Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute; Toronto Lung Transplant Program, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute.
J Heart Lung Transplant. 2015 Jun;34(6):849-57. doi: 10.1016/j.healun.2015.01.003. Epub 2015 Jan 16.
Normothermic ex vivo lung perfusion (EVLP) is a preservation technique that allows reassessment of donor lungs before transplantation. We hypothesized that the endothelin-1 (ET-1) axis would be associated with donor lung performance during EVLP and recipient outcomes after transplantation.
ET-1, Big ET-1, endothelin-converting enzyme (ECE), and nitric oxide (NO) metabolites were quantified in the perfusates of donor lungs enrolled in a clinical EVLP trial. Lungs were divided into 3 groups: (I) Control: bilateral transplantation with good early outcomes defined as absence of primary graft dysfunction (PGD) Grade 3 (PGD3) ; (II) PGD3: bilateral lung transplantation with PGD3 any time within 72 hours; and (III) Declined: lungs rejected after EVLP.
There were 25 lungs in Group I, 7 in Group II, and 16 in Group III. At 1 and 4 hours of EVLP, the perfusates of Declined lungs had significantly higher levels of ET-1 (3.1 ± 2.1 vs. 1.8±2.3 pg/ml, p = 0.01; 2.7 ± 2.2 vs. 1.3 ± 1.1 pg/ml, p = 0.007) and Big ET-1 (15.8 ± 14.2 vs. 7.0 ± 6.5 pg/ml, p = 0.001; 31.7 ± 17.4 vs. 19.4 ± 9.5 pg/ml, p = 0.007) compared with Controls. Nitric oxide metabolite concentrations were significantly higher in Declined and PGD3 lungs than in Controls. For cases of donation after cardiac death, PGD3 and Declined lungs had higher ET-1 and Big ET-1 levels at 4 hours of perfusion compared with Controls. At this time point, Big ET-1 had excellent accuracy to distinguish PGD3 (96%) and Declined (92%) from Control lungs.
In donation after cardiac death lungs, perfusate ET-1 and Big ET-1 are potential predictors of lung function during EVLP and after lung transplantation. They were also associated with non-use of lungs after EVLP and thus could represent useful biomarkers to improve the accuracy of donor lungs selection.
常温体外肺灌注（EVLP）是一种保存技术，可在移植前重新评估供肺。我们假设内皮素-1（ET-1）轴与 EVLP 期间供肺的功能以及移植后的受体结局相关。
在一项临床 EVLP 试验中，对纳入的供肺灌流液中 ET-1、Big ET-1、内皮素转换酶（ECE）和一氧化氮（NO）代谢物进行了定量分析。肺分为 3 组：（I）对照组：双侧肺移植，早期无原发性移植物功能障碍（PGD）3 级（PGD3）；（II）PGD3 组：在 72 小时内任何时间双侧肺移植 PGD3 级；（III）衰竭组：EVLP 后肺排斥。
组 I 有 25 个肺，组 II 有 7 个，组 III 有 16 个。在 EVLP 的 1 小时和 4 小时，衰竭组的灌流液中 ET-1（3.1 ± 2.1 与 1.8 ±2.3 pg/ml，p = 0.01；2.7 ± 2.2 与 1.3 ± 1.1 pg/ml，p = 0.007）和 Big ET-1（15.8 ± 14.2 与 7.0 ± 6.5 pg/ml，p = 0.001；31.7 ± 17.4 与 19.4 ± 9.5 pg/ml，p = 0.007）明显更高。与对照组相比，NO 代谢物浓度在衰竭和 PGD3 组中明显更高。对于心脏死亡后的供体，PGD3 和衰竭组在 4 小时灌注时的 ET-1 和 Big ET-1 水平明显高于对照组。在这个时间点，Big ET-1 能够很好地区分 PGD3（96%）和衰竭组（92%）与对照组。
在心脏死亡后的供体肺中，灌流液中的 ET-1 和 Big ET-1 可能是 EVLP 期间和肺移植后肺功能的潜在预测因子。它们还与 EVLP 后肺的不使用相关，因此可能是提高供体肺选择准确性的有用生物标志物。
