Mikaelyn Miles, University of Utah
Pediatrics
Altering myocardial growth interferes with hemodynamic parameters such as blood flow or pressure, and subsequently alters vascular development. We hypothesized that experimentally increasing hemodynamic stress by conotruncal banding during early heart development would result in a remodeling of the arterial wall. The outflow tract of a stage-21 (3_-d) chick embryo was constricted with an overhand knot of a 10-0 nylon suture, and the embryo was returned to the incubator. Normal embryo was not operated. We harvested the embryo at stage-34 (8-d), and fixed the heart in diastole with 0.025 μg/Kg diltiazem in 4% paraformaldehyde. Transverse sections of the carotid artery were stained with H&E staining, and the dorsal aorta was treated with rhodamin-phalloidin-smooth muscle antibody staining. En face sections of the aorta were examined under confocal microscopy. Morphometric analysis was quantitated using customized MatLab software for filament-actin alignment and density. Data are presented as mean±SEM, and analyzed by Student’s t test and ANOVA with statistical significance defined as a p value of less than 5%. Both right and left carotid arteries in the conotruncal banded heart had a thinner vessel wall when compared to the arteries of the normal embryos. Some vessels in the conotruncal banded hearts displayed dilation and variation in size between the right and left coronary arteries. The overall filament length in the dorsal aorta between the normal and banded hearts (39.8±4.3 vs. 29.6±2.7 μm, respectively) was statistically different (p<0.05). The filaments were also widely spaced in the conotruncal banded hearts. Altered growth in the developing heart caused by altering the hemodynamics results in secondary abnormalities in development due to abnormal vascular architecture. These factors may be important in the understanding of myocardial development with defects such
as coarctation of the aorta, vascular rings, aortic stenosis and interrupted aortic arch.