Bioengineering Analysis of Three-Dimensional Electromechanical Interactions in the Heart

心脏壁的三维肌肉结构是心脏机械和电功能及其相互作用的基本决定因素。这项研究的主要目的是开发从解剖学和生物学角度详细的心脏电力学计算模型，并使用新的实验方法进行测试。计算模型和实验模型将一起用于研究有关心脏电力学的结构和分子决定因素的假设。其具体目的是：1.心肌纤维排列成板层，在壁内具有独特的结构，这种结构在不同地区是不同的。我们将检验这一假设，即这种分层组织影响心脏的电气和机械特性，有助于在健康期间实现最佳性能。这种结构的改变可能会导致健康问题。这将通过结构成像和测量、计算建模以及使用磁共振成像和高速光学成像的机械和电学特性的功能成像相结合来探索。心肌纤维在心壁中分支和张开。这种模式可以在一些遗传性心脏病中表现出来。我们将研究这样一种假设，即纤维分支的统计模式影响心壁的机械和电学特性。这些研究将使用理论建模、自动微结构组织分析、计算建模和基因工程小鼠品系的实验研究。心脏电脉冲触发机械收缩，但我们和其他人也表明机械负荷也影响电特性和节律紊乱的风险。我们将探讨这样的假设，即特定的壁力学模式可以通过拉伸激活的离子通道和其他细胞机制影响心肌的电生理。这些研究将使用生物学上详细的、动态的三维计算模型，这将通过在离体心中的实验测量来验证。这些研究还将调查局部机械特性对心律失常风险的影响。为了帮助加强国家科学和工程基础设施，我们将部署基于网络的心脏计算模型版本，继续让本科生参与研究并扩大我们的少数群体外展工作；并举办行业支持的工作坊。这项研究将开发新的实验和计算模型，将在理解基本心脏生理学和生物物理学、药物发现和生物医学工程设计以及用于教育、培训和协作的模拟环境中得到应用。

0086482McCullochThe three-dimensional muscle structure of the heart walls is a fundamental determinant of cardiac mechanical and electrical functions and their mutual interactions. The main objective of the proposed research is to develop anatomically and biologically detailed computational models of cardiac electromechanics, and to test them using novel experimental methods. The computational and experimental models will be used together to investigate hypotheses regarding the structural and molecular determinants of cardiac electromechanics. The specific aims are:1. Cardiac muscle fibers are arranged into laminae with a characteristic architecture that varies regionally within the walls. We will test the hypothesis that this layered organization affects cardiac electrical and mechanical properties, contributing to optimal performance during health. Alterations in this structure could contribute to health failure. This will be explored by a combination of structural imaging and measurement, computational modeling, and functional imaging of mechanical and electrical properties using magnetic resonance imaging and high-speed optical imaging.2. Cardiac muscle fibers branch and splay in the heart wall. This pattern can be disarrayed in some inherited heart diseases. We will investigate the hypothesis that the statistical pattern of fiber branching affects the mechanical and electrical properties of the heart walls. These studies will use theoretical modeling, automated microstructural tissue analysis, computational modeling and experimental studies in genetically engineered mouse strains.3. Cardiac electrical impulses trigger mechanical contraction, but we and others have also shown that mechanical loading also affects electrical properties and the risk of rhythm disorders. We will investigate the hypothesis that the specific patterns of wall mechanics can affect the electrophysiology of cardiac muscle through stretch-activated ion channels and other cellular mechanisms. These studies will use a biologically detailed, dynamic, three-dimensional computational models, which will be validated by experimental measurements in isolated hearts. These studies will also investigate the effects of regional mechanical properties on the risk of arrhythmia.4. To help enhance the national science and engineering infrastructure, we will deploy web-based versions of the computational models of the heart, continue to involve undergraduates in research and expand our minority outreach efforts; and hold an industry-supported workshop.The new experimental and computational models to be developed in this research will have applications in understanding basic cardiac physiology and biophysics, in drug discovery and biomedical engineering design, and in simulation environments for education, training and collaboration.