Propafenone in the Conscious Dog with Chronic Atrioventricular Block

The chronotropic effects of propafenone were studied in the conscious dog with chronic atrioventricular block. Propafenone at 0.5-4 mg/kg, i.e., at plasma levels within the assumed therapeutic range, dose relatedly raises atrial rate. This effect falls off and bradycardia is even observed at 0.5 and 1 mg/kg once plasma levels have dropped below 330 +/- 31 ng/ml. After atropine, propafenone (2 mg/kg) lowers atrial rate, after propranolol it raises it, and after pindolol it does not modify it. Propafenone dose relatedly raises ventricular rate, although again this effect subsequently reverses at 4 mg/kg. After atropine, propranolol, and pindolol, propafenone (2 mg/kg) instead of initially raising ventricular rate lowers it lastingly. It initially lowers mean blood pressure according to dose. At 2 mg/kg neither this effect nor the plasma levels are modified by the antagonists. The beta-blocking potency is 1/40th that of propranolol as determined against isoproterenol-induced cardioacceleration. These results show that the atrial cardioacceleration due to propafenone results from direct and reflex vagolytic action and that the bradycardia at low plasma levels (buffered by the vagolytic effect at high levels) seems due to its membrane-stabilizing action. They also show that the initial ventricular cardioacceleration is a reflex response to its hypotensive effect, whereas the ventricular bradycardia at high doses is attributable to its membrane-stabilizing action and its albeit weak beta-blocking action.