Effects of Dantrolene and Verapamil on Atrioventricular Conduction and Cardiovascular Performance in Dogs

Abstract

The effects of intravenous dantrolene sodium, alone and in combination with verapamil, upon atrioventricular conduction, cardiovascular function, and neuromuscular function were studied in chloralose-urethane anesthetized dogs. Hemodynamic variables (systemic arterial, central venous, and pulmonary arterial pressures and cardiac output) and His-bundle electrograms were monitored, and measurements were made during atrial pacing at 175 beats/min, as well as at the spontaneous heart rate. In one part of the study animals received dantrolene sodium incrementally at 30-min intervals to cumulative doses of 1, 2.5, 5, and 10 mg/kg. Subsequently, verapamil was administered incrementally at 30-min intervals to cumulative doses of 0.1, 0.2, 0.4, and 0.6 mg/kg. In the second part of the study, dogs received identical dosage sequences, but verapamil preceded dantrolene administration. Dantrolene caused no significant depression of atrioventricular conduction or cardiac performance but did increase systemic vascular resistance at doses above 2.5 mg/kg. Verapamil alone (greater than or equal to 0.2 mg/kg) or with dantrolene (greater than or equal to 0.1 mg/kg) increased the atrial-His-bundle conduction interval. In the presence of verapamil, dantrolene (greater than or equal to 2.5 mg/kg) decreased cardiac index and increased pulmonary artery occlusion pressure. Although 0.6 mg/kg verapamil depressed cardiac index and increased pulmonary artery occlusion pressure, this effect was observed at 0.4 mg/kg after prior treatment with dantrolene. Verapamil did not augment the dose-dependent twitch depression observed with dantrolene. Dantrolene alone had no apparent effect on atrioventricular conduction and caused little enhancement of the effects of verapamil. However, each drug appeared to enhance the myocardial depressant effects of the other.