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.


METHODS
Prospective, randomized, placebo-controlled therapeutic trial.


METHODS
Adult male Sprague-Dawley rats.


METHODS
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.
Mobley
Steven Ross
SR
Divisions of Facial Plastic and Reconstructive Surgery, Department of Otolaryngology, University of Miami School of Medicine, Miami, FL, USA
Glassberg
Marilyn K
MK
Luebke
Anne
A
Perlyn
Chad A
CA
Davis
Richard E
RE
D000287:Administration, Topical; D000818:Animals; D019332:Endothelin-1 / Q000096:biosynthesis*; D008297:Male; D023421:Models, Animal; D009336:Necrosis; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology*; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D013524:Surgical Flaps / Q000098:blood supply* / Q000502:physiology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D019332:Endothelin-1; D014665:Vasodilator Agents; D009543:Nifedipine