Richardson William J, Clarke Samantha A, Quinn T Alexander, Holmes Jeffrey W
Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA.
Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, USA.
Compr Physiol. 2015 Sep 20;5(4):1877-909. doi: 10.1002/cphy.c140067.
Once myocardium dies during a heart attack, it is replaced by scar tissue over the course of several weeks. The size, location, composition, structure, and mechanical properties of the healing scar are all critical determinants of the fate of patients who survive the initial infarction. While the central importance of scar structure in determining pump function and remodeling has long been recognized, it has proven remarkably difficult to design therapies that improve heart function or limit remodeling by modifying scar structure. Many exciting new therapies are under development, but predicting their long-term effects requires a detailed understanding of how infarct scar forms, how its properties impact left ventricular function and remodeling, and how changes in scar structure and properties feed back to affect not only heart mechanics but also electrical conduction, reflex hemodynamic compensations, and the ongoing process of scar formation itself. In this article, we outline the scar formation process following a myocardial infarction, discuss interpretation of standard measures of heart function in the setting of a healing infarct, then present implications of infarct scar geometry and structure for both mechanical and electrical function of the heart and summarize experiences to date with therapeutic interventions that aim to modify scar geometry and structure. One important conclusion that emerges from the studies reviewed here is that computational modeling is an essential tool for integrating the wealth of information required to understand this complex system and predict the impact of novel therapies on scar healing, heart function, and remodeling following myocardial infarction.
在心脏病发作期间,一旦心肌死亡,在数周的时间里它会被瘢痕组织所取代。愈合瘢痕的大小、位置、组成、结构及力学特性,都是心肌梗死幸存者预后的关键决定因素。虽然瘢痕结构在决定泵功能和重塑方面的核心重要性早已得到认可,但事实证明,设计通过改变瘢痕结构来改善心脏功能或限制重塑的疗法非常困难。许多令人兴奋的新疗法正在研发中,但要预测它们的长期效果,需要详细了解梗死瘢痕如何形成、其特性如何影响左心室功能和重塑,以及瘢痕结构和特性的变化如何反馈,不仅影响心脏力学,还影响电传导、反射性血流动力学代偿以及瘢痕形成本身的持续过程。在本文中,我们概述心肌梗死后的瘢痕形成过程,讨论在愈合梗死背景下心脏功能标准测量指标的解读,接着阐述梗死瘢痕的几何形状和结构对心脏机械和电功能的影响,并总结迄今为止旨在改变瘢痕几何形状和结构的治疗干预经验。从这里回顾的研究中得出的一个重要结论是,计算建模是整合理解这个复杂系统所需的大量信息,并预测新疗法对心肌梗死后瘢痕愈合、心脏功能和重塑影响的重要工具。