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Improved Survival of Murine Island Skin Flaps by Prevention of Reperfusion Injury

Tatlidede, Soner H. M.D.; Murphy, Adrian D. M.B., M.R.C.S.I.; McCormack, Michael C. B.S.; Nguyen, John T. M.D.; Eberlin, Kyle R. M.D.; Randolph, Mark A. M.A.S.; Moore, Francis D. Jr M.D.; Austen, William G. Jr M.D.

Plastic & Reconstructive Surgery:
doi: 10.1097/PRS.0b013e3181a071e8
Experimental: Original Articles
Abstract

Background: Studies have demonstrated that blocking a single specificity of self-reactive immunoglobulin M with a 12–amino acid peptide mimic of the antigen of immunoglobulin M can attenuate murine intestinal and skeletal muscle injury following ischemia and reperfusion. The aim of this study was to ascertain whether peptide (P8) had protective effects in an axial island skin flap model, where tissue loss is attributed to ischemia-reperfusion injury.

Methods: Dorsal lateral thoracic artery island skin flaps (3.5 × 1.5 cm) were elevated in 82 male C57BL/6 mice and rendered ischemic for 10 hours by placing a 7-mm microclamp on the vascular pedicle followed by 7 days of reperfusion. Group I (n = 7), the sham group, had no clamp placed. Group II (n = 21) had clamp placement but no other treatment. Thirty minutes before clamp placement, group III (n = 18) received 0.25 cc of saline intravenously, group IV (n = 18) received 25 μg/0.25 cc P8 peptide, and group V (n = 7) received 25 μg/0.25 cc random 12-mer peptide. Animals in group VI (n = 11) underwent two cycles of 20 minutes of ischemic preconditioning before 10 hours of ischemia. After 1 week of reperfusion, percent necrosis was measured and results were compared using analysis of variance and an unpaired t test.

Results: In animals treated with P8 peptide, flap necrosis was 14.61 ± 2.77 percent. This represents a statistically significant, 56 percent reduction in flap necrosis compared with controls (p < 0.001).

Conclusion: These data demonstrate that prevention of ischemia-reperfusion injury with P8 peptide produces a significant reduction in necrosis of treated flaps.

Author Information

Boston, Mass.

From the Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, and Brigham and Women’s Hospital, Harvard Medical School.

Received for publication July 8, 2008; accepted November 14, 2008.

Presented at the 53rd Annual Meeting of the Plastic Surgery Research Council Meeting, in Springfield, Illinois, May 28 through 31, 2008, and at the 49th Annual Meeting of the New England Society of Plastic and Reconstructive Surgeons, in Manchester, Vermont, June 4 through 7, 2008.

Disclosure: Francis D. Moore, Jr., M.D., is a cofounder of DecImmune Therapeutics, which holds the license to develop this P8 technology. He currently acts as a consultant for DecImmune, Inc. None of the other authors has a financial interest in any of the products, devices, or drugs mentioned in this article.

Michael C. McCormack, B.S., 15 Parkman Street, Wellman Building, Room 629, Boston, Mass. 02114, mcmccormack@partners.org

©2009American Society of Plastic Surgeons