Effect of tadalafil on reduction of necrosis in the ischemic zone in a rat comb burn model
Abstract
OBJECTIVES
A major goal of burn management is to reduce the progression of necrosis in the zone of ischemia surrounding the central zone of necrosis. A rat comb burn model is often used to assess the progression of necrosis in the zone of ischemia. We compared various combinations of naproxen [NPX], N-acetyl cysteine [NAC], and tadalafil [TD] (a phosphodiesterase-5 inhibitor used as a vasodilator to treat erectile dysfunction) in a rat comb burn model to determine their effects on injury progression.
METHODS
We created two comb burns on the backs of 40 anesthetized Sprague-Dawley rats using a brass comb with four rectangular prongs preheated in boiling water and applied for 30s, resulting in four rectangular 10×20mm full-thickness burns separated by three 5×20mm unburned interspaces, representing the ischemic zones. We randomized five animals each to daily oral gavage with TD (1mg/kg), NPX (10mg/kg), NAC (500mg/kg), NAC+NPX, TD+NPX, TD+NAC, TD+NPX+NAC, or normal saline [NS]. Wounds were observed daily for gross evidence of necrosis in the unburned interspaces and full-thickness biopsies from the interspaces were evaluated with Hematoxylin & Eosin seven days after injury for histological evidence of necrosis.
RESULTS
The percentages of interspaces with histological evidence of necrosis at day seven were TD-40%, NPX-93%, NAC-97%, NS-87%, TD+NPX-50%, TD+NAC-40%, TD+NPX+NAC-33%, and NPX+NAC-60% (P<0.001). Repeated measures ANOVA demonstrated reduced gross percentage of…
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