To test for the presence of tears in myocyte membranes, U-M researchers used a special fluorescent dye, which cannot penetrate an intact cell membrane. After a 20 percent stretch, control myocytes remained stable and showed no fluorescence, while myocytes from mdx mice became unstable, started shaking and showed a steady increase in fluorescence, providing direct evidence for membrane damage.
When U-M scientists repeated the stretch test after bathing both types of cells with a solution of poloxamer 188, they found that it restored the ability of mdx myocytes to handle a 20 percent stretch without damage or increased levels of calcium. P188 had no effect on normal myocytes.
The next step was testing the ability of P188 to prevent cardiac damage in the hearts of mdx mice. They found that an intravenous infusion of P188 in mdx mice restored the volume of the heart's main pumping chamber to the volume of normal mice ?a direct effect of P188's ability to restore normal elastic properties in individual cardiac myocytes.
To examine the effects of P188 on mdx hearts under stress, U-M researchers gave the mice a drug called dobutamine to make the heart work harder and faster for 30 minutes.
"During the stress test, 40 percent of the untreated mdx mice progressed to cardiac failure," says DeWayne Townsend, D.V.M., Ph.D., a post-doctoral fellow and co-first author of the study. "Even those that didn't reach the threshold were doing poorly. The control mice, on the other hand, did just fine throughout the whole procedure. When we gave the mdx mice an infusion of P188 before the dobutamine, none of the mdx mice went into cardiac failure. The polyoxamer had an instant corrective effect in the mdx mice, which really surprised us."
In future research, U-M scientists want to te
Source:University of Michigan