title: Effect of active site-inactivated factor VIIa on ischaemia/reperfusion injury in a porcine flap model.
abstract: In free flap surgery, restored blood flow following a lengthy ischaemic period may lead to necrosis as a result of ischaemia/reperfusion (IR) injury. This injury comprises both proinflammatory and prothrombotic events, where the tissue factor/factor VIIa complex probably has a key role. Active site-inactivated factor VIIa (FFR-rFVIIa) exerts an antithrombotic effect by binding to tissue factor without initiating coagulation. In this study we have evaluated the potential protective effects of FFR-rFVIIa in IR injury. Bilateral musculocutaneous latissimus dorsi flaps in 16 pigs were made ischaemic for eight hours, then given 1 mg/kg/flap of FFR-rFVIIa or vehicle intra-arterially, and reperfused for 10 hours. The viable:necrotic tissue ratio, and accumulation of radiolabelled leucocytes, fibrinogen, and platelets were measured. There was no effect on tissue survival, but radiolabelled components in viable tissue were increased, though not significantly so. We conclude that FFR-rFVIIa did not prevent IR injury, indicating that tissue factor-mediated coagulation is not an important determinant of IR injury in this setting.
authors.affiliation: Department of Plastic and Reconstructive Surgery, University Hospital, Malmö, Sweden. t@soderstrom.nu
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Söderström
authors.forename: Lene
authors.initials: L
authors.lastname: Birk-Sørensen
authors.forename: Henrik
authors.initials: H
authors.lastname: Holst-Jensen
authors.forename: Ulla
authors.initials: U
authors.lastname: Hedner
authors.forename: Björn
authors.initials: B
authors.lastname: Arnljots
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D015942:Factor VIIa / Q000627:therapeutic use*; D005260:Female; D009336:Necrosis; D011994:Recombinant Proteins / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D013524:Surgical Flaps / Q000098:blood supply* / Q000473:pathology; D013552:Swine
chemical_list: D011994:Recombinant Proteins; D015942:Factor VIIa