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Muscle Fatigue Drug May Fight Heart Failure

It seems to plug calcium leaks that cause tiring in muscles, study says

TUESDAY, Feb. 12, 2008 (HealthDay News) -- An experimental drug may help fatigued athletes and patients weakened by heart failure regain their energy, say physiologists at Columbia University Medical Center.

Tests on mice and humans found that, after extreme exercise regimens, tiny leaks of calcium continuously enter the muscle cells, according to the study published online in the Feb. 11 issue of the Proceedings of the National Academy of Sciences. The leak weakens the force produced by the muscle and also turns on a protein-digesting enzyme that damages the muscle fibers, leading to the overall feeling of exhaustion for days or weeks afterward.

This same leak was previously discovered by Columbia researchers in the muscles of animals with heart failure.

The researchers then developed an experimental drug to plug these leaks, and tested it on mice subjected to daily three-hour swims over three weeks. Without the drugs, mice were exhausted. With the drug, the mice were still energetic, had lost less exercise capacity after three weeks, and their muscles showed fewer signs of calcium leakage, atrophy and less muscle damage.

While extreme athletes, such as marathoners, often regain their strength and vigor after several days, the findings suggest the drug may provide relief from the severe exhaustion that prevents patients with chronic heart failure from performing simple tasks.

"People with chronic heart failure are subject to this same kind of muscle leak and damage constantly, even without doing any exercise," study senior author Dr. Andrew Marks, chairman of Columbia's department of physiology and cellular biophysics, said in a prepared statement. "One of these patients' most debilitating symptoms is muscle weakness and fatigue, which can be so bad they can't get out of bed, brush their teeth or feed themselves."

Plans are under way to test the drug at other medical centers in patients with heart failure to see if it relieves fatigue and improves heart function. Even if successful, it will take several years before the drug will be commercially available.

Fatigue experienced by heart failure patients does not stem from reduced blood and oxygen being supplied to the muscles by the heart, as one might expect. Instead, Marks' previous research in muscles of mice with heart failure suggested the cause is calcium leak in muscle cells, which reduce the ability of a single muscle to contract repeatedly before losing force.

"We then had a hunch that the process that produces fatigue in heart failure patients also may be responsible for the fatigue felt by athletes after a marathon or extreme training," study first author Andrew Bellinger said in a prepared statement. "Our new paper shows that fatigue in both patients and athletes probably stems from the same leak."

More information

The U.S. Centers for Disease Control and Prevention has more facts about heart failure.

SOURCE: Columbia University Medical Center, news release, Feb. 11, 2008
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