August 11, 1994
Media Contact:Joann Rodgers
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"It's hard to overstate the potential implications in practical terms..."

The causes of fatal irregularities in the heartbeat may not be problems with the electrical connections between heart cells, as long believed, but problems in a basic energy-producing process inside the cells, according to a study by researchers at Johns Hopkins.

Doctors believe the new theory will open up completely new approaches for diagnosis and treatment of arrhythmias, which can fatally strike persons with no prior history of heart problems. The researchers published their work in this week's issue of Science.

"It's hard to overstate the potential implications in practical terms," says Eduardo Marban, M.D., Ph.D., lead researcher on the project. "What we're describing in this paper represents a fundamentally new mechanism for cardiac arrhythmias."

The Hopkins team studied individual muscle cells from the ventricles, or lower chambers, of a guinea pig's heart.

After measuring the cells' responses to certain electrical stimuli, Marban and his research team induced stress in the cells by removing their energy source (glucose); when stimulated again, the cells' ability to react decreased, disappeared and then increased again.

"We believe what's driving this cyclical behavior is glycolysis, a fundamental method of making energy in the cell when there's no oxygen around," explains Marban.

Among the enzymes that control glycolysis, the most important is an "incredibly smart" one known as phosphofructokinase. Normally this enzyme is very sensitive to the cells' energy needs, efficiently switching glycolysis on and off in accordance with those needs.

Under metabolic stress, though, this switch can jam in the "on" position, Marban says. The changes this error produces in the cell alter the cell's skin or membrane, interfering with the cell's ability to respond to electrical stimulation.

Marban believes this same effect may produce a disruption that grows to affect the electrical pattern of the entire heart. His next step in proving the theory is to study how resistance to stimulation affects networks of cells.

If doctors confirm the theory, Marban believes a number of new treatment options will open up. Researchers could, for example, seek out drugs that block the changes in the cell membrane that make it resistant to electrical stimulation. Alterations in diet also may be able to prevent the glycolytic process from going awry.

-- JHMI --
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