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首页> 外文期刊>The Journal of Thoracic and Cardiovascular Surgery >Characterization of a pig-to-goat orthotopic lung xenotransplantation model to study beyond hyperacute rejection.
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Characterization of a pig-to-goat orthotopic lung xenotransplantation model to study beyond hyperacute rejection.

机译：猪到山羊原位肺异种移植模型的表征，以研究超急​​性排斥反应。

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BACKGROUND: A pig-to-goat orthotopic lung xenograft model was developed to test whether depletion of goat xenoreactive antibodies against pig red blood cells would prolong pig lung xenograft survival. METHODS: Adult goats with anti-pig xenoreactive antibodies underwent left pneumonectomy followed by orthotopic transplantation of pig left lung (group 1) or immunodepletion of their xenoreactive antibodies by extracorporeal right pig lung perfusion before transplantation without (group 2) or with (group 3) complete clampage of the right pulmonary artery. In group 4, goat left lungs were orthotopically transplanted into pigs and served as negative controls (pig serum does not have anti-goat xenoreactive antibodies). Each study group included 5 animals. Immunosuppression in surviving recipients included cyclosporine and azathioprine. RESULTS: Group 1 recipients died 7 +/- 3 hours after xenograft reimplantation of severe pulmonary hypertension and dysfunction and vasogenic shock, with little evidence of histologic xenograft injury. Group 2 xenografts had a stable circulatory and respiratory function on reperfusion and survived 9 +/- 4 days. Group 3 animals also tolerated complete occlusion of the right pulmonary artery, and xenografts assured the total respiratory support for 4 +/- 1 days. After immunodepletion, goat serum showed no detectable titers of xenoreactive antibodies, which began to reappear by postoperative day 2, where xenografts showed histologic stigmata of acute (humoral and cellular-mediated) rejection that evolved to a complete xenograft necrose at death. Group 4 xenografts showed scattered features of acute rejection 5 +/- 1 days after the operation. CONCLUSIONS: Pig left lung xenografts can provide prolonged and complete respiratory support after depletion of goat xenoreactive antibodies, but they ultimately necrose once recipient xenoreactive antibodies return to pretransplantation values.
机译：背景：建立了猪对山羊原位肺异种移植模型，以测试消除针对猪红细胞的山羊异种反应性抗体是否会延长猪肺异种移植物的存活。方法：成年山羊用抗猪异种反应抗体进行左肺切除，然后进行猪左肺原位移植（第1组），或在不进行（第2组）或联合（第3组）移植前通过体外右猪肺灌注免疫清除其异种反应性抗体。完全夹紧右肺动脉。在第4组中，将山羊左肺原位移植到猪中并用作阴性对照（猪血清中没有抗山羊异种反应性抗体）。每个研究组包括5只动物。幸存者的免疫抑制作用包括环孢霉素和硫唑嘌呤。结果：第1组接受者在异种移植物重度肺动脉高压，功能障碍和血管生成性休克后7 +/- 3小时死亡，几乎没有组织学异种移植物损伤的证据。第2组异种移植物在再灌注时具有稳定的循环和呼吸功能，并存活9 +/- 4天。第3组动物也耐受右肺动脉的完全闭塞，并且异种移植确保了4 +/- 1天的总呼吸支持。免疫耗竭后，山羊血清显示没有可检测到的异种反应抗体效价，该异种抗体在术后第2天开始重新出现，异种移植物表现出急性（体液和细胞介导的）排斥反应的组织学柱头，在死亡时演变为完整的异种移植物坏死。第4组异种移植术后5 +/- 1天表现出分散的急性排斥反应。结论：猪的左肺异种移植物可在山羊异种反应性抗体耗尽后提供长期和完整的呼吸支持，但一旦受体异种反应性抗体恢复到移植前值，它们最终消失。

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