无回流现象和再灌注损伤。机制和治疗

M. Gilyarov, I. Ivanov, E. Konstantinova, N. I. Raschetnova, N. Shostak
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摘要

目前,治疗st段抬高型心肌梗死患者的关键方法之一是尽可能快速、完全和稳定地恢复梗死相关动脉的血流量。然而,在某些情况下,尽管冠状动脉血流恢复,但心肌再灌注不可能达到充分。这种现象被称为无回流。由于缺乏诊断无回流的统一方法,其发生率差异很大,从2%到44%不等。心肌灌注不足会导致更高的死亡率——从7.4%到30.3%不等,同时也会导致更严重的心肌重塑。长期以来,远端栓塞被认为是经皮冠状动脉介入治疗的主要机制之一。然而,常规使用保护装置并没有显示出对结果和预后的显著影响,尽管在某些临床情况下是合理的。心肌细胞钙超载、细胞水肿、坏死、凋亡直接对缺血性损伤起重要作用,心肌再灌注使缺血性损伤明显加重,并在微循环床层面形成阻塞。通过激活细胞免疫、剧烈炎症和原位血栓形成,正在积累更多关于免疫介导损伤的数据。尽管在动物实验中取得了成功,但某些药物的临床使用结果却模棱两可。根据欧洲心脏病学会/欧洲心胸外科协会(ESC / EACTS) 2018年的最新建议,GPIIb / IIIa血小板受体抑制剂推荐用于无回流病例。除此之外,根据文献,尼可地尔和硝普钠以及IL-1β拮抗剂似乎很有希望。选择性冠状动脉内低温作为一种非药物治疗方法,在初步研究中也显示出其有效性和安全性。到目前为止,很明显,无回流现象是一个复杂的级联反应的表现,包括缺血、再灌注和免疫相关损伤,以及远端栓塞。考虑到其对不良结局和晚期并发症的发生率的重要贡献,似乎有必要引入统一的诊断、预防和治疗方法,这需要高质量的临床研究。
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No-reflow phenomenon and reperfusion injury. Mechanisms and treatment
Currently, one of the key methods of treating a patient with ST-elevation myocardial infarction is to restore blood flow to the infarct-related artery as quickly, completely and steadily as possible. However, in some cases, it is not possible to achieve adequate myocardial reperfusion, despite the restoration of coronary blood flow. This phenomenon was named no-reflow. Due to the lack of a unified approach to the diagnosis of no-reflow, its occurrence varies widely – from 2 to 44 %. Failure to achieve adequate myocardial perfusion leads to a higher mortality rate – from 7.4 to 30.3 %, as well as to more aggressive remodeling of the myocardium. For a long time, distal embolization in percutaneous coronary intervention was considered one of the leading mechanisms. However, the routine use of protective devices did not show a pronounced effect on the outcome and prognosis, although it is justified in certain clinical situations. Ischemic injury directly plays a significant role due to overload of cardiomyocytes with calcium, cellular edema, necrosis and apoptosis, which is significantly aggravated by myocardial reperfusion and forms obstruction at the level of the microcirculatory bed. More data is being accumulated about immune-mediated injury through activation of cellular immunity, intense inflammation and thrombosis in situ. Despite the success in the animal experiment, the clinical use of certain groups of drugs showed an ambiguous results. According to the latest recommendations European Society of Cardiology / European Association for Cardio-Thoracic Surgery (ESC / EACTS) 2018, GPIIb / IIIa platelet receptor inhibitors are recommended in the case of no-reflow. Besides this, according to the literature nicorandil and sodium nitroprusside, as well as IL-1β antagonists, seem to be promising. As a non-drug therapy, selective intracoronary hypothermia also has shown its effectiveness and safety in a pilot study. To date, it is clear that the no-reflow phenomenon is a manifestation of a complex cascade of reactions, including ischemic, reperfusion and immune-related injury, as well as distal embolization. Considering its significant contribution to the frequency of adverse outcomes and late complications, it seems necessary to introduce unified approaches to the diagnosis, prevention and treatment of no-reflow, which requires high-quality clinical studies.
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