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Protective Effect of Ischemic Preconditioning against Liver Injury after Major Hepatectomy Using the Intermittent Pringle Maneuver in Swine

Objective: To investigate whether ischemic preconditioning (IP) protects the liver against ischemia-reperfusion injury (I/R-I) after major hepatectomy through intermittent hepatic pedicle clamping (IC) in a swine liver resection model. Background: Although many studies have reported a protective effect of IP against continuous hepatic ischemia, it has not been elucidated whether IP protects the liver against I/R-I after hepatectomy using IC. This is the first study to evaluate the effect of IP in a swine major hepatectomy model using IC. Methods: Pigs (n = 12) were divided into 2 groups (IP or non-IP). In the IP group, livers were subjected to IP (10 min ischemia and 10 min reperfusion) before liver resection using IC (15 min ischemia and 5 min reperfusion). A left hemihepatectomy was then performed using IC in both groups. Hemodynamic changes and plasma concentrations of aspartate aminotransferase, lactate dehydrogenase, lactic acid and hyaluronic acid were measured at 60, 120 and 180 min after hepatectomy. Apoptosis (TUNEL staining and electron microscopy), plasma tumor necrosis factor-α (TNF-α) and NO2–/NO3– were evaluated for 180 min after hepatectomy. Results: There were no significant differences in body weight, blood loss, resected liver weight, Pringle time or hemodynamic changes between the 2 groups. IP significantly reduced plasma aspartate aminotransferase levels for 180 min after hepatectomy (IP: 135.8 ± 13.5 vs. non-IP: 199 ± 16.8 IU/l; p = 0.018). In the non-IP group, apoptotic changes in sinusoidal endothelial cells were observed with increased plasma TNF-α levels. IP protected liver injury from increase in plasma TNF-α (p = 0.042). Significantly fewer apoptotic cells were seen in the IP than in the non-IP group (p = 0.002). Plasma levels of lactate dehydrogenase, lactic acid and NO2–/NO3– in the IP group tended to be lower than those in the non-IP group. Conclusions: IP prior to hepatectomy with IC resulted in less hepatic injury and apoptotic cell death than in livers not subjected to IP. IP with IC has the potential to improve the clinical postoperative course of patients undergoing hepatectomy.