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Expression of Endothelin 1 in Rat Random-Pattern Skin Flaps Treated With Topical Nifedipine
Steven Ross Mobley, MD;
Marilyn K. Glassberg, MD;
Anne Luebke, PhD;
Chad A. Perlyn, MD;
Richard E. Davis, MD
Arch Facial Plast Surg. 2003;5:78-82.
Objective To evaluate the relative tissue concentrations of the endogenous vasoactive peptide endothelin 1 (ET-1) in random-pattern skin flaps (RPSF) treated with either topical anti-ischemic drug therapy (nifedipine) or placebo.
Design Prospective, randomized, placebo-controlled therapeutic trial.
Subjects Adult male Sprague-Dawley rats.
Intervention Experimental subjects underwent caudally based RPSFs using the modified McFarlane technique. Subjects received either topical anti-ischemic drug therapy (nifedipine; n = 6) or inert carrier ointment (placebo; n = 6). Treatment was initiated immediately following flap closure and continued every 6 hours for 5 days. At the end of the treatment period, the animals were killed and the concentration of ET-1 was determined using enzyme-linked immunosorbent assay. Representative tissues from nifedipine- and placebo-treated skin flaps were also analyzed for ET-1 using immunohistochemical stains.
Results The ET-1 levels in the distal (necrotic) flap segments were increased by 4.53 pg/mL over baseline (nonnecrotic) flaps in the placebo-treated animals and decreased by 4.70 pg/mL below baseline in the nifedipine-treated group (P = .03).
Conclusions The correlation between tissue levels of ET-1 and the severity of tissue necrosis suggests that ET-1 may play a pivotal role in ischemic injury of RPSFs. Moreover, treatment with topical nifedipine may antagonize the vasoconstrictive effects of ET-1. Although immunohistochemical analysis revealed ET-1 staining within the flap microvasculature, no quantitative differences were detected between the nifedipine- and placebo-treated flaps. Further studies are needed to define the role of ET-1 in RPSF necrosis.
From the Divisions of Facial Plastic and Reconstructive Surgery, Department of Otolaryngology (Drs Mobley, Luebke, Perlyn, and Davis) and Pulmonary and Critical Care Medicine, Vascular Biology Institute, Department of Medicine (Dr Glassberg), University of Miami School of Medicine, Miami, Fla.
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