This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Congenital heart disease affects nearly 1% of all newborns. The etiology is for the large part unknown, and the treatment options sometimes limited. During prenatal development, myocardial mass increases by addition of new cells (hyperplasia), while soon after birth, the mechanism switches to increase in cell size (hypertrophy). Adequate mechanical loading is a critical factor in proper development of the embryonic heart. Our long-term goal is to provide scientific foundations for prenatal repair of selected forms of congenital disease, which should be superior to current postnatal palliative options. In this proposal, we would like to utilize the chick model of left heart hypoplasia, which mimics the deadly human hypoplastic left heart syndrome, to test three potential approaches for prenatal restoration of left ventricular mass. The main hypothesis is that prenatal intervention to correct carefully selected cases of congenital heart disease can be more beneficial in the long term, since such early intervention holds greater potential to restore normal heart structure and function in affected babies.
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