FIG. 1. Basic technique of homotransplantation. a, Ilonor liver readv for transplant. Note aortic graft removed in continuity with hepatic artery and livcr graft. b, Rccipicnt with portacaval shunt and liver removed. c, Donor liver in place.

Recently, considerable information has been obtained on the behavior of liver homografts, by Moore et al. [8] and in our own laboratory [10,11]. The large and immunologically active liver homografts were rejected in roughly the same time sequence as smaller and less complex tissues. In our studies, the manner of rejection differed from the usual situation in that widespread changes were evoked in the host reticuloendothelial system, involving the lungs, kidneys, lymph nodes, bone marrow and other organs. The functional response of the transplanted liver was substantially the same, both in Moore's studies [8] and in our own [11]. In all our animals, jaundice developed by the fifth day, and the animals died from one to sixteen days later.In the present study, other abdominal viscera were added to the liver, to constitute a relatively enormous multiorgan graft consisting of the liver, spleen, pancreas, omentum, stomach, small bowel and colon. The behavior of the liver as a constituent of the multivisceral graft was compared with that previously studied with homotransplantation of the liver alone. Since the graft contains the major portion of the reticuloendothelial system of the body, particular attention was paid to the possibility of a graft versus host reaction. METHODSAdult healthy dogs from 10 to 20 kg. in weight were used in thirty-eight transplantation experiments. The animals were dewormed, passively immunized against distemper, and prepared for surgery with a two or three day bowel preparation, using cathartics and 2 gm. of neomycin sulphate per day. All recipient dogs were females, and most donors were males. The donor dogs were 1 to 5 kg. lighter than the recipients. The animals were anesthetized with 25 to 30 mg. sodium pentobarbital and placed on respirators. Arterial pressures were monitored continuously during and after operation.Blood chemical and hematologic studies were made before and at intervals after surgery. After death, complete autopsies were promptly performed and the tissues prepared for histologic study. TECHNIC OF OPERATION Preparation of Donor TissuesUsing two surgical teams, the operation was started in donor and recipient dogs at the same time. The donor animal was first cooled to 28° to 30°C. by immersion in an ice bath. The abdomen was opened and the entire abdominal aorta mobilized, ligating and dividing all branches, except the superior mesenteric artery and coeliac axis. (Fig. 1 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript mesenteric ganglia, were severed. The stomach was transected at the esophagogastric junction ( Fig. 1) and closed in two layers. The colon was transected in the descending or sigmoid portions. A No. 17 gauge needle was inserted into the portal vein, and the liver was perfused with 1,000 cc. iced lactated Ringer's solution. During the last half of the perfusion, the dog was bled to death. The vena cava was then transected above and below the liver. The aorta was cut free well above the coeliac axis. The specimen was immediately re...

In a contemporary report, the technical problems and complications encountered with homotransplantation of the dog liver were described (15). As occurs with other vascularized homografts, the liver appeared to be rejected by the host after a characteristic time interval, usually 6 to 10 days.The present study is concerned with an analysis of events, both in the homografted liver and the host, in 18 dogs which survived 4 or more days after liver transplantation, long enough presumably for homograft rejection to occur. This included postmortem and tissue studies, as well as chemical and hematologic determinations during life. Strong histologic evidence has been obtained of widespread participation of the host reticuloendothelial system in the rejection, quite comparable to that seen after bacterial and foreign protein immunization. MethodsThe techniques used for liver transplantation have been previously described (15). The homograft was positioned in the liver fossa, after removal of the recipient dog's liver, and splenectomy was performed. Arterialization and internal biliary drainage were carried out with a uniform technique in all 18 experiments. Venous pathways were reconstructed with three variations: (a) anatomically, 8 cases; (b) anatomically with the addition of a small portacaval shunt, 6 cases; and (c) by diversion of both the splanchnic and vena caval flows through the liver, 4 cases. Although the method used was profoundly influential in determining early mortality, the type of venous connection was not an important factor in most of parameters analyzed in the present study, and the results apply to all dogs, unless otherwise stated.Adult mongrel dogs were used. The donor and recipient were always chosen for obviously different color and general appearance. In about one-half the experiments, the donor and recipient were different sexes. Blood studies were obtained preoperatively and every 2, 3, or 4 days thereafter, and the removed blood was replaced with immediate transfusion. In a few animals, transfusions were also given for the treatment of late gastrointestinal hemorrhage. All chemical studies were standard determinations, made in a clinical laboratory. Autopsies were performed promptly, usually within an hour and never longer than 8 hours after death, and the specimens fixed in formalin. Hematoxylin-eosin stains were always used, and in some cases additional tissue stains were employed. Results SurvivalSurvival times in 18 dogs are shown in Figure 5. Ninety per cent of the deaths occurred between the fifth and the tenth days. contributed to death, evidence will be presented that graft rejection played an important role in most cases. Clinical behaviorThe dogs with the most satisfactory course were those with anatomic venous reconstruction. They were usually able to eat after the second postoperative day. Diet generally consisted of brown sugar water and bread, but some of the dogs were hungry for and allowed to eat meat. Although the dietary intake of dogs with other than anatomic venous connect...

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