Remote postconditioning attenuates ischemia/reperfusion injury in rat skeletal muscle through mitochondrial ATP-sensitive K⁺ channel-dependent mechanism

The authors investigated whether a remote postconditioning (remote post-con) procedure attenuated skeletal muscle ischemia/reperfusion (I/R) injury. We determined the optimal protocol of remote post-con and investigated its mechanism. Ischemia was induced for 3 hours in rat left hindlimb and three protocols of remote post-con were applied in right hindlimb just before the end of ischemia. The first (10-second group) involved two cycles of 10 seconds of occlusion followed by 10 seconds of reperfusion. The second (5-minute group) involved two cycles of 5 minutes of occlusion/reperfusion. The third (10-minute group) involved two cycles of 10 minutes of occlusion/reperfusion. In 5- and 10-minute groups, wet/dry ratio and muscle fiber edema were significantly lower than control group. Muscle contractility was preserved in 5- and 10-minute groups. An injection of 5-hydroxydecanoate (a specific blocker of mitochondrial ATP-sensitive K⁺ [mK_ATP] channels) impaired this effect. This study demonstrates that remote post-con preserves muscle contractility and reduces tissue edema and necrosis, possibly through the activation of mK _ATP channels. We suggest that two cycles of 5 minutes of occlusion followed by 5 minutes of reperfusion are optimal protocols of remote post-con in skeletal muscle I/R injury.