Mitochondrial K-ATP channel opening is important during index ischemia andfollowing myocardial reperfusion in ischemic preconditioned rat hearts

We have previously demonstrated that K-ATP channel openers administered jus t prior to and throughout reperfusion induce cardioprotection in the blood- perfused canine heart, However, a recent report suggests that the mitochond rial K-ATP channel is only a trigger of ischemic preconditioning (TPC). The se recent data are, however, in contrast to most previous investigations th at suggested that activation of the mitochondrial K-ATP channel is an impor tant downstream mediator of cardioprotection. Therefore, we examined the ro le of the mitochondrial K-ATP channel as a downstream mediator of IPC in a rat model by administering the selective mitochondrial It, channel antagoni st, 5-hydroxydecanoate (5-HD), at several points during IPC. Infarct size ( IS) was determined by tetrazolium chloride staining and expressed as a perc ent of the area at risk (AAR). Control animals had an IS/AAR of 58.4 +/- 0. 6 and IS/AAR was reduced to 6.2 +/- 1.7 following IPC, 5-HD (10 mg/kg), att enuated cardioprotection when administered either 5 min prior to the IPC st imulus (40.4 +/- 1.4), during the reperfusion phase of the IPC stimulus (39 .7 +/- 5,9), or 5 min prior to reperfusion during prolonged ischemia (34.3 +/- 6.9). Additionally, when 5-HD was administered at 5 mg/kg during the re perfusion phase of index ischemia plus 5 min prior to IPC or plus during th e reperfusion phase of IPC, cardioprotection was also attenuated (36.3 +/- 5.5 and 43.8 +/- 6.9, respectively). These data suggest that activation of the mitochondrial It,, channel is an important downstream regulator of myoc ardial protection with effects lasting into the reperfusion period followin g prolonged ischemia, (C) 2001 Academic Press.