Intrinsic sympathomimetic activity and the effects of beta-adrenergic blocking drugs on vulnerability to ventricular fibrillation

Beta-adrenergic blocking agents differ considerably in their effects on myocardial excitable properties. The possibility that intrinsic sympathomimetic activity might contribute to such differences has not been adequately explored. This study examined the influence of intrinsic sympathomimetic activity on the electrophysiologic effects of three agents with varying degrees of such activity. Intravenous propranolol (0.5 mg/kg), oxprenolol (0.5 mg/kg) and pindolol (0.05 mg/kg) were administered in 16 anesthetized dogs. The effects of the drugs on ventricular vulnerability were studied over a 2 hour period. Propranolol and oxprenolol raised the ventricular fibrillation threshold by 42 and 56%, respectively. In contrast, pindolol resulted in an elevation of only 25%. After depletion of endogenous norepinephrine stores using reserpine, pindolol led to a decrease of the ventricular fibrillation threshold, which was reversed by propranolol. These data indicate that intrinsic sympathomimetic activity of beta-adrenergic blocking agents substantially alters their ultimate effect on myocardial excitable properties.