VF threshold after P ( p < 0.02). Beta blockade exerts a significant electrophysiologic effect in the feline ventricle. Protection against VF induced in both short-term and long-term infarction is coincident with an increase in ventricular refractoriness and with prevention of inducibility by programmed stimulation.