Hypothermia and controlled reperfusion: two non-pharmacologic methods which diminish ischemia-reperfusion injury in skeletal muscle

The mechanisms of ischemia-reperfusion (I-R) injury in skeletal muscle remain controversial. We have previously reported two non-pharmacologic methods to salvage skeletal muscle from I-R injury, post-ischemic hypothermia and controlled reperfusion. In all experiments, both canine gracilis muscles were subjected to six hours of ischemia followed by one hour of reperfusion. Controlled reperfusion was achieved by partially occluding one gracilis artery to limit the rate of reperfusion blood flow to its pre-ischemic rate, while the contralateral artery was allowed to perfuse freely at a normal rate. Post-ischemic hypothermia was achieved by cooling one gracilis muscle to 21 degrees centigrade (hypothermic reperfusion) after 5 hours of warm ischemia, while the opposite gracilis muscle was maintained at ambient temperature (normothermic reperfusion). Both methods resulted in a significant diminution in muscle infarct and edema. The mechanisms by which this is accomplished are currently unknown, but may be related to a diminished inflammatory response to ischemia. This review of these methods suggests that the hyperemic rate of reperfusion blood flow is a significant factor in the pathophysiology of post-reperfusion edema, and that significant control of skeletal muscle reperfusion injury may be achieved by limiting the rate of reperfusion blood flow or by applying post-ischemic hypothermia.