Expression of endothelin 1 in rat random-pattern skin flaps treated with topical nifedipine

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 nifedipinetreated 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.