Hyperbaric oxygen improves healing in stressed animals

Hyperbaric oxygen almost completely reverses the delay in wound healing caused by chronic stress and restores normal patterns of healing in mice, according to Phillip T. Marucha, D.M.D., Ph.D., a researcher at the University of Illinois at Chicago.

The molecular biologist has contributed to the growing body of literature demonstrating that while acute stress can stimulate an immune response, chronic stress adversely affects the body's immune mechanisms. It can blunt the response to vaccination, dampen a broader inflammatory response and retard wound healing.

Stress and healing

He also cited earlier studies. "If you put killed bacteria on a wound, it contracts more, but with a stressed animal, it doesn't. So there was something wrong with the contraction process."

When he measured the bacteria in wounds of animals, "I was amazed to see five logs more bacteria (10⁵) in stressed animals than in non-stressed animals."

Looking more closely, Dr. Marucha saw normal or increased numbers of phagocytes present at the wound site of stressed animals, so the problem wasn't in the trafficking of those immune cells; it had to be their functionality. Accordingly, there was decreased production of hydrogen peroxide and the downstream production of hypochlorous acid (HOCl).

"We came to the conclusion that oxygen was important because oxygen plays such a significant role in microbial clearance and because an important hypoxia regulated gene, iNOS, was upregulated," Dr. Marucha explains.

Oxygen clearly plays role

Oxygen was the missing element in this pathway; there were much lower levels of it in the wounds of stressed animals than in the wounds of unstressed controls.

He tells Dermatology Times, "If oxygen can't get to the tissue, we may not have enough oxygen to kill bacteria."

The quest to get more oxygen to tissue led Dr. Marucha to investigate hyperbaric oxygen (HBO). His lab showed that restraint-stressed mice had a 2- to 5-log increase in opportunistic bacteria and a 30 percent delay in healing compared to non-stressed controls.

In a pair of articles published over the summer in Brain, Behavior, and Immunity, Dr. Marucha extended the work to show that restraint-stressed mice that were placed in a hyperbaric oxygen chamber twice a day for two-hour sessions of 100 percent pure oxygen at 2.5 atmospheres of pressure did not experience retarded healing.

Non-stressed animals that received HBO showed little benefit, which comports with the literature in the field.

Dr. Marucha explains, "That probably is because the role of oxygen in wound healing already is optimized by nature in a normal animal. It is only when you impair it in some way that you can show that oxygen is important in that process."

In other words, replacing a deficit is beneficial; going beyond that level is not.

Implications for future application

Dr. Marucha says, "Hyperbaric oxygen restores normal wound healing. We don't know yet whether it is because it directly kills the bacteria, produces more signaling molecules, or that it stimulates collagen production that contracts and closes the wound."

Dr. Marucha is realistic about clinical therapeutic applications of his findings.

"We can't put everybody in a hyperbaric oxygen chamber to heal everyday wounds; it is too expensive and difficult to manage non-toxic use. But there are things we can do to improve oxygen flow to peripheral wounds."

It may be possible to restore optimal levels of oxygen incrementally by using a combination of techniques.