Recombinant human manganese superoxide dismutase attenuates early but not delayed skeletal muscle dysfunction following reperfusion injury

Objectives: to assess the efficacy of recombinant human manganese superoxid e dismutase (rhMnSOD) in prevention of early and late skeletal muscle ischa emia-reperfusion injury mediated by superoxide (O-2(-)). Design: randomised controlled trial. Materials: seventy-two Sprague-Dawley rats (250-350 g) randomised to receiv e either 7.5 mg/kg of rhMnSOD or saline. Four hours of ischaemia was induce d in the cremaster muscle by dissecting free and clamping its vascular supp ly. Cremaster muscle contractile function was assessed following 90 minutes , 24, 48 hours and one week of reperfusion. Electrophysiological muscle fun ction was assessed using electrical field stimulation in an organ bath syst em. Results: muscle function in the untreated groups following ischaemia reperf usion was significantly reduced at 90 minutes, 24, 48 hours and one week of reperfusion (p<0.05). rhMnSOD significantly protected and maintained norma l muscle function at 24 and 48 hours (p<0.001). However at one week of repe rfusion there was a reduction in function of the treated muscle, such that there was no significant difference between treated and untreated muscle at this point in time. Conclusions: these data demonstrate that skeletal muscle dysfunction after ischaemia reperfusion injury is attenuated at 24 and 48 hrs of reperfusion by the superoxide scavenger rhMnSOD. This protective effect is not maintain ed after seven days of reperfusion.