Effect of tadalafil on reduction of necrosis in the ischemic zone in a rat comb burn model

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 30 s, resulting in four rectangular 10 × 20 mm full-thickness burns separated by three 5 × 20 mm unburned interspaces, representing the ischemic zones. We randomized five animals each to daily oral gavage with TD (1 mg/kg), NPX (10 mg/kg), NAC (500 mg/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 interspace area undergoing necrosis in all groups that included TD, compared with all groups not including TD (P < 0.001). There were no differences among the various treatments within the groups that did or did not include TD. Conclusions: Daily oral therapy with tadalafil reduces necrosis in the unburned interspaces compared with naproxen, NAC, or their combination in a rat comb burn model. Addition of naproxen or NAC to tadalafil does not further reduce injury progression.