| Project/Area Number |
12671172
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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 |
General surgery
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| Research Institution | KITASATO UNIVERSITY |
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Principal Investigator |
SATO Koshi Kitasato Univ.School of Medicine Associate Professor, 医学部, 助教授 (40118815)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Yoshiya Kitasato Univ.School of Medicine Research Associate, 医学部, 助手 (40203187)
MATSUMOTO Yutaka Kitasato Univ.School of Medicine Research Associate, 医学部, 助手 (90301473)
ITABASHI Koichi Kitasato Univ.School of Medicine Research Associate, 医学部, 助手 (50265659)
KAKITA Akira Kitasato Univ.School of Medicine Professor, 医学部, 教授 (90109439)
TAKAHASHI Tsuyoshi Kitasato Univ.School of Medicine Assistant Professor, 医学部, 講師 (70245405)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | brain death / liver / hepatic tissue flow / protease inhibitor |
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| Research Abstract |
Background/aims : We examined the protective effects of a protease inhibitor, urinary trypsin inhibitor (UTI), on brain dead livers associated with systemic hemodynamic instability. Methods : Brain death was induced by inflating a balloon catheter placed in the epidural space in rats followed by intravenous administration of UTI for 6 hours. The hemodynamic, functional and morphological changes in the liver were examined. Results : The induction of brain death resulted in a significant decrease in both mean arterial pressure (MAP) and hepatic tissue flow (HTF), and an increase in serum AST and cytokines such as tumor necrosis factor (TNF)-alpha and cytokines-induced neutrophil chemoattractant (CINC). An increase in the number of sequestered neutrophils and enhanced expressions of intercellular adhesion molecules (ICAM)-1 and CINC were also noted in the liver. The treatment with UTI significantly restored HTF to basal level without affecting MAP, and decreased the number of sequestered neutrophils in the hepatic sinusoids, suppressed the expression of ICAM-1 and CINC in the sinusoids, inhibited the production of serum TNF-alpha and CINC, and inactivated Kupffer cells. Conclusions : Intravenous administration of UTI is likely to ease unfavorable effects on the hepatic microvasculature evoked by brain death.
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