Finding triggers of birth defects in an embryo heart

October 30, 2012

Researchers at Case Western Reserve University have found a way to create three-dimensional maps of the stress that circulating blood places on the developing heart in an animal model – a key to understanding triggers of heart defects.

The team has begun testing the technology to uncover how alcohol, drugs and other factors set off events that result in defects found in newborn humans.

Passing drag on the that line the growing heart, a phenomenon called shear stress, which has been linked to changes in gene expression that results in defects, most often in the valves. But precisely how they're connected is unclear.

"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 new study. "Now that we have the tool, we can start to figure that out."

"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, a PhD student in Rollins' lab and lead author. Their work is published in the current online issue of the Optical Society of America's journal Express.

The pair teamed with research assistant professor Michael W. Jenkins; senior research associate Shi Gu; Lee Barwick, an undergraduate researcher now at Brigham Young University; and Michiko Watanabe, a professor of pediatrics at Case Western Reserve School of Medicine.

To look at the structure of the developing heart and blood flow, the researchers modified a technology called Doppler optical coherence tomography. Called OCT for short, they shine an infrared laser on the heart.

The reflections measured at various depths are used to create a three-dimensional image in much the same manner submariners use sonar to picture their surroundings in the deep sea. But the researchers add the dimension of time, creating movies of blood flow through the structures, needed to map shear stress.

They take their first images at two days, during a stage of heart development called cardiac looping. This is when the simple straight tube that's an embryo heart turns clockwise into a helix, forming the beginnings of two atria and two ventricles. They take more images at three days and again at eight days, when the septum, the wall between the left and right sides of the heart, has formed.

Working with Ganga Karunamuni, a pediatrics research associate at the school of medicine, the team is now pursuing a slate of experiments testing the quail heart model's response to and will also test exposure to mental health drugs called selective serotonin receptor inhibitors. Alone or together, they can alter shear stress.

They are exposing the model to alcohol at a stage called gastrulation, when the embryo changes from two sheets of cells to a multi-layered organism.

This is a critical stage for induction of birth defects, Peterson said. In humans, it's an early stage when a woman may not know that she is pregnant.

Rollins said clinical applications are a long way off but the team has begun talking about possibilities.

"If it became feasible to screen a fetus for abnormal heart function," he said, "it might be possible to intervene with drugs, with gene therapy." Or, by using non-invasive pulses of infrared light to make the contract on demand – another technology the team is developing with clinical colleagues in Pediatric Cardiology– to prevent or treat defects before birth.

Explore further: Newborns should be screened for heart defects, study shows

Related Stories

Newborns should be screened for heart defects, study shows

May 2, 2012
There is now overwhelming evidence that all babies should be offered screening for heart defects at birth, according to a major new study published online in The Lancet.

Depressed heart function from stress improved by a simple sugar

July 19, 2011
Enhancing the production of ATP (adenosine triphosphate), an energy carrying molecule in heart cells, may shorten the heart’s recovery time after a heart attack or heart surgery.

New mouse model helps explain gene discovery in congenital heart disease

June 26, 2012
Scientists now have clues to how a gene mutation discovered in families affected with congenital heart disease leads to underdevelopment of the walls that separate the heart into four chambers. A Nationwide Children's Hospital ...

'ROCK' off: Study establishes molecular link between genetic defect and heart malformation

February 6, 2012
UNC researchers have discovered how the genetic defect underlying one of the most common congenital heart diseases keeps the critical organ from developing properly. According to the new research, mutations in a gene called ...

Recommended for you

Hormone discovery marks breakthough in understanding fertility

December 12, 2017
Scientists at The University of Nottingham have shown, for the first time, that a naturally occurring hormone plays a vital part in regulating a woman's fertility, a discovery that could lead to better diagnosis and treatment ...

Study reveals Viagra to be 'ineffective' for fetal growth restriction

December 8, 2017
A University of Liverpool led international clinical trial has found an anti-impotence drug to be ineffective at improving outcomes for pregnancies complicated by fetal growth restriction.

Obese first-time mums more likely to have premature babies

December 4, 2017
Obese women are up to three times more likely to have a premature child during their first pregnancy, according to a study from University College Dublin.

Stillbirth is not just stillbirth—more information is needed

December 4, 2017
Forty two babies are stillborn in Australia every week, and 60 per cent of them are recorded as "unexplained".

First baby from a uterus transplant in the US born in Dallas

December 2, 2017
The first birth as a result of a womb transplant in the United States has occurred in Texas, a milestone for the U.S. but one achieved several years ago in Sweden.

Living in a 'war zone' linked to delivery of low birthweight babies

November 28, 2017
Mums-to-be living in war zones/areas of armed conflict are at heightened risk of giving birth to low birthweight babies, finds a review of the available evidence published in the online journal BMJ Global Health.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.