Evaluation of combined administration of verapamil and disopyramide in dogs

The electrophysiologic and hemodynamic effects of concurrent administration of verapamil and disopyramide were studied in morphine-chloralose-anesthetized dogs. Twenty-one dogs were studied; seven received verapamil alone, seven received disopyramide alone, and seven received the two drugs in combination. Both drugs were administered by intravenous infusion, resulting in sustained plasma levels within the therapeutic range. Effects were measured every 30 min and compared with baseline (pretreatment) values. In all three groups heart rate and cardiac output decreased slightly; however, the effect produced by the combination was not significantly different from that produced by either drug alone. Most of the electrophysiologic changes observed in the combined-treatment dogs could be attributed to the individual effects of either verapamil or disopyramide and were not suggestive of any interaction between these two drugs. In the combined-treatment dogs the atrial and ventricular refractoriness increased in the same way as with disopyramide alone, and the spontaneous discharge rate of the sinus node and the conduction through the atrioventricular node were slowed as with verapamil alone. However, a significant prolongation of the sinus node recovery time occurred in the combined-treatment dogs. Five of the seven dogs experienced at least one episode of sinus arrest following pacing. The profile of effects observed may be dependent, in part, on the model we utilized. However, our data suggest that the combination of verapamil and disopyramide may produce severe sinus node depression.