Findings in rats show promise for 'buying time' in victims of lethal
hemorrhage
SEATTLE, July 1 /PRNewswire/ -- For the first time, researchers have
demonstrated that the administration of minute amounts of inhaled or
intravenous hydrogen sulfide, or H2S -- the molecule that gives rotten eggs
their sulfurous stench -- significantly improves survival from extreme
blood loss in rats.
Cell biologist Mark B. Roth, Ph.D., and colleagues in the Basic
Sciences Division of Fred Hutchinson Cancer Research Center, in
collaboration with surgeon Robert K. Winn, Ph.D., and colleagues at UW
Medicine's Harborview Medical Center, report their findings online ahead of
print in The Journal of Trauma Injury, Infection, and Critical Care. The
article is slated for the July print issue, which comes out on July 10.
The researchers successfully used H2S to induce a state of reversible
metabolic hibernation as a way to reduce death from insufficient blood
supply to organs and tissues in a rat model of lethal hemorrhage. (Federal
regulations mandate the use of such animal models in preclinical research
to test the safety and effectiveness of various procedures and treatments
before they can be tested in humans.)
They found that 75 percent of rats (18 of 24) given inhaled hydrogen
sulfide and 67 percent of rats (eight of 12) given intravenous hydrogen
sulfide survived at least two weeks -- the duration of the monitoring
period -- after losing more than half of their blood for an extended
period. In contrast, long-term survival rates for the untreated rats in the
two control groups were 23 percent (three of 13) and 14 percent (one of
seven), respectively.
"Our goal is to develop life-saving treatment for critically ill people
suffering from acute, sustained blood loss, such as in a car accident or on
the battlefield," said senior author Roth. "These findings have obvious
implications for the military, but they also have tremendous implications
for the civilian population."
The U.S. Defense Advanced Research Projects Agency and the U.S. Defense
Services Office funded the research. The ultimate goal: designing
self-injectable hydrogen-sulfide kits that critically injured soldiers
could use in the field to temporarily dim their metabolism and reduce their
oxygen demand. This would help "buy time" until they could get medical
attention.
"The military feels that if a soldier can be kept alive for at least
three hours, that would allow time for the situation to be stabilized and
the scene of the incident secured enough to allow evacuation of that
soldier to an area where he or she can get medical attention," Roth said.
Roth's study, which attempted to mimic a similar scenario, involved 56
rats, each of which underwent controlled hemorrhage to remove 60 percent of
their blood for three hours before re-infusion with Lactated Ringer's
solution to replace lost blood volume.
The rats were divided into two groups. In the first group, 24 rats were
put into a controlled atmosphere of room air laced with 300 parts per
million H2S while 13 served as controls. The H2S was administered about 20
minutes after initiation of blood removal and was supplied for about 20
minutes, until the end of the bleed. In the second group, 12 rats received
a single intravenous dose of sulfide solution about 20 minutes after the
initiation of blood removal while seven served as controls.
In both test groups, the rats maintained a reduced yet stable level of
carbon-dioxide production, a surrogate measure of metabolism. Once H2S was
removed, metabolic rates returned to normal. In contrast, the untreated
animals steadily grew metabolically weaker from blood loss until the point
of death.
Functional and behavioral testing among the long-term survivors (those
that lived more than two weeks after hemorrhage) showed no observable
defects. In fact, the rodents that were bred produced normal-sized litters
of healthy pups.
How does hydrogen-sulfide treatment prevent death from profound and
sustained blood loss? One possibility is that in reducing metabolism, H2S
also reduces oxygen demand, which allows crucial neurons in the
hippocampus, the part of the brain that controls autonomic functions such
as breathing and heartbeat, to withstand low oxygen levels due to
hemorrhage.
Another mechanism may be that hydrogen sulfide, which is naturally
present in the blood, is lost during hemorrhage and must be replaced to
maintain life processes.
In April 2005 Roth and colleagues made headlines worldwide when they
reported, in the journal Science, the first use of H2S to induce a state of
reversible hibernation in mice. Roth's latest research represents the next
step in demonstrating hydrogen sulfide's potential to treat ischemic
injuries caused by conditions such as severe blood loss, hypothermia,
cardiac arrest and stroke.
At Fred Hutchinson Cancer Research Center, our interdisciplinary teams
of world-renowned scientists and humanitarians work together to prevent,
diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers,
including three Nobel laureates, bring a relentless pursuit and passion for
health, knowledge and hope to their work and to the world. For more
information, please visit fhcrc.org.
CONTACT
Kristen Woodward
206-667-5095
kwoodwar@fhcrc.org
SOURCE Fred Hutchinson Cancer Research Center
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Related links:
http://www.fhcrc.org
CONTACT:
Kristen Woodward of Fred Hutchinson Cancer
Research Center, +1-206-667-5095, kwoodwar@fhcrc.org
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