Kelly Dympna M, Demetris A Jake, Fung John J, Marcos Amadeo, Zhu Yue, Subbotin Vladimir, Yin Lu, Totsuka Eishi, Ishii Tomohiro, Lee Ming C, Gutierrez Jorge, Costa Guilherme, Venkataraman Raman, Madariaga Juan R
Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Liver Transpl. 2004 Feb;10(2):253-63. doi: 10.1002/lt.20073.
Increasing shortage of cadaveric grafts demands the utilization of living donor and split liver grafts. The purpose of this study was to 1) define the "small-for-size" graft in a pig liver transplant model 2) evaluate pathological changes associated with small-for-size liver transplantation. Pigs were divided into four groups based on the volume of transplanted liver: (a) control group (n=4), 100% liver volume (LV) (b) group I (n=8), 60% LV (c) group II (n=8), 30% LV (d) group III (n=15), 20% LV. Tacrolimus and methyl prednisone were administered as immunosuppression. Animals were followed for 5 days with daily serum biochemistry, liver biopsies on day 3 and 5 for light microscopy, and tissue levels of thymidine kinase (TK) and ornithine decarboxylase (ODC). Liver grafts were weighed pretransplant and at sacrifice. All the recipients of 100%, 60%, and 30% grafts survived. Transplantation of 20% grafts (group III) resulted in a 47% mortality rate. Group III animals showed significantly prolonged prothrombin times (p<0.05), elevated bilirubin levels (p<0.05), and ascites. The rate of regeneration, as indicated by TK activity and graft weight was inversely proportional to the size of the transplanted graft. The severity of the microvascular injury was inversely proportional to graft size and appeared to be the survival-limiting injury. Frank rupture of the sinusoidal lining, parenchymal hemorrhage, and portal vein injury were prominent in group III animals 1 hour following reperfusion. This study established a reproducible large animal model of partial liver grafting; it defined the small-for-size syndrome in this model and described the associated microvascular injury.
尸体供肝的日益短缺促使人们使用活体供肝和劈离式肝移植。本研究的目的是：1）在猪肝移植模型中定义“小体积”移植物；2）评估与小体积肝移植相关的病理变化。根据移植肝的体积将猪分为四组：（a）对照组（n = 4），移植100%肝体积（LV）；（b）I组（n = 8），移植60%LV；（c）II组（n = 8），移植30%LV；（d）III组（n = 15），移植20%LV。给予他克莫司和甲基泼尼松进行免疫抑制。对动物进行5天的跟踪观察，每天检测血清生化指标，在第3天和第5天进行肝活检以进行光镜检查，并检测胸苷激酶（TK）和鸟氨酸脱羧酶（ODC）的组织水平。在移植前和处死时对肝移植物进行称重。接受100%、60%和30%移植物的所有受者均存活。移植20%移植物（III组）导致47%的死亡率。III组动物的凝血酶原时间显著延长（p<0.05），胆红素水平升高（p<0.05），并出现腹水。以TK活性和移植物重量表示的再生率与移植移植物的大小成反比。微血管损伤的严重程度与移植物大小成反比，似乎是限制存活的损伤。在再灌注后1小时，III组动物中窦状隙内衬的明显破裂、实质出血和门静脉损伤较为突出。本研究建立了一个可重复的部分肝移植大型动物模型；它在该模型中定义了小体积综合征，并描述了相关的微血管损伤。
