Multiscale Modeling of Left and Right Ventricular Function

Computational modeling has the potential to significantly impact our understanding of the cardiovascular system. From cell level to organ level, the left and right ventricles of the heart are functionally and structurally distinct. Factors such as geometry, fiber architecture, contractile properties, as well as the pressure loading environment, cause the ventricles to respond to disease and therapy in different ways. Surprisingly, many of these key factors are ignored in current computational (finite element) modeling approaches, leading to inaccurate representations of heart function. This is driven by the fact that most research has focused primarily on the left ventricle. Only in recent years has the importance of right ventricular function been addressed. To overcome this knowledge gap, the proposed research will investigate fundamental differences related to cellular level function and incorporate this into an organ level finite element model of the heart. The goal of this proposal is to use novel multi-scale techniques to integrate cellular level measurements into a functionally accurate bi-ventricular model of the heart. This will be accomplished with a three phase research plan: (1) cellular level experiments will be conducted on cardiac myocytes from both ventricles in order to measure differences in force, calcium transients, and shortening velocity, (2) organ level data will be collected in living animals using cardiac MRI and catheterization in order to measure geometry, wall deformation, and pressure in each ventricle, and (3) computational algorithms will be developed to create multi-scale finite element models that couple function at the cell level to the organ level. The experimental measurements will provide validation to ensure accuracy of the computational method.