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不同膜式氧合器中中性粒细胞胞外陷阱(NETs)的发生率:市售涂层膜的体外初步实验

Incidence of neutrophil extracellular traps (NETs) in different membrane oxygenators: pilot in vitro experiments in commercially available coated membranes.

作者信息

Foltan M, Dinh D, Gruber M, Müller T, Hart C, Krenkel L, Schmid C, Lehle K

机构信息

Department for Cardiac, Thoracic and Cardiovascular Surgery, University Hospital Regensburg, Regensburg, Germany.

Department for Anaesthesiology, University Hospital Regensburg, Regensburg, Germany.

出版信息

J Artif Organs. 2025 Jan 8. doi: 10.1007/s10047-024-01486-4.

DOI:10.1007/s10047-024-01486-4
PMID:39775204
Abstract

Neutrophil extracellular traps (NETs) were detected in blood samples and in cellular deposits of oxygenator membranes during extracorporeal membrane oxygenation (ECMO) therapy and may be responsible for thrombogenesis. The aim was to evaluate the effect of the base material of gas fiber (GF, polymethylpentene) and heat exchange (HE) membranes and different antithrombogenic coatings on isolated granulocytes from healthy volunteers under static culture conditions. Contact of granulocytes with membranes from different ECMO oxygenators (with different surface coatings) and uncoated-GFs allowed detection of adherent cells and NETotic nuclear structures (normal, swollen, ruptured) using nuclear staining. Flow cytometry was used to identify cell activation (CD11b/CD62L, oxidative burst) of non-adherent cells. Uncoated-GFs were used as a reference. Within 3 h, granulocytes adhered to the same extent on all surfaces. In contrast, the ratio of normal to NETotic cells was significantly higher for uncoated-GFs (56-83%) compared to all coated GFs (34-72%) (p < 0.001) with no difference between the coatings. After material contact, non-adherent cells remained vital with unchanged oxidative burst function and the proportion of activated cells remained low. The expression of activation markers was independent of the origin of the GF material. In conclusion, the polymethylpentene surfaces of the GFs already induce NET formation. Antithrombogenic coatings can already reduce the proportion of NETotic nuclei. However, it cannot be ruled out that NET formation can induce thrombotic events. Therefore, new surfaces or coatings are required for future ECMO systems and long-term implantable artificial lungs.

摘要

在体外膜肺氧合(ECMO)治疗期间,在血液样本和氧合器膜的细胞沉积物中检测到中性粒细胞胞外陷阱(NETs),其可能是血栓形成的原因。目的是评估气体纤维(GF,聚甲基戊烯)和热交换(HE)膜的基础材料以及不同的抗血栓涂层对健康志愿者分离的粒细胞在静态培养条件下的影响。粒细胞与来自不同ECMO氧合器(具有不同表面涂层)的膜以及未涂层的GF接触后,使用核染色可检测到贴壁细胞和NETotic核结构(正常、肿胀、破裂)。流式细胞术用于鉴定非贴壁细胞的细胞活化(CD11b/CD62L,氧化爆发)。未涂层的GF用作对照。在3小时内,粒细胞在所有表面上的粘附程度相同。相比之下,未涂层的GF(56-83%)的正常细胞与NETotic细胞的比例显著高于所有涂层的GF(34-72%)(p<0.001),各涂层之间无差异。材料接触后,非贴壁细胞保持活力,氧化爆发功能不变,活化细胞比例保持较低。活化标志物的表达与GF材料的来源无关。总之,GF的聚甲基戊烯表面已经诱导NET形成。抗血栓涂层已经可以降低NETotic核的比例。然而,不能排除NET形成会诱导血栓形成事件。因此,未来的ECMO系统和长期可植入人工肺需要新的表面或涂层。

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本文引用的文献

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Computer based visualization of clot structures in extracorporeal membrane oxygenation and histological clot investigations for understanding thrombosis in membrane lungs.基于计算机的体外膜肺氧合中凝块结构可视化及组织学凝块研究,以了解膜肺中的血栓形成。
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静脉-静脉体外膜肺氧合期间游离DNA的临床相关性
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Bioinspired Approaches to Engineer Antithrombogenic Medical Devices for Vascular Intervention.仿生学方法在血管介入医疗器械抗血栓工程中的应用。
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Extended Cellular Deposits on Gas Exchange Capillaries Are Not an Indicator of Clot Formation: Analysis of Different Membrane Oxygenators.气体交换毛细血管上的细胞外沉积物增加并非血栓形成的指标:不同膜式氧合器的分析
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Neutrophil extracellular traps are increased after extracorporeal membrane oxygenation support initiation and present in thrombus: A preclinical study using sheep as an animal model.体外膜氧合支持启动后中性粒细胞细胞外陷阱增加,并存在于血栓中:使用绵羊作为动物模型的临床前研究。
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Coagulation abnormalities in patients with COVID-19 on venovenous ECLS increased risk for technical complications and support times but had no impact on survival.COVID-19 患者在接受静脉-静脉体外膜肺氧合(ECLS)治疗时出现凝血异常会增加技术并发症和支持时间的风险,但对生存率没有影响。
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