Inhibitory effect of moricizine on reperfusion induced tachyarrhythmias in rats--a comparison study with disopyramide and mexiletine.

Abstract

Acute ligation of proximal left coronary artery was performed on forty male Sprague-Dawley rats. Five min later, occlusion was released in order to evaluate the effectiveness of the 3 antiarrhythmic drugs in eliminating reperfusion ventricular arrhythmias. The drugs evaluated were moricizine (5 mg/kg), disopyramide (DSP) (5 mg/kg) and mexiletine (MXT) (5 mg/kg), which were administered intravenously 5 min before ligation of the coronary artery. Compared to control rats that underwent identical experimental procedures, all 3 drugs significantly lowered the mortality rate from 90% of the control group to 20, 20 and 0% for moricizine, DSP and MXT groups. The incidence of ventricular fibrillation (Vf) was also decreased significantly by these drugs. The duration of ventricular tachycardia (VT) and Vf of surviving rats in drug groups were 111.7 +/- 35.0 sec, 71.6 +/- 29.4 sec and 32.9 +/- 14.6 sec for moricizine, DSP and MXT, respectively. Many of the drug treated rats could be restored to the normal sinus rhythm and survived. All 3 drugs slowed the heart rate significantly, but as for the blood pressure only MXT showed significant suppressing effect. In conclusion, moricizine has the same significant preventive effect on reperfusion induced ventricular tachyarrhythmias as DSP and MXT.