α- and β-adrenergic effects of epinephrine on ventricular pacemakers in dogs

We studied the effects of epinephrine on idioventricular rhythm in 15 adult dogs with chronic heart block induced by the injection of formalin into the His bundle. Atropine (0.1 mg/kg) was given intravenously to attenuate any potential vagal effects, and epinephrine was infused in graded doses of 0.1-10.0 μg.kg^-1.min^-1. Two different responses were seen. In 12 dogs there was a concentration-dependent increases in ventricular rate following epinephrine infusion. These animals then were given the β-blocker propranolol (0.5 mg/kg iv), and the epinephrine infusions were repeated. In this situation epinephrine concentrations less than 0.1 μg.kg^-1 induced a decrease in ventricular rate without an associated change in arterial blood pressure. This decrease in rate was abolished by the α-blocker phentolamine. It therefore appears that an α-adrenergic effect on ventricular automaticity can occur in the intact animals. When this does not occur initially, it can be unmasked by propranolol and results in a slowing of ventricular rate unrelated to changes in blood pressure.