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Meat Preservative Could Preserve Human Heart

In animal studies, sodium nitrite reduced damage after cardiac arrest by 67%

THURSDAY, April 14, 2005 (HealthDay News) -- Sodium nitrite, a chemical best known as a meat preservative, could preserve cardiac muscle after a heart attack, researchers report.

The chemical's only medical use now is to treat cyanide poisoning. But animal studies show the body has a small store of sodium nitrite that in times of emergency is converted to nitric oxide, which is known to increase blood flow by widening blood vessels, according to Dr. Mark Gladwin, head of the vascular therapeutics section of the cardiovascular branch at the National Heart, Lung, and Blood Institute. He is co-author of a report on the studies in the May issue of the Journal of Clinical Investigation.

"In the year 2000, we discovered that in the human body, as blood circulates from arteries to veins, nitrite levels drop, as if nitrite is used by the body," Gladwin said. "Nitrite is converted to nitric oxide, a very powerful blood vessel-dilating molecule. Based on that, we thought we could use sodium nitrite as a way of delivering nitric oxide to the body."

Gladwin expressed that thought at a meeting attended by David Lefer, a professor of physiology and cardiology at Louisiana State University Health Sciences Center in Shreveport, whose laboratory has long experience in working with nitric oxide.

And so a collaboration began.

"We're sort of the NO guys, and we got hooked up with the nitrite guys and it got interesting," said Lefer, using the chemical formula name for nitric oxide.

In a series of experiments with mice, infusions of small amounts of sodium nitrite were found to reduce the amount of cardiac tissue killed in a heart attack by 67 percent, the researchers reported. The infusions also reduced the damage done to liver tissue that was subjected to deliberate injury.

The preservative effect was seen only when very small amounts of sodium nitrite were infused, enough to raise concentrations very slightly. "The doses were very low, barely higher than the circulating level," Gladwin said. "We think we have stumbled on the natural process the body uses to defend itself."

The experimental work now has been expanded to larger animals such as pigs, whose bodies more closely resemble those of humans. "If it works in these larger models, we will go to human studies in heart attacks," Gladwin said. "So far, it looks like it translates up."

The idea is to give a small infusion in the minutes after someone arrives at an emergency room with a heart attack and is getting artery-opening treatment such as angioplasty, he said. "We anticipate that we would give one dose of nitrite to reduce the size of the heart attack after blood flow is restored," Gladwin said.

The dose has to be kept small, Lefer added. "Our body does have nitrite in blood and nitrite in tissue," he said. "Sometimes it's overwhelmed, and there is just not enough around in tissues..., so we add a small amount that can be protective."

Gladwin envisions other medical uses of sodium nitrite. He is studying its use as a way to help adults with sickle cell disease, in which abnormal hemoglobin reduces blood flow. He also sees a role in organ transplantation.

"When you harvest a liver now, it must be transplanted in 12 to 24 hours," Gladwin said. "Nitrite could potentially preserve the organ longer, so you would have more time to get it to a recipient."

Limited human experiments have begun with healthy volunteers. "We now have given sodium nitrite to more than 50 healthy humans," Gladwin said. "We have found that very low doses of nitrite widen arteries and improve blood flow."

More information

An explanation of how nitric oxide helps the heart is given in the announcement of why three Americans who discovered its value were awarded the 1998 Nobel Prize in medicine.

SOURCES: Mark Gladwin, M.D., head, vascular therapeutics section, cardiovascular branch, National Heart, Lung, and Blood Institute, Bethesda, Md.; David Lefer, Ph.D, professor, physiology and cardiology, Louisiana State University Health Sciences Center, Shreveport; May 2005 Journal of Clinical Investigtion
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