Carbon monoxide may benefit heart patients in small amounts

WASHINGTON -- Tests on mice and rats indicate that the potentially deadly gas carbon monoxide -- inhaled at very low concentrations -- may help arteries damaged in angioplasty and transplants.

Scientists say it is too soon to say the therapy would help people.

Clogged arteries often are widened by inflating a small balloon inside them. This procedure can damage the cells lining the blood vessel, causing them to grow and thicken. Similar problems can occur when arteries are transplanted. This thickening can require further treatment.

Researchers at the University of Pittsburgh and Harvard Medical School report that exposing rats and mice to low levels of carbon monoxide -- the poisonous gas emitted from faulty furnaces or cars left running in garages -- prevents this excessive cell growth.

Rats and mice that had angioplasty were exposed to the gas for an hour, before the procedure, while rats with artery grafts were exposed several weeks after their transplants. The level of exposure was less than 1/25th of what would be considered toxic, a researcher said.

No ill effects

The animals suffered no ill effects and experiments are now being done in pigs, the scientists reported Sunday in the online edition of the journal Nature Medicine.

"These findings demonstrate a significant protective role for (carbon monoxide) in vascular injury," said Leo Otterbein, an assistant professor at the University of Pittsburgh School of Medicine.

Two years ago, David J. Pinsky of Columbia University reported that carbon monoxide could be beneficial to animals that had suffered severe lung injury by helping block the formation of blood clots.

Pinsky, who was not part of the new research group, welcomed the work.

"It is premature to conclude that this therapy would be useful in humans. However, the accumulating evidence certainly argues for rigorous study," Pinsky said.

Dr. Augustine M. K. Choi, a member of the Pittsburgh group, agreed on the need for caution. "It is exciting that CO at low doses can be beneficial, but we still have a lot of work to do on how to deliver CO safely," he said.

Otterbein, lead author of the study, explained that the idea of using carbon monoxide stemmed from the finding that an enzyme in the body, Heme oxygenase, produces CO. When injuries occur the amount of the enzyme increases, producing more CO.

"We thought, maybe its purpose is to somehow counter the inflammation," he said.

Otterbein's team at Pittsburgh exposed mice and rats to one hour of air containing 250 parts per million of carbon monoxide before a balloon angioplasty was performed.

In animals that had breathed only air, artery wall thickening caused by the treatment began to appear at 20 days to 30 days and was significant at 50 days to 60 days. This thickening was reduced by about 70 percent in animals that had been exposed to the gas.

The Harvard Medical School group did the transplant experiments, exposing rats to carbon monoxide for 56 days following the surgery. Cell wall thickening was reduced by about 60 percent in the treated animals, Dr. Fritz H. Bach said.

Dr. Brian S. Zuckerbraun, general surgery resident at the University of Pittsburgh School of Medicine, said the best treatments available now for clogged arteries are angioplasty, stents -- wire mesh tubes to prop open the arteries -- or bypass surgery.

"But these have their limitations and a significant failure rate. If you could pretreat patients with CO it might result in a better long-term outcome," he said.

Otterbein said the research suggests that the protective effect of carbon monoxide stems from its ability to block the activation and activity of white blood cells, which normally move to the site of an injury and cause the inflammation.

It also appears to reduce the proliferation of smooth muscle cells along the arteries, he added.

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Nature Medicine: http://www.nature.com/naturemedicine