Sildenafil for Attenuating Hepatic Ischemia-Reperfusion Injury and Promoting Liver Regeneration After Major (65%) Hepatectomy: A Porcine Pilot Study
Abstract
Introduction Hepatic ischemia-reperfusion (I/R) injury is a major driver of post-hepatectomy liver failure (PHLF) and contributes to morbidity after major liver resection. Sildenafil, a selective phosphodiesterase-5 (PDE-5) inhibitor, has shown protective effects against I/R injury in cardiac, renal, and rodent hepatic models, but pre-clinical data in large animals undergoing major hepatectomy are scarce. The aim of this study is to evaluate whether perioperative oral sildenafil attenuates I/R injury and enhances liver regeneration after 65% hepatectomy combined with 45 minutes of warm ischemia in a porcine model. Methods Fourteen male domestic pigs (28-39 kg) were randomly allocated to two groups of seven. Animals in the control group (Group A) underwent 65% hepatectomy with 45 minutes of continuous portal triad clamping (Pringle maneuver). Animals in the sildenafil group (Group B) underwent the same operation but additionally received oral sildenafil 0.3 mg/kg every eight hours, beginning 24 hours before surgery and continuing for seven postoperative days. Hemodynamic parameters, arterial blood gases, liver function tests (including bilirubin and markers of hepatocellular injury (ALT, AST, LDH), prothrombin time (PT), aPTT), and inflammatory markers (tumor necrosis factor-α (TNF-α), IL-1, IL-6, malondialdehyde (MDA), C-reactive protein) were measured at predefined time points up to 24 hours from reperfusion and on postoperative day 7. Histopathology and…
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