Date of Award
Master of Science (MS)
Hemodynamic forces drive remodeling of the early cardiac system in embryonic development. Perturbations of normal cardiac blood flow can cause the formation of defects and malformations within the cardiac system. Specifically, changes in hemodynamics can cause the formation of different congenital heart defects. The formation of heart defects has been studied; however, vasculature specific defects caused by changes in blood flow patterns in the early cardiac system have not been studied to the same degree. In this thesis, the effects of hemodynamic changes on arterial development were studied. Outflow tract banding (OTB) was used to cause a local increase in peak blood flow velocity in the outflow tract (OFT) of the early chick embryonic heart and resultant changes in the downstream dorsal aorta (DA) were studied. OTB was performed at 3 days of incubation, the suture was removed 24 hours later, and the embryo was studied at different time points up to 18 days of incubation. Hemodynamic measurements were taken at the OFT and the DA before and after OTB to see how changes in blood flow patterns in the early embryonic cardiac system affect development of the DA and its extracellular matrix (ECM) proteins. Elastin and collagen were of specific interest. Doppler ultrasound was used to show that OTB led to an increase in blood velocity in the OFT after banding and a decrease in velocity in the DA after 3 days of incubation (immediately after suture removal). No difference in DA velocity was seen at 10 days of incubation (6 days after suture removal). Two-photon imaging was used to show that changes in blood flow velocity due to OTB caused no discernable difference in aortic elastin or collagen organization through 11 days of incubation. It is likely that longer incubation periods (beyond 11 days) are needed in future work to investigate changes in the DA ECM amount and organization due to OTB.
Dr. Jessica Wagenseil
Dr. Spencer Lake Dr. Amit Pathak