June 17, 2003 ROCHESTER, Minn. -- A colorless, odorless gas that kills more than 500 Americans each year plays an important role in maintaining healthy digestion, according to findings of a Mayo Clinic study published Tuesday in Proceedings of the National Academy of Sciences.
The researchers have discovered that carbon monoxide (CO), the leading cause of accidental poisoning deaths, is normally present in the digestive system and helps regulate smooth-muscle contraction in the gastrointestinal (GI) tract. These contractions must be finely tuned to move food through the stomach and bowels, and differences in CO concentration are essential to orchestrating this movement.
"Across the thickness of the the gut's wall, it continuously makes carbon monoxide from a specific cell type in a perfectly regulated gradient: more on one edge and less on the other," explains Gianrico Farrugia, M.D., the Mayo Clinic gastroenterologist who together with Joseph Szurszewski, Ph.D., a Mayo Clinic physiologist, led the study. "It is remarkable that this gradient exists in the gut's muscle wall, which is only a few millimeters thick, and that normal physiology is so finely tuned that a dangerous gas can be used as a regulator of normal function."
Carbon monoxide poisonings typically result from breathing fumes from faulty furnaces or heaters that do not completely burn their fuel. Within the body, however, CO is not just normal, but essential.
Food moves through the GI tract in response to smooth-muscle contractions. Without carbon monoxide, the muscle wall would contract with each electrical impulse in an all-or-none manner. But varying CO concentrations along the muscle wall act like a dimmer switch: higher concentrations make it contract less vigorously, while areas with less CO squeeze more tightly. This enables the body to modulate contractions that propel food through the system.
"There is now a growing body of evidence suggesting that CO may have significant clinical treatment applications," says Dr. Farrugia. "Initial studies suggest that administering low doses of CO to animals before surgery reduces postoperative loss of intestinal function, the number one cause of prolonged hospital stays after abdominal surgery. CO is a potent anti-hypertensive and anti-inflammatory agent, and can prevent kidney damage after injury."
"The major problem at the moment is delivery of a gas to the right site, and until we get that sorted out it would be difficult to use as ongoing therapy for motility disorders," he continues. "Some new CO-releasing compounds have some promise, however. Carbon monoxide appears to have a lot of potential as a therapeutic agent both in the GI tract and outside, but other than for short-term inhaled use we still have a ways to go before we can entertain the use of CO in clinical practice."
Other authors of the paper, "A Major Role for Carbon Monoxide as an Endogenous Hyperpolarizing Factor in the Gastrointestinal Tract," include Sha Lei, M.D.; Xue Lin, M.D.; Steven Miller, Ph.D.; Karl Nath, M.D.; Christopher Ferris, M.D., Ph.D. and Michael Levitt, M.D.
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