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

要开展临床肝移植(L-TX)，必须完善L-TX的相关技术和手术管理的方方面面。在无肝期，我们用生物泵对犬进行静脉转流。在常规使用生物泵转流方法的同时所作的心脏动力学分析显示，在整个无肝期都保持了接近正常的生理状态。应用生物泵的转流组存活率为79%(34条犬)，而被动转流组(21条)和非转流组(38条)的存活率为52-57%。存活率的显著提高证明了目前的外科技术已经足够完善，可以应用于临床。为了阐明新发现的枯草链霉菌FK506(FK)的免疫抑制作用，我们在杂种狗身上进行了同种异体肝移植。肌肉注射FK 0.1 mg/kg组(30.6±15.3天)较未用免疫抑制组(8.4±1.7天)明显延长。然而，用FK治疗的狗很消瘦，容易感染，尽管采取了预防措施，给药量低于最佳治疗剂量，但仍显示出新药的毒性。小剂量无毒FK联合咪唑立宾、环孢素可明显延长小鼠的生存期(12.5±4.0d)。在完善了L-TX的手术方法后，我们进行了肝、胰腺、十二指肠腹部器官簇移植。每十只狗中就有四只存活超过24小时。其中一人存活了240天。

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.