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Growing Hearts Go With the Flow

8 January 2003 (All day)
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Shear madness. Spinning blood fills the ventricle in a 4.5-day-old zebrafish embryo. (Colored arrows show the direction of particle movement.)

Without a beating heart, no blood can flow. That's obvious, but the converse also appears to be true: Without flowing blood, the beating heart cannot grow and develop properly, according to a new study that measures and manipulates the fluid forces on the vessel walls of the embryonic heart.

Researchers have suspected for some time that flowing blood helps the heart develop. Fluid forces can cause cultured cardiac cells to alter gene expression patterns and rearrange their cytoskeleton. But without measurements of the forces, scientists couldn't prove the connection.

To track and measure blood flow in developing zebrafish hearts, bioengineer Jay Hove of the California Institute of Technology in Pasadena and his colleagues borrowed tricks from genetics and engineering. Taking advantage of the naturally see-through zebrafish embryo, the team selected a transgenic version that expressed green fluorescent protein in the cardiac valves, which made the structures in the heart easier to visualize. Then, using laser light, they followed a small group of red blood cells through the heart. After calculating the velocity and path of these cells, the team could recreate flow patterns in the heart.

For a small embryo, the blood moved surprisingly fast, 0.5 cm/s. It also looped into vortices. Because the blood in the 150-micrometer-long embryonic heart is so viscous, the speed and turbulence of the blood causes the vessel walls to experience a high shear stress--like a skateboarder would experience upon falling and sliding across pavement. To test whether this affects the early heart, Hove's team used small beads to block blood flow in the zebrafish heart at 37 hours, when the heart is little more than a tube. Without blood flow for four and a half days, the heart developed an abnormal third chamber and malformed valves, the team reports in the 9 January issue of Nature. Control embryos developed normally, verifying that lack of oxygen or nutrients didn't cause the abnormalities.

“This study is ground-breaking because of the novel approach taken by the investigators,” says cardiologist Kent Thornburg of Oregon Health and Science University in Portland. Until now, he says, researchers have had to rely on theoretical models to study the physical forces that guide the development of the heart.

Related sites
Jay Hove's Web page
Cardiovascular bioengineering at Oregon Health and Science University

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