Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands.
Department of Pulmonary Diseases, University Medical Center Groningen, Groningen, The Netherlands.
PLoS One. 2021 Dec 2;16(12):e0260705. doi: 10.1371/journal.pone.0260705. eCollection 2021.
The process of brain death (BD) detrimentally affects donor lung quality. Ex vivo lung perfusion (EVLP) is a technique originally designed to evaluate marginal donor lungs. Nowadays, its potential as a treatment platform to repair damaged donor lungs is increasingly studied in experimental models. Rat models for EVLP have been described in literature before, yet the pathophysiology of BD was not included in these protocols and prolonged perfusion over 3 hours without anti-inflammatory additives was not achieved. We aimed to establish a model for prolonged EVLP of rat lungs from brain-dead donors, to provide a reliable platform for future experimental studies. Rat lungs were randomly assigned to one of four experimental groups (n = 7/group): 1) healthy, directly procured lungs, 2) lungs procured from rats subjected to 3 hours of BD and 1 hour cold storage (CS), 3) healthy, directly procured lungs subjected to 6 hours EVLP and 4), lungs procured from rats subjected to 3 hours of BD, 1 hour CS and 6 hours EVLP. Lungs from brain-dead rats showed deteriorated ventilation parameters and augmented lung damage when compared to healthy controls, in accordance with the pathophysiology of BD. Subsequent ex vivo perfusion for 6 hours was achieved, both for lungs of healthy donor rats as for pre-injured donor lungs from brain-dead rats. The worsened quality of lungs from brain-dead donors was evident during EVLP as well, as corroborated by deteriorated ventilation performance, increased lactate production and augmented inflammatory status during EVLP. In conclusion, we established a stable model for prolonged EVLP of pre-injured lungs from brain-dead donor rats. In this report we describe tips and pitfalls in the establishment of the rat EVLP model, to enhance reproducibility by other researchers.
脑死亡（BD）过程会损害供体肺的质量。离体肺灌注（EVLP）是一种最初设计用于评估边缘供体肺的技术。如今，它作为一种修复受损供体肺的治疗平台，在实验模型中越来越受到研究。以前已经有文献描述了用于 EVLP 的大鼠模型，但这些方案中并未包含 BD 的病理生理学，也没有实现超过 3 小时的无抗炎添加剂的延长灌注。我们旨在建立一种从脑死亡供体中进行长时间 EVLP 的大鼠模型，为未来的实验研究提供可靠的平台。大鼠肺随机分为以下四个实验组（每组 n = 7）：1）健康、直接采集的肺；2）采集自经历 3 小时 BD 和 1 小时冷藏（CS）的大鼠的肺；3）健康、直接采集的肺，经历 6 小时 EVLP；4）采集自经历 3 小时 BD、1 小时 CS 和 6 小时 EVLP 的大鼠的肺。与健康对照相比，脑死亡大鼠的肺通气参数恶化，肺损伤增加，符合 BD 的病理生理学。随后，健康供体大鼠和脑死亡供体预先受损的肺均能进行 6 小时的离体灌注。EVLP 期间，脑死亡供体肺的质量恶化更为明显，通气性能恶化，乳酸生成增加，炎症状态加重。总之，我们建立了一种稳定的大鼠 EVLP 模型，用于预损伤的脑死亡供体肺。本报告描述了建立大鼠 EVLP 模型的技巧和陷阱，以提高其他研究人员的可重复性。
