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Chemical 'band-aid' prevents heart failure in mice with muscular dystrophy

t muscle cells, and vulnerable to damage when stretched.

"That's where poloxamer 188 comes in," Metzger adds. "It assists the heart to be more compliant during the relaxation phase ?allowing more blood to flow into the heart. We demonstrated this effect at the level of individual heart muscle cells, and it turned out to be true at the organ level, also."

The key to the U-M discovery was technology developed by Soichiro Yasuda, Ph.D., a post-doctoral fellow and co-first author of the study. He created a device to allow the simultaneous measurement of force and intracellular calcium concentration in individual myocytes as they are stretched. Yasuda's device uses microcarbon fibers stuck by electrostatic attraction to each end of a single cardiac myocyte. As the myocyte is stretched between the carbon fibers, a transmitter on one fiber measures the amount of stretch and a force transducer on the other fiber measures the contractile force of the cell in response to that stretch.

"It's like stretching a rubber band," Yasuda says. "You can do specific controlled stretches and record the force generated by the cell. We found that myocytes from normal mice easily handled a 20 percent stretch in length, while myocytes from dystrophin-deficient or mdx mice had about 70 percent more passive tension in response to the stretch. Compared to normal myocytes, mdx myocytes were stiffer and resistant to stretching. When they were stretched repeatedly, they started shaking and eventually contracted and died."

"It's a physiologically relevant test, because it mimics what happens in the heart muscle when myocytes must relax and stretch to make room for incoming blood filling the heart," says Metzger, who is affiliated with the U-M's Cardiovascular Center. "This shows, for the first time, the effect of a deficit of dystrophin on individual cardiac myocytes. Our hypothesis was that stretching created small tears or holes in the myocyte membrane, which allow
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Source:University of Michigan


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