EFFECTS OF MAGNESIUM-SULFATE ON THE CANINE CARDIOVASCULAR-SYSTEM COMPLICATING ASTEMIZOLE OVERDOSE

Polymorphic ventricular arrhythmias induced by astemizole overdose hav e been reported to be successfully managed with intravenous magnesium sulfate. This study was de signed to assess the effects of magnesium s ulfate on the cardiovascular system, complicating astemizole overdose, the better to understand the therapeutic utility and undesirable effe cts of magnesium sulfate. Beagle dogs were anesthetized with halothane inhalation (n = 6). Monophasic action potential of the right ventricl e, electrocardiogram, and systemic and left ventricular pressure were continuously monitored. Cardiac output was measured by a thermodilutio n method. Effective refractory period of thr right ventricle was asses sed by programed electrical stimulation. An intentionally high dose of astemizole (3 mg/kg, i.v.) prolonged the repolarization and refractor y period, while it decreased the sinus automaticity, ventricular contr action, and conduction. A canine antiarrhythmic dose of magnesium sulf ate (100 mg/kg, i.v.) was additionally injected 1 h after i.v, astemiz ole. Magnesium sulfate increased the atrioventricular conduction time, electrical vulnerability, and preload of the left ventricle, while it decreased the blood pressure and cardiac output, besides the effects similar to those observed after i.v. astemizole. The plasma concentrat ion of astemizole was at least 10 times higher than its therapeutic co ncentration during the experimental period. Magnesium sulfate could be expected to act as a calcium channel blocker during astemizole overdo se; however, it may not antagonize the proarrhythmic effects of astemi zole.