How heart is formed in the embryo helps explain congenital heart disease

Published on April 5, 2005 at 3:11 PM · No Comments

Children's Hospital of Pittsburgh Cardiologist Bradley B. Keller, MD, and his research team are discovering details in the lab that explain how the heart is formed in the embryo. This knowledge improves the chances of doctors identifying fetuses who can benefit from intervention to treat congenital defects.

Doctor's in the Heart Center at Children's are redefining what has typically been called early detection. With technologically advanced tools including echocardiography they are looking inside fetal hearts and spotting abnormalities months before babies are born.

Through fetal diagnosis, doctors can actually see the heart and valve structures and detect the most serious form of heart disease in children by 20 weeks of gestation, the mid-point in pregnancy.

In some cases, Dr. Keller turns to the embryo of a chick or a mouse to shed light on how the heart functions and how it acquires its normal structure during its earliest days. In his lab, the avian embryo is an experimental model capable of being modified to allow for the study of specific heart conditions.

For example, hypoplastic left heart syndrome is created by simply tying a small suture around the developing atrium, which alters how blood flows into the heart and reduces the flow on the left side. "If blood flow is reduced to the left side of the heart, the structures on that side of the heart will not grow and the embryo will have hypoplastic left heart syndrome – exactly as we see it in patients," said Dr. Keller, chief of cardiology at Children's. "We can then identify the changes in structure and function associated with this condition and determine if we can reverse this condition by fetal intervention."

To get even more from such models, Children's is participating in the development of new high-resolution imaging systems that allows scientists to peer inside the embryonic heart when it is a small as 2 millimeteres, measure blood flow, and visualize heart function prior to the completion of cardiac valve formation.

Using mice models, researchers are studying how interactions between the pregnant mother and embryo influence how the heart forms and functions. To do so, an operating room environment was created – replete with anesthesia, blood pressure monitoring, surgical techniques and imaging capabilities – to study the mother and embryo simultaneously and observe interactions, such as the effect of low oxygen or how certain medications taken by the mother affect developing heart function and embryo survival.

Researchers in Dr. Keller's lab also are using heart muscle cells from the chick and mouse embryos to regenerate "tissue-engineered" heart tissues in order to understand how the mechanical environment triggers heart muscle cells to mature and divide. It is all part of learning more about the heart as a dynamic, moving element during development, when dividing cells are forming the heart while constantly exposed to stretching, twisting and other forces.

"Because our long-term goal is to repair the heart using a patient's own cells and tissues, cell transplant, for example, we have to understand their native environment," Keller added.

Congenital heart disease is of particular interest to Dr. Keller and his team – who follow their patients from prior to birth well into adulthood. Improvements in general diagnostic cardiology and interventions that open up heart valves or close holes in the heart using catheters and minimally invasive techniques are helping young patients avoid major surgery.

Children's doctors have made great strides in diagnosing problems with echocardiology, a safe, noninvasive procedure that uses high frequency sound waves to deliver a detailed picture of the heart. Children's also is expanding its interventional cardiac catheterization lab to take advantage of new ways to use catheters as therapeutic devices and is partnering with local biotechnology companies to develop novel approaches that optimize both software and the catheters used for interventional procedures.

At Children's, researchers are studying tissue engineering for ways to regulate how heart muscle cells grow and mature, hoping that someday such science can be used to repair abnormalities in the heart of children. But, detection is the first step.

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