title: C1 esterase inhibitor ameliorates ischemia reperfusion injury in a swine musculocutaneous flap model.
abstract: OBJECTIVE
  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.
  
  
  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 × 103U/L vs. 1,586 ± 767 U/L [P = 0.04] and 429 × 103± 214 × 103U/L vs. 213 × 103± 156 × 103U/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.
authors.affiliation: United States Army Institute of Surgical Research, Fort Sam Houston, TX.
authors.forename: C Anton
authors.initials: CA
authors.lastname: Fries
authors.affiliation: Department of Surgery, University of Texas Health Science Center at San Antonio, San Antonio, TX.
authors.forename: Carole Y
authors.initials: CY
authors.lastname: Villamaria
authors.affiliation: MDW/Science and Technology, 59, Joint Base, San Antonio, TX.
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Spencer
authors.affiliation: United States Army Institute of Surgical Research, Fort Sam Houston, TX.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Rasmussen
authors.affiliation: United States Army Institute of Surgical Research, Fort Sam Houston, TX.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Davis
mesh_terms: D000818:Animals; D050718:Complement C1 Inhibitor Protein / Q000627:therapeutic use*; D051056:Complement Inactivating Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D064827:Myocutaneous Flap / Q000098:blood supply*; D015427:Reperfusion Injury / Q000188:drug therapy*; D013552:Swine
chemical_list: D050718:Complement C1 Inhibitor Protein; D051056:Complement Inactivating Agents