Selective mitochondrial KATP channel activation results in antiarrhythmic effect during experimental myocardial ischemia/reperfusion in anesthetized rabbits

We investigated the effects of administration of non-hypotensive doses of ATP-sensitive K+ channel (K-ATP) openers (nicorandil and aptikalim), and a specific mitochondrial K-ATP channel blocker (5-hydroxydecanoate) prior to and during coronary occlusion as well as prior to and during post-ischemic reperfusion on survival rate, ischemia/reperfusion-induced arrhythmias and myocardial infarct size in anesthetized albino rabbits. Arrhythmias were induced by reperfusion following a 20 min ligation of the left main coronary artery with a releascable silk ligature. Early intervention by intravenous infusion of nicorandil (100 mug/kg bolus + 10 mug/kg/min) or aprikalim (10 mug/kg bolus + 0.1 mug/kg/min) just before and during ischemia increased survival rate (86% and 75% vs. 55% in the control group), significantly decreased the incidence and severity of life-threatening arrhythmias and myocardial infaret size. The antiarrhythmic and cardioprotective effects of both nicorandil and aprikalim were abolished by pretreating the rabbits with 5-hydroxydecanoate (5 mg/kg, i.v. bolus). In conclusion, intervention by intravenous administration of nicorandil and aprikalim (through the selective activation of mitochondrial K-ATP channels) increased survival rate and exhibited antiarrhythmic and cardioprotective effects during coronary occlusion and reperfusion in anesthetized rabbits when administered prior to and during coronary occlusion. (C) 2002 Elsevier Science B.V All rights reserved.