During development, the heart transforms from a smooth-walled tube with some circumferentially aligned myofilaments to a four-chambered pump with a complex but highly organized fiber architecture. The applicant contends that this transformation likely involves a dynamic interaction between genetic and environmental factors. The proposed research seeks to investigate the role that biomechanical forces play in this process. The long-term goal of this research is to use experiments and computational models to determine the biomechanical principles that regulate myocardial remodeling during development. The biological model for the proposed research is the embryonic chick heart during stages 10 to 24 (1 to 4 days of a 21-day incubation period). First, the morphological and biomechanical properties of the heart will be determined for normal and perturbed ventricular pressures. At each stage, a three-dimensional computer representation for the heart geometry will be generated that includes the trabecular and muscle-fiber architecture, and combined extension-inflation and indentation tests will provide material properties. This information then will be used as the basis for developing a finite element model for the embryonic heart. The model will include the effects of large deformation, anisotropy, muscle activation, and complex geometry. Wall strains will be measured for model validation. Next, the remodeling response of myocytes cultured on elastic membranes subjected to dynamic biaxial stretch will be studied. The data from these experiments will be used to formulate biomechanical remodeling rules, which will be incorporated into the computational model. Finally, the model will be used to investigate the mechanics of ventricular remodeling.
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