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

Thai P. Tran, Huiyin Tu, Iraklis I Pipinos, Robert Leo Muelleman, Hassan Albadawi, Yulong Li

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

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 Q10 (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.

Original languageEnglish (US)
Pages (from-to)328-334
Number of pages7
JournalEuropean Journal of Pharmacology
Volume650
Issue number1
DOIs
StatePublished - Jan 10 2011

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Keywords

  • Infarct size
  • Ischemia-reperfusion injury
  • Mitochondria
  • Superoxide
  • Tourniquet

ASJC Scopus subject areas

  • Pharmacology

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