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STANFORD-For those who like a tipple of wine, the latest results from Stanford scientists will be as easy to swallow as a well-aged red. The researchers have found that an amount of alcohol equivalent to that found in one to two drinks protects the heart from the kind of damage suffered during a heart attack. They have also learned how the protective benefit occurs. 

The experiments - so far tried only in rats - showed that exposing the heart to alcohol for 10 to 20 minutes immediately before insult was protective. The amount of alcohol sufficient to reduce damage to the heart by 70 percent was equivalent to one to two alcoholic drinks consumed by a person. 

"We need to determine if it is true for humans, but this is not an outrageously high level," said Daria Mochly-Rosen, PhD, associate professor of molecular pharmacology and senior author of two related studies on the topic published in the October 26 Proceedings of the National Academy of Sciences. "This is the first study to show that a brief exposure to levels of alcohol that are really tolerated well - even for those worried about addiction - provides protection," she said. 

A heart attack is often the result of a blockage in one of the arteries supplying blood to the heart muscle. The blockage causes a condition known as ischemia, in which heart cells are strangled of oxygen and nutrients, and quickly die. Little can be done to save these cells. But many surrounding cells are exposed to what Mochly-Rosen calls "nasty stuff" released by the dying cells, and these vulnerable cells appear to be protected by the alcohol, she explained. 

In addition to ischemia suffered during a heart attack, the heart's blood supply is interrupted and similar damage may occur in several other instances. 

"There are two situations in which the time of infarct is clearly marked: transplantation and any kind of open chest surgery," said Mochly-Rosen. Hearts harvested for transplantation suffer a period of ischemia before they reach the recipient, and during open heart surgery there is also a period of ischemia, Mochly-Rosen explained. She believes that patients in both groups may benefit from exposure to alcohol, administered intravenously, just prior to the procedure, and is hoping to launch a clinical trial to test her theory. 

In addition to determining that small amounts of alcohol can be good for the heart, members of Mochly-Rosen's lab have figured out how the benefit arises. They found that alcohol turns on an enzyme called epsilon protein kinase C (PKC), and they have since focused their efforts on finding a substance, other than alcohol, that will activate it. 

While alcohol protects the heart by activating epsilon PKC, it can also switch on lots of other things inside the cell, which may be undesirable, said Mochly-Rosen. She and her colleagues designed a very small protein fragment, or peptide, that specifically activates epsilon PKC. When the researchers added the peptide to heart cells grown in vitro, it protected the cells from ischemic damage by turning on epsilon PKC. Benefits were also seen in the hearts of mice that were genetically engineered to produce the peptide soon after birth. Mochly-Rosen and her collaborator, Gerald W Dorn II, MD, from the University of Cincinnati, found that these mice had normal, healthy hearts; but due to the peptide, they suffered less damage and recovered more quickly from ischemic insults than did the hearts of normal mice. 

The researchers are continuing to study epsilon PKC and related enzymes to find out just how they work to protect the heart muscle. They are also investigating how best to turn this basic research into clinical benefits. The peptide itself is probably unsuitable as a medicine, but it will serve as a template for drug development, said Mochly-Rosen. It might lead to a drug patients can take when experiencing chest pain, the way nitroglycerin is currently taken to increase blood flow to the heart, she said. 

Colleagues in the department of molecular pharmacology who contributed to the studies include senior scientist Che-Hong Chen, PhD, and research associate Tamar Liron, MsC. Miriam C. Souroujon, PhD, Mary O. Gray, MD, and Michael Csukai, PhD, were involved with the research when they were in the department but have since left Stanford and are now at The Open University of Israel, Tel-Aviv; the University of California-San Francisco; and Zeneca Agrochemicals, Berkshire, UK; respectively. Researchers at the University of Cincinnati also contributed. 

Funding was provided by the National Institutes of Health. 
 

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