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心脏钙敏感受体激动剂、肌敏感受体激动剂和线粒体增敏剂:JACC 每周综述专题。

Cardiac Calcitropes, Myotropes, and Mitotropes: JACC Review Topic of the Week.

机构信息

Inova Heart and Vascular Institute, Falls Church, Virginia.

Department of Medicine, Division of Cardiovascular Medicine, University of Maryland School of Medicine, Baltimore, Maryland.

出版信息

J Am Coll Cardiol. 2019 May 14;73(18):2345-2353. doi: 10.1016/j.jacc.2019.02.051.

Abstract

The term "inotrope" is familiar and intimately connected with pharmaceuticals clinically used for treatment of low cardiac output with cardiogenic shock. Traditional inotropic agents exert their effect by modulating calcium signaling in the myocardium. Their use is associated with poor long-term outcomes. Newer molecules in development intend to break from calcium mediation and the associated detrimental long-term effects by targeting distinct mechanisms of action to improve cardiac performance. Thus, "inotropy" does not sufficiently describe the range of potential novel pharmaceutical products. To enhance communication around and evaluation of current, emerging, and potential therapies, this review proposes a novel nuanced and holistic framework to categorize pharmacological agents that improve myocardial performance based on 3 myocardial mechanisms: calcitropes, which alter intracellular calcium concentrations; myotropes, which affect the molecular motor and scaffolding; and mitotropes, which influence energetics. Novel chemical entities can easily be incorporated into this structure, distinguishing themselves based on their mechanisms and clinical outcomes.

摘要

“正性肌力药”这一术语为人们所熟知,并与临床用于治疗心源性休克伴心输出量降低的药物密切相关。传统的正性肌力药物通过调节心肌中的钙信号来发挥作用。它们的使用与不良的长期预后相关。正在开发的新型分子旨在通过靶向不同的作用机制来改善心脏功能,从而打破钙介导及其相关的长期不良影响。因此,“正性肌力作用”并不能充分描述潜在新型药物的范围。为了加强对现有、新兴和潜在疗法的交流和评估,本综述提出了一个新颖的、细致入微的整体框架,根据 3 种心肌机制对改善心肌功能的药理学药物进行分类:调节细胞内钙浓度的钙敏剂;影响分子马达和支架的肌动剂;以及影响能量代谢的线粒体激动剂。新型化学实体很容易融入这一结构,根据其作用机制和临床结果将其区分开来。

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