Role of granulocyte elastase in ischemia/reperfusion injury of rat liver

Shigeki Kushimoto, Kenji Okajima, Mitsuhiro Uchiba, Kazunori Murakami, Naoaki Harada, Hiroaki Okabe, Kiyoshi Takatsuki

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)


Objective: To investigate the role of granulocyte elastase in ischemia/reperfusion injury of liver, the effect of ONO-5046, a granulocyte elastase inhibitor, was examined in ischemia/reperfusion-induced liver injury in rats. Design: Prospective, randomized, controlled study. Setting: Research laboratory at a university medical center. Subjects: Male Wistar rats, weighing 220 to 280 g. Interventions: Animals receiving continuous intravenous infusion of ONO-5046 (50 mg/kg/hr) were subjected to hepatic ischemia/reperfusion. Hepatic damage was evaluated by effects on bile formation capacity, plasma clearance of indocyanine green, and serum aminotransferase concentrations after ischemia/reperfusion. Measurements and Main Results: Hepatic dysfunction, observed after 60 mins of ischemia/reperfusion, led to a reduction in bile flow and to a decrease in the plasma clearance of indocyanine green. These indicators of hepatic dysfunction were prevented, to a large extent, by administration of ONO- 5046. Serum concentrations of aminotransferases increased after hepatic ischemia/reperfusion, peaking at 12 hrs of reperfusion. Increases in serum concentrations of aminotransferases were significantly inhibited by ONO- 5046. Conclusion: Granulocyte elastase derived from activated leukocytes may play a critical role in hepatic dysfunction and the subsequent hepatic injury induced by ischemia/reperfusion.

Original languageEnglish
Pages (from-to)1908-1912
Number of pages5
JournalCritical Care Medicine
Issue number11
Publication statusPublished - 1996 Nov


  • critical illness
  • granulocyte elastase
  • hepatic ischemia
  • indocyanine green
  • ischemia/reperfusion
  • liver
  • neutrophil
  • reperfusion injury


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