This SCOR proposal for a Pediatric Cardiovascular Disease Center is a series of fundamental studies aimed at understanding the biomechanical aspects of cardiac development to normal cardiovascular development and human congenital cardiac defects. The heart is the first functioning organ in the embryo. The embryonic heart is transformed by genetic and epigenetic factors from a tube to a four chambered heart. Errors in this development process produce a wide spectrum of congenital heart defects. Rapid advances in molecular and cellular biology are identifying genetic pathways integral to development. Less is known, however, about the mechanical forces that drive morphogenesis and growth from uncoiling of the DNA strand prior to transcription to the cardiac pumping cycle. Thus, the biomechanical forces at all levels of the developing heart have a central role in formation of the heart and circulation. The long term aid of this SCOR Project is to define supports sophisticated analytic techniques in three cores: Bioengineering, Cardiovascular Physiology and Morphometry to understand mechanisms that interrelate function and form during normal and abnormal cardiovascular morphogenesis. Four projects apply the multidisciplinary expertise available in each core to study: 1. The heart rate and blood flow velocity variability in the human from 10 to 18 weeks gestation. 2. Ventricular/vascular coupling during cardiovascular development. 3. Biomechanical modeling of growth and morphogenesis of the embryonic hear. 4. Atrial/ventricular coupling during cardiovascular development. These studies are fundamental to understanding the biomechanical environment of the developing heart and circulation and provide important information on pathogenetic mechanisms of congenital and acquired cardiovascular disease in humans.
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