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Heart development depends on a delicate interplay between genetic and environmental factors. Congenital heart disease (CHD) affects about 1% of newborn babies and is the leading, non-infectious cause of death among children. Although genes that contribute to CHD have been identified, most CHD cases (~95%) cannot be explained by genetic anomalies. Interestingly, blood flow through the heart has been recognized as a key factor affecting cardiac development, with abnormal blood flow conditions during early embryonic development leading to cardiac defects. Blood flow conditions in the embryo can be affected by several factors, including mother’s nutrition, diabetes, or placental anomalies. Further, blood flow is affected by cardiac structural changes, and thus even in clear cases of genetically-induced CHD, anomalous blood flows generated by the cardiac defect lead to ‘secondary’ detrimental effects that affect heart development. Neither the mechanisms by which abnormal blood flow dynamics lead to cardiac defects, nor the dynamics of the normal beating heart and of normal blood flow inside the heart during early development have been fully elucidated.
The interaction between blood flow and cardiac tissues generates mechanical stimuli on cardiac cells that are key in modulating heart development. Cardiac cells sense and respond to these mechanical stimuli, and in doing so, they modulate cardiac growth and remodeling. To better understand this modulation, quantification of heart dynamics and mechanical stimuli is necessary. Our goal is to understand normal changes in blood flow over developmental stages and the effect of altered mechanical stimuli on cardiac development. To this end, we study the heart of chicken embryos, since at very early stages of development the hearts of human and chickens are very similar and developmental processes are highly conserved among vertebrate species. We focus on a specific heart segment that is very sensitive to hemodynamic conditions, the heart outflow tract, at early embryonic stages. During these stages, the heart is tubular, but beats, and pumps blood. We use a combination of imaging data, physiological measurements, and computational modeling to better understand the mechanics of the early developing heart, and study the effects of hemodynamics on cardiac development. This talk will describe some of our current efforts to understand normal cardiac development and how abnormal blood flow conditions lead to congenital heart defects and CHD.