重新思考再同步:探索超越壁运动控制的心脏再同步机制

Khalid Chakir, David A. Kass
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引用次数: 7

摘要

心脏再同步化(Cardiac resynchronization, CRT)是临床上广泛应用于治疗因传导延迟导致心衰患者功能下降和收缩不协调的一种治疗方法。它在心力衰竭治疗中是独一无二的,因为它可以急性和慢性地增强收缩功能,并延长生存期。虽然改进的腔室机械-能量学被认为是CRT益处的主要机制,但新的动物模型数据揭示了治疗中新颖且在许多情况下独特的细胞和分子修饰。这些变化的例子包括转录组和应激激酶信号的显著区域异质性的逆转,参与电复极化的离子通道功能的改善,肌节功能和钙处理的增强以及β -肾上腺素能反应的上调,以及线粒体蛋白质组靶向变化相关的线粒体能量效率的提高。对这些机制的探索可能会揭示出CRT如何确实使衰竭的心脏收缩更多,完成更多的工作,而不会加重长期衰竭的关键见解。这些变化可能为适合CRT的患者提供更多的生物学标记,并为一般心力衰竭的新治疗途径指明方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Rethinking resynch: Exploring mechanisms of cardiac resynchronization beyond wall motion control

Rethinking resynch: Exploring mechanisms of cardiac resynchronization beyond wall motion control

Cardiac resynchronization (CRT) is a widely used clinical treatment for heart failure patients with depressed function and discoordinate contraction due to conduction delay. It is unique among heart failure treatments as it both acutely and chronically enhances systolic function and also prolongs survival. While improved chamber mechano-energetics has been considered a primary mechanism for CRT benefit, new animal model data are revealing novel and in many instances unique cellular and molecular modifications from the treatment. Examples of these changes are the reversal of marked regional heterogeneity of the transcriptome and stress kinase signaling, improved ion channel function involved with electrical repolarization, enhanced sarcomere function and calcium handling and up-regulation of beta-adrenergic responses, and improved mitochondrial energetic efficiency associated with targeted changes in the mitochondrial proteome. Exploration of these mechanisms may reveal key insights into how CRT can indeed get the failing heart to contract more and perform more work, yet not worsen long-term failure. These changes may provide a more biological marker for both the appropriate patients for CRT and point the way for new therapeutic avenues for heart failure in general.

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