Tourniquet-induced acute ischemia-reperfusion injury in mouse skeletal muscles Involvement of superoxide

Although arterial limb tourniquet is one of the first-line treatments to prevent exsanguinating hemorrhage in both civilian pre hospital and battlefield casualty care prolonged application of a limb tourniquet can lead to serious ischemia-reperfusion injury However the underlying pathomechanisms of tourniquet-induced ischemia-reperfusion injury are still poorly understood Using a murine model of acute limb ischemia-reperfusion we investigated if acute limb ischemia-reperfusion injury is mediated by superoxide overproduction and mitochondrial dysfunction Hind limbs of C57/BL6 mice were subjected to 3 h ischemia and 4 h reperfusion via placement and release of a rubber tourniquet at the greater trochanter Approximately 40% of the gastrocnemius muscle suffered infarction in this model Activities of mitochondrial electron transport chain complexes including complex I II III and IV in the gastrocnemius muscle were decreased in the ischemia-reperfusion group compared to sham Superoxide production was increased while activity of manganese superoxide dismutase (MnSOD the mitochondria-targeted SOD isoform) was decreased in the ischemia-reperfusion group compared to the sham group Pretreatment with tempol (a SOD mimetic 50 mg/kg) or co-enzyme Q(10) (50 mg/kg) not only decreased the superoxide production but also reduced the Infarct size and normalized mitochondrial dysfunction in the gastrocnemius muscle Our results suggest that tourniquet-induced skeletal muscle ischemia-reperfusion injuries including infarct size and mitochondrial dysfunction may be mediated via superoxide overproduction and reduced antioxidant activity In the future this murine ischemia-reperfusion model can be adapted to mechanistically evaluate anti ischemic molecules in tourniquet-induced skeletal muscle injury (C) 2010 Elsevier B V All rights reserved