Interrelation between the parameters of endogenous vascular regulation, oxidative stress and the markers of inflammatory response in COVID-19 patients while on extracorporeal membrane oxygenation

E. Klychnikova, S. Zhuravel, I. V. Ivanov, O. Nikitina, E. Tazina, A. Bulanov, A. M. Talyzin, K. Popugaev, V. Vladimirov, S. Petrikov, A. Bogdanova
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Abstract

Introduction. Extracorporeal membrane oxygenation has found wide application in clinical practice during the COVID-19 pandemic. Oxidative stress, endothelial dysfunction, and systemic inflammatory response syndrome play an important role in the pathogenesis of COVID-19. Our research was designed to study correlations in-between those factors and the impact of extracorporeal membrane oxygenation on them.Aim. The study of systemic inflammatory response and endothelial function in patients with COVID-19 during extracorporeal membrane oxygenation.Material and methods. In the course of a prospective study, we examined 100 COVID-19 patients aged 26 to 75 years, median 55 years [47;60], who were treated at the N.V. Sklifosovsky Research Institute for Emergency Medicine, using extracorporeal membrane oxygenation. As a control group (normal), 25 practically healthy people whose median age was 32 years [25;39] were examined. The function of the vascular endothelium was assessed by the content of nitric oxide stable metabolites in the blood serum and the level of angiotensin-converting enzyme. Next, the ratio of nitric oxide metabolite to angiotensin-converting enzyme level was calculated, reflecting the imbalance between endotheliumdependent vasodilation and vasoconstriction. To assess the severity of oxidative stress in blood serum, malondialdehyde was determined as a marker of lipid peroxidation. The state of the antioxidant system was assessed in terms of total antioxidant status of blood serum. The presence of an imbalance in the system of lipid peroxidation and the antioxidant system total antioxidant status was judged by the oxidative stress coefficient, i.e. the ratio of malondialdehyde to the total antioxidant activity.Results. The analysis showed the presence and progression of endothelial dysfunction, impaired vascular regulation, activation of free radical processes, the presence of an imbalance in the prooxidant/antioxidant system, as well as the progression of the inflammatory process with a decrease in the level of markers of the COVID-19 severity.Conclusion. Further studies of the correlation between endothelial damage and the severity of the systemic inflammatory response syndrome may be of fundamental importance for explaining the pathophysiological mechanisms of COVID-19 course and developing new treatments for such patients.
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COVID-19患者体外膜氧合时内源性血管调节参数、氧化应激与炎症反应标志物的相互关系
介绍。在新冠肺炎大流行期间,体外膜氧合在临床实践中得到了广泛应用。氧化应激、内皮功能障碍和全身炎症反应综合征在COVID-19的发病机制中起重要作用。我们的研究旨在探讨这些因素之间的相关性以及体外膜氧合对它们的影响。体外膜氧合对COVID-19患者全身炎症反应和内皮功能的影响。材料和方法。在一项前瞻性研究中,我们检查了100例年龄在26至75岁之间的COVID-19患者,中位年龄为55岁[47;60],他们在N.V. Sklifosovsky急诊医学研究所接受体外膜氧合治疗。选取年龄中位数为32岁的实际健康人群25例作为对照组(正常)[25;39]。采用血清一氧化氮稳定代谢物含量和血管紧张素转换酶水平评价血管内皮功能。接下来,计算一氧化氮代谢物与血管紧张素转换酶水平的比值,反映内皮依赖性血管舒张和血管收缩之间的不平衡。为了评估血清中氧化应激的严重程度,丙二醛被确定为脂质过氧化的标志物。以血清总抗氧化状态评价抗氧化系统状态。通过氧化应激系数,即丙二醛与总抗氧化活性的比值来判断脂质过氧化系统和抗氧化系统中是否存在失衡。分析显示,内皮功能障碍、血管调节功能受损、自由基过程激活、促氧化/抗氧化系统失衡,以及炎症过程的进展,并伴有COVID-19严重程度标志物水平的下降。进一步研究内皮损伤与全身炎症反应综合征严重程度的相关性,可能对解释COVID-19病程的病理生理机制和开发新的治疗方法具有重要意义。
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