Acute mountain sickness and sleep disturbances differentially influence cognition and mood during rapid ascent to 3000 and 4050 m.

The impact of acute mountain sickness (AMS) and sleep disturbances on mood and cognition at two altitudes relevant to the working and tourist population is unknown. Twenty unacclimatized lowlanders were exposed to either 3000 m (n = 10; 526 mmHg) or 4050 m (n = 10; 460 mmHg) for 20 h in a hypobaric chamber. AMS prevalence and severity was assessed using the Environmental Symptoms Questionnaire (ESQ) and an AMS-C score ≥ 0.7 indicated sickness. While sleeping for one night both at sea level (SL) and high altitude (HA), a wrist motion detector was used to measure awakenings (Awak, events/h) and sleep efficiency (Eff, %). If Eff was ≥85%, individuals were considered a good sleeper (Sleep+). Mood and cognition were assessed using the Automated Neuropsychological Assessment Metric and Mood Scale (ANAM-MS). The ESQ and ANAM-MS were administered in the morning both at SL and after 20 h at HA. AMS severity (mean ± SE; 1.82 ± 0.27 vs. 0.20 ± 0.27), AMS prevalence (90% vs. 10%), depression (0.63 ± 0.23 vs. 0.00 ± 0.24) Awak (15.6 ± 1.6 vs. 10.1 ± 1.6 events/h), and DeSHr (38.5 ± 6.3 vs. 13.3 ± 6.3 events/h) were greater (p < 0.05) and Eff was lower (69.9 ± 5.3% vs. 87.0 ± 5.3%) at 4050 m compared to 3000 m, respectively. AMS presence did not impact cognition but fatigue (2.17 ± 0.37 vs. 0.58 ± 0.39), anger (0.65 ± 0.25 vs. 0.02 ± 0.26), depression (0.63 ± 0.23 vs. 0.00 ± 0.24) and sleepiness (4.8 ± 0.4 vs. 2.7 ± 0.5) were greater (p < 0.05) in the AMS+ group. The Sleep- group, compared to the Sleep+ group, had lower (p < 0.05) working memory scores (50 ± 7 vs. 78 ± 9) assessed by the Sternberg 6-letter memory task, and lower reaction time fatigue scores (157 ± 17 vs. 221 ± 22), assessed by the repeated reaction time test. Overall, AMS, depression, DeSHr, and Awak were increased (p < 0.05) at 4050 m compared to 3000 m. In addition, AMS presence impacted mood while poor sleep impacted cognition which may deteriorate teamwork and/or increase errors in judgement at HA.

Impact of 2 days of staging at 2500-4300 m on sleep quality and quantity following subsequent exposure to 4300 m.

The impact of 2 days of staging at 2500-4300 m on sleep quality and quantity following subsequent exposure to 4300 m was determined. Forty-eight unacclimatized men and women were randomly assigned to stage for 2 days at one of four altitudes (2500, 3000, 3500, or 4300 m) prior to assessment on the summit of Pikes Peak (4300 m) for 2 days. Volunteers slept for one night at sea level (SL), two nights at respective staging altitudes, and two nights at Pikes Peak. Each wore a pulse oximeter to measure sleep arterial oxygen saturation (sSpO2 , %) and number of desaturations (DeSHr, events/hr) and a wrist motion detector to estimate sleep awakenings (Awak, awakes/hr) and sleep efficiency (Eff, %). Acute mountain sickness (AMS) was assessed using the Environmental Symptoms Questionnaire and daytime SpO2 was assessed after AMS measurements. The mean of all variables for both staging days (STG) and Pikes Peak days (PP) was calculated. The sSpO2 and daytime SpO2 decreased (p < 0.05) from SL during STG in all groups in a dose-dependent manner. During STG, DeSHr were higher (p < 0.05), Eff was lower (p < 0.05), and AMS symptoms were higher (p < 0.05) in the 3500 and 4300 m groups compared to the 2500 and 3000 m groups while Awak did not differ (p > 0.05) between groups. At PP, the sSpO2 , DeSHr, Awak, and Eff were similar among all groups but the 2500 m group had greater AMS symptoms (p < 0.05) than the other groups. Two days of staging at 2500-4300 m induced a similar degree of sleep acclimatization during subsequent ascent to 4300 m but the 2500 m group was not protected against AMS at 4300 m.

