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Studies on the mechanism and treatment of ischemia-reperfusion injury of the liver

Research Project

Project/Area Number 02454317
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionShimane Medical University

Principal Investigator

NAGASUE Naofumi  Assoc. Prof., Surgery II, 医学部, 助教授 (40117198)

Co-Investigator(Kenkyū-buntansha) HAYASHI Takafumi  Assistant, Surgery II, 医学部, 助手 (80243426)
TANIURA Hiroyuki  Assistant, Surgery II, 医学部, 助手 (80171833)
CHANG Yu-chung  Assistant, Surgery II, 医学部, 助手 (20188501)
KOHNO Hitoshi  Lecturer, Surgery II, 医学部, 講師 (60145951)
Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1991: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1990: ¥5,100,000 (Direct Cost: ¥5,100,000)
Keywordsliver / transplantation / ischemia-reperfusion / superoxide / calcium / mitochondria / lysosome / cyclosporine / 肝 / 阻血再潅流障害 / ライソゾーム酵素 / クッパー細胞 / 活性酸素 / FK506 / サイクロスポリンA / 肝移植 / 肝阻血 / 再潅流障害 / カルシウムイオン / FKー506 / ケトン体比
Research Abstract

Ischemia and reperfusion of the liver are innevitable processes in hepatic transplantation. How are various types of hepatic injury produced by ischemia deteriorate or ameliorate by reperfusion ? This question was studied in terms of intrahepatic calcium level, oxgen derived free radicals and mitochondrial function. In addition, the effects of cyclosporin A and FK506 and Verapamil were investigated in terms of these parameters. The following results were obtained by this study.
(1) Changes in tissue calcium during ischemia and reperfusion of the liver Ca^<2+> in the liver did not change during ischemia but was immediately elevated after reperfusion. The elevated Ca^<2+> was soon expelled from the liver when the ischemic time was short. Upon prolonged ischemia, hepatic Ca^<2+> was reelevated, which was related to the extent of tissue injury and animal death. The release of superoxide did not play a major role in the changes of Ca^<2+> level.
(2) Role of the Kupffer cell in ischemia-reperf … More usion injury of the liver More severe tissue injury was found after ischemia-reperfusion when Kupffer cells were preliminarily activated by zymosan. TNF alpha and beta were not involved in the process, but increased production of superoxide seemed to play an important role.
(3) Plasma activities of lysosomal enzymes in porcine liver transplantation After liver grafting in pigs, plasma activities of beta-galactosidase, beta-glucosidase and beta-glucuronidase increased with their peaks at 3 hours, which returned to normal within 2 to 3 days. These changes reflected the severity of liver injury well.
(4) Effects of cyclosporin A and FK506 on ischemia-reperfusion injury of the liver Pretreatment with these two drugs showed a protective effect on ischemia-reperfusion injury of the canine and porcine livers. The effect seemed to be mediated through lysosomal stabilization and protection of mitochondrial morphology and function.
(5) Effect of Verapamil on prolonged liver ischemia and reperfusion Despite numerous works reporting the beneficial effect of Verapamil on liver ischemia, this drug was not effective on 180 minute warm ischemia, showing that the effect of Verapamil differs according to the ischemic time. Less

Report

(4 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Hayashi T: "Beneficial effect of cyclosporine pretreatment in canine liver ischemia:Enzymatic and electronmicroscopic studies." Transplantation. 52. 116-121 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yamanoi A: "Attenuation of ischemia-reperfusion injury of the liver in dogs by cyclosporine:A comparative study with allopurinol and methylprednisolone." Transplantation. 52. 27-30 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yamanoi A: "Failure of pretreatment with cyclosporine to reduce ischemic liver injury after hepatic artery ligation." Transplantatin. 52. 569-570 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tsai-Chang CW: "Plasma lysosomal enzymes after liver transplantation in the pig." Enzyme. 45. 145-154 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kimoto T: "Influence of hepatic macrophage activation by zymosan in ischemia-reperfusion injury of the liver." Surgical Research Communications. 13. 45-57 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kumar DD: "The salutary effect of FK506 in ischemia-reperfusion injury of the canine liver." Transplantation. 54. 583-588 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hayashi T: "Beneficial effect of cyclosporine in canine liver ischemia: Enzymatic and electron-microscopic studies." Transplantation. 52. 116-121 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yamanoi: "Attenuation of ischemia-reperfusion injury of the liver in dogs by cyclosporine: A comparative study with allopurinol and methylprednisolone." Transplantation. 52. 27-30 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yamanoi A: "Failure of pretreatment with cyclosporine to reduce ischemia liver injury after hepatic artery ligation in pigs." Transplantation. 52. 569-570 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tsai-Chang CW: "Plasma lysosomal enzymes after liver transplantation in the pig." Enzyme. 45. 145-154 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kimoto T: "Influence of hepatic macrophage activation by zymosan in ischemia-reperfusion injury of the liver." Surgical Research Communications. 13. 45-57 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kumar DD: "The salutary effect of FK506 in ischemia-reperfusion injury of the canine liver." Transplantation. 54. 583-588 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Uchida M: "Calcium in pig livers following ischemia and reperfusion." Journal of Hepatology.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kumar DD: "FK506 pretreatment effectively prevents the ischemic injury of the dearterialized canine liver." Transplantation.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Uchida M: "Effect of verapamil on hepatic reperfusion injury after prolonged ischemia in pigs." Transplantation.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Takemoto Y: "Change in calcium content of the liver during hepatic ischemia-reperfusion in dogs." Transplantation.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yamanoi A: "Beneficial effect of donor pretreatment with cyclosporine in porcine liver transplantation." Surgical Research Communications.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tsai-Chang CW: "Plasma Lysosomal enzymes after liver transplantation in the pig" Enzyme. 45. 145-154 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kimoto T: "Influence of hepatic macrophage activation by zymosan in ischemia-reperfusion injury of the liver" Surgical Research Communications. 13. 45-57 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kumar DD: "The salutary effect of FK507 in ischemia-reperfusion injury of the canine liver" Transplantation. 54. 583-588 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Uchida M: "Calcium in pig livers following ischemia and reperfusion" Journal of Hepatology.

    • Related Report
      1992 Annual Research Report
  • [Publications] Yamanoi A: "Beneficial effect of donor pretreatment with cyclosporine in porcine liver transplantation" Surgical Research Communications.

    • Related Report
      1992 Annual Research Report
  • [Publications] Hayashi T: "Beneficial effect of cyclosporin pretreatment in canine liver ischemia." Transplantation. 52. 116-121 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Yamanoi A: "Attenuation of ischemiaーreperfusion injury of the liver in dogs by cyclosporine:A comparative study with allopurinol and methylprednisolone." Transplantation. 52. 27-30 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Yamanoi A: "Failure of pretreatment with cyclosporine to reduce ischemic liver injury after hepatic artery ligation in pigs." Transplantation. 52. 569-570 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Dahr DK: "Salutary effect of FK506 in ischemiaーreperfusion injury of the canine liver." Transplantation.

    • Related Report
      1991 Annual Research Report
  • [Publications] Kimoto T: "Influence of hepatic macrophage activation by zymosan in ischemiaーreperfusion injury of the liver." Surgical Research Communications.

    • Related Report
      1991 Annual Research Report
  • [Publications] Uchida M: "Hepatic tissue Calcium concentration as a useful parameter of ischemiaーreperfusion injury of the liver." Surgery.

    • Related Report
      1991 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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