The new study was conducted by scientists with the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) in collaboration with investigators supported by the National Institute of Diabetes and Digestive and Kidney Diseases at Louisiana State University Health Sciences Center and published in the May issue* of The Journal of Clinical Investigation.
The scientists found that low concentrations of sodium nitrite had a strong protective effect – preventing cell death in the hearts and livers of mice undergoing experimental heart attack and liver injury. In the heart study, nitrite reduced the size of the area of dead tissue known as an infarct by 67 percent compared to control animals given nitrate, another nitrogen compound. This potent protective effect was observed at concentrations of nitrite in blood that were only slightly higher than the physiological normal levels in blood.
The study, led by David Lefer, Ph.D., of Louisiana State University Health Sciences Center in Shreveport and Mark Gladwin, M.D., Head of the Vascular Therapeutics Section of the NHLBI's Cardiovascular Branch, follows another study conducted by the NIH research team that found that infusions of sodium nitrite into the human circulation leads to the production of nitric oxide (NO), a strong blood vessel dilating molecule that increases blood flow. The conversion of nitrite to NO will occur only in tissue or blood that is very low in oxygen. It was this finding that triggered the team's interest in sodium nitrite as a treatment/preventive for the tissue damage and cell death that can occur in conjunction with organ transplantation, heart attack, and treatment of a heart attack.
In both the liver and heart components of the current study, the research team compared the effects of both lower and higher concentrations of nitrite versus control treatments of saline or nitrate, a chemical compound that is related to nitrite but cannot convert to NO in the blood. Surprisingly, they found that only low concentrations of nitrite provided protection against injury.
The investigators are currently studying the mechanism for the protective effect of sodium nitrite and they believe it is related in some way to the conversion of nitrite to nitric oxide.
"The remarkable thing about nitrite is that it is only converted to nitric oxide in the organs and tissues with the lowest oxygen levels, allowing for targeted NO delivery – and thus improved blood flow -- to tissues under stress. More research is needed to look at the effectiveness of nitrite in various organs and disease states in humans," said NHLBI's Gladwin who is also an investigator in the Critical Care Medicine Department, NIH Clinical Center.
Gladwin is currently studying the use of sodium nitrite as a way to help adults with sickle cell disease. It is hoped that this treatment will reverse the effect of decreased blood flow due to the patients' "sickled" blood cells. Patients with sickle cell disease have abnormal hemoglobin molecules in their red blood cells. The molecules damage the red cells, causing them to change into a crescent or sickle shape and stick to blood vessel walls. This can lead to narrowed, or blocked, blood vessels leading to pain, damage, and anemia.
Further studies either underway or in planning translate the new findings to humans. These studies evaluate sodium nitrite's effect on heart attacks, kidney failure, solid organ transplantation, cerebral vasospasm (a complication of a ruptured aneurysm leading to reduced blood flow and possible stroke), and high blood pressure in the lungs in babies.
To arrange an interview with Dr. Gladwin, contact the NHLBI Communications Office at 301-496-4236. To interview Dr. Lefer, contact the LSU Office of Information Services at 318-675-5408.
NHLBI is part of the National Institutes of Health (NIH), the Federal Government's primary agency for biomedical and behavioral research. NIH is a component of the U.S. Department of Health and Human Services. NHLBI press releases and fact sheets, including a fact sheet on sickle cell anemia, can be found online at www.nhlbi.nih.gov
*"Cytoprotective Effects of Nitrite During In Vivo Ischemia-Reperfusion of the Heart and Liver" appears online on the Journal of Clinical Investigation Web Site – in advance of the print publication of the May issue.
Journal
Journal of Clinical Investigation