Brenner P, Reichenspurner H, Schmoeckel M, Wimmer C, Rucker A, Eder V, Meiser B, Hinz M, Felbinger T, Hammer C, Reichart B
Department of Cardiac Surgery, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany.
Transpl Int. 2000;13 Suppl 1:S508-17. doi: 10.1007/s001470050392.
To prevent hyperacute xenograft rejection (HXR) caused by preformed natural antibodies (XNAb) after orthotopic heart xenotransplantation (oXHTx) of landrace pig hearts into baboons, we used immunoadsorption of immunoglobulins IgG, IgM and IgA and complement with the reusable Ig-Therasorb column. In addition to functional data, tissue was sampled for histological, immunohistochemical and electron microscopical analysis. We performed three oXHTx of landrace pig hearts to baboons using extracorporeal circulation (ECC) connected to the immunoadsorption unit. Intraoperative treatment consisted of four cycles of immunoabsorption (IA). One oXHTx of a baboon without IA served as a control. A mismatch of donor and recipient heart size was prevented by selecting a 30-40% lower body weight of donor pigs than recipients. Four cycles of IA removed more than 80% of IgG, IgM and IgA, 86% of antipig antibodies and 66% of complement factors C3 and C4 from plasma. The graft of the control animal failed after 29 min. Orthotopic xenotransplantation with IA was selectively terminated after 100 min, 11 h and 21 h, respectively without any histological signs of HXR in light and electron microscopy. After weaning off from ECC these donor xenografts showed sufficient function with normal ECG and excellent cardiac output in echocardiography and invasive measurement (1.93 +/- 0.035 l/min). The myocardium of the control xenograft demonstrated more deposits of Ig and complement components (C3, C4) than in the IA group. Baboons survive HXR after orthotopic pig heart xenotransplantation due to antibody depletion by reusable Ig-Therasorb column treatment. Long-term survival in an orthotopic baboon xenotransplantation model after IA, especially in combination with transgenic pig organs, could be a reliable preclinical trial for future clinical xenotransplantation programs.
为防止将长白猪心脏原位心脏异种移植（oXHTx）到狒狒体内后，由预先形成的天然抗体（XNAb）引起的超急性异种移植排斥反应（HXR），我们使用可重复使用的Ig - Therasorb柱对免疫球蛋白IgG、IgM和IgA以及补体进行免疫吸附。除功能数据外，还采集组织进行组织学、免疫组织化学和电子显微镜分析。我们使用连接免疫吸附单元的体外循环（ECC），将三只长白猪心脏移植到狒狒体内进行oXHTx。术中治疗包括四个免疫吸附（IA）周期。一只未进行IA的狒狒接受的oXHTx作为对照。通过选择体重比受体低30 - 40%的供体猪，避免了供体和受体心脏大小不匹配。四个IA周期从血浆中去除了超过80%的IgG、IgM和IgA、86%的抗猪抗体以及66%的补体因子C3和C4。对照动物的移植物在29分钟后失败。进行IA的原位异种移植分别在100分钟、11小时和21小时后选择性终止，光镜和电镜下均无HXR的任何组织学迹象。从ECC撤机后，这些供体异种移植物表现出足够的功能，心电图正常，超声心动图和侵入性测量显示心输出量良好（1.93±0.035升/分钟）。对照异种移植物的心肌显示出比IA组更多的Ig和补体成分（C3、C4）沉积。由于可重复使用的Ig - Therasorb柱治疗可清除抗体，狒狒在原位猪心脏异种移植后可存活HXR。IA后原位狒狒异种移植模型中的长期存活，特别是与转基因猪器官联合使用时，可能是未来临床异种移植计划可靠的临床前试验。