Altitude, Acute Mountain Sickness, and Acetazolamide: Recommendations for Rapid Ascent.

Toussaint, Claudia M., Robert W. Kenefick, Frank A. Petrassi, Stephen R. Muza, and Nisha Charkoudian. Altitude, acute mountain sickness, and acetazolamide: recommendations for rapid ascent. High Alt Med Biol. 22:5-13, 2021. Background: Sea level natives ascending rapidly to altitudes above 1,500 m often develop acute mountain sickness (AMS), including nausea, headaches, fatigue, and lightheadedness. Acetazolamide (AZ), a carbonic anhydrase inhibitor, is a commonly used medication for the prevention and treatment of AMS. However, there is continued debate about appropriate dosing, particularly when considering rapid and physically demanding ascents to elevations above 3,500 m by emergency medical and military personnel. Aims: Our goal in the present analysis was to evaluate and synthesize the current literature regarding the use of AZ to determine the most effective dosing for prophylaxis and treatment of AMS for rapid ascents to elevations >3,500 m. These circumstances are specifically relevant to military and emergency medical personnel who often need to ascend rapidly and perform physically demanding tasks upon arrival at altitude. Methods: We conducted a literature search from April 2018 to February 2020 using PubMed, Google Scholar, and Web of Science to identify randomized controlled trials that compared AZ with placebo or other treatment with the primary endpoint of AMS incidence and severity. We included only research articles/studies that focused on evaluation of AZ use during rapid ascent. Results: Four doses of AZ (125, 250, 500, and 750 mg daily) were identified as efficacious in decreasing the incidence and/or severity of AMS during rapid ascents, with evidence of enhanced effectiveness with higher doses. Conclusions: For military, emergency medical, or other activities involving rapid ascent to altitudes >3,500 m, doses 500-750 mg/day within 24 hours of altitude exposure appear to be the most effective for minimizing symptoms of AMS.

New metric of hypoxic dose predicts altitude acclimatization status following various ascent profiles.

Medical personnel need practical guidelines on how to construct high altitude ascents to induce altitude acclimatization and avoid acute mountain sickness (AMS) following the first night of sleep at high altitude. Using multiple logistic regression and a comprehensive database, we developed a quantitative prediction model using ascent profile as the independent variable and altitude acclimatization status as the dependent variable from 188 volunteers (147 men, 41 women) who underwent various ascent profiles to 4 km. The accumulated altitude exposure (AAE), a new metric of hypoxic dose, was defined as the ascent profile and was calculated by multiplying the altitude elevation (km) by the number of days (d) at that altitude prior to ascent to 4 km. Altitude acclimatization status was defined as the likely presence or absence of AMS after ~24 h of exposure at 4 km. AMS was assessed using the Cerebral Factor Score (AMS-C) from the Environmental Symptoms Questionnaire and deemed present if AMS-C was ≥0.7. Other predictor variables included in the model were age and body mass index (BMI). Sex, race, and smoking status were considered in model development but eliminated due to inadequate numbers in each of the ascent profiles. The AAE (km·d) significantly (P < 0.0001) predicted AMS in the model. For every 1 km·d increase in AAE, the odds of getting sick decreased by 41.3%. Equivalently, for every 1 km·d decrease in AAE, the odds of getting sick increased by 70.4%. Age and BMI were not significant predictors. The model demonstrated excellent discrimination (AUC = 0.83 (95% CI = 0.79-0.91) and calibration (Hosmer-Lemeshow = 0.11). The model provides a priori estimates of altitude acclimatization status resulting from the use of various rapid, staged, and graded ascent profiles.

