Bioengineering Analysis of Three-Dimensional Electromechanical Interactions in the Heart

0086482 McCulloch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。拟议的研究的主要目标是开发解剖学和生物学上详细的计算模型的心脏电动力学，并使用新的实验方法来测试它们。计算和实验模型将一起使用，以调查关于心脏电动力学的结构和分子决定因素的假设。具体目标是：1. 心肌纤维排列成具有在壁内区域性变化的特征性结构的层。我们将测试的假设，这种分层的组织影响心脏的电气和机械性能，有助于在健康期间的最佳性能。这种结构的改变可能导致健康失败。这将通过结合结构成像和测量、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气特性的功能成像来探索。 心肌纤维在心壁内有分支和张开。这种模式在某些遗传性心脏病中可能会被打乱。我们将调查的假设，纤维分支的统计模式影响心脏壁的机械和电气性能。这些研究将使用理论建模、自动化显微组织分析、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，机械负荷也会影响电特性和心律失常的风险。我们将研究的假设，壁力学的特定模式可以影响心肌的电生理通过拉伸激活的离子通道和其他细胞机制。这些研究将使用生物学上详细的、动态的、三维的计算模型，这些模型将通过离体心脏的实验测量来验证。这些研究还将调查区域机械特性对疟疾风险的影响。 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，继续让大学生参与研究，并扩大我们的少数民族外联工作;并举办一个行业支持的研讨会。这项研究中开发的新的实验和计算模型将应用于理解基本的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，培训和合作的模拟环境。

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.