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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Cardiovascular and Pulmonary Research A Study Section (CVA)
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Washington University
Biomedical Engineering
Schools of Engineering
Saint Louis
United States
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Damon, Brooke J; RĂ©mond, Mathieu C; Bigelow, Michael R et al. (2009) Patterns of muscular strain in the embryonic heart wall. Dev Dyn 238:1535-46
Chabert, Steren; Taber, Larry A (2002) Intramyocardial pressure measurements in the stage 18 embryonic chick heart. Am J Physiol Heart Circ Physiol 282:H1248-54
Taber, L A; Chabert, S (2002) Theoretical and experimental study of growth and remodeling in the developing heart. Biomech Model Mechanobiol 1:29-43
Voronov, Dmitry A; Taber, Larry A (2002) Cardiac looping in experimental conditions: effects of extraembryonic forces. Dev Dyn 224:413-21
Taber, L A (2001) Biomechanics of cardiovascular development. Annu Rev Biomed Eng 3:1-25
Taber, L A; Humphrey, J D (2001) Stress-modulated growth, residual stress, and vascular heterogeneity. J Biomech Eng 123:528-35
Taber, L A; Zahalak, G I (2001) Theoretical model for myocardial trabeculation. Dev Dyn 220:226-37
Taber, L A; Ng, S; Quesnel, A M et al. (2001) Investigating Murray's law in the chick embryo. J Biomech 34:121-4
Taber, L A (1998) Mechanical aspects of cardiac development. Prog Biophys Mol Biol 69:237-55
Taber, L A (1998) An optimization principle for vascular radius including the effects of smooth muscle tone. Biophys J 74:109-14

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