During early cardiac development, the embryonic heart, like the mature heart, adjust cardiac mass to functional load. However, the embryonic heart has primitive atrioventricular and conotruncal cushions, no functional conduction system and no coronary arteries. Therefore, the structurally simple embryonic heart matches cardiac growth to hemodynamic demand using local tissue and cellular mechanisms. Technical advances now allow the integrated study of hemodynamics and biomechanics in the embryonic heart. This proposal for a Physician Scientist Award outlines a comprehensive research and didactic schedule to perform the analysis and modelling of ventricular mechanics in the chick embryo during cardiac morphogenesis.
The aim of this proposal is to provide the candidate with the skills to pursue his research goals as an independent investigator at the completion of the award. PHASE ONE concentrates on normal cardiac development and includes a graduate curriculum in Mechanical Engineering to develop a foundation in biomechanical analysis and theory. PHASE TWO expands the project to include development under chronic changes in loading conditions, and continues the curriculum sufficient for a Ph.D. in Mechanical Engineering. Performance during PHASE ONE, defense of the PHASE TWO proposal, and PHASE TWO progress will be reviewed by a Faculty Advisory Committee. The research proposal is focused on defining the link between cardiac mechanics with growth during early morphogenesis. The experimental protocol includes: 1) simultaneous measurement of physiology and morphology (servo-null pressure, pulsed-Doppler blood flow, and video microscopy of ventricular area); 2) description of the tissue geometry and contractile element orientation of the developing ventricle (light and electron microscopy); 3) definition of the material properties of the heart (strain, compression, and permeability testing); and 4) mathematical modelling of ventricular stress-strain and stress-growth relationship (linear deformations, finite elements, and non-linear effects). This data is crucial in understanding the mechanical-biological factors which regulate cardiac development. The results of this work will also provide a working model for the interpretation of data now available on the developing human embryo.
