Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
Leuven Lung Transplant Unit, BREATHE, Department of Chronic Diseases and Metabolism (Chrometa), KU Leuven, Leuven, Belgium.
Eur J Cardiothorac Surg. 2022 Dec 2;63(1). doi: 10.1093/ejcts/ezac483.
Primary graft dysfunction resulting from ischaemia-reperfusion injury remains a major obstacle after lung transplantation (LTx) and is associated with morbidity and mortality. Continuous release of inflammatory cytokines, due to the process of ischaemia and reperfusion, triggers a complex cascade of apoptosis and necrosis resulting in graft dysfunction. Previous studies demonstrated successful graft improvement by cytokine filtration during ex vivo lung perfusion. We hypothesize that plasma cytokine filtration with CytoSorb® during in vivo graft perfusion immediately after implantation may attenuate ischaemia-reperfusion injury after left LTx in a porcine model.
Left porcine LTx was performed with allografts preserved for 24 h at 4°C. In the treatment group [T] (n = 7), a veno-venous shunt was created to insert the cytokine filter (CytoSorbents, Berlin, Germany). In the sham group [S] (n = 4), the shunt was created without the filter. Haemodynamic parameters, lung mechanics, blood gases and plasma cytokines were assessed during 6 h in vivo reperfusion.
During 6 h of reperfusion, significant differences in plasma pro-inflammatory cytokine [interferon (IFN)-α, IFN-γ and interleukin (IL)-6] concentrations were observed between [T] and [S], but surprisingly with higher plasma levels in the [T] group. Plasma concentrations of other pro-inflammatory cytokines (IL-1β, IL-12p40, IL-4, IL-6, IL-8, IFN-α, IFN-γ and tumour necrosis factor-α) and anti-inflammatory cytokines (IL-10) did not find any evidence for a difference. Furthermore, our study failed to show meaningful difference in haemodynamics and blood gases. Also, no statistically significant differences were found between [T] and [S] in biopsies and wet-to-dry ratio at the end of the experiment.
In our porcine left LTx model cytokine filtration did not achieve the intended effect. This is in contrast to previous studies with CytoSorb use during ex vivo lung perfusion as a surrogate LTx model. Our findings might highlight the fact that the theoretical benefit of inserting an additional cytokine adsorber to improve graft function in clinical practice should be critically evaluated with further studies.
缺血再灌注损伤导致的原发性移植物功能障碍仍然是肺移植（LTx）后的主要障碍，并与发病率和死亡率相关。由于缺血和再灌注过程，炎症细胞因子的持续释放引发了导致移植物功能障碍的细胞凋亡和坏死的复杂级联反应。先前的研究表明，在体外肺灌注过程中通过细胞因子过滤可成功改善移植物。我们假设在植入后立即对活体供体肺进行体内灌注时，使用 CytoSorb®进行血浆细胞因子过滤可能会减轻猪模型中左 LTx 后的缺血再灌注损伤。
使用在 4°C 下保存 24 小时的同种异体进行左猪 LTx。在治疗组[T]（n=7）中，创建了一个静脉-静脉分流以插入细胞因子过滤器（CytoSorbents，柏林，德国）。在假手术组[S]（n=4）中，创建了一个没有过滤器的分流。在体内再灌注 6 小时期间评估血流动力学参数、肺力学、血气和血浆细胞因子。
在再灌注的 6 小时内，在[T]和[S]之间观察到血浆前炎症细胞因子[干扰素（IFN）-α、IFN-γ 和白细胞介素（IL）-6]浓度的显著差异，但令人惊讶的是，[T]组的血浆水平更高。其他前炎症细胞因子（IL-1β、IL-12p40、IL-4、IL-6、IL-8、IFN-α、IFN-γ 和肿瘤坏死因子-α）和抗炎细胞因子（IL-10）的血浆浓度未发现差异的证据。此外，我们的研究未能表明在血液动力学和血气方面有明显差异。此外，在实验结束时，[T]和[S]之间在活检和湿重/干重比方面也没有发现统计学上的显著差异。
在我们的猪左 LTx 模型中，细胞因子过滤未达到预期效果。这与之前使用 CytoSorb 在体外肺灌注中作为替代 LTx 模型时的使用研究结果形成对比。我们的发现可能强调了这样一个事实，即在临床实践中，为改善移植物功能而插入额外的细胞因子吸附剂的理论益处应该通过进一步的研究进行批判性评估。
