Carbon monoxide inhibitor controls traumatic bleeding

Apr 6 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.

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.

"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.

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.