Two-Day Residence at 2500 m to 4300 m Does Not Affect Subsequent Exercise Performance at 4300 m.

PURPOSE: To determine the efficacy residing for 2 d at various altitudes while sedentary (S) or active (A; ~90 min hiking 2 d) on exercise performance at 4300 m. METHODS: Sea-level (SL) resident men (n = 45) and women (n = 21) (mean ± SD; 23 ± 5 yr; 173 ± 9 cm; 73 ± 12 kg; V˙O2peak = 49 ± 7 mL·kg·min) were randomly assigned to a residence group and, S or A within each group: 2500 m (n = 11S, 8A), 3000 m (n = 6S, 12A), 3500 m (n = 6S, 8A), or 4300 m (n = 7S, 8A). Exercise assessments occurred at SL and 4300 m after 2-d residence and consisted of 20 min of steady-state (SS) treadmill walking (45% ± 3% SL V˙O2peak) and a 5-mile, self-paced running time trial (TT). Arterial oxygen saturation (SpO2) and HR were recorded throughout exercise. Resting SpO2 was recorded at SL, at 4 and 46 h of residence, and at 4300 m before exercise assessment. To determine if 2-d altitude residence improved 4300 m TT performance, results were compared with estimated performances using a validated prediction model. RESULTS: For all groups, resting SpO2 was reduced (P < 0.01) after 4 h of residence relative to SL inversely to the elevation and did not improve after 46 h. Resting SpO2 (~83%) did not differ among groups at 4300 m. Although SL and 4300 m SS exercise SpO2 (97% ± 2% to 74% ± 4%), HR (123 ± 10 bpm to 140 ± 12 bpm) and TT duration (51 ± 9 to 73 ± 16 min) were different (P < 0.01), responses at 4300 m were similar among all groups, as was actual and predicted 4300 m TT performances (74 ± 12 min). CONCLUSIONS: Residing for 2 d at 2500 to 4300 m, with or without daily activity, did not improve resting SpO2, SS exercise responses, or TT performance at 4300 m.

Acute Mountain Sickness is Reduced Following 2 Days of Staging During Subsequent Ascent to 4300 m.

OBJECTIVE: To determine whether 2 days of staging at 2500-3500 m, combined with either high or low physical activity, reduces acute mountain sickness (AMS) during subsequent ascent to 4300 m. METHODS: Three independent groups of unacclimatized men and women were staged for 2 days at either 2500 m (n = 18), 3000 m (n = 16), or 3500 m (n = 15) before ascending and living for 2 days at 4300 m and compared with a control group that directly ascended to 4300 m (n = 12). All individuals departed to the staging altitudes or 4300 m after spending one night at 2000 m during which they breathed supplemental oxygen to simulate sea level conditions. Half in each group participated in ∼3 hours of daily physical activity while half were sedentary. Women accounted for ∼25% of each group. AMS incidence was assessed using the Environmental Symptoms Questionnaire. AMS was classified as mild (≥0.7 and <1.5), moderate (≥1.5 and <2.6), and severe (≥2.6). RESULTS: While staging, the incidence of AMS was lower (p < 0.001) in the 2500 m (0%), 3000 m (13%), and 3500 m (40%) staged groups than the direct ascent control group (83%). After ascent to 4300 m, the incidence of AMS was lower in the 3000 m (43%) and 3500 m (40%) groups than the 2500 m group (67%) and direct ascent control (83%). Neither activity level nor sex influenced the incidence of AMS during further ascent to 4300 m. CONCLUSIONS: Two days of staging at either 3000 or 3500 m, with or without physical activity, reduced AMS during subsequent ascent to 4300 m but staging at 3000 m may be recommended because of less incidence of AMS.

Wearable physiological sensors and real-time algorithms for detection of acute mountain sickness.

