NHLBI Study: The Promise of New
Medical Uses for Sodium Nitrite for Heart Attack
and Organ Damage
Sodium nitrite, a naturally occurring chemical and
common meat preservative, is only used medically to
treat cyanide poisoning. But if the results of a new
animal study hold up under further research in people,
the chemical may one day be used to protect and preserve
tissue and organ function after heart attack, high risk
abdominal surgery, and organ transplantation.
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
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
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.