Remnant Liver Injury after Hepatectomy with the Pringle Maneuver and its Inhibition by an iNOS Inhibitor (ONO-1714) in a Pig Model

Abstract

Although hepatectomy is often performed with the Pringle maneuver, the problem of remnant liver injury is not fully solved. We examined the remnant liver injury of hepatectomy under the Pringle maneuver and its relation to inducible nitric oxide synthase (iNOS) in a pig hepatectomy model. Pigs were subjected to a total of eight Pringle maneuvers followed by re-perfusion. The pigs were divided into the following three groups: Control group; only Pringle maneuver, liver resection (LR) group; hepatectomy under the Pringle maneuver, and ONO group; and hepatectomy under the Pringle maneuver with an iNOS inhibitor (ONO-1714). We investigated the changes in serum aminotransferase (AST), lactate dehydrogenase (LDH), NO(2)(-)+NO(3)(-) (NOx), the hepatic tissue blood flow (HTBF), the cellular distribution of endothelial and inducible nitric oxide synthase, nitrotyrosine, infiltration of neutrophils, and thrombocyte-thrombi by immunohistochemistry. The serum AST, LDH, NOx levels in the LR group were significantly higher than those in the Control group. The formation of iNOS, nitrotyrosine, thrombocyte-thrombi, and infiltration of neutrophils were recognized in the LR group. These findings were inhibited in the ONO group. These results indicate that remnant liver injury appeared after hepatectomy with the Pringle maneuver. iNOS was involved in these injuries and the iNOS inhibitor attenuated the injury.