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ESTABLISHMENT AND EVALUATION OF ANIMAL MODELS TO ELUCIDATE THE PATHOPHYSIOLOGY OF MULTIPLE ORGAN DYSFUNCTION SYNDROME

Research Project

Project/Area Number 11671526
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionTohoku University (2001)
Nippon Medical School (1999-2000)

Principal Investigator

KOIKE Kaoru  Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (10267164)

Co-Investigator(Kenkyū-buntansha) SHINOZAWA Yotaro  Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (30129465)
YAMAMOTO Yasuhiro  Nippon Medical School, Medicine, Professor, 医学部, 教授 (70125079)
辻井 厚子  日本医科大学, 医学部, 助手 (50227401)
Project Period (FY) 1999 – 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: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordsintestine / ischemia / reperfusion injury / phospholipase A2 / rat / mouse / lung injury / liver injury
Research Abstract

[1] We have previously reported that intestinal ischemia-reperfusion (I/R) produced lung injury via a mechanism which involves phospholipase A2 (PLA2) activation. In this study we hypothesized that group IIA PLA2 is the responsible isozyme. Intestinal I/R provoked intestinal leak, liver injury, and lung leak, while tissue PLA2 activity was decreased in the intestine, unchanged in the liver, and increased in the lung. Serum PLA2 activities increased in the portal and systemic circulation during ischemia. Pretreatment with S-5920/LY315920Na eliminated PLA2 activities in all tissues and sera, and only abolished lung leak. Intestinal ischemia-reperfusion appears to produce lung injury via a mechanism which involves group IIA PLA2 activation. Intestinal I/R is likely to promote intestinal and hepatic injury independent of group IIA PLA2.
[2] While various animal models have been used to elucidate what causes multiple organ failure, definite methods to estimate systemic organ damage, especial … More ly endothelial injury, have not well been established in mice. We attempted to establish simple methods that enable us to detect intestinal, pulmonary, and hepatic injury in a murine model of intestinal I/R. Adult female BALB/c mice underwent 45 minutes of superior mesenteric artery occlusion. Two and 6 hours after reperfusion, microvascular permeability and edema formation in the intestine, lung, and liver, were quantitated by Evans blue method (EB) and wet/dry ratio (W/D), respectively. Liver function was also measured by plasma alanine aminotransferase (ALT) and total bilirubin (T-Bil) concentrations. In BALB/c mice, intestinal injury was detected by EB and W/D, and increased pulmonary permeability was measured by EB. Liver injury was quantitated by EB, W/D, and T-Bil. In C57BL/6 mice, intestinal injury was estimated by EB and W/D, lung leak by EB, and liver injury by W/D, ALT, and T-Bil. While slight difference was observed between those two strains of mice, intestinal, pulmonary and hepatic injury could be successfully estimated by the combination of EB, W/D, ALT and T-Bil in a murine model of intestinal I/R. These methods may become useful in mice not only to delineate the mechanisms linking intestinal I/R and remote organ injury but also in other fields of shock research. Less

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report

Research Products

(14 results)

All Other

All Publications (14 results)

  • [Publications] Y.Matsuura, K.Koike et al.: "Detection of Remote organ injury after intestinal ischemia-Reperfusion in mice"日本救急医学会雑誌. (In Press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K.Koike, Y.Yamamoto, et al.: "Group IIA phospholipase Az mediates lung injury in intestinal ischemia-reperfusion"Annals of Surgery. 232. 90-97 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K.Koike, Y.Yamamoto: "Splanchnic hypoperfusion in critically ill patients"日本外傷学会雑誌. 13. 80-87 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 小池薫, 山本保博: "MOFの現状と治療の将来"ICU & CCU. 23. 165-171 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 小池薫, 山本保博: "腹部臓器虚血と遠隔臓器障害"日本外科学会雑誌. 100. 357-360 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 小池薫(分担): "クリティカルケア(SIRS・ショック・MODS)"医学書院(相川直樹、青木克憲編集). 277 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yuriko Matsuura, Kaoru Koike, Atsuko Tsujii, Saeed Samarghandian, Shigeki Kushimoto, Yasuhiro Yamamoto: "A method to detect remote organ injury after intestinal ischemia-reperfusion in mice"Journal of Japanese Association far Acute. Medicien. In press. (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kaoru Koike, Yasuhiro Yamamoto, Yozo Hori, Takashi Ono: "Group IIA phospholipase A_2 mediates lung Injury in intestinal ischemia-reperfusion"Ann Surg. 232. 90-97 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koike K, Yamamoto Y: "Splanchnic hypoperfusion in critically ill patients"Journal of Japanese Association for Surgery of Trauma. 13. 80-87 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koike K, Yamamoto Y: "Multiple organ failure: Now and future"ICU & CCU. 23. 165-171 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koike K, Yamamoto Y: "Splanchnic hypoperfusion and remote organ injury"Journal of Japanese Society for Surgery. 100. 357-360 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Critical Care/SIRS, Shock, and MODS. (Eds; Aikawa N and Aoki K) K. Koike: "Ischemia-reperfusion injury"lgakushoin. 36-42 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y.Matsuura, K.Koike et al.: "Detection of Remoted organ Injury after Intestinal Ischemia-Reperfusion in Mice"日本救急医学会雑誌. (In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kaoru Koike, et al: "Group IIA phospholipase A_2 mediates lung injury in"Annals of Surgery. 232. 90-97 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 1999-03-31   Modified: 2016-04-21  

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