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The effects of dl-propranolol, d-propranolol, and ICI 46037, a quaternary analog of propranolol, on the functional refractory period and conduction time of the atrioventricular transmission system were studied in anesthetized dogs. dl-Propranolol, 0.5 mg/kg, prolonged the functional refractory period, increased the conduction time, and reduced the maximum frequency of A-V transmission. Larger doses (5 mg/kg) produced only a small additional depression of A-V transmission. In contrast, neither d-propranolol nor ICI 46037, 0.5 mg/kg, depressed A-V transmission. Larger doses of both drugs prolonged both the functional refractory period and the conduction time, the magnitude of the response being quantitatively similar to that produced by increasing the dose of dl-propranolol from 0.5 mg/kg to 5 mg/kg. The intravenous administration of glucagon, 2 μg/kg, promptly restored normal A-V conduction in animals that had received dl- or d-propranolol, but was ineffective in those which had received ICI 46037. It was concluded that propranolol depresses A-V transmission by both specific (beta-receptor blockade) and nonspecific mechanisms, the former being the more important. In addition, it appears that glucagon is capable of reversing the cardiodepressant action of propranolol on A-V transmission, a finding which may have considerable clinical importance.

Effects of Beta-Receptor Blockade and Glucagon on the Atrioventricular Transmission System in the Dog