A Possible Advance in Reducing Heart-attack Damage

A new therapy that slows leakage from cardiac blood vessels after a heart attack appears to reduce long-term damage and improve survival odds, researchers say.

A new therapy that slows leakage from cardiac blood vessels after a heart attack appears to reduce long-term damage and improve survival odds, researchers say. The discovery of a protein that sparks the breakdown of heart blood vessels after an attack was reported Monday in the Journal of Clinical Investigation. “Immediately following a heart attack, blood vessels near the site of injury become leaky, causing fluid accumulation in the healthy area of the heart surrounding the injured site,” said David Cheresh, a professor of immunology at the Scripps Research Institute in La Jolla, Calif. He led the research team. “Until now, nobody has realized the extent to which this leak response (called edema) damages heart tissue and causes long-term tissue injury. We discovered a way to block this process and thus save heart tissue from irreversible damage.” Early tests of this inhibitor drug on lab animals that mirror human heart attacks have shown reductions in heart damage by 40 percent to 60 percent. More than 1 million Americans suffer heart attacks each year; about half of them fatal. Current treatment of heart attacks involves breaking up blockage to the artery in order to restore blood flow to the heart either with “clot-busting” drugs or balloon catheters and wire mesh stents intended to shore up weakened artery sections. But because the heart is starved of oxygen, Cheresh said, tissue damage may keep worsening even after blockage is removed, leading to a cascade of cell deaths in the heart muscle and leaving scar tissue that weakens the heart and causes it to pump blood less effectively. The key is a cell-growth factor called VEGF. It promotes the growth of new blood vessels and also causes existing ones to leak. Cheresh and colleagues discovered a few years ago that mice born without the ability to make a protein that activates VEGF don’t have leaky blood vessels. These animals showed a high degree of resistance to the damaging effects of a heart attack because the protein, called Src, is needed to break down blood-vessel linings. Researchers started looking for a drug that might inhibit this process without blocking the beneficial effects of new blood-vessel growth. The new blockade, even if given as late as six hours after a heart attack, drastically reduced tissue injury and increased long-term survival in tests using lab animals to mimic heart attacks in humans. “This early protection reduces the loss of cardiac tissue and thus the necessity for replacement by a functionally inadequate scar,” Cheresh said. (Source: Scripps Howard News Service: Lee Bowman: MedLine Plus: March 2004)