| Project/Area Number |
08671461
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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 |
Digestive surgery
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| Research Institution | Oita Medical University |
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Principal Investigator |
KAWANO Katsunori Oita Medical University, Dept.of Surg.I,Assistant Professor, 医学部, 講師 (00274754)
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| Co-Investigator(Kenkyū-buntansha) |
KITANO Seigo Oita Medical Universiy, Dept.of Surg.I,Professor, 医学部, 教授 (90169871)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1997: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Hepatic microcirculation / In vivo microscopy / Liver ischemia / Liver transplantation / Neutrophil adhesion |
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| Research Abstract |
Background
The aim of the studies were to analyze, using the in vivo microscopic technique, the hepatic microcirculation during liver ischeniia and reperfusion, which was unavoidable in clinical liver transplantation and hepatic resection. In order to develop the new therapeutic strategies, inhibition of neutrophil adherence to vascular endothelia was attempted.
Results
1. Neutrophil adherence to hepatic vascular endothelia In a rat liver transplantation model, the liver graft was harvested and stored for 18 hours at 4ﾟC in UW solution. Then the hepatic microcirculation was investigated using in vivo microscopy following implantation. Sinusoidal perfusion rates were significantly lower in stored and transplanted liver (64%) compared with non-transplanted control liver (99%). Neutrophil adhesion to both sinusoidal endothelium (328/mm^2) and postsinusoidal venules (PSVs) were remarkably increased 24 hours following reperfusion of the liver graft.
2. Amelioration of ischemia/reperfusion injur
… More
y using FK5O6 and anti-neutrophil adhesion molecule antibody
An anti-CD 11b/CD 18 monoclonal antibody (clone 1B6, Repligen Co., Ltd.) was intravenously administered 30 minutes before and 6 hours after implantation of the 18-hour stored liver. The antibody therapy significantly improved graft survival (100% in the treated animals and 50% in the control) and reduced reperfusion injury to the liver as estimated serum ALT levels at 24 hours following transplantation. This was associated with significant inhibition of neutrophil adhesion to the sinusoidal endothelium (81/mm^2). An iMmunosuppressant, FK506, had similar effect ; prevented oxidative hepatic injury following cold preservation and transplantation by reducing the number of neutrophils permanently adhering to the sinusoids (15.4/mm^2 in FK-treated animals and 67.9/mm^2 in the control at 60 minutes following).
Conclusion
These studies clearly demonstrated the causative role of neutrophils in hepatic injury following ischemia and reperfusion and suggested the possible clinical use of FK506 and antibody against neutrophil adhesion for the therapy. Less
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