APROTININ IN ISCHEMIA-REPERFUSION INJURY - FLAP SURVIVAL AND NEUTROPHIL RESPONSE IN A RAT SKIN FLAP MODEL

Multiple drugs have been used in experimental skin flap models to redu ce the effects of reperfusion ischemia. The effects of antiproteases, however, have not been studied. A skin flap ischemia reperfusion model was developed in the rat to study the effects that aprotinin, a broad -spectrum antiserine protease, would have on skin flap viability. Thir ty-two male rats underwent elevation of a ventral pedicled skin flap b ased on the superficial inferior epigastric artery. The flaps were sub jected to 10 hr of warm ischemia by clamping the neurovascular pedicle followed by reperfusion. Aprotinin or saline (control) was administer ed systemically via the contralateral femoral vein either before or af ter the ischemic insult. Full-thickness skin biopsies were obtained at 1, 8, and 24 hr into reperfusion. Biopsies were evaluated for neutrop hil concentration (using a myeloperoxidase [MPO] assay) and thromboxan e B-2 [TxB(2)] content. Flap survival was calculated at 1 week using s tandardized photography and computer-assisted digital imaging. Aprotin in given before an ischemic insult significantly improved flap surviva l compared to saline controls (52.3% alive vs. 29.6%, P = 0.0132, unpa ired t-test). Aprotinin given after ischemia did not significantly inf luence flap survival (28.8% vs. 34.4% in saline controls, P = 0.708). MPO levels in the aprotinin preischemia treatment group were significa ntly less at 1 and 8 hr into reperfusion, indicating decreased neutrop hil numbers. No statistical difference in TxB(2) levels was noted in e ither group at any time after reperfusion. Aprotinin significantly imp roves skin flap survival when given prior to but not after an ischemic insult. Aprotinin appears to lower the concentration of neutrophils i n skin flaps pretreated with the drug. Reperfused skin flap levels of thromboxane B-2 are unaffected by the pre- or postischemic administrat ion of aprotinin, (C) 1998 Wiley-Liss, Inc.