Naoshi Kamada

In orthotopic liver transplantation in the rat, cuff techniques have been developed for anastomoses of the portal vein and bile duct. These techniques have shortened the clamping time of the portal vein and have resulted in fewer biliary complications improving survival of the liver graft. Eighty-three per cent of the grafted animals have survived for 1 week and several animals have survived for more than 6 months. We believe that use of the cuff method technically simplifies microvascular anastomoses. It may be particularly useful for anastomosis of the portal vein after machine preservation of the donor rat liver.

Department of Surgery University of Cambridge Addenbrooke's Hospital Hills Road Cambridge CB2 2QQ, United Kingdom

In this experiment, we investigated the effect of daily injection or continuous slow infusion of either DA (MHC haplotype, RT1a) serum or soluble DA class 1 MHC antigen or its complexes with monoclonal antibody on rejection of heterotopic heart allograft in the combination of PVG.RT1a (RT1a) donor into PVG (RT1c) recipient. DA serum delayed significantly both the early and late rejection of PVG.RT1a heart grafts in PVG recipients. Removal of soluble class I MHC antigen from DA serum by affinity chromatography on a monoclonal anti-class I antibody column completely abolished the immunosuppressive effect. Continuous infusion of purified soluble class I antigen from DA rat liver, even from day 4 after heart grafting, induced a significant prolongation of graft survival. This effectiveness was donor-specific and amplified by the mixture of monoclonal anti-class 1 (RT1a) antibody with DA serum--this being induced only by using continuous infusion but not by daily injection. The results indicate that soluble class I antigen can act as a specific immunosuppressive agent in allograft rejection and that its effect is amplified by monoclonal anti-class 1 antibody.

We have demonstrated that DA hearts grafted into PVG rats were completely protected from rejection by simultaneous liver transplantation from the same donor. In subsequent experiments PVG animals were given DA hearts followed 5 or 6 days later by livers from the same donor strain. Instead of the expected rapid rejection, all the grafts survived for at least 18 days, despite showing definite graft-swelling, a reliable clinical sign of early rejection, immediately prior to liver transplantation. In all 13 rats the heart size returned to normal and a strong beat returned within a few days. 6 animals survived indefinitely with healthy, beating heart grafts and the remaining 7 animals died of liver transplant rejection, but in these animals also the hearts were beating normally immediately prior to death. Histological examination of the hearts revealed no active rejection, but there was extensive myocardial scarring, compatible with resolution of a rejection reaction. It seems, therefore, that the liver grafts had entirely absorbed the vigorous immune response, terminating that which had already begun in the heart. This immunosuppressive effect was donor-specific and far more powerful than that of the immunosuppressive agent cyclosporine.