A Protective Effect of Sivelestat From Ischemia/Reperfusion Injury in a Porcine Hepatectomy Model

Abstract

Summary of background data: Sivelestat sodium hydrate (Sive), a neutrophil elastase inhibitor, has been approved as a worldwide therapeutic drug for acute lung injury associated with systemic inflammatory response syndrome. Yet how Sive influences hepatic ischemic reperfusion (I/R) injury and liver regeneration has not been clarified. Objective: We investigated the effect of Sive against hepatic I/R injury and liver regeneration using porcine hepatectomy model, and found that Sive contributes significantly in increasing the liver volume. Methods: We induced 1-hour ischemia by occluding the vessels and the bile duct of the right and median lobes. About 40% left hepatectomy was performed after reperfusion. A total of 6 animals received Sive (10 mg/kg/h) intravenously and 6 control animals received physiologic saline (10 mg/kg/h) from commencement of laparotomy. Remnant liver volume, hemodynamics, and liver function test were compared between the groups. Expressions of TRL4 mRNA in hepatic tissues were examined using RT-PCR. Apoptosis and cell proliferation were demonstrated by TUNEL staining. Results: AST, LDH, and LA levels at 5 minutes after reperfusion were significantly lower in Sive group than in the control group. Sive significantly increased the liver volume, yet did not have any effect for liver regeneration. Conclusion: Sive is considered to reduce hepatic injury in the early phase of I/R injury.