Johns Hopkins Gazette: August 22, 1994

New Theory Changes View of Arrhythmia
By Michael Purdy

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 lead to new
approaches for diagnosis and treatment of arrhythmias, which
can fatally strike people with no prior history of heart
problems. The research was published in the Aug. 12 issue of
    "It's hard to overstate the potential implications in
practical terms," said Eduardo Marban, 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, Dr. Marban and the research team induced
stress in the cells by removing their energy source
(glucose); when stimulated again, the cells' ability to react
decreased, disappeared, 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," Dr. Marban said.
    Among the enzymes that control glycolysis, the most
important is an "incredibly smart" one known as
phosphofructokinase, Dr. Marban said. Normally this enzyme is
very sensitive to the cells' energy needs, efficiently
switching glycolysis on and off in accordance with those
    Under metabolic stress, though, this switch can jam in
the "on" position, Dr. Marban said. 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
    Dr. Marban believes the 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, Dr. Marban believes a
number of new treatment options will be available.
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 prevent
the glycolytic process from going awry.
    The report is the initial research developed in the
Johns Hopkins Institute for the Prevention of Sudden Cardiac
Death, one of the first centers of its kind in the United
States. Each year in America, approximately 300,000 sudden
cardiac deaths occur.
    "SCD is so tragic because it takes people in the prime
of their lives with no warning," said Dr. Marban, the
institute's director.    

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