Department of Surgery, Division of Cardiac Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
J Surg Res. 2013 Jul;183(1):75-83. doi: 10.1016/j.jss.2012.11.012. Epub 2012 Nov 27.
Although ex vivo lung perfusion (EVLP) is increasingly being used to evaluate and manipulate potential donor lungs before lung transplantation (LTx), data on the biochemistry of lungs during EVLP are limited. In this study, we examined the physiology and biochemistry of human lungs on an EVLP circuit.
We recovered unallocated double lungs in standard fashion and split them into single lungs. All lungs received a nebulized arginase inhibitor, 2-S-amino-6-boronohexanoic acid (ABH), at either the onset (n = 6) or after 3 h (n = 8) of EVLP. Serial biochemical analysis included levels of arginase, endogenous nitric oxide synthase (eNOS), cyclic guanosine monophosphate, and reactive oxygen species. We considered lungs transplantable if they sustained a PaO2:FiO2 ≥ 350 in addition to stable pulmonary function during EVLP.
We recovered a total of 14 single lungs. We deemed three single lungs from different donors to be transplantable after EVLP. These lungs had superior oxygenation, lower carbon dioxide, and more stable pulmonary artery pressures. Transplantable lungs had higher baseline levels of eNOS and higher final levels of cyclic guanosine monophosphate than non-transplantable lungs. Early ABH administration was associated with a transient increase in dynamic compliance.
In this biochemical characterization of lungs deemed unsuitable for LTx, early levels of eNOS and late levels of cyclic guanosine monophosphate appear to be associated with improved allograft function during EVLP. In addition, nebulized ABH is associated with a significant increase in dynamic compliance. These data suggest that biochemical markers during EVLP may predict acceptable allograft function, and that this platform can be used to biochemically manipulate donor lungs before LTx.
尽管体外肺灌注（EVLP）越来越多地被用于在肺移植（LTx）前评估和操作潜在供肺，但有关 EVLP 期间肺的生物化学数据有限。在这项研究中，我们检查了 EVLP 回路中人类肺的生理学和生物化学。
我们以标准方式回收未分配的双肺，并将其分为单肺。所有肺均接受雾化的精氨酸酶抑制剂 2-S-氨基-6-硼代己酸（ABH），在 EVLP 开始时（n=6）或 3 小时后（n=8）给予。连续的生化分析包括精氨酸酶、内源性一氧化氮合酶（eNOS）、环鸟苷单磷酸和活性氧的水平。如果肺在 EVLP 期间维持 PaO2：FiO2≥350 并且肺功能稳定，则认为其可移植。
我们总共回收了 14 个单肺。我们认为 EVLP 后有三个来自不同供体的单肺可移植。这些肺具有更好的氧合作用、更低的二氧化碳和更稳定的肺动脉压。可移植的肺在 EVLP 期间具有更高的 eNOS 基线水平和更高的最终环鸟苷单磷酸水平。早期 ABH 给药与动态顺应性的短暂增加有关。
在这项被认为不适合 LTx 的肺的生化特征研究中，早期的 eNOS 水平和晚期的环鸟苷单磷酸水平似乎与 EVLP 期间移植物功能的改善相关。此外，雾化 ABH 与动态顺应性的显著增加有关。这些数据表明，EVLP 期间的生化标志物可能预测可接受的移植物功能，并且该平台可用于在 LTx 前对供肺进行生化操作。
