Effects of antiarrhythmic agents on isoproterenol-induced ventricular fibrillation in heavy rats: a possible model of sudden cardiac death.

Heavy male Sprague-Dawley rats die of ventricular fibrillation within 2 to 3 h after isoproterenol administration. Thus, the isoproteronol-treated heavy rat would be a useful model for screening drugs that may prevent sudden cardiac death. Isoproterenol (1 mg/kg s.c.) caused ventricular fibrillation in 79% of 121 vehicle-pretreated heavy rats (greater than 500 g); 82% of the fibrillating rats died, but the remaining 18% spontaneously reverted and survived. A protecting agent should increase the number of survivors by reducing the incidence of ventricular fibrillation and/or by increasing the incidence of spontaneous reversions. Pretreatment (i.p.) with quinidine (40 mg/kg), procainamide (40 mg/kg), phenytoin (40 mg/kg), clofilium (5 mg/kg), verapamil (10 mg/kg), or propranolol (10 mg/kg) reduced the incidence of isoproterenol-induced ventricular fibrillation and death; bretylium (10 mg/kg) and nicotinic acid (100 mg/kg) had no effect. A lower dose of propranolol (2.5 mg/kg) or clofilium (1.5 mg/kg) but not quinidine (10 mg/kg), procainamide (10 mg/kg), or phenytoin (10 mg/kg) also reduced the incidence of ventricular fibrillation. Only clofilium tended to increase the incidence of spontaneous reversions.