Inhaled Nitrite Therapy May Help Babies Suffering in a Low-Oxygen State
Scientists from the National Institutes of Health (NIH) Clinical
Center and the Loma Linda University School of Medicine have found
that use of an inhaled nitrite spray may help babies diagnosed with
persistent pulmonary hypertension of the newborn (PPHN). Premature
newborns and those with pneumonia or heart problems often develop
PPHN. This often-fatal disease causes high blood pressure in an
infant’s lungs and places the baby in a low-oxygen state.
The collaborative study findings are reported in Nature Medicine
(September 12, 2004 online version; October, 2004, print version).
Nitrite, a simple salt in the blood that dilates the blood vessels
in the lungs, reacts with de-oxygenated hemoglobin (the respiratory
protein of the blood) and is converted to nitric oxide when the
human body is in a low-oxygen state. Nitric oxide or NO is a short-lived
gas produced by cells lining the blood vessels and has an important
role in regulating blood flow. The NIH-Loma Linda research team
theorized that the naturally-occurring conversion of nitrite to
nitric oxide might help babies with high blood pressure in the lungs.
The researchers thought the nitrite conversion mechanism might act
to lower the lung blood pressure and thus raise oxygen levels.
The NIH-Loma Linda research team studied the effect of nitrite
inhalation in an animal model of PPHN. They compared the administration
of NO to the administration of plain nitrite.
“Nitrite inhalation rapidly reduced pulmonary pressures by
65 percent” said Christian Hunter, PhD, a fellow in the NIH
Clinical Research Training Program for Medical and Dental Students
and fourth-year Loma Linda medical student and lead author of the
study. “The nitrite had a much longer effect than the nitric
oxide. In one case, we administered the inhaled nitrite for 20 minutes
and the high blood pressure levels were reversed for an hour.”
Mixing nitrite with plain saline, filling a plastic inhaler and
then administering it holds great potential for becoming a much
simpler and more economical way to treat newborns, according to
principal investigator Mark Gladwin, MD, Critical Care Medicine
Department, NIH Clinical Center. “The current clinical standard
for treating these infants is to administer nitric oxide gas every
day through a complex delivery system which requires high-level
monitoring not available in small community hospitals or developing
countries,” he said. “This approach costs thousands
of dollars a day and the delivery systems themselves run tens of
thousands of dollars. Our findings demonstrate this has potential
to be done in an easier and more cost-effective manner.”
“This research shows that a common agent found in nature
can have profound health benefits worldwide,” said Dr. John
I. Gallin, NIH Clinical Center director. “It emphasizes the
importance of persistent, ongoing clinical research to life and
health. This is the type of work that will continue and expand when
the Clinical Center opens the Mark O. Hatfield Clinical Research
Center later this year.”
Nitrite is also available for human use as an antidote for cyanide
poisoning and is used in meat curing.
Further research is necessary to determine the safety and efficacy
of inhaled nitrite for human use. Plans are underway to begin clinical
trials by early 2005. Scientists from the National Heart, Lung and
Blood Institute, NIH; the National Institute of Diabetes, Digestive
and Kidney Diseases, NIH; and the Center for Perinatal Biology and
Division of Neonatology, Loma Linda University School of Medicine
also participated in this study.
The Clinical Center is the clinical research hospital for the National
Institutes of Health (NIH). Through clinical research, physicians
and scientists translate laboratory discoveries into better treatments,
therapies and interventions to improve the nation's health. NIH
will open its new hospital, the Mark O. Hatfield Clinical Research
Center, later this year.