Cardiovascular Research Laboratory

Congenital cardiovascular (CV) malformations represent one of the leading causes of morbidity and mortality in children and adults, however, it remains unclear how congenital CV malformations occur. The heart is the first functioning organ during embryogenesis and begins to beat 18 days post-conception in humans. The primitive embryonic heart then rapidly transforms from a pulsatile, straight tube into the complex 4-chamber adult heart within the first 8 weeks in human pregnancy and within 5 days in the chick embryo. It is during this critical period of development that most congenital heart defects originate. Yet, detection of altered CV structure and function may not occur until many days, months, or years later.

Our research laboratories investigate the physiology and biomechanics of developing CV systems in chick and mouse embryos in order to better understand the structural and functional maturation of the normal heart and blood vessels and the causes for congenital heart disease.

Our laboratory has pioneered the integrated use of microinstruments to measure blood pressure, blood flow, and cardiac chamber dimensions in the 1 millimeter diameter embryonic heart. Because embryonic CV structural and functional maturation in chick and mouse embryos resembles human development, we can use these animal models to determine the relationship between biomechanical loading conditions and morphogenesis. For example, we have produced a model of hypoplastic left heart syndrome (HLHS) in the chick embryo by chronically reducing left ventricular filling via partial left-atrial ligation (LAL). We have also created experimental models of increased ventricular work via narrowing of the ventricular outflow tract (conotruncal banding - CTB) and by unilateral vitelline artery ligation (VAL).

In order to better understand the interactions between mother and fetus (in mammals) that may contribute to altered CV morphogenesis, we also investigate maternal and embryonic/fetal CV function in pregnant rodents using high resolution ultrasound as well as invasive techniques.

Our laboratory also serves as a core facility to determine CV structure and function in mature animals undergoing experimental protocols to evaluate novel therapies (cells, materials, devices, software) to treat congenital and acquired heart disease.