Originally created 05/01/01

Deadly gas may also be beneficial in treating lung injuries



WASHINGTON -- The old saying that what doesn't kill you makes you stronger may apply - in a way - to the toxic gas carbon monoxide.

Long feared as a dangerous and often deadly part of pollution, inhaled carbon monoxide has been found to benefit mice with damaged lungs.

The result could suggest new treatments for people following heart attack and stroke. But the toxic gas must be administered with care, and some question whether the benefits are enough to justify the potential danger.

CO, a colorless, odorless component of industrial emissions, cigarette smoke and exhaust has long been known to be hazardous. It starves cells of oxygen by replacing oxygen molecules in the blood and, in sufficient concentrations, can be deadly.

But at lower doses it may have therapeutic value, the new findings indicate.

When mice with severe lung damage resulting from a cutoff of blood flow were given inhaled carbon monoxide, some 70 percent survived, compared to just 10 percent of mice who didn't get the CO, according to a paper in the May issue of the journal Nature Medicine.

When blood flow is cut off, clots form in small blood vessels around the site. CO helps promote the clot-dissolving process, allowing blood flow to be re-established, explained Dr. David J. Pinsky of the Columbia University College of Physicians and Surgeons in New York, a member of the research team.

If, after more testing, such a treatment could be used in humans, it would "likely be eminently practical and relatively inexpensive," Pinsky said.

Scenarios in which low dose carbon monoxide may be tested might include lung transplantation, stroke, heart attack, severe bacterial infections or before surgery when there might be an interruption in blood flow, such as coronary artery bypass grafting, he added.

He stressed the importance of a careful monitoring system to avoid giving toxic levels of this potent gas.

Christoph Thiemermann of St. Bartholomew's and the Royal London School of Medicine and Dentistry in London was more cautious.

"These findings, however, do not suggest that we should rush to treat patients with acute lung injury with CO-inhalation therapy, as the dangers of CO-inhalation outweigh the benefits," Thiemermann said in a commentary accompanying Pinsky's paper.

The body naturally produces some carbon monoxide and Pinsky conducted his experiment both in normal mice and in mice genetically engineered to lack their own CO.

Following the lung damage, survival of the normal mice rose from 10 percent to 70 percent with CO treatment. Inhalation improved survival in the genetically altered mice from zero to 50 percent.

Pinsky explained that when a cutoff of blood triggers the clotting process, the body's own clot-dissolving machinery is suppressed by a natural protein called PAI-1.

"Carbon monoxide significantly reduces the body's production of this suppressor protein, and therefore, promotes dissolution of the clot," he said. "This relieves the obstruction in small blood vessels and permits blood flow to be re-established to the organ."

The body's own production of carbon monoxide probably evolved to protect the blood flow to vital organs, and providing extra carbon monoxide by inhalation seems to give an added boost, Pinsky said.