Histopathologic alterations associated with the transplanted homologous dog liver

Brock, Donald R.; Starzl, Thomas E.

doi:10.1016/0014-4800(62)90020-5

Cited by 12 publications

(6 citation statements)

References 12 publications

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“…From the foregoing experiences, as well as from previous studies in which immunosuppressive therapy was not used, [2][3][4][5][6]8,15 a number of conclusions appear to be justified concerning the requirements which must be met before livers can be transplanted with improved results. The requisites for success are more stringent and manifold than with renal homotransplantation, and the total problem is accordingly more complex.…”

Section: Discussionmentioning

confidence: 99%

Experimental and Clinical Homotransplantation of the Liver*

Starzl¹,

Marchioro²,

Huntley³

et al. 1965

Annals of the New York Academy of Sciences

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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. NIH Public Access 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...

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Section: Discussionmentioning

confidence: 99%

Experimental and Clinical Homotransplantation of the Liver*

Starzl¹,

Marchioro²,

Huntley³

et al. 1965

Annals of the New York Academy of Sciences

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“…Large animal models were first used to develop the technical and surgical aspects of allotransplantation. In 1961, a surgical technique of heart allograft in dogs, which led to Barnard's first human cardiac transplant in South Africa in 1967, was developed (11,12,13,14); similarly, liver allotransplantation was developed in pig and dog models to eventually allow the first human liver transplant (15,16,17,18,19). Calne and co-workers clearly initiated the first step of allotransplantation in humans by showing prolonged survival of renal allografts in beagles (1).…”

Section: Animal Modelsmentioning

confidence: 99%

The importance of large animal models in transplantation

Dehoux

Gianello²

2007

Front Biosci

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Animal models have been extensively used in transplantation research. However, animal experimentation is contentious and subject to legal and ethical restrictions. Most experiments are carried out on rodents, but crucial prerequisites for the development of safe pre-clinical protocols in biomedical research are needed through suitable large animal models. In transplantation particularly, large animal models have developed dramatically. This article provides an overview of the large animal models commonly used to evaluate organ transplant experiments and analyzes the specificity of several models in various situations such as induction of allospecific tolerance and xenotransplantation. The key determination that remains be addressed is the most appropriate species and strains to model human immune and physiological systems. Because of their phylogenetic and physiologic similarities to man, non-human primates play an increasingly important role in pre-clinical testing. Nevertheless, a number of studies have shown the pig to be a reliable large animal model for transplantation research, and the availability of genetically defined or modified pigs establishes a stronger position for pigs as a large animal model.

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“…The relative proportion of hepatic mass represented by the biliary compartment increased more rapidly in Model A transplants; to some degree at least this appeared to be the result of rapid hepatocellular atrophy (Fig. [3][4][5][6] and Table 1). Within 7 tralsplants decreased to approximately one-half that in Model B transplants.…”

Section: Syngeneic L;e Trarmplantsmentioning

confidence: 99%