BACKGROUND By causing inflammation and tissue damage, neutrophil extracellular traps (NETs) constitute an underlying mechanism of aspiration-induced lung injury, a major factor of the low utilization of donor lungs in lung transplantation (LTx). METHODS To determine whether NET removal during ex vivo lung perfusion (EVLP) can restore lung function and morphology in aspiration-damaged lungs, gastric aspiration lung injury was induced in 12 pigs. After confirmation of acute respiratory distress syndrome, the lungs were explanted and assigned to NET removal connected to EVLP (treated) (n = 6) or EVLP only (nontreated) (n = 6). Hemodynamic measurements were taken, and blood and tissue samples were collected to assess lung function, morphology, levels of cell-free DNA, extracellular histones, and nucleosomes as markers of NETs, as well as cytokine levels. RESULTS After EVLP and NET removal in porcine lungs, PaO2/FiO2 ratios increased significantly compared to those undergoing EVLP alone (p = 0.0411). Treated lungs had lower cell-free DNA (p = 0.0260) and lower levels of extracellular histones in EVLP perfusate (p= 0.0260) than nontreated lungs. According to histopathology, treated lungs showed less immune cell infiltration and less edema compared with nontreated lungs, which was reflected in decreased levels of proinflammatory cytokines in EVLP perfusate and bronchoalveolar lavage fluid. CONCLUSIONS To conclude, removing NETs during EVLP improved lung function and morphology in aspiration-damaged donor lungs. The ability to remove NETs during EVLP could represent a new therapeutic approach for LTx and potentially expand the donor pool for transplantation.

中文翻译：

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通过离体去除中性粒细胞胞外陷阱来恢复丢弃的猪肺。


背景 中性粒细胞胞外陷阱 （NETs） 通过引起炎症和组织损伤，构成了误吸诱导肺损伤的潜在机制，这是肺移植 （LTx） 中供体肺利用率低的主要因素。方法 为确定离体肺灌注 （EVLP） 期间去除 NET 是否能恢复误吸损伤肺的肺功能和形态，对 12 头猪进行了胃吸入肺损伤。在确认急性呼吸窘迫综合征后，将肺移植并分配到与 EVLP 相关的 NET 去除（治疗）（n = 6）或仅 EVLP（未治疗）（n = 6）。进行血流动力学测量，并收集血液和组织样本以评估肺功能、形态、游离 DNA 水平、细胞外组蛋白和核小体作为 NETs 标志物的核小体以及细胞因子水平。结果 猪肺去除 EVLP 和 NET 后，与单独接受 EVLP 的患者相比，PaO2/FiO2 比率显着增加 （p = 0.0411）。与未处理的肺相比，处理后的肺具有较低的游离 DNA （p = 0.0260） 和 EVLP 灌注液中细胞外组蛋白的水平较低 （p = 0.0260）。根据组织病理学，与未治疗的肺相比，治疗后的肺表现出较少的免疫细胞浸润和较少的水肿，这反映在 EVLP 灌注液和支气管肺泡灌洗液中促炎细胞因子水平降低。结论 总之，在 EVLP 期间去除 NETs 可改善误吸受损供体肺的肺功能和形态。在 EVLP 期间去除 NETs 的能力可能代表 LTx 的一种新治疗方法，并可能扩大移植的供体库。