title: Remnant liver injury after hepatectomy with the pringle maneuver and its inhibition by an iNOS inhibitor (ONO-1714) in a pig model.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Hokkaido, Japan. kukita@sapmed.ac.jp
authors.forename: Kazuma
authors.initials: K
authors.lastname: Kukita
authors.forename: Tadashi
authors.initials: T
authors.lastname: Katsuramaki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kikuchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Meguro
authors.forename: Minoru
authors.initials: M
authors.lastname: Nagayama
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kimura
authors.forename: Masato
authors.initials: M
authors.lastname: Isobe
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
mesh_terms: D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006498:Hepatectomy / Q000009:adverse effects* / Q000379:methods; D006574:Heterocyclic Compounds, 2-Ring / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000201:enzymology / Q000473:pathology*; D008102:Liver Circulation; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D013552:Swine; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis
chemical_list: C407360:7-chloro-3-imino-5-methyl-2-azabicyclo(4.1.0)heptane; D000578:Amidines; D004791:Enzyme Inhibitors; D006574:Heterocyclic Compounds, 2-Ring; C002744:3-nitrotyrosine; D014443:Tyrosine; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III