There is substantial evidence that morphogenesis and cardiovascular phenotype depend upon mechanical loading of the heart during early stages of development. The actual mechanisms, however, have not been determined. We hypothesize that a control law exists, which governs the state of stress and/or strain in the embryonic heart cell through growth and morphogenesis. The control system is parametric in nature and operates in a closed- loop feedback regime to alter both the passive and active components of the heart. As a step towards documenting the existence of such a control law, we propose to identify the control of stress and strain in the normal heart and examine the response to perturbed hemodynamic pressure. The experimental model is the embryonic chick heart between stages 18 to 31.
The specific aims are to: (1) Use confocal scanning laser microscopy to obtain morphological data and information on trabecular and myofibrillar patterns and densities. The three-dimensional geometry of the heart will be reconstructed from these scans. Both the normal and perturbed heart will be characterized. (2) Measure the mechanical properties of the embryonic heart under normal and perturbed loading. Extension, ramp-and-hold, and inflation tests will be used and appropriate forms of a constitutive relationship constructed. (3) Identify a relationship governing reduction in error between the controlled variables and the reference input by combining the results from Aims (1) and (2). The geometrical models from Aim (1) will be used to construct a realistic finite element representation of the heart with the results of Aim (2) providing material properties. The models will be solved and various measures of stress and strain compared between the normal and pressure-perturbed hearts. These comparisons, in addition to comparisons of geometrical data from Aim (1) and material property data from Aim (2), will be used to indicate possible forms of the control law and growth laws. The results of this study will provide insight into the mechanisms of mechanical sensing and control in heart development and into the relationship between mechanical environment and phenotype. Further study may also yield insight into congenital cardiovascular malformations, a major cause of morbidity and mortality in children and adults.
| Miller, Christine E; Wong, Chandra L; Sedmera, David (2003) Pressure overload alters stress-strain properties of the developing chick heart. Am J Physiol Heart Circ Physiol 285:H1849-56 |
