Activated protein C improves ischemic flap survival and modulates proangiogenic and antiinflammatory gene expression.

Abstract Flap necrosis remains a major complication in reconstructive surgery. The authors evaluated whether systemic activated protein C, a natural serum anticoagulant with anti-inflammatory, proangiogenic, and cytoprotective properties, can improve ischemic skin flap survival. Cranially based dorsal cutaneous flaps were elevated on 44 rats. Animals received intravenous injections of activated protein C (25 microg/kg) or saline. Rats were divided into three groups depending on the timing of the first injection: postoperative (45 minutes postoperatively, n = 12), late preoperative (45 minutes preoperatively, n = 5), and early preoperative (3 hours preoperatively, n = 5). In all groups, second and third injections were performed at 3 and 24 hours postoperatively. Flap survival was measured on day 7. Histological and real-time polymerase chain reaction specimens were collected on days 2 and 7 and at 3 and 24 hours, respectively. Postoperative activated protein C improved flap survival (68.9 +/- 4.3 percent) compared with control treatment (39.3 +/- 1.5 percent; p