Department of Cardiothoracic-, Transplant, and Vascular Surgery, Hannover Medical School, Hannover, Germany.
Division of Transplant Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Am J Transplant. 2021 Dec;21(12):3831-3839. doi: 10.1111/ajt.16784. Epub 2021 Aug 24.
Allogeneic lung transplantation (LuTx) is considered the treatment of choice for a broad range of advanced, progressive lung diseases resistant to conventional treatment regimens. Ischemia reperfusion injury (IRI) occurring upon reperfusion of the explanted, ischemic lung during implantation remains a crucial mediator of primary graft dysfunction (PGD) and early allo-immune responses. Ex vivo lung perfusion (EVLP) displays an advanced technique aiming at improving lung procurement and preservation. Indeed, previous clinical trials have demonstrated a reduced incidence of PGD following LuTx utilizing EVLP, while long-term outcomes are yet to be evaluated. Mechanistically, EVLP may alleviate donor lung inflammation through reconditioning the injured lung and diminishing IRI through storing the explanted lung in a non-ischemic, perfused, and ventilated status. In this work, we review potential mechanisms of EVLP that may attenuate IRI and improve organ quality. Moreover, we dissect experimental treatment approaches during EVLP that may further attenuate inflammatory events deriving from tissue ischemia, shear forces or allograft rejection associated with LuTx.
同种异体肺移植(LuTx)被认为是治疗多种对常规治疗方案有抵抗力的晚期、进行性肺部疾病的首选方法。在植入过程中,供体肺再灌注时发生的缺血再灌注损伤(IRI)仍然是原发性移植物功能障碍(PGD)和早期同种免疫反应的关键介质。离体肺灌注(EVLP)是一种旨在改善肺获取和保存的先进技术。事实上,先前的临床试验表明,利用 EVLP 进行 LuTx 可降低 PGD 的发生率,而长期结果仍有待评估。从机制上讲,EVLP 可以通过重新调节受损的肺来减轻供体肺的炎症,并通过将供体肺置于非缺血、灌注和通气状态来减轻 IRI。在这项工作中,我们回顾了 EVLP 减轻 IRI 和改善器官质量的潜在机制。此外,我们还剖析了 EVLP 期间可能进一步减轻与 LuTx 相关的组织缺血、剪切力或同种异体排斥引起的炎症事件的实验治疗方法。