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.