Quantifying function in the zebrafish embryonic heart: A study on the role of timed mechanical cues

Congenital heart defects are a relatively common problem, yet the cause is unknown in the large majority of cases. A significant amount of past research has shown that there is a link between altered blood-induced mechanical stress and heart development. However, very little research has been done to examine the effect of altered loading timing. During embryonic development, the heart undergoes a drastic change in morphology from its original valveless tube structure to a complete multi-chambered pump with valves. Blood flow dynamics are consequently altered significantly as well. Given the changes occurring through this period, it is hypothesized that significant and persistent decreases in heart function occur when cardiac loading is altered during certain time windows of early development.;The main objectives of this work were to (1) develop a methodology to quantify heart function in the embryonic zebrafish from high-speed bright field images, (2) develop a model for temporary and noninvasive alteration of cardiac loading, and (3) apply the methodology to normal and treated embryos to determine whether certain time windows of altered loading are more impactful than others. Results indicated that altered loading during the tube and early looping stages of development produce persistent changes in heart morphology along with accompanying decreases in cardiac function. Altered loading during late cardiac looping resulted in temporary changes in function which did not persist through the latest time point measured.;This work has produced extensive tools for quantifying heart function from high speed images and presents a new model for altered cardiac loading in the zebrafish. Results support the hypothesis that the heart is more sensitive to altered loading during certain windows in development. This provides new insight into how congenital defects may develop and sets the stage for future experiments investigating the effects of altered loading on heart development.