Naval Submarine Medical Research Laboratory (NSMRL) scientists presented their findings how expired nitric oxide (NOexp) can be used as a non-invasive physical indicator of hyperbaric (high-pressure) oxidative stress to divers during the annual Undersea Hyperbaric Medicine Annual Scientific Meeting in Rio Grande, Puerto Rico June 27.

Navy Special Operation Divers use closed circuit underwater breathing devices that operate at high molecular oxygen (O2) levels. These high levels limit mission length and can cause lung problems. Because of these restrictions, NSMRL has over the past 12 years led a series of human oxygen exposure testing over a wide range of surrounding pressures and time, and developed an experimental model of the temporary changes that occur in expired nitric oxide following diving stress.

“Exhaled expired nitric oxide was studied as an indicator of airway inflammation and oxidative stress in a variety of lung diseases. However, at first the importance of expired nitric oxide as a gauge of the oxidative stress response of the lungs to excessive oxygen under operational diving conditions was unclear,” said Dr. David Fothergill, science director of the Naval Submarine Medical Research Laboratory. “To be useful to our warfighter we needed to establish a well-defined relationship between oxygen exposure and the changes in expired nitric oxide.”

During their presentation, “Validation of an exhaled nitric oxide model pulmonary hyperoxic stress,” Fothergill and his colleagues explained how they can accurately predict the relative change in expired nitric oxide after prolonged dry and immersed dives. Their results show a decrease in expired nitric oxide that occurs when breathing high partial pressures of oxygen for prolonged periods, and how it offers a potential window into the amount of oxidative stress experienced by the pulmonary system during a hyperbaric oxygen exposure.

They further explained how the percentage change in expired nitric oxide occurs during an oxygen exposure can now be accurately predicted from a negative exponential function of the hyperoxic dose of the exposure.

“Individuals with low levels of expired nitric oxide appear to be at most risk of experiencing symptoms of pulmonary oxygen toxicity, especially during a challenging exposure to hyperbaric oxygen,” Fothergill said. “Oxygen toxicity can cause damage to a diver’s lung tissue or even cause lung failure. Our findings permit us to emphasize health and resilience as key components of warfighter performance.”

Fothergill and his colleagues Lt. Cmdr. Warren Ross, an undersea medical officer and Dr. John Florian, a senior research physiologist and the head of Warfighter Human Performance at the Navy Experimental Diving Unit, agree the relative decrease in expired nitric oxide occurs following a lengthy dive reflects a pulmonary hyperoxic stress response for challenging oxygen exposures, can be accurately predicted from the oxygen dose of the dive profile.

“For the first time we now have a non-invasive biomarker, which will allow us to predict a diver’s vulnerability to respiratory oxygen toxicity,” said Ross.

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