Inosine attenuates tourniquet-induced skeletal muscle reperfusion injury

Background. Adenosine attenuates skeletal muscle reperfusion injury, but it s short half-life in vivo limits potential therapeutic benefits. The aim of this study was to ascertain whether inosine, a stable adenosine metabolite , modulates skeletal muscle reperfusion injury. Materials and methods. C57BL/6 mice were randomized (8-10 per group) to six groups: time controls; inosine (100 mg/kg) before anesthesia; 2 h of bilat eral tourniquet hindlimb ischemia; I/R (2 h of bilateral tourniquet hindlim b ischemia, 3 h of reperfusion); inosine (100 mg/kg) before I/R; drug vehic le before I/R. Serum tumor necrosis factor (TN-F)-alpha and macrophage infl ammatory protein (MIP)-2 were measured before ischemia and at the end of re perfusion. Tissue edema was determined by wet/dry weight ratios. Tissue leu cosequestration was assessed by the myeloperoxidase (MPO) content. Results. At the end of reperfusion, inosine pretreatment resulted in lower MPO levels in muscle (P = 0.02) and lung (P = 0.0002) than saline pretreatm ent. Similarly, muscle (P = 0.04) and lung (P = 0.02) wet/dry ratios were s ignificantly reduced with inosine but not with saline pretreatment. At the end of reperfusion, serum proinflammatory cytokine levels (TNF-alpha and MI P-2) were significantly reduced (P < 0.05) compared to preischemia levels f ollowing inosine pretreatment but not saline pretreatment. Ischemia alone d id not alter any of the parameters assessed. Conclusions. These findings demonstrate that pretreatment with inosine atte nuates the local and systemic proinflammatory responses associated with ske letal muscle reperfusion injury. (C) 2001 Academic Press.