C1 esterase inhibitor ameliorates ischemia reperfusion injury in a swine musculocutaneous flap model

Purpose Free tissue transfer is a powerful reconstructive surgical technique. The ischemia reperfusion injury (IRI) at revascularization affects the flap and the patient; reducing this insult could improve outcomes. This study evaluated the effect of C1 esterase inhibitor (C1‐inh) on IRI in a porcine musculocutaneous flap model. Materials and methods A musculocutaneous flap was transferred from the limb to the neck of 12 swine. Flaps underwent a 3‐hour ischemic interval prior to revascularization. Intervention group flaps (n = 6) were perfused intra‐arterially with 100U C1‐inh at the commencement of the ischemic period; controls (n = 6) received heparinized saline solution. Protocol duration was 14 days; markers of reperfusion injury (creatine kinase [CK], aspartate transaminase [AST], tumor necrosis factor‐alpha) were evaluated. Results All flaps from the intervention group were viable at 14 days; five of six control flaps were viable at 14 days (P = 1). Systemic levels of biomarkers of tissue necrosis and inflammation were reduced in the intervention group. On post‐operative day one, statistically significant reductions in mean levels of AST and CK were demonstrated (2,293 ± 1 × 103 U/L vs. 1,586 ± 767 U/L [P = 0.04] and 429 × 103 ± 214 × 103 U/L vs. 213 × 103 ± 156 × 103 U/L [P = 0.002], respectively). Flaps of both groups healed in their recipient locations, no adverse reactions were observed. Conclusions C1‐inh is protective of IRI and may have utility in free tissue transfer, vascularized composite allotransplantation, and spare parts surgery. © 2016 Crown copyright. Microsurgery © 2016 Wiley Periodicals, Inc. Microsurgery 37:142–147, 2017.