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  • Title: Effect of tadalafil on reduction of necrosis in the ischemic zone in a rat comb burn model.
    Author: Singer AJ, Towery H, McClain SA.
    Journal: Burns; 2018 Sep; 44(6):1427-1432. PubMed ID: 29895403.
    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 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.
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