ESTABLISHMENT OF IMMUNOSUPPRRESIVE METHOD FOR CLINICAL DISCORDANT XENOGENEIC CARDIAC TRANSPLANTATION

A.恒河猴和猪的免疫学评价1)抗猪抗体(用滴定法测定抗红细胞抗体，用ELISA法测定抗内皮细胞或白细胞抗体)2)混合淋巴细胞培养(MLC)抗猪淋巴细胞(MLC)抗猪淋巴细胞3)用抗人淋巴细胞检测恒河猴淋巴细胞亚群。B.在猪到狒狒心脏移植模型中，序贯异位心脏移植延长异种心脏移植存活时间。众所周知，天然抗体在猪到狒狒心脏移植模型的超急性排斥反应(HAR)中起主要作用。在本研究中，相继移植了三到四个猪心脏，以确定需要多少个相继移植的心脏才能吸收抗猪抗体(Ab)到可能不会导致最后一次移植心脏HAR的水平。材料与方法用FK506和CAM分别以12 mg/kg和50 mg/kg剂量口服，连续2周后移植。每只狒狒都接受了t…。更多的HREE到4个顺序的异位HTX，来自与右颈的受体狒狒几乎相同大小的猪。除最后一个移植物外，在被拒绝后不久取出移植物，如果未被拒绝，则在HTX后2小时取出移植物。于受者股动脉(FA)和移植物冠状静脉窦(CS)采血检测抗猪红细胞抗体。结果所有移植物均在HTX后30min内发生超急性排斥反应。2例二次移植于HTX后2小时内被排斥。2肝移植后2小时内二次、三次移植均未发生排斥反应。一例移植物在HTX后存活一天，因排斥反应而被逮捕。另一只在HTX后存活了6天，而另外两只在最后一只移植后死于低血压。在各个时间点上，狒狒FA中的抗体均高于移植物CSs，在连续HTX后抗体逐渐下降，最后在最后一次移植物移植前检测不到。所有移植物在组织学上均有大量出血和心肌细胞坏死，提示HAR，而第二和第三移植物仅显示某种缺血性改变并伴有心肌细胞坏死。结论用两个以上大小与受体大小相同的心脏来吸收狒狒抗猪抗体，可以将抗猪抗体降低到不会引起随后移植的HAR的水平。较少

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