Until the present time, whole-organ hepatic homotransplantation has been a disappointing procedure, both in experimental animals and in man. The operation itself carries a high immediate risk, especially in the dog, which is peculiarly subject to an anoxic hepatic injury termed "outflow block." In reported canine experiments, the majority of animals have failed to recover from the acute effects of operation. Because of the fact that it has not been possible to obtain a consistently satisfactory preparation, evaluations of the efficacy of immunosuppressive regimens for the prevention of rejection have never been published.In the following remarks, attention will be directed to the influence of therapy with azathioprine, or azathioprine plus prednisone, upon the rejection process in dogs and in five patients receiving hepatic homografts after removal of their own livers. Since efforts to obtain long-term survival were eventually futile in both groups, an analysis of the reasons for failure will be attempted. Finally, alternative solutions will be presented which are designed to avoid the many pitfalls that have thus far precluded success.
Orthotopic Homotransplantation in Dogs Using Living DonorsTwenty-five dogs had replacements of their own livers with hepatic homografts obtained from living canine donors, employing a previously described technique. 1 The donor organs were removed from healthy animals, which had been cooled to 30-32° C. At the moment the hepatic arterial circulation was interrupted, perfusion of the liver was begun with chilled lactated Ringer's solution (10-15° C.) through the portal vein. The inferior vena caval and portal systems of the recipient dog, which must be temporarily occluded during insertion of the liver, were joined with a temporary portacaval anastomosis and then decompressed with a single external by-pass (FIGURE 1) from the inferior to the superior vena caval systems. 1 The upper vena caval, lower vena caval, hepatic arterial, and portal venous anastomoses were done in that order, and the temporary portacaval anastomosis subsequently taken down so that the vascular supply to the homograft was essentially normal. 1 Internal biliary drainage was provided with a loop cholecystenterostomy. Two to 10 mg./kg. per day of azathioprine were given postoperatively to all animals (FIGURES 2 and 3), supplemented in a few cases with 20 to 100 mg. per day of subcutaneous prednisolone or prednisone (FIGURE 3).Eleven of the 25 animals lived for less than three days after operation (TABLE 1). Ten of the early deaths were due to hemorrhage, either into the peritoneal cavity or the * Aided by Grants A-6283, A-6344, HE07735, AM 07772, AI 04152, and OG 27 from the U. S. Public Health Service. † Markle Scholar.
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Author ManuscriptAnn N Y Acad Sci. Author manuscript; available in PMC 2011 August 11. gastrointestinal tract, and in all of these cases there was some evidence of hepatic outflow block. With this syndrome, the liver becomes swollen and congested, and frequently hemorr...
