The effects of topical nitric oxide on healing of partial thickness porcine burns

Abstract

Background: Nitric oxide is a wound mediator that promotes wound healing. We hypothesized that topical application of nitric oxide would speed reepithelialization, enhance angiogenesis, and reduce scar thickness in a partial thickness porcine burn model.

Methods: While under general anesthesia, 20 partial thickness burns were created on the backs of four female Yorkshire swine using a 2.5cm×2.5cm×7.5cm, 150-g aluminum bar, preheated to 80°C and applied for 20s. The necrotic epidermis was removed and the burns were randomized to low, medium, and high concentrations of a novel nitric-oxide (NO) releasing drug or its ointment vehicle applied 3 times weekly for 28 days. Full thickness punch biopsies were performed at 8, 11, 14 and 28 days after injury to determine percentage wound reepithelialization and scar thickness using H&E staining and blood vessel density using CD31 staining.

Results: At day 11, the percentages (SD) wound reepithelialization were: control, 26.3 (34.6); low NO, 23.9 (36.9); medium NO, 43.3 (42.9); and high NO, 59.9 (43.6); ANOVA, P=0.02. The number of CD31 stained blood vessels at days 8 and 11 were greater in wounds treated with high dose NO vs. controls (48.1 vs. 22.9 [P<0.001] and 44.0 vs. 33.5 [P=0.05] per 1mm² respectively). Scar thicknesses (SD) in mm at day 28 by treatment allocation were: control, 4.8 (1.2); low NO, 4.7 (1.2); medium NO, 4.3 (1.2); and high NO, 4.1 (1.0); P=0.22.

Conclusions: Treatment of partial thickness porcine burns with high concentrations of topical NO resulted in earlier reepithelization and increased angiogenesis but not reduced scar thickness compared with its control vehicle in a partial thickness porcine burn model.

Keywords: Angiogenesis; Healing; Nitric-oxide; Partial thickness burns; Porcine model; Reepithelialization; Scar thickness.