We investigated the effects of pinacidil, an ATP-sensitive potassium channel opener, and of glibenclamide, an ATP-sensitive potassium channel inhibitor, on the incidence of arrhythmias and sudden cardiac death after coronary artery ligation in conscious rats. Occlusion of the left main coronary artery was produced by tightening a previously placed loose silk ligature. In the control group (n = 25) only 40% and 24% of the animals survived for 15 min and 16 hr after coronary artery ligation, respectively. Intravenous pretreatment with 0.1, 0.3 or 1 mg/kg pinacidil increased the survival rate to 67% (n = 15), 70% (n = 20) and 67% (n = 12) in the first 15 min and to 60%, 55% and 67% in the first 16 hr, respectively. Glibenclamide pretreatment (5.0 mg/kg i.p.) improved the survival rate at both time-points to 87% (n = 16). Both types of pretreatment significantly decreased the incidence of life-threatening arrhythmias and increased the number of animals that survived without developing any arrhythmia. In conclusion, the present findings demonstrate that in conscious rats, pretreatment with pinacidil and pretreatment with glibenclamide, although they obviously have different mechanisms of action, may result in a very similar final outcome with respect to arrhythmias and sudden cardiac death during the acute phase of experimental myocardial infarction.