Background New strategies to mitigate ischemia during REBOA and to prolong its maximal duration are needed. We hypothesized that simple external cooling of the hind limbs would decrease ischemia-reperfusion injury following prolonged Zone 3 REBOA. Methods 12 swine were anesthetized, instrumented, splenectomized then underwent 15% total blood volume hemorrhage. Animals were randomized to hypothermia or control followed by 4 hours of Zone 3 REBOA, resuscitation with shed blood, and 3 hours of critical care. Physiologic parameters were continuously recorded, and laboratory specimens were obtained at regular intervals. Baseline and end-of-study muscle biopsies were obtained for histologic analysis. Results There were no significant differences between groups at baseline or after hemorrhage. Maximum creatine kinase was significantly lower in the hypothermia group compared to the normothermia group (median [IQR] = 3,445 U/mL [3,380-4,402] vs 22,544 U/mL [17,030-24,981]); p
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