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.
G L
GL
Johnson
S J
SJ
Ehrreich
A N
AN
el-Hage
T
T
Balazs
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001835:Body Weight; D001950:Bretylium Tosylate / Q000627:therapeutic use; D003645:Death, Sudden / Q000517:prevention & control*; D004195:Disease Models, Animal; D004562:Electrocardiography; D007545:Isoproterenol; D008297:Male; D009525:Niacin / Q000627:therapeutic use; D010672:Phenytoin / Q000627:therapeutic use; D011342:Procainamide / Q000627:therapeutic use; D011433:Propranolol / Q000627:therapeutic use; D000644:Quaternary Ammonium Compounds; D011802:Quinidine / Q000627:therapeutic use; D051381:Rats; D014693:Ventricular Fibrillation / Q000139:chemically induced / Q000628:therapy*; D014700:Verapamil / Q000627:therapeutic use
D000889:Anti-Arrhythmia Agents; D000644:Quaternary Ammonium Compounds; D009525:Niacin; D010672:Phenytoin; D001950:Bretylium Tosylate; C022799:clofilium; D011433:Propranolol; D014700:Verapamil; D011802:Quinidine; D011342:Procainamide; D007545:Isoproterenol