Common chemical to the rescue
2008-05-26 13:24
Chicago - An experimental therapy to restore blood flow to tissues damaged by vascular disease can rapidly improve circulation by stimulating the growth of new blood vessels, according to an animal study released on Monday.
In experiments on mice, researchers showed that daily shots of sodium nitrite generated new blood vessels and restored blood flow in ischemic, or oxygen-starved tissues, in just three to seven days - a fraction of the time it would ordinarily take.
"This is one of the most effective agents for inducing new blood vessel growth that we have seen to date in our research," said Christopher Kevil, an associate professor of pathology at Louisiana State University Health Sciences Centre in Shreveport.
Ischemia is a hallmark of peripheral artery disease, peripheral vascular disease and diabetes.
The condition occurs when diseased arteries interrupt or diminish the blood supply to the tissues of the arms and legs depriving them of oxygen and vital nutrients.
The condition can severely limit limb function and cause cramping and fatigue in the legs, but there are few effective treatments capable of replenishing the cells and reinvigorating the tissue in such cases.
Previous research has shown that nitric oxide (NO) or nitric oxide "donor" therapy can stimulate new blood vessels, returning blood flow to normal, but when the compound is administered in certain forms, it can cause a drop in blood pressure and other side effects.
Cheap, readily available compound
For this experiment, the investigators decided to test a novel NO donor - sodium nitrite - in a mouse model of ischemia.
Sodium nitrite is a cheap and readily available compound that is often used as a food preservative, but more importantly is metabolised to NO in the body, but only in ischemic or oxygen-starved tissues.
The investigators induced ishcemia in the hind legs of mice by tying off the animals' femoral arteries to cut off the blood flow to the limb. They then injected them with low-dose sodium nitrite twice a day.
By the third day of therapy, the animals' hind legs were showing signs of new blood vessel growth or angiogenesis. By the seventh day of therapy, the blood supply was almost back to normal.
In contrast, in a group of "control" mice that were not given any treatment for ischemia in their hind legs, it took 28 days for circulation to return to normal.
"The treatment has tremendous potential for stimulating angiogenesis to alleviate the discomfort caused by ischemia, and at the dosages we used, sodium nitrite is safe and far below any toxicity threshold," said Kevil.
"Moreover, our work also suggests that sodium nitrite therapy could be beneficial for stimulating angiogenesis and tissue healing after ischemic events seen in stroke and heart attacks."
The paper appears in the Proceedings of the National Academy of Sciences.