Polyadenosine Diphosphate–Ribose Polymerase Inhibition Modulates Skeletal Muscle Injury Following Ischemia Reperfusion

HYPOTHESIS Polyadenosine diphosphate–ribose polymerase (PARP) has been implicated as a mediator of inflammation and tissue necrosis in murine models of human stroke and myocardial infarction. This study was designed to determine whether PARP modulates skeletal muscle injury and cytokine-growth factor levels during ischemia-reperfusion. DESIGN Prospective controlled animal study. SETTING Medical school–affiliated university hospital. INTERVENTIONS Mice were divided into 2 groups—treated (PJ) and untreated; all mice were subjected to unilateral hind limb tourniquet ischemia followed by 4 or 48 hours of reperfusion. In treated mice, PJ34, an ultrapotent-specific PARP inhibitor was given immediately before ischemia and prior to reperfusion. A group of PARP-1 knockout mice (PARP−/−) were also subjected to hind limb ischemia followed by 48 hours of reperfusion. MAIN OUTCOME MEASURES After ischemia-reperfusion, muscle was harvested for measurement of edema, viability, cytokine, and vascular endothelial growth factor content. RESULTS The PJ34-treated mice had increased skeletal muscle viability when compared with the untreated mice after 4 and 48 hours of reperfusion (P.05), and it exceeded that of untreated mice (P