Studies on the rejection of the transplanted homologous dog liver

Abstract

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...

Experimental and Clinical Homotransplantation of the Liver*

“…Rejection per se was not a clearly demonstrable factor in the inability to obtain longer survivors. The characteristic sequence of rejection observed in untreated animals, in which hepatic failure is invariably manifest after four to six days, [2][3][4] was prevented by the immunosuppressive regimen (FIGURES 2 and 3). Jaundice was late in onset (FIGURE 3), or was prevented altogether (FIGURE 2) in virtually every case.…”

Histopathologic alterations associated with the transplanted homologous dog liver

“…The technical problems and clinical course after transplantation of the homologous dog liver have been recently described (Moore et al, 1960;Starzl et al, 1960Starzl et al, , 1961. The rejection pattern was similar to that seen with other vascularized homografts.…”

“…The occurrence of mononuclear, lymphocytic and plasmacytic infiltrates in the donor organ is uniformly cited in early phases of whole organ [spleen (Moore et al, 1960), kidney (Dempster, 1953;Hume et al, 1960;Simonsen et al, 1953), liver (Moore et al, 1960;Starzl et al, 1961)] homotransplantation. A similar infiltrate is seen in freegrafts of skin (Medawar, 1944).…”

Liver, Biliary Tract and Pancreas

“…(122,160,161) Here the agent of injury is homograft rejection. Liver function is initially normal, but all measurable parameters progressively deteriorate from the fourth or fifth day until the death of the animal.…”