Introduction: Approximately 3-10% of microsurgical procedues are subject to vascular compromise. We propose that tissue loss is compounded not only by the increased ischemia time (and IR injury) but also by the increased (hyperthermic) ambient temperatures of normal body heat and the placement of postoperative free flap patients in warm rooms(80 degrees F). We Hypothesize that compromised flaps maintained in a hypothermic environment, will observe improved survival. Methods: The rat rectus femoris muscle flap was elevated on its major pedicle and sujected to 4 hours of ischemia. The flaps were then exposed to either hypothermia(50 degrees F) or ambient temperatures of 72 degrees F during the early perfusion period. Following 1 hour of perfusion, complete venous occlusion of the muscle flap was accomplished by placing clamps across the venous outflow. Following 4 hours of venous occlusion, the clamps were removed. This simulated a the clinical scenario of a salvage attempt of free flaps that develop subsequent venous occlusion and require re-exploration. The flaps were then allowed to reperfuse at normal body temperature. Muscle necrosis and muscle edema were assessed following 24 hours of this reperfusion. A microarray cDNA analysis was preformed on each group to observe changes in gene expression of the different muscle groups. Results: Hypothermic exposed muscles (n=4) demonstrated decreased muscle necrosis compared to the room temperature exposed muscles (n=4) following 4 hours of venous occlusion (9.3+/- 5.7% versus 93.6 +/- 8.9% necrosis; p< 0.001). Hypothermic exposed muscles demonstrated a trend towards improved edema (1.79 +/-0.36 versus 1.89 +/-0.28 wet to dry weight ratio;p=0.684). The gene expression anaysis of the the muscle groups revealed a significant number of up-regulated and down-regulated genes most notably egr-1 which was up-regulated 104 fold. Conclusion; These preliminary results suggest a role for exposure of elective free flaps to regional hypothermia during the early reperfusion period to provide protection from IR injury associated with venous occlusion. The variations in gene expression are discussed.