Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Int J Mol Sci. 2024 Oct 3;25(19):10680. doi: 10.3390/ijms251910680.
Extracorporeal membrane oxygenation (ECMO) is a life-saving intervention for patients with circulatory and/or pulmonary failure; however, the rate of complications remains high. ECMO induces systemic inflammation, which may activate and damage the endothelium, thereby causing edema and organ dysfunction. Advancing our understanding in this area is crucial for improving patient outcomes during ECMO. The goal of this review is to summarize the current evidence of the effects of ECMO on endothelial activation and damage in both animals and patients. PubMed and Embase databases were systematically searched for both clinical and animal studies including ECMO support. The outcome parameters were markers of endothelial activation and damage or (in)direct measurements of endothelial permeability, fluid leakage and edema. In total, 26 studies (patient = 16, animal = 10) fulfilled all eligibility criteria, and used VA-ECMO ( = 13) or VV-ECMO ( = 6), or remained undefined ( = 7). The most frequently studied endothelial activation markers were adhesion molecules (ICAM-1) and selectins (E- and P-selectin). The levels of endothelial activation markers were comparable to or higher than in healthy controls. Compared to pre-ECMO or non-ECMO, the majority of studies showed stable or decreased levels. Angiopoietin-2, von Willebrand Factor and extracellular vesicles were the most widely studied circulating markers of endothelial damage. More than half of the included studies showed increased levels when compared to normal ranges, and pre-ECMO or non-ECMO values. In healthy animals, ECMO itself leads to vascular leakage and edema. The effect of ECMO support in critically ill animals showed contradicting results. ECMO support (further) induces endothelial damage, but endothelial activation does not, in the critically ill. Further research is necessary to conclude on the effect of the underlying comorbidity and type of ECMO support applied on endothelial dysfunction.
体外膜肺氧合（ECMO）是治疗循环和/或肺功能衰竭患者的一种救生干预措施；然而，并发症的发生率仍然很高。ECMO 会引起全身炎症，从而激活和损伤内皮细胞，导致水肿和器官功能障碍。深入了解这一领域对于改善 ECMO 期间患者的预后至关重要。本综述的目的是总结 ECMO 对动物和患者内皮细胞激活和损伤的现有证据。系统地检索了 PubMed 和 Embase 数据库，以获取包括 ECMO 支持在内的临床和动物研究。观察指标为内皮细胞激活和损伤的标志物，或内皮通透性、液体渗漏和水肿的直接或间接测量。共有 26 项研究（患者 16 项，动物 10 项）符合所有纳入标准，使用 VA-ECMO（13 项）或 VV-ECMO（6 项），或未定义（7 项）。最常研究的内皮激活标志物是粘附分子（ICAM-1）和选择素（E-和 P-选择素）。内皮激活标志物的水平与健康对照组相当或更高。与 ECMO 前或非 ECMO 相比，大多数研究显示稳定或降低的水平。血管生成素-2、血管性血友病因子和细胞外囊泡是最广泛研究的内皮损伤的循环标志物。超过一半的纳入研究显示与正常范围和 ECMO 前或非 ECMO 值相比，水平升高。在健康动物中，ECMO 本身会导致血管渗漏和水肿。危重病动物中 ECMO 支持的效果显示出相互矛盾的结果。ECMO 支持在危重病中进一步诱导内皮损伤，但不会引起内皮激活。需要进一步研究以确定潜在合并症和所应用的 ECMO 支持类型对内皮功能障碍的影响。
