Nitric Oxide Gas May Hold Key to Nonhealing Wounds

By Betsy Bates

VANCOUVER, B.C. -- In the frustrating treatment of chronic wounds, Brian Kunimoto, M.D., and associates at the University of British Columbia think nitric oxide gas may be of benefit.

A naturally produced, lipophilic molecule, nitric oxide, unlike antibiotics, easily penetrates biofilms, well-organized populations of bacteria that can form in chronic, difficult-to-heal wounds.

"I call it a smoking gun," said Dr. Kunimoto, director of the Wound Healing Clinic at Vancouver Hospital and Health Sciences Centre.

He explained that nitric oxide combines with reactive oxygen to create "an entire soup of bacteriocidal intermediates," in a wound, and poisons the iron enzyme aconitase.

In the presence of this onslaught, "unless a bacterium can quickly develop into an anaerobic organism, it will die," he said at the annual meeting of the Pacific Dermatologic Association.

Nitric oxide also deaminates DNA and enhances the damaging effects of hydrogen peroxide when it is present as a reactive oxygen intermediate.

When asked to comment on this study, Frank Pomposelli, M.D., clinical chief of vascular surgery at Beth Israel Deaconess Medical Center, Boston stated: "I'm surprised at the mechanism described by the authors." He added, "I think of nitric oxide as a vasodilator and would have thought its mechanism of action was due to vasodilatation."

Studies at the University of British Columbia found that bacterial counts, including Staphylococcus aureus, pseudomonas, and methicillin-resistant S. aureus, plummeted to zero within hours of exposure to gaseous nitric oxide.

Home therapy involving nighttime exposure to the gas quickly healed a 2-year-old, nonhealing ankle ulcer in a 55-year-old man with severe venous disease, said Dr. Kunimoto, who recently published the case (J. Cutan. Med. Surg. 2004;8:233-9).

"This is remarkable for this gentleman, [considering] we worked on him for 2 years and got nowhere," he said. "We've shifted the balance in favor of the host."

The Canadian government recently approved funding for a large study of nitric oxide gas to see if results can be duplicated in other nonhealing wounds.

BACTERIAL COUNTS, INCLUDING MRSA, PLUMMETED TO ZERO WITHIN HOURS OF EXPOSURE TO GASEOUS NITRIC OXIDE.