Department of Thoracic Surgery, University Hospital Zurich-University of Zurich, Zurich, Switzerland.
Department of Surgical Research, University Hospital Zurich-University of Zurich, Zurich, Switzerland.
J Thorac Cardiovasc Surg. 2021 Feb;161(2):e109-e121. doi: 10.1016/j.jtcvs.2019.12.128. Epub 2020 Feb 20.
Improvement in ex vivo lung perfusion protocols could increase the number of donors available for transplantation and protect the lungs from primary graft dysfunction. We hypothesize that perfusate adsorption during ex vivo lung perfusion reconditions the allograft to ischemia-reperfusion injury after lung transplantation.
Donor pig lungs were preserved for 24 hours at 4°C, followed by 6 hours of ex vivo lung perfusion according to the Toronto protocol. The perfusate was additionally adsorbed through a CytoSorb adsorber (CytoSorbents, Berlin, Germany) in the treatment group, whereas control lungs were perfused according to the standard protocol (n = 5, each). Ex vivo lung perfusion physiology and biochemistry were monitored. Upon completion of ex vivo lung perfusion, a left single lung transplantation was performed. Oxygenation function and lung mechanics were assessed during a 4-hour reperfusion period. The inflammatory response was determined during ex vivo lung perfusion and reperfusion.
The cytokine concentrations in the perfusate were markedly lower with the adsorber, resulting in improved ex vivo lung perfusion physiology and biochemistry during the 6-hour perfusion period. Post-transplant dynamic lung compliance was markedly better during the 4-hour reperfusion period in the treatment group. Isolated allograft oxygenation function and dynamic compliance continued to be superior in the adsorber group at the end of reperfusion, accompanied by a markedly decreased local inflammatory response.
Implementation of an additional cytokine adsorber has refined the standard ex vivo lung perfusion protocol. Furthermore, cytokine removal during ex vivo lung perfusion improved immediate post-transplant graft function together with a less intense inflammatory response to reperfusion in pigs. Further studies are warranted to understand the beneficial effects of perfusate adsorption during ex vivo lung perfusion in the clinical setting.
改进体外肺灌注方案可以增加可供移植的供体数量,并保护肺免受原发性移植物功能障碍的影响。我们假设,在体外肺灌注过程中,灌流液的吸附可以使同种异体肺在肺移植后重新适应缺血再灌注损伤。
供体猪肺在 4°C 下保存 24 小时,然后根据多伦多方案进行 6 小时的体外肺灌注。在治疗组中,灌流液通过 CytoSorb 吸附器(CytoSorbents,柏林,德国)进行额外的吸附,而对照组肺则按照标准方案进行灌注(每组 5 个)。监测体外肺灌注生理学和生物化学。完成体外肺灌注后,进行左单肺移植。在 4 小时的再灌注期间评估氧合功能和肺力学。在体外肺灌注和再灌注期间测定炎症反应。
吸附器可显著降低灌流液中的细胞因子浓度,从而改善 6 小时灌注期间的体外肺灌注生理学和生物化学。在治疗组中,再灌注 4 小时期间,动态肺顺应性明显改善。在再灌注结束时,吸附器组的单独同种异体肺氧合功能和动态顺应性仍持续较好,局部炎症反应明显减轻。
实施附加细胞因子吸附器改进了标准的体外肺灌注方案。此外,体外肺灌注过程中细胞因子的去除改善了移植后即刻移植物功能,同时减轻了再灌注时的炎症反应。需要进一步研究以了解在临床环境中体外肺灌注过程中灌流液吸附的有益效果。