University of Kragujevac, Faculty of Medical Sciences, Department of Physiology, Svetozara Markovica 69, 34 000 Kragujevac, Serbia.
1st Moscow State Medical University IM Sechenov, Department of Human Pathology, Trubetskaya street 8, 119991 Moscow, Russia.
Can J Physiol Pharmacol. 2021 Jan;99(1):18-29. doi: 10.1139/cjpp-2020-0276. Epub 2020 Aug 15.
Myocardial ischaemia-reperfusion (I/R) injury is a well-known term for exacerbation of cellular destruction and dysfunction after the restoration of blood flow to a previously ischaemic heart. A vast number of studies that have demonstrated that the role of mineralocorticoids in cardiovascular diseases is based on the use of pharmacological mineralocorticoid receptor (MR) antagonists. This review paper aimed to summarize current knowledge on the effects of MR antagonists on myocardial I/R injury as well as postinfarction remodeling. Animal models, predominantly the Langendorff technique and left anterior descending coronary artery occlusion, have confirmed the potency of MR antagonists as preconditioning and postconditioning agents in limiting infarct size and postinfarction remodeling. Several preclinical studies in rodents have established and proved possible mechanisms of cardioprotection by MR antagonists, such as reduction of oxidative stress, reduction of inflammation, and apoptosis, therefore limiting the infarct zone. However, the results of some clinical trials are inconsistent, since they reported no benefit of MR antagonists in acute myocardial infarction. Due to this, further studies and the results of ongoing clinical trials regarding MR antagonist administration in patients with acute myocardial infarction are being awaited with great interest.
心肌缺血再灌注(I/R)损伤是一个众所周知的术语,用于描述缺血心脏血流恢复后细胞破坏和功能障碍的加重。大量研究表明,盐皮质激素受体(MR)拮抗剂的药理学作用与心血管疾病有关。本文旨在总结 MR 拮抗剂在心肌缺血再灌注损伤以及梗死后重构中的作用的最新知识。动物模型,主要是 Langendorff 技术和左前降支冠状动脉闭塞,已经证实了 MR 拮抗剂作为预处理和后处理剂的效力,可限制梗死面积和梗死后重构。一些啮齿动物的临床前研究已经确定并证明了 MR 拮抗剂的可能的心脏保护机制,例如减少氧化应激、减少炎症和细胞凋亡,从而限制梗死区。然而,一些临床试验的结果并不一致,因为它们报告 MR 拮抗剂在急性心肌梗死中没有益处。因此,人们非常关注正在进行的临床试验中关于急性心肌梗死后给予 MR 拮抗剂的结果,以进一步研究。