The purpose of this study was to evaluate the blockage of polymorphonuclear neutrophil endothelial adhesion by using a monoclonal antibody to the intercellular adhesion molecule 1 (ICAM-1) ligand to prevent ischemiareperfusion injury in rat skin flaps. A skin and subcutaneous tissue flap (3.0 cm × 4.5 cm) supplied by the superficial epigastric artery and vein including the femoral vessels was isolated unilaterally in 45 male SpragueDawley rats and clamped for 9 hours (groups II and III) or 12 hours (groups IV and V) of ischemia. Five animals in group I were sham-operated only with 5 minutes of ischemia. Animals in groups II (n = 10) and IV (n = 10) received 0.05 mg of monoclonal antibody to ICAM-1 (0.20 mg/kg) in 0.5 ml of 0.9% normal saline intravenously 15 minutes before reperfusion; those in groups III (n = 10) and V (n = 10) received 0.5 ml of normal saline. The flaps were assessed histologically, by measuring viable and nonviable areas, and by diffuse reflectance spectroscopy to determine the ratio of oxyhemoglobin to deoxyhemoglobin. Flap measurements revealed that the average area of flap survival was 90.6 ± 12.8 percent in group II and 18.3 ± 19.6 percent in the control group (III) (p< 0.002). In the animals subjected to 12 hours of ischemia, those treated with monoclonal antibody to ICAM-1 (group IV) were 57.1 ± 23.1 percent viable, which was significantly greater than the control animals (group V), in which only 0.3 ± 1.0 percent of the flap was viable. Analysis of the diffuse reflectance spectra showed a hyperemic response during the first 10 minutes after reperfusion in animals treated with monoclonal antibody to ICAM-1. In group III, however, the spectra demonstrated a decreased amount of oxyhemoglobin, indicating decreased reperfusion of the flap after ischemia when compared with group II. Histopathologically, few inflammatory changes could be observed in groups I, II, and the viable areas of group IV. Marked damage was observed in groups III and V. We concluded that treating ischemic skin flaps with monoclonal antibody to ICAM-1 was effective for alleviating reperfusion injury after 9 or 12 hours of warm ischemia. The reactive hyperemic response determined by diffuse reflectance spectroscopy in groups II and IV correlated with areas of flap survival. Antibodies to particular adhesion molecules, such as ICAM-1, have potential clinical utility in that they could be administered, individually or together, to patients immediately before reestablishing perfusion after free-tissue transfer or replantation to block the adverse effects attributed to reperfusion injury. (Plast. Reconstr. Surg. 101: 1586, 1998).
From the Division of Plastic Surgery, Department of Surgery, Wellman Laboratories of Photomedicine, Department of Dermatology, Massachusetts General Hospital, and Harvard Medical School. Received for publication February 11, 1997; revised June 13, 1997.
Presented at the 40th Annual Meeting of the Plastic Surgery Research Council, in New York, New York, May 17 to 20, 1995, and at the 50th American Society for Surgery of the Hand, in San Francisco, California, September 13 to 16, 1995 (Winner of the Sumner L. Koch Award).
W. P. Andrew Lee, M.D.
Division of Plastic Surgery
Massachusetts General Hospital, WACC 453
55 Fruit Street
Boston, Mass. 02114