Induced Changes in Ventilatory Responsiveness and Altitude Exposure

This study will determine if modulating reduction/oxidation (redox) status through a temporary increase in the blood ratio of reduced-to-oxidized glutathione (i.e., GSH/GSSG) will increase carotid body chemosensitivity and thus increase ventilation and arterial oxygen saturation (SaO2) during 32 hours of hypobaric hypoxia exposure to 3500 m (11,500 feet). To that end, the study will use an FDA-approved oral suspension form of acetylcysteine (ACCY) to modulate blood redox status under controlled conditions in the Hypobaric Chamber Facility at the USARIEM. Up to 30 healthy, active-duty military personnel or civilians from the local area will be recruited. Two independent treatment groups (placebo and ACCY; up to 15 in each group) will be assessed at sea level and altitude using a between-group experimental design. The two groups will be matched as closely as possible by age, ventilation, fitness, and gender prior to treatment assignment. Neither the staff nor the volunteers will know the treatment received by the groups until the study is completed. Included will be only those men and women who: are 18 to 39 years old, were born at altitudes below 2100 m (7000 feet), are not taking medications that interfere with oxygen delivery and transport (includes sedatives, sleeping aids, tranquilizers and any medication that depresses ventilation, diuretics, alpha and beta blockers); and have no evidence of any physical, mental, and/or medical conditions that would make the proposed study relatively more hazardous. All volunteers will participate over the two-week long study period in multiple standardized assessments that include resting (e.g., resting ventilation, SaO2, questionnaires), sleeping (e.g., heart rate, SaO2) and exercise (e.g., steady-state and time-trial performance, SaO2) measurements. The potential risks to test volunteers include the risks associated with hypobaric hypoxia exposure (e.g., acute mountain sickness [AMS; headache, nausea, insomnia]) and those associated with exercise (e.g., acute musculoskeletal strains and sprains, blisters). The investigators are not aware of any studies reporting problems during oral administration of ACCY in the doses or duration to be used in the present study. There are no direct benefits to the volunteers, except the knowledge of how well they performed at altitude and on the tests in which they participated. If the use of ACCY proves effective at altitude, then soldiers deployed to altitude in the future may have a means to beneficially increase ventilation and SaO2 in a manner similar to that experienced during natural altitude acclimatization.