Ehrsam Jonas Peter, Arni Stephan, Weisskopf Miriam, Nowack Miriam, Inci Ilhan
School of Medicine, University of Zurich, Zurich, Switzerland.
Klinik Hirslanden Zurich, Thoracic Surgery Clinic, Zurich, Switzerland.
JTCVS Open. 2023 Jul 4;15:497-507. doi: 10.1016/j.xjon.2023.06.011. eCollection 2023 Sep.
Ischemia-reperfusion injury often coincides with a cytokine storm, which can result in primary graft dysfunction following lung transplantation. Our previous research has demonstrated allograft improvement by cytokine adsorption during ex vivo lung perfusion. The aim of this study was to investigate the effect of in vivo extracorporeal cytokine adsorption in a large animal model.
Pig left lung transplantation was performed following 24 hours of cold ischemic storage. Observation period after transplantation was 24 hours. In the treatment group (n = 6), extracorporeal CytoSorb adsorption was started 30 minutes before reperfusion and continued for 6 hours. A control group (n = 3) did not receive adsorber treatment.
During adsorption, we consistently noticed a significant decrease in plasma proinflammatory interleukin (IL)-2, trends of less proinflammatory, tumor necrosis factor- α, IL-1α, and granulocyte-macrophage colony-stimulating factor as well as significantly reduced systemic neutrophils. In addition, a significantly lower peak airway pressure was detected during the 6 hours of adsorption. After 24 hours of observation, when evaluating the left lung allograft independently, we observed significantly improved CO2 removal, partial pressure of oxygen/inspired oxygen fraction ratio, and less acidosis in the treatment group. At autopsy, bronchoalveolar lavage results exhibited significantly lower recruitment of cells and less pro-inflammatory IL-1α, IL-1β, IL-6, and IL-8 in the treatment group. Histologically, the treatment group had a strong trend, indicating less neutrophil invasion into the alveolar space.
Based on our findings, cytokine adsorption during and after reperfusion is a viable approach to reducing posttransplant inflammation following lung transplantation. CytoSorb may increase the acceptance of extended criteria donor lungs, which are more susceptible to ischemia-reperfusion injury.
缺血再灌注损伤常与细胞因子风暴同时发生，这可能导致肺移植后原发性移植物功能障碍。我们之前的研究表明，在体外肺灌注期间通过细胞因子吸附可改善同种异体移植物。本研究的目的是在大型动物模型中研究体内体外细胞因子吸附的效果。
猪左肺移植在冷缺血保存24小时后进行。移植后的观察期为24小时。治疗组（n = 6）在再灌注前30分钟开始体外CytoSorb吸附，并持续6小时。对照组（n = 3）未接受吸附剂治疗。
在吸附过程中，我们持续观察到血浆促炎白细胞介素（IL）-2显著降低，促炎细胞因子肿瘤坏死因子-α、IL-1α和粒细胞-巨噬细胞集落刺激因子呈减少趋势，以及全身中性粒细胞显著减少。此外，在吸附的6小时内检测到气道峰压显著降低。观察24小时后，单独评估左肺同种异体移植物时，我们观察到治疗组的二氧化碳清除显著改善、氧分压/吸入氧分数比值升高且酸中毒减轻。尸检时，支气管肺泡灌洗结果显示治疗组细胞募集显著减少，促炎细胞因子IL-1α、IL-1β、IL-6和IL-8减少。组织学上，治疗组有明显趋势表明中性粒细胞向肺泡腔的浸润减少。
基于我们的研究结果，再灌注期间及之后的细胞因子吸附是减少肺移植后移植后炎症的可行方法。CytoSorb可能会提高对更易发生缺血再灌注损伤的扩大标准供体肺的接受度。
