INTRODUCTION: Ischemia/reperfusion (I/R) injury is a pathologic phenomenon observed in microvascular surgery which results in failure of revascularized tissue despite the presence of a technically well-performed anastomosis. This study examined the role of complement in skeletal muscle I/R injury. Human C1-esterase inhibitor (C1-INH) is a naturally occurring protein that binds to and inhibits the activated C1r/C1s-esterase complex of the complement pathway. A synthetic 13 amino acid peptide with a similar inhibitory effect on the activated C1r/C1s complex was also examined in this study.

METHODS: Eighteen rats weighing 125-150g underwent 3h ischemia and 3h reperfusion of the right extensor digitorum longus (EDL) muscle. An intravenous infusion of C1-INH (100 mg/kg), peptide (5mg/kg), or human serum albumin control (n=6 per group) lasting 10min was started 10min before reperfusion. After 3h reperfusion, the EDL underwent in vitro contractile testing. Contractile forces were normalized to the contralateral untreated, non-ischemic EDL.

RESULTS: There was a significant overall increase in tetanic contractile force of the reperfused EDL in both C1-INH and peptide groups compared to control across stimulation frequencies of 70Hz, 100Hz, and 120Hz (p<.01). Maximum improvement occurred with peptide treatment at 120Hz stimulation, with an increase in force from 38.4±10.9% of normal in controls to 52.4±8.9% of normal in peptide-treated rats (p<.05). There were no significant differences between C1-INH and peptide groups.

DISCUSSION: Our results suggest that inhibition of complement has a beneficial effect on skeletal muscle contractile function in early reperfusion. Treatment with either an endogenous inhibitor (C1-INH) or a synthetic peptide inhibitor yields similar results. Inhibition of complement represents a potential therapeutic approach to preventing I/R injury.