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.

Inclusion Criteria:

Exclusion Criteria:

- Volunteers with the following criteria will be EXCLUDED from participation:

Less than 18 years of age Greater than 39 years of age Born at altitudes greater than 2134
m (7000 ft) Living in areas that are more than 1220 m (4,000 feet), or have traveled to
areas that are more than 1220 m for more than a few days within the last 2 months.

Abnormal [Hb]/Hct levels or presence of hemoglobin S Known allergies to sulfonamide
derivatives Smokers who smoke more than 5 cigarettes per day Tobacco chewers If military,
unable to pass the 2-mi run portion of the Army Physical Fitness Test, or equivalent If
civilian, not currently running or exercising for at least 20 min/day, 3X/week in
"aerobic" activities (e.g., running, biking. swimming, basketball, etc) If they do not
want to walk or run multiple times for 1 to 3 hours on a treadmill Unable to meet the U.S.
Army height/weight standards Not willing to sleep in bunk beds in a small room (8 feet by
8 feet) with 1 to 3 other volunteers (male and/or female) for 3 nights. If they are
claustrophobic Women who are pregnant or planning to conceive during the study period
Women who are not willing to take urine pregnancy tests Not willing to drink an eight
ounce solution of diet soda that may contain ACCY up to three times per day and then not
willing to suck on a peppermint mint right after drinking the solution.

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) Evidence of any physical, mental, and/or medical conditions that
would make the proposed studies relatively more hazardous. Evidence of prior HAPE or HACE
diagnosis Evidence of apnea or other sleeping disorders Evidence of asthma If applicable,
unwilling to stop taking all supplements for the two weeks of participation If applicable,
all medications (prescription or over-the-counter) must be approved by the PI, and/or the
OMSO.