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针对晚钠电流、心律失常和舒张功能障碍的新治疗选择。

New treatment options for late Na current, arrhythmias, and diastolic dysfunction.

作者信息

Maier Lars S

机构信息

Abteilung Kardiologie und Pneumologie/Herzzentrum, Deutsches Zentrum für Herzkreislaufforschung, Georg-August-Universität Göttingen, Robert-Koch-Strasse 40, 37075, Göttingen, Germany.

出版信息

Curr Heart Fail Rep. 2012 Sep;9(3):183-91. doi: 10.1007/s11897-012-0099-3.

DOI:10.1007/s11897-012-0099-3
PMID:22767404
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3406311/
Abstract

The late Na current is of pathophysiological importance for the heart. Ranolazine is an innovative anti-ischemic and antianginal agent that inhibits the late Na current, thereby reducing the Na-dependent Ca-overload, which improves diastolic tone and oxygen handling during myocardial ischemia. In addition, ranolazine seems to exert beneficial effects on diastolic cardiac function. Moreover, there are experimental and clinical data about its antiarrhythmic properties. A beneficial atrial selectivity of ranolazine has been suggested that may be helpful for the treatment of atrial fibrillation. The purpose of this review article is to discuss possible future clinical indications based on novel experimental and preclinical results and the significance of the available data.

摘要

晚钠电流对心脏具有病理生理学重要性。雷诺嗪是一种创新的抗缺血和抗心绞痛药物，它抑制晚钠电流，从而减少钠依赖性钙超载，改善心肌缺血期间的舒张期张力和氧处理。此外，雷诺嗪似乎对心脏舒张功能有有益作用。而且，有关于其抗心律失常特性的实验和临床数据。有人提出雷诺嗪具有有益的心房选择性，这可能有助于治疗心房颤动。这篇综述文章的目的是基于新的实验和临床前结果讨论未来可能的临床适应证以及现有数据的意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcf3/3406311/970063fe0af0/11897_2012_99_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcf3/3406311/a6f18be7178d/11897_2012_99_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcf3/3406311/970063fe0af0/11897_2012_99_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcf3/3406311/a6f18be7178d/11897_2012_99_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcf3/3406311/970063fe0af0/11897_2012_99_Fig2_HTML.jpg

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本文引用的文献

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Ranolazine decreases mechanosensitivity of the voltage-gated sodium ion channel Na(v)1.5: a novel mechanism of drug action.雷诺嗪降低电压门控钠离子通道 Na(v)1.5 的机械敏感性：一种新的药物作用机制。
Circulation. 2012 Jun 5;125(22):2698-706. doi: 10.1161/CIRCULATIONAHA.112.094714. Epub 2012 May 7.
2
Second chance for dronedarone after recent setback?近期受挫后，决奈达隆能否迎来第二次机会？
Lancet. 2012 Feb 18;379(9816):601. doi: 10.1016/s0140-6736(12)60251-7.
3
Ranolazine improves cardiac diastolic dysfunction through modulation of myofilament calcium sensitivity.
Curr Heart Fail Rep. 2014 Dec;11(4):354-65. doi: 10.1007/s11897-014-0223-7.
4
Therapeutic interventions for heart failure with preserved ejection fraction: A summary of current evidence.射血分数保留的心力衰竭的治疗干预措施：当前证据总结
World J Cardiol. 2014 Feb 26;6(2):67-76. doi: 10.4330/wjc.v6.i2.67.
5
CrossTalk proposal: The late sodium current is an important player in the development of diastolic heart failure (heart failure with a preserved ejection fraction).相互作用假说：晚钠电流在舒张性心力衰竭（射血分数保留的心力衰竭）的发生发展中起重要作用。
J Physiol. 2014 Feb 1;592(3):411-4. doi: 10.1113/jphysiol.2013.262261.
雷诺嗪通过调节肌丝钙敏感性改善心脏舒张功能障碍。
Circ Res. 2012 Mar 16;110(6):841-50. doi: 10.1161/CIRCRESAHA.111.258251. Epub 2012 Feb 16.
4
Arrhythmogenic left atrial cellular electrophysiology in a murine genetic long QT syndrome model.致心律失常性左心房细胞电生理学在一种鼠遗传性长 QT 综合征模型中的研究。
Cardiovasc Res. 2011 Oct 1;92(1):67-74. doi: 10.1093/cvr/cvr166. Epub 2011 Jun 14.
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Ranolazine for the treatment of heart failure with preserved ejection fraction: background, aims, and design of the RALI-DHF study.雷诺嗪治疗射血分数保留的心力衰竭：RALI-DHF 研究的背景、目的和设计。
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6
Reactive oxygen species-activated Ca/calmodulin kinase IIδ is required for late I(Na) augmentation leading to cellular Na and Ca overload.活性氧诱导的 Ca/钙调蛋白激酶 IIδ 对于晚期 I(Na)增强导致细胞内 Na 和 Ca 过载是必需的。
Circ Res. 2011 Mar 4;108(5):555-65. doi: 10.1161/CIRCRESAHA.110.221911. Epub 2011 Jan 20.
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Suppression of re-entrant and multifocal ventricular fibrillation by the late sodium current blocker ranolazine.雷诺嗪抑制折返性和多灶性室性颤动。
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Improvement in left ventricular systolic and diastolic performance during ranolazine treatment in patients with stable angina.雷诺嗪治疗稳定型心绞痛患者左心室收缩和舒张功能的改善。
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Synergistic effect of the combination of ranolazine and dronedarone to suppress atrial fibrillation.雷诺嗪与决奈达隆联合抑制心房颤动的协同作用。
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