Selective mitochondrial K_ATP 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 aprikalim), 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 releaseable silk ligature. Early intervention by intravenous infusion of nicorandil (100 μg/kg bolus+10 μg/kg/min) or aprikalim (10 μg/kg bolus+0.1 μg/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 infarct 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.