| Project/Area Number |
07671691
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | NIPPON MEDICAL SCHOOL |
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Principal Investigator |
KOIKE Kaoru Nippon Medical School, Medicine (Critical Care), Assistant, 医学部, 助手 (10267164)
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| Co-Investigator(Kenkyū-buntansha) |
KUDO Ichiro Showa University, Pharmacy, Professor, 薬学部, 教授 (30134612)
YAMAMOTO Yasuhiro Nippon Medical School, Medicine (Critical Care), Professor, 医学部, 教授 (70125079)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | adult respiratory distress syndrome / multiple organ dysfunction syndrome / phospholipase A2 / small intestine / ischemia / trauma / shock / infection / 出血性ショック / 敗血症性ショック / IL-6 / IL-8 / 好中球エラスターゼ / ヒスタミン |
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| Research Abstract |
*1*Phospholipase A_2 (PLA_2) has been postulated as a key mediator in the development of adult respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODF) following severe trauma, hemorrhagic shock and severe infection. Our clinical research syggested that serum type II PLA_2 increased markedly in the patients of critical illness.
*2*Hypoperfusion to the gut has been suggested to cause MODF following severe trauma and hemorrhagic shock. The study using RI angiography showed that disproportionate intestinal hypoperfusion persisted for a long period even after blood pressure recovered.
*3*We have developed a gut ischemia-reperfusion (I/R) rat model and found that superior mesenteric artery clamp and declamp induces lung injury by a PLA_2-dependent mechanism. The subtype analysis revealed that the most part of PLA_2 existing in the ischemic gut was secretory type II.Furthermore, the pretreatment with type II PLA_2 inhibitor, S-5920, blocked gut I/R-induced lung injury.
*4*These findings suggest that type II PLA_2 plays an impirtant role in the development of ARDS and MODF after severe teauma, hemorrhagic shock and severe infection. Type II PLA_2 inhibitor may become am useful drug for prevention and treatmnt of ARDS and MODS in critically injured patients.
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