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Surgical Techniques of Canine Liver Transplantation and the Immunosuppressive Effects of the Newly Discovered FK506

犬肝移植手术技术及新发现的FK506的免疫抑制作用

基本信息

批准号：
63570608
负责人：
SATO Koshi
金额：
$ 1.15万
依托单位：
Kitasato University, School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1990
项目状态：
已结题

项目摘要

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.

要开始临床肝移植手术，必须完善与肝移植相关的技术技能和各方面的手术管理。在无肝期，我们用生物泵对犬进行静脉旁路。与常规旁路Bio-Pump方法同时进行的心脏动力学分析表明，在整个无肝期，生理机能保持接近正常。此外，在使用Bio-Pump的旁路组中，存活率为79%（34只狗），而被动旁路组（21只狗）和采用袖带技术进行血管吻合的非旁路组（38只狗）的存活率为52-57%。生存率的显著提高证实了目前的手术技术已经足够完善，可以进入临床L-TX。为了阐明从筑波链霉菌中分离到的FK506 （FK）的免疫抑制作用，我们对杂种狗进行了肝脏同种异体移植。肌肉注射0.1mg/Kg/d的FK显著延长了犬的生存期（30.6+15.3 d），而未注射免疫抑制组的生存期为8.4+1.7 d。然而，用FK治疗的狗消瘦且易感染，显示出新药的毒性，尽管预防措施将剂量控制在最佳治疗剂量下。无毒性小剂量FK与米佐利滨和环孢素联合用药可明显延长生存期（12.5+4.0天）。在L-TX手术技术完善后，我们研究了肝、胰、十二指肠腹腔脏器簇移植。10只狗中有4只存活超过24小时。其中一人存活了240天。