| Project/Area Number |
11470237
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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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 | UNIVERSITY TSUKUBA |
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Principal Investigator |
TAKADA Yasutsugu TSUKUBA UNIVERSITY, INSTITUTE OF CLINICAL MEDICINE, ASSOCIATE PROFESSOR, 臨床医学系, 講師 (10272197)
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| Co-Investigator(Kenkyū-buntansha) |
TANIGUCHI Hideki TSUKUBA UNIVERSITY, INSTITUTE OF CLINICAL MEDICINE, ASSOCIATE PROFESSOR, 臨床医学系, 講師 (70292555)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2000: ¥4,200,000 (Direct Cost: ¥4,200,000)
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| Keywords | AUXILIARY PARTIAL ORTHOTOPIC LIVER TRANSPLANTATION / PIG / AMANITIN / LPS / FULMINANT HEPATIC FAILURE / REGENERATION / 補助的肝移植 / エンドトキミン / 肝移植 |
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| Research Abstract |
<Experiment 1> The purpose of this study was to develop a clinically relevant porcine model of fulminant hepatic failure (FHF) by means of administration of amatoxin and endotoxin. Pigs were intraportally administered 0.1 mg/kg of alpha-amanitin plus (n=9). All the pigs died within 96 hours with a significant increase in AST at 24 hr (9757±2167 IU/L). In addition, they demonstrated severe metabolic disorders such as serum lactate accumulation, hypoglycemia, coagulopathy, plasma amino acid imbalance, and hyperammonemia. Intracranial pressure significantly increased to 17.8±2.5 mm Hg immediately before death. Reversal of FHF in these pigs following orthotopic liver transplantation confirmed that the toxicity is liver-specific and that the graft liver is unaffected. This porcine model of FHF induced by a combination of amanitin and LPS will be of much use in the development of new therapies for human FHF.<Experiment 2> A porcine auxiliary partial orthotopic liver transplantation (APOLT) model for FHF was developed in the next study. A left lobe partial liver graft procured from a healthy donor was transplanted in the recipient in the orthotopic position after the toxin administration and left lobectomy. All the pigs survived more than 2 weeks after APOLT.Liver biopsy specimens one week after APOLT revealed regeneration of the diseased native liver. Even after the ligation of the left portal vein and left hepatic artery at one week, pigs subsequently survived with satisfactory liver function. Thus, we have established a porcine APOLT model against FHF induced by our newly developed method using amanitin and LPS.In this model, blood supply to the grafts was sufficient without portal diversion. Regeneration of the diseased native liver appeared to be accomplished in about one week, and full restoration of its function was confirmed by the survival after inflow occlusion of the graft liver.
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