Department of Anaesthesiology, Ludwig Maximilian University Munich, Munich, Germany.
Xenotransplantation. 2010 May-Jun;17(3):243-9. doi: 10.1111/j.1399-3089.2010.00587.x.
Heterotopic thoracic heart transplantation may be an alternative to the established heterotopic abdominal or orthotopic cardiac xenotransplantation model as it combines the safety of heterotopic transplantation with the benefit of a working heart model.
In a first series of two animals, we tested the surgical feasibility of this procedure with non-transgenic pig hearts transplanted into pre-sensitized baboons (killed after weaning from cardiopulmonary bypass). In a second group (n = 2), double-transgenic alpha(1,3)galactosyl-transferase knock out/hCD46 pig hearts were transplanted into naïve baboons after immunoadsorption. The immunosuppressive regimen consisted of anti-CD20-mAb, tacrolimus, sirolimus, MMF and steroids.
The first baboon was successfully transplanted, but died of an air embolism, while in the second animal graft survival was 50 days with the recipient in good physical condition. One rejection reaction was successfully treated by immunoadsorption, ATG and the proteasome inhibitor bortezomib. Post-mortem histopathology showed no evidence for humoral or cellular rejection of the cardiac xenograft.
This is the first description of a heterotopic thoracic pig-to-baboon heart transplantation. The procedure combines the advantages of a working heart model with the safety of heterotopic transplantation. In contrast to orthotopic transplantation, the recipient heart can assist the donor heart during episodes of rejection. We believe that the heterotopic thoracic model may accelerate the progress into the clinical application of cardiac xenotransplantation. However, successful combination of this heterotopic transplantation with an experimental model of cardiac failure may be needed before this technique can be promoted to clinical trials.
异位胸腔心脏移植可能是一种替代已建立的异位腹部或原位心脏异种移植模型的方法，因为它结合了异位移植的安全性和工作心脏模型的益处。
在第一个系列的两个动物中，我们用非转基因猪心移植到预先致敏的狒狒（从心肺旁路手术后断奶后死亡）中测试了该手术的可行性。在第二组（n = 2）中，双转基因α（1,3）半乳糖基转移酶敲除/hCD46 猪心在免疫吸附后被移植到未致敏的狒狒中。免疫抑制方案包括抗 CD20-mAb、他克莫司、西罗莫司、MMF 和类固醇。
第一只狒狒成功移植，但死于空气栓塞，而第二只动物的移植物存活了 50 天，受者身体状况良好。一次排斥反应通过免疫吸附、ATG 和蛋白酶体抑制剂硼替佐米成功治疗。尸检组织病理学显示心脏异种移植物无体液或细胞排斥反应的证据。
这是首例描述异位胸腔猪-狒狒心脏移植的报道。该手术将工作心脏模型的优点与异位移植的安全性结合在一起。与原位移植相比，在排斥反应期间，受体心脏可以协助供体心脏。我们相信，异位胸腔模型可能会加速心脏异种移植临床应用的进展。然而，在将这种异位移植与心脏衰竭的实验模型成功结合之前，可能需要将该技术推广到临床试验。
