Heart Attack Therapy Prevents Long-Term Damage

Animal study finds novel method prevents dangerous leakage

MONDAY, March 15, 2004 (HealthDayNews) -- A new way to treat heart attacks, aimed at inhibiting the leakage of fluid from the blood vessels of the heart, may prevent long-term damage and save more lives, a new study finds.

The research, done at the Scripps Research Institute in La Jolla, Calif., has so far been completed only in animals. It appears in the March 15 issue of the Journal of Clinical Investigation.

The new treatment takes a different approach than standard heart attack care, says lead researcher David A. Cheresh, a professor of immunology at Scripps. "The first thing that is done when a patient suffers a heart attack is to open up the vessel," Cheresh says.

But experts have long known the occluded vessel is just part of the problem after a heart attack. Right after the attack, the blood vessels near the site of the injury become leaky, causing fluid accumulation in the healthy area of the heart, Cheresh says.

The leakage is a result of the oxygen deprivation that occurs after a heart attack. The oxygen deprivation leads, in turn, to the production of a protein called vascular endothelial growth factor (VEGF). VEGF has a beneficial effect and an adverse effect -- it promotes new blood vessel growth but also causes the unwanted side effect of vessel permeability, which leads to the leaking.

"That leak response leads to very serious side effects and consequences and contributes to, we have found, the lion's share of actual injured tissue around the heart muscle," Cheresh says.

The leak response, he says, "begins the process of an irreversible cascade, even if the vessel that caused the original injury is opened up."

In the laboratory, Cheresh's team studied animals that lacked the gene that governs the leak response, and gave them heart attacks. "The heart attacks are essentially minimal," Cheresh says. "They are maybe one third as bad."

Next, Cheresh and his team treated normal animals with a compound that inhibited this leaky effect without blocking the beneficial growth of new blood vessels, using a drug that "turns off the leak response by turning off an enzyme [that helps to regulate it]." The enzyme the compounds blocked is called Src kinase; doing so successfully prevented the fluid buildup after a heart attack.

"We didn't appreciate how much of the actual long-term damage in the heart can be accounted for by simply turning off the leak response," Cheresh says.

"It's a great paper," says Dr. Valentin Fuster, past president of the American Heart Association and director of the Cardiac Institute at Mount Sinai School of Medicine in New York City. "My reaction is very positive."

The research, he adds, unravels the basic mechanism by which heart attack size increases and shows that by blocking one element, it helps minimize the damage.

By the end of summer, Cheresh hopes to begin clinical trials of the drugs in heart attack patients.

More than 1 million people in the United States suffer a heart attack every year, according to the American Heart Association. About 515,000 heart attacks each year prove fatal, according to the National Heart, Lung, and Blood Institute.

Someday, Cheresh speculates, standard care after a heart attack will involve opening up the vessel, either by giving a clot-busting drug or inserting a balloon, and then stopping the leak associated with the attack to prevent long-term damage to the heart.

More information

To find out about risk factors for heart disease, visit the American Heart Association, which also has a page on heart attacks.

SOURCES: David A. Cheresh, Ph.D., professor, immunology, Scripps Research Institute, La Jolla, Calif.; Valentin Fuster, M.D., past president, American Heart Association, and director, Cardiac Institute, Mount Sinai School of Medicine, New York City; March 15, 2004, Journal of Clinical Investigation
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