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MEASURES AGAINST HEPATIC FAILURE AFTER LIVER TRANSPLANTATION : BASIC INVESTIGATION ON PRECONDITIONING OF THE DONOR LIVER

Research Project

Project/Area Number 12670466
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionTHE UNIVERSITY OF TOKYO

Principal Investigator

ARAI Masahiro  The UNIV. OF TOKYO, FACULTY OF MEDICINE, INSTRUCTOR, 医学部・附属病院, 助手 (60271566)

Co-Investigator(Kenkyū-buntansha) IKEDA Hitoshi  The UNIV. OF TOKYO, FACULTY OF MEDICINE, INSTRUCTOR, 医学部・附属病院, 助手 (80202422)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥2,700,000 (Direct Cost: ¥2,700,000)
KeywordsLIVER TRASNPLANTATION / ISCHEMIA REPERFUSION / KUPFFER CELLS / SUPEROXIDE / ADENOSINE / ISCHEMIC PRECONDITIONING / 活性酵素
Research Abstract

When liver is stored and transplanted, sinusoidal endothelial cell injury and activation of Kupffer cells appeared in the early phase of reperfusion, leading to massive hepatic necrosis via microcirculatory disturbance. A brief period of ischemia and reperfusion render tissues resistant against prolonged ischemia, a phenomenon called ischemic preconditioning. We previously reported that ischemic preconditioning decreases sinusoidal endothelial cell injury and Kupffer cell activation, and as the result, improves recipient survival after liver transplantation.In the supported period by the grant, we revealed that l) ischemic preconditioning decreases superoxide production after storage/reperfusion, 2) this effect is reversed by pretreatment with adenosine Al receptor antagonist and 3) liver perfusion with adenosine Al agonist decreases superoxide production after storage/reperfusion like ischemic preconditioning. It is concluded that adenosine released during preconditioning ischemia decreases superoxide production by Kupffer cells after storage/reperfusion via Al receptor pathway. We are at present investigating whether adenosine directly affects Kupffer cells or not using in vitro model.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Arai M.: "Ischemic preconditioning decreases superoxide production in Kupffer cells after storage/reperfusion via an adeneside A1 receptor pathway"Hepatology. 32. 249A (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Arai M.: "Contribution of adeuosiue Az receptors and cyclic adeuosiue wsuophosphate to protective ischemic preconditiconing of siuusoidal endotuelial cells agaiust stsrage/reperfusion injury in rat livers"Hepatology. 32. 297-302 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Arai M.: "Ischemic preconditioning of rat lcrors against cold srorage-reperfucion injury : role of non paramedical cells and the phaeton of heterolo legenes precaiditiaring"Liver Transplantation. 7. 292-299 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Arai M, Thurman RG, and Lemasters JJ.: "Contribution of adenosine A_2 receptors and cyclic adenosine monophosphate to protective ischemic preconditioning of sinusoidal endothelial cells against storage/reperfusion injury in rat livers"Hepatology. 32. 297-302 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Arai M, Tejima K, Ikeda H, Tomiya T, Yanase M, Inoue Y, Nagashima K, Lemasters JJ, and Fujiwara K.: "Ischemic preconditioning decreases superoxide production in Kupffer cells after storage/reperfusion via an adenosine Al receptor pathway"Hepatology. 32. 297-302 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Arai M, Thurman RG, and Lemasters JJ.: "Ischemic preconditioning of rat livers against cold storage-reperfusion injury : role of nonparenchymal cells and the phenomenon of heterologous preconditioning"Liver Transpl. 7. 292-9 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Arai M: "Contribution of adenosine A_2 receptors and cyclic adenosine monophosphate to protective ischemic preconditioning of sinusoidal endothelial cells against storage/reperfusion injury in rat livers"Hepatology. Vol32. No2. 297-302 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Arai M: "Ischemic preconditioning of rat livers against cold storage-reperfusion injury : role of nonparenchymal cells and the phenomenon of heterologous preconditioning"Liver Transplantation. Vol7, No4. 292-299 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 新井雅裕: "Ischemic preconditioning decreases superoxide production in Kupffer cells after storage/reperfusion via an adenosine A1 receptor pathway."Hepatology. Vol32,No4. 249A (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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