ESTABLISHMENT OF IMMUNOSUPPRRESIVE METHOD FOR CLINICAL DISCORDANT XENOGENEIC CARDIAC TRANSPLANTATION

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A.Immunological Assessment of Baboon and Pigs1) Establishment of assay of anti-pig antibody (against red blood cells by titration method and against endothelial cells or leukocytes by ELISA)2) Mixed lymphocte culture (MLC) of baboon lymphocytes against pig lymphocytes3) Assay of subpopulation of baboon lymphocytes using anti-human lymphocytesB.Prolonged xenograft survival by sequential heterotopic heart transplantation in pig-to-baboon model.It has been well known that natural antibodies playd a major role in hyperacute rejection (HAR) in a pig-to-baboon cardiac xenograft model. In the present study, baboons were transplanted three to four pig hearts sequentially to determine how many sequentially transplant hearts are necessary to absorb anti-pig antibody (Ab) to the level that may not cause HAR in the last transplanted heart. Materials and Methods 4 baboons received FK506 and CAM in oral doses of 12 mg/Kg and 50 mg/Kg for 2 weeks before transplantation (HTx). Each baboons underwent t … More hree to four sequential heterotopic HTx from pigs of the almost same size as the recipient baboon in the right neck. Grafts except the last one were removed soon after rejected or 2 hours after HTx if not rejected. Blood was sampled from the femoral artery (FA) of the recipient and the coronary sinus (CS) of the graft to measure anti-pig red-blood-cell Ab.Results All first graft was hyperacutely rejected within 30 minutes after HTx. 2 second grafts was rejected within 2 hours after HTx. 2 second and all third grafts were not rejected within 2 hours after HTx. One graft survived one day after HTx and arrested because of rejection. Another graft survived for 6 days after HTx, while the other two baboons died of hypotension after the last graft was transplanted. In each point, Ab in the baboon FA was higher than that in the graft CS.Ab in the baboon FA decreased gradually after sequential HTx and finally became undetected before the last graft was transplanted. All first grafts showed histologically massive hemorrhage and myocyte necrosis which suggested HAR,while the second and third grafts showed only some kind of ischemic changes with myocyte necrosis. Conclusion These data suggested that absorption of baboon anti-pig antibody using more than two hearts of the same size as the recipient baboon may reduce anti-pig Ab to the level that did not cause HAR in the subsequent graft. Less