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 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.
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