Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, Toronto, Ontario, Canada.
Department of Thoracic Surgery, Kyoto University Hospital, Kyoto, Japan.
Am J Physiol Lung Cell Mol Physiol. 2020 Jul 1;319(1):L61-L70. doi: 10.1152/ajplung.00256.2019. Epub 2020 Apr 1.
The application of ex vivo lung perfusion (EVLP) has significantly increased the successful clinical use of marginal donor lungs. While large animal EVLP models exist to test new strategies to improve organ repair, there is currently no rat EVLP model capable of maintaining long-term lung viability. Here, we describe a new rat EVLP model that addresses this need, while enabling the study of lung injury due to cold ischemic time (CIT). The technique involves perfusing and ventilating male Lewis rat donor lungs for 4 h before transplanting the left lung into a recipient rat and then evaluating lung function 2 h after reperfusion. To test injury within this model, lungs were divided into groups and exposed to different CITs (i.e., 20 min, 6 h, 12 h, 18 h and 24 h). Experiments involving the 24-h-CIT group were prematurely terminated due to the development of severe edema. For the other groups, no differences in the ratio of arterial oxygen partial pressure to fractional inspired oxygen ([Formula: see text]/[Formula: see text]) were observed during EVLP; however, lung compliance decreased over time in the 18-h group ( = 0.012) and the [Formula: see text]/[Formula: see text] of the blood from the left pulmonary vein 2 h after transplantation was lower compared with 20-min-CIT group ( = 0.0062). This new model maintained stable lung function during 4-h EVLP and after transplantation when exposed to up to 12 h of CIT.
离体肺灌注 (EVLP) 的应用显著增加了边缘供体肺的临床成功使用。虽然存在大型动物 EVLP 模型来测试改善器官修复的新策略,但目前还没有能够维持长期肺活力的大鼠 EVLP 模型。在这里,我们描述了一种新的大鼠 EVLP 模型,满足了这一需求,同时能够研究由于冷缺血时间 (CIT) 引起的肺损伤。该技术涉及在将左肺移植到受体大鼠之前,对雄性 Lewis 大鼠供体肺进行 4 小时的灌注和通气,然后在再灌注后 2 小时评估肺功能。为了在该模型中测试损伤,将肺分为几组,并暴露于不同的 CIT(即 20 分钟、6 小时、12 小时、18 小时和 24 小时)。由于严重水肿的发展,涉及 24 小时-CIT 组的实验提前终止。对于其他组,在 EVLP 期间,动脉血氧分压与吸入氧分数的比值 ([Formula: see text]/[Formula: see text]) 没有差异;然而,18 小时组的肺顺应性随时间推移而降低( = 0.012),并且与 20 分钟-CIT 组相比,移植后 2 小时左肺静脉血中的 [Formula: see text]/[Formula: see text] 较低( = 0.0062)。当暴露于长达 12 小时的 CIT 时,这种新模型在长达 4 小时的 EVLP 期间和移植后维持稳定的肺功能。