Fetal heart development can be interrupted or altered by a number of external factors – drugs, medications and alcohol are the three most common. These interruptions or alterations ultimately result in a heart defect. Unfortunately, the stage in which defects tend to happen, mothers may be unaware that they are pregnant, so they may end up damaging their growing baby’s heart unknowingly.
As blood cells pass through the heart, cells may drag on the endothelial cells. This dragging, otherwise known as shear stress, has been linked to changes in gene expression that can result in heart defects, particularly valve defects. How the stress is connected is unknown, however. Researchers at Case Western Reserve University hope to better understand this phenomenon so that they can develop methods for treating heart defects in-utero.
“Alcohol exposure may affect shear stress by modulating the heart rate, but it may also involve vigor and/or timing of the contraction,” said Andrew Rollins, associate professor of biomedical engineering and senior author of the study. “Now that we have the tool, we can start to figure that out.”
That tool, a modified version of the Doppler optical coherence tomography (OCT for short) used by submarines to picture their surroundings in the deep sea, shines an infrared laser on the heart. The laser provides reflections of the heart, measured at various depths and then helps researchers create a three-dimensional image of the heart. Researchers then add the dimension of time, which enables them to create “movies” of blood flowing through the heart and its structure.
Images are first taken at two days, a heart development stage known as cardiac looping. It is at this stage in which the simple straight line that serves as an embryo’s heart turns clockwise to form a helix. This is the beginning formation of two atria and two ventricles. Images are taken again at three days and eight days, the stage in which the septum – the wall that separates the left and right sides of the heart – have formed.
“We’re analyzing early and late development of the heart and trying to make the connections that result in valve dysfunction,” said Lindsy M. Peterson, PhD student in Rollins’ lab and lead author on the study.
With the mapping technology in place, researchers have now paired with Ganga Karunamuni, a pediatrics research associate at the school of medicine. They are now pursuing potential experiments for testing the quail heart modes response to alcohol exposure. They also plan to test how mental health drugs, selective serotonin receptor inhibitors, alter shear stress.
For their first experiment, researchers are exposing the model to alcohol at gastrulation, a stage in which the embryo changes from two sheets of cells to a multi-layered organism. Peterson says that it is in this critical stage in which many birth defects occur; it is also during this stage that a woman may not know she is pregnant.
Rollins says that clinical applications are a long ways off. However, the team has already started to talk about the possibilities of treatment.
“If it became feasible to screen a fetus for abnormal heart function,” Rollins said. “It might be possible to intervene with drugs, with gene therapy.”
Researchers are also examining the possibility of using non-invasive pulses of infrared light to make the heart contract on demand. They are already working with colleagues in Pediatric Cardiology to develop this technology. If successful, this treatment may be able to treat or prevent heart defects long before an infant is born.
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