Immunosuppressive therapy and organ preservation in liver transplantation
Grant-in-Aid for General Scientific Research (B)
|Allocation Type||Single-year Grants|
|Research Institution||Nagoya University|
TAKAGI Hiroshi Nagoya Univ. School of Med., Professor, 医学部, 教授 (70154755)
ORIHARA Akira Nagoya Univ. School of Med., Assistant Prof., 医学部, 助手 (90242867)
NONAMI Toshiaki Nagoya Univ. School of Med., Assistant Prof., 医学部, 助手 (80189422)
YOKOYAMA Itsuo Nagoya Univ. School of Med., Assistant Prof., 医学部, 講師 (60240206)
HARADA Akio Nagoya Univ. School of Med., Assistant Prof., 医学部, 講師 (50198909)
NAKAO Akimasa Nagoya Univ. School of Med., Associate Prof., 医学部, 助教授 (70167542)
岸本 若彦 名古屋大学, 医学部, 助手 (90221209)
|Project Period (FY)
1991 – 1992
Completed(Fiscal Year 1992)
|Budget Amount *help
¥4,700,000 (Direct Cost : ¥4,700,000)
Fiscal Year 1992 : ¥1,900,000 (Direct Cost : ¥1,900,000)
Fiscal Year 1991 : ¥2,800,000 (Direct Cost : ¥2,800,000)
|Keywords||liver transplantation / preservation / reperfusion injury / oxygen free radial / FK506 / thromboxane B2 / thromboxane A2 / endotherial cell|
1. Immunosuppressive Therapy
In rats which were given FK506,immuno-histochemical study showed a marked histological change of the endothelial cells. This finding suggests a possibility of toxic side effect of this drug.
In the allotransplant models, it is suggested that a short course of FK506 provided a sufficient immunosuppression.
2. Liver Graft Preservation
The rat liver preserved in UW solution showed less endothelial injury and less impairment of peripheral vascular perfusion as well as higher tissue nucleotides level than in EuroCollins solution.
In the experiment of rat liver perfusion, Carolina rinse solution showed a protective effect against sinusoidal injury caused by reperfusion. In the pig liver transplant models, graft survivals were better in the animals which were treated with Carolina rinse solution than those without it. Postoperative transaminases were lower and graft histology was better in the group rinsed with Carolina solution than that without it.
3. Liver Graft Protection
Preoperative administration of cyclosporine or FK506 provided better blood flow in the liver graft, less transaminasemia and less production of free radicals than the grafts which were not given the drugs preoperatively. It is demonstrated that these drugs can minimize reperfusion injury.
It was shown that liver glutathione level lowered during preservation. However, this was prevented by the administration of glutathione precursors.
Administration of thromboxane A2 synthetase inhibitors to the donor animals lnduced improvement of graft circulation after transplantation.
Above findings confirms that donor and recipient management is of prime importance in the liver transplantation.
Key Words: liver transplantation, preservation, reperfusion injury, oxygen free radial, FK506, thromboxane B2, thromboxane A2, endotherial cell
Research Products (11results)