Bioengineering Analysis of Three-Dimensional Electromechanical Interactions in the Heart

University Of California-San Diego, La Jolla CA

Investigators

Abstract

0086482 McCulloch The 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.