Carbon Monoxide Inhibitor
Controls Traumatic Bleeding Without Restricting
Circulation To Rest Of Body
SAN FRANCISCO (April 5, 2006) – A chemical that blocks
carbon monoxide (CO) has been used for the first time to arrest traumatic
bleeding in rats, according to a Tulane University research team.
The study of CO in the tissues -- including its role in
diabetes, cardiac dysfunction, hypertension and asthma -- has become the
subject of increasing interest for researchers. However, this is the first
time scientists are looking at its role in soft tissue trauma, said lead
researcher Mary E. McCarty, who presented the study at an APS session at
Experimental Biology 2006.
Small amounts of CO exist in the tissues, the result of
the breakdown of a blood component known as heme. Carbon monoxide helps
control blood pressure by dilating blood vessels, McCarty said. Her team
reasoned that blocking the dilating action of CO would cause injured blood
vessels to constrict, limiting bleeding and maintaining adequate blood
pressure.
The research is still a long way from use in humans.
But if successful, this new line of inquiry could eventually help stanch
massive bleeding in instances of soft tissue trauma and help reduce the need
for blood transfusions of patients facing lengthy surgery, among other uses.
McCarty is one of 12 finalists for a David S. Bruce
Undergraduate Research Award from The American Physiological Society
(APS). She will present the study at an APS-sponsored session at
Experimental Biology 2006.
*Paper presentation: “Inhibitors of
endogenously-formed CO arrest bleeding and confer protection in a model of
severe hepatic injury,” 12:45 p.m.-3 p.m. Wednesday, April 5, Shock,
903.16/Board #D16, Convention Center, Exhibit Hall D. The poster is on
view 7:30 a.m. – 3:30 p.m. Research was by Mary E. McCarty, Fruzsina K.
Johnson, Christine S. Lin, Robert A. Johnson, Department of Physiology,
Tulane University Health Sciences Center, New Orleans, and William Durante,
Department of Medicine, Baylor College of Medicine, Houston.
In addition, McCarty will present the research as part
of the Regulation of Cerebrovascular Function in Health and Disease
symposium, which begins 3:15 p.m., Sunday, April 2, Convention
Center, 256, Mezzanine West. McCarty will present at 4:35 p.m.
Related to endothelium
“We wanted to apply our knowledge of CO production in
the tissues to traumatic injury,” McCarty said. “We’re looking at CO’s
function in the peripheral circulatory system, in particular, at the effect
it has on the endothelium.”
A serious laceration damages the vascular endothelium,
comprised of cells lining the blood vessels, by pulling and tearing it. When
the endothelium is torn, it disrupts the production of nitric oxide synthase
(NOS), a blood vessel dilator that is even more powerful than CO. The loss
of NOS production at the area of tissue damage helps control bleeding,
because the vessels dilate less without it. However, CO continues to dilate
the vessels around the wound, and that is why it is important to inhibit CO,
the remaining vessel dilator.
“One of the great things about what we’ve found is that
by blocking the effects of CO, only the area of endothelial damage
constricts,” McCarty said. “The undamaged vessels continue to get blood to
the other areas of the body.” This control of bleeding at the site of the
trauma while allowing circulation in the rest of the body is one of the most
exciting aspects of the study, she said.
Trauma to liver
In the study’s first phase, the researchers removed
tiny blood vessels, known as arterioles, from rats, and put the vessels in a
chamber that simulated the body’s blood flow. They removed the endothelium
in half the blood vessels, to simulate what happens in soft tissue trauma
that causes massive bleeding. The researchers left the endothelium intact in
the second group of blood vessels.
When the researchers administered a drug that blocks
CO, they found that the vessels with the intact endothelium dilated as
expected, because the endothelium produces the dilator NOS. But vessels with
damaged endothelium, in which NOS was inhibited, constricted. This showed
that blocking carbon monoxide narrows the blood vessel opening under
conditions of massive soft tissue trauma, and limits bleeding.
In the second phase, the researchers anesthetized two
groups of rats, lacerated the livers and measured the drop in blood pressure
over two hours. The blood pressure of the rats that received the CO blocker
remained higher for a longer time and significantly prolonged survival.
“It’s exciting because it can have so many
implications,” McCarty said of the research. Not only could it be used to
save wound victims and reduce the need for transfusions for surgery
patients, but the principal could be applied as a precaution to soldiers in
battle zones. In fact, it may be possible to provide a diet that contains
the preventative treatment.
Editor’s Note: For
further information or to schedule an interview with a member of
the research team, please contact Christine Guilfoy at the APS newsroom @
415.905.1024 (March 31-April 5); 978.290.2400 (cell), 301.634.7253
(office), or
cguilfoy@the-aps.org; or Donna Krupa or (703) 967-2751 (cell) or
(301) 634-7209 (office).
Go to
http://www.faseb.org/meetings/eb2006/call/ and click on “Searchable
Program Planner and Itinerary Builder to find the searchable online program
for EB.
Funding: The National Institutes of Health and
the U.S. Department of Defense supported this research.
* * *
The
American Physiological Society was founded in 1887 to foster basic and
applied bioscience. The Bethesda, Maryland-based society has more than
10,000 members and publishes 14 peer-reviewed journals containing almost
4,000 articles annually.
APS
provides a wide range of research, educational and career support and
programming to further the contributions of physiology to understanding the
mechanisms of diseased and healthy states. In May 2004, APS received
the Presidential Award for Excellence in Science,
Mathematics and Engineering Mentoring (PAESMEM).
# # #
Experimental Biology is an annual
scientific meeting convened by the Federation of American Societies of
Experimental Biology, including the American Physiological Society (APS)
and other biomedical societies. The meeting features “nominated” lectures,
symposia, research presentations, awards, a job placement center, and an
exhibit of scientific equipment, supplies, and publications. This year’s
participating Societies are APS, American Association of
Anatomists, American Society for Biochemistry and Molecular Biology,
American Society for Investigative Pathology, American Society for
Nutritional Sciences, and the American Society for Pharmacology and
Experimental Therapeutics.
