New York, NY – April 27, 2001 — A toxic component of industrial emissions, exhaust and cigarette smoke, carbon monoxide starves our cells of oxygen by replacing oxygen molecules in the blood. Exposure to carbon monoxide can have fatal consequences. But surprisingly, according to a new study by Columbia University researchers, carbon monoxide may also have a life-saving effect when blood vessels are blocked, such as during heart attack or stroke. The results “point to potential therapeutic uses for inhaled carbon monoxide,” the study’s authors say. The paper is published in the May issue of Nature Medicine.
Lead author David J. Pinsky, M.D., associate professor of medicine at the Columbia University College of Physicians & Surgeons, also has signaled a need for caution. “There’s more work that needs to be done to identify the conditions under which this is useful and the doses that are safe,” he said. “Like many other molecules that are beneficial in the right doses, too much of them can have a lethal effect.”
Carbon monoxide (CO) appears to help restore blood flow to organs threatened with a cut off blood supply, according to the authors. It does so by enhancing the body’s own clot-dissolving mechanisms and by dilating blood vessels. The researchers demonstrated the results in mice.
At lower than lethal doses, it seems, “CO can paradoxically either imperil or salvage tissue by disparate mechanisms,” the authors report.
The body itself produces carbon monoxide when a part of the organism becomes oxygen-starved due to blood vessel blockage, a condition called ischemia. The carbon monoxide is created as part of a natural process in which an enzyme called heme oxygenase type 1 breaks down vital molecules called hemes, when the cells carrying them wear out.
Through as-yet poorly understood mechanisms, heme oxygenase type 1 levels rise during ischemia, stepping up this process and increasing carbon monoxide levels.
Carbon monoxide next activates an enzyme called guanylate cyclase, which aids in blood vessel dilation and eases the way for blood flow, restoring needed oxygen to the tissues. This, in turn, prevents other harmful processes, such as the activation of a gene that leads to increased production of plasminogen activator inhibitor-1. This is a substance that inhibits dissolution of blood clots, and therefore would worsen the condition if allowed to function. In this process, carbon monoxide’s activation of guanylate cyclase may be especially critical. This is because during ischemia, there is a steep drop in the levels of the compound that usually does this job, nitric oxide.
Future research will include a more detailed analysis of the molecular processes involved and studies of other situations in which carbon monoxide may have benefits Dr. Pinsky said.
The research was supported by the U.S. Public Health Service of the National Institutes of Health.
# # # #