Department of Surgery, University of Virginia Health System, Charlottesville, VA, USA.
J Thorac Cardiovasc Surg. 2012 Nov;144(5):1208-15. doi: 10.1016/j.jtcvs.2012.07.056. Epub 2012 Aug 31.
Ex vivo lung perfusion (EVLP) is a promising modality for the evaluation and treatment of marginal donor lungs. The optimal timing of EVLP initiation and the potential for rehabilitation of donor lungs with extended warm ischemic times is unknown. The present study compared the efficacy of different treatment strategies for uncontrolled non-heart-beating donor lungs.
Mature swine underwent hypoxic arrest, followed by 60 minutes of no-touch warm ischemia. The lungs were harvested and flushed with 4°C Perfadex. Three groups (n = 5/group) were stratified according to the preservation method: cold static preservation (CSP; 4 hours of 4°C storage), immediate EVLP (I-EVLP: 4 hours EVLP at 37°C), and delayed EVLP (D-EVLP; 4 hours of CSP followed by 4 hours of EVLP). The EVLP groups were perfused with Steen solution supplemented with heparin, methylprednisolone, cefazolin, and an adenosine 2A receptor agonist. The lungs then underwent allotransplantation and 4 hours of recipient reperfusion before allograft assessment for resultant ischemia-reperfusion injury.
The donor blood oxygenation (partial pressure of oxygen/fraction of inspired oxygen ratio) before death was not different between the groups. The oxygenation after transplantation was significantly greater in the D-EVLP group than in the I-EVLP or CSP groups. The mean airway pressure, pulmonary artery pressure, and expression of interleukin-8, interleukin-1β, and tumor necrosis factor-α were all significantly reduced in the D-EVLP group. Post-transplant oxygenation exceeded the acceptable clinical levels only in the D-EVLP group.
Uncontrolled non-heart-beating donor lungs with extended warm ischemia can be reconditioned for successful transplantation. The combination of CSP and EVLP in the D-EVLP group was necessary to obtain optimal post-transplant function. This finding, if confirmed clinically, will allow expanded use of nonheart-beating donor lungs.
体外肺灌注（EVLP）是评估和治疗边缘供体肺的一种很有前途的方法。目前尚不清楚 EVLP 启动的最佳时机以及延长热缺血时间的供体肺的康复潜力。本研究比较了不同治疗策略对非心脏死亡供体肺的疗效。
成熟猪经历缺氧性停搏，随后进行 60 分钟的无接触性热缺血。采集肺脏并用 4°C Perfadex 冲洗。根据保存方法将三组（每组 5 只）分层：冷静态保存（CSP；4 小时 4°C 储存）、即刻 EVLP（I-EVLP：37°C 下 4 小时 EVLP）和延迟 EVLP（D-EVLP；4 小时 CSP 后进行 4 小时 EVLP）。EVLP 组用肝素、甲基强的松龙、头孢唑啉和腺苷 2A 受体激动剂补充的 Steen 溶液进行灌注。然后将肺脏进行同种异体移植，并在移植物评估前进行 4 小时受体再灌注，以评估由此产生的缺血再灌注损伤。
死亡前各组供体血液氧合（氧分压/吸入氧分数比值）无差异。移植后，D-EVLP 组的氧合明显优于 I-EVLP 或 CSP 组。D-EVLP 组的平均气道压、肺动脉压和白细胞介素-8、白细胞介素-1β 和肿瘤坏死因子-α 的表达均显著降低。只有 D-EVLP 组的移植后氧合超过可接受的临床水平。
延长热缺血的非心脏死亡供体肺可以通过再处理来成功移植。D-EVLP 组中 CSP 和 EVLP 的联合使用是获得最佳移植后功能所必需的。如果这一发现得到临床证实，将允许扩大使用非心脏死亡供体肺。
