1990 Fiscal Year Final Research Report Summary
Surgical Techniques of Canine Liver Transplantation and the Immunosuppressive Effects of the Newly Discovered FK506
| Project/Area Number |
63570608
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | Kitasato University, School of Medicine |
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Principal Investigator |
SATO Koshi Kitasato University School of Medicine Department of Surgery, Assistant Professor, 医学部, 講師 (40118815)
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| Co-Investigator(Kenkyū-buntansha) |
IMAI Kiyoshi Kitasato University, School of Medicine Department of Surgery, Assistant Profess, 助手 (10176472)
TAKISHIMA Tsunemasa Kitasato University, School of Medicine Department of Surgery, Assistant Profess, 医学部, 講師 (00154948)
NAKAYAMA Yoshisake Kitasato University, School of Medicine Department of Surgery, Assistant Profess, 医学部, 講師 (90155896)
OSAKABE Tsuneo Kitasato University, School of Medicine Department of Surgery, Assistant Profees, 医学部, 講師 (60146404)
YOKOTA Kazuhiko Kitasato University, School of Medicine Department of Surgery, Assistant Profess, 医学部, 非常勤講師 (40112669)
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| Project Period (FY) |
1988 – 1990
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| Keywords | Canine Liver Transplantation / Orthotopic Liver Transplantation / Immunosuppression / Bio-Pump / Anhepatic Phase / FK506 / Cyclosprine / Mizoribine |
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| Research Abstract |
To begin clinical liver transplantation (L-TX), technical skill and all aspects of operative management related to L-TX must be perfected. We affected venous bypass on the canine with a Bio-pump during the anhepatic phase. Cardiodynamic profiles made concurrently with routine use of the Bio-Pump method of bypass indicated that near-normal physiology was maintained throughout the anhepatic phase. Moreover, in the bypass groups making use of the Bio-Pump the survival rate was 79% (34dogs), whereas 52-57% was noted in passive bypass group (21 dogs) and the nonbypass group employing a cuff technique for vascular anstomosis (38 dogs). This dramatic gain in the survival rate verifies that present surgical techniques are sufficiently refined for launching into clinical L-TX.
To elucidate the immunosuppressive effects of the newly discovered FK506 (FK) isolated from Streptomyces tsukubaensis, hepatic allotransplantation was performed in the mongrel dog. The survival period was prolonged considerably in dogs treated with FK, 0.1mg/Kg/day injected intramuscularly (30.6+15.3 days), incontrast to that of without immunosuppression (8.4+1.7 days). However, the dogs treated with FK were emaciated and susceptible to infection, showing the toxicity of the new drug in spite of precautions to administer amounts under the optimal therapeutic dose. FK administered in nontoxic small doses in combination with mizoribine and cyclosporine showed the sight prolongation of survival period (12.5+4.0 days).
After the perfection of surgical techniques of L-TX, we have examined the abdominal organ cluster transplantation with liver, pancreas and duodenum. Four out of ten dogs survived over 24 hours. One of them survived 240 days.
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