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在长时间冷保存后对人类供体肺进行带有灌注液净化的肺灌注

lung perfusion with perfusate purification for human donor lungs following prolonged cold storage.

作者信息

Wei Dong, Gao Fei, Yang Zhenkun, Wang Wei, Chen Yinglun, Lu Yan, Chen Jingyu

机构信息

Transplant Center, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214023, China.

Jiangsu Engineering Research Center of Organ Lung Preservation, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214023, China.

出版信息

Ann Transl Med. 2020 Feb;8(3):38. doi: 10.21037/atm.2019.10.17.

DOI:10.21037/atm.2019.10.17
PMID:32154283
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7036627/
Abstract

BACKGROUND

Ex vivo lung perfusion (EVLP) has developed as the most effective technique for estimating marginal donor lungs. This study attempted to extend the EVLP running time to 12 hours with a dialyzer rather than periodically replacing the perfusate.

METHODS

Human donor lungs rejected by the clinical lung transplantation (LTx) team were obtained. After cold storage lasting 18-24 hours, lungs were randomly assigned to 2 groups: a control group and a perfusate purification (PP) group. The control group underwent EVLP in the traditional way, while a dialyzer was added into the circuit as a bypass in the PP group. The effects on lung function, microenvironment, inflammatory response, and cell death were evaluated.

RESULTS

A total of 8 rejected donor lungs were obtained and each group was assigned to 4 cases of EVLP. Three cases were prematurely terminated because of serious lung edema and decreased lung function. There were no significant differences in airway pressure, pulmonary artery pressure, and oxygen concentration between the two groups in the first 8 hours. The pH in the control group was significantly lower than that in the PP group, and the levels of potassium and lactate were significantly higher than those in the PP group. Inflammatory markers increased in both groups, while IL-6 and IL-10 were higher in the PP group in the first 6 hours. Hematoxylin and eosin (HE) staining revealed lung injuries in both groups, but no significant difference was noted in the HE-stained slides. There were significantly more TUNEL-positive cells in the control group (69.5%±4.0%) than in the PP group (47.5%±3.9%) (P=0.000).

CONCLUSIONS

Using the modified method of EVLP reduces the high cost caused by exchanging perfusion fluid per hour and could prolong the normothermic preservation time of donor lungs.

摘要

背景

体外肺灌注(EVLP)已发展成为评估边缘供肺最有效的技术。本研究试图通过使用透析器而非定期更换灌注液,将EVLP运行时间延长至12小时。

方法

获取被临床肺移植(LTx)团队拒收的人类供肺。在持续18 - 24小时的冷保存后,将肺随机分为两组:对照组和灌注液净化(PP)组。对照组采用传统方式进行EVLP,而PP组在回路中添加透析器作为旁路。评估其对肺功能、微环境、炎症反应和细胞死亡的影响。

结果

共获取8个被拒收的供肺,每组分配4例进行EVLP。3例因严重肺水肿和肺功能下降而提前终止。两组在前8小时的气道压力、肺动脉压力和氧浓度无显著差异。对照组的pH值显著低于PP组,钾和乳酸水平显著高于PP组。两组炎症标志物均升高,而PP组在前6小时的IL - 6和IL - 10水平更高。苏木精和伊红(HE)染色显示两组均有肺损伤,但HE染色切片中未观察到显著差异。对照组的TUNEL阳性细胞(69.5%±4.0%)明显多于PP组(47.5%±3.9%)(P = 0.000)。

结论

采用改良的EVLP方法可降低每小时更换灌注液所带来的高成本,并可延长供肺的常温保存时间。

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本文引用的文献

1
lung perfusion prior to transplantation: an overview of current clinical practice worldwide.移植前的肺灌注:全球当前临床实践概述
J Thorac Dis. 2019 Apr;11(4):1635-1650. doi: 10.21037/jtd.2019.04.33.
2
Incorporating ex-vivo lung perfusion into the UK adult lung transplant service: an economic evaluation and decision analytic model.将体外肺灌注纳入英国成人肺移植服务:一项经济评估与决策分析模型
BMC Health Serv Res. 2019 May 22;19(1):326. doi: 10.1186/s12913-019-4154-6.
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Prof. Shaf Keshavjee: innovating lung transplantation and facing the challenges of the unknown.沙夫·凯沙维吉教授:创新肺移植技术,直面未知挑战。
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Inactivating hepatitis C virus in donor lungs using light therapies during normothermic ex vivo lung perfusion.在常温离体肺灌注过程中使用光照疗法使供体肺中的丙型肝炎病毒失活。
Nat Commun. 2019 Jan 29;10(1):481. doi: 10.1038/s41467-018-08261-z.
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Prediction of transplant outcome after 24-hour ex vivo lung perfusion using the Organ Care System in a porcine lung transplantation model.应用 Organ Care System 对猪肺移植模型行 24 小时体外肺灌注对移植后结果的预测。
Am J Transplant. 2019 Feb;19(2):345-355. doi: 10.1111/ajt.15075. Epub 2018 Sep 12.
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Lung transplant after prolonged ex vivo lung perfusion: predictors of allograft function in swine.长时间离体肺灌注后肺移植:猪同种异体肺功能的预测因素。
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Normothermic ex-vivo preservation with the portable Organ Care System Lung device for bilateral lung transplantation (INSPIRE): a randomised, open-label, non-inferiority, phase 3 study.采用便携式 Organ Care System Lung 装置常温离体肺保存进行双侧肺移植(INSPIRE):一项随机、开放标签、非劣效性、3 期研究。
Lancet Respir Med. 2018 May;6(5):357-367. doi: 10.1016/S2213-2600(18)30136-X. Epub 2018 Apr 9.
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Lactate and Immunosuppression in Sepsis.脓毒症中的乳酸与免疫抑制。
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Cytokine filtration modulates pulmonary metabolism and edema formation during ex vivo lung perfusion.细胞因子过滤可调节体外肺灌注期间的肺代谢和水肿形成。
J Heart Lung Transplant. 2017 May 20. doi: 10.1016/j.healun.2017.05.021.
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