Carbon monoxide inhibitor controls traumatic bleeding, Tulane University researchers show

SAN FRANCISCO 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.

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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 Mayer Resnick or 301.332.4402 (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 10,500 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.


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