This is a minireview of potential wearable physiological sensors and algorithms (process and equations) for detection of acute mountain sickness (AMS). Given the emerging status of this effort, the focus of the review is on the current clinical assessment of AMS, known risk factors (environmental, demographic, and physiological), and current understanding of AMS pathophysiology. Studies that have examined a range of physiological variables to develop AMS prediction and/or detection algorithms are reviewed to provide insight and potential technological roadmaps for future development of real-time physiological sensors and algorithms to detect AMS. Given the lack of signs and nonspecific symptoms associated with AMS, development of wearable physiological sensors and embedded algorithms to predict in the near term or detect established AMS will be challenging. Prior work using [Formula: see text], HR, or HRv has not provided the sensitivity and specificity for useful application to predict or detect AMS. Rather than using spot checks as most prior studies have, wearable systems that continuously measure SpO2 and HR are commercially available. Employing other statistical modeling approaches such as general linear and logistic mixed models or time series analysis to these continuously measured variables is the most promising approach for developing algorithms that are sensitive and specific for physiological prediction or detection of AMS.

Is normobaric hypoxia an effective treatment for sustaining previously acquired altitude acclimatization?

This study examined whether normobaric hypoxia (NH) treatment is more efficacious for sustaining high-altitude (HA) acclimatization-induced improvements in ventilatory and hematologic responses, acute mountain sickness (AMS), and cognitive function during reintroduction to altitude (RA) than no treatment at all. Seventeen sea-level (SL) residents (age = 23 ± 6 yr; means ± SE) completed in the following order: 1) 4 days of SL testing; 2) 12 days of HA acclimatization at 4,300 m; 3) 12 days at SL post-HA acclimatization (Post) where each received either NH (n = 9, [Formula: see text] = 0.122) or Sham (n = 8; [Formula: see text] = 0.207) treatment; and 4) 24-h reintroduction to 4,300-m altitude (RA) in a hypobaric chamber (460 Torr). End-tidal carbon dioxide pressure ([Formula: see text]), hematocrit (Hct), and AMS cerebral factor score were assessed at SL, on HA2 and HA11, and after 20 h of RA. Cognitive function was assessed using the SynWin multitask performance test at SL, on HA1 and HA11, and after 4 h of RA. There was no difference between NH and Sham treatment, so data were combined. [Formula: see text] (mmHg) decreased from SL (37.2 ± 0.5) to HA2 (32.2 ± 0.6), decreased further by HA11 (27.1 ± 0.4), and then increased from HA11 during RA (29.3 ± 0.6). Hct (%) increased from SL (42.3 ± 1.1) to HA2 (45.9 ± 1.0), increased again from HA2 to HA11 (48.5 ± 0.8), and then decreased from HA11 during RA (46.4 ± 1.2). AMS prevalence (%) increased from SL (0 ± 0) to HA2 (76 ± 11) and then decreased at HA11 (0 ± 0) and remained depressed during RA (17 ± 10). SynWin scores decreased from SL (1,615 ± 62) to HA1 (1,306 ± 94), improved from HA1 to HA11 (1,770 ± 82), and remained increased during RA (1,707 ± 75). These results demonstrate that HA acclimatization-induced improvements in ventilatory and hematologic responses, AMS, and cognitive function are partially retained during RA after 12 days at SL whether or not NH treatment is utilized.NEW & NOTEWORTHY This study demonstrates that normobaric hypoxia treatment over a 12-day period at sea level was not more effective for sustaining high-altitude (HA) acclimatization during reintroduction to HA than no treatment at all. The noteworthy aspect is that athletes, mountaineers, and military personnel do not have to go to extraordinary means to retain HA acclimatization to an easily accessible and relevant altitude if reexposure occurs within a 2-wk time period.

Quantitative model of hematologic and plasma volume responses after ascent and acclimation to moderate to high altitudes.

Despite decades of research, the magnitude and time course of hematologic and plasma volume (PV) changes following rapid ascent and acclimation to various altitudes are not precisely described. To develop a quantitative model, we utilized a comprehensive database and general linear mixed models to analyze 1,055 hemoglobin ([Hb]) and hematocrit (Hct) measurements collected at sea level and repeated time points at various altitudes in 393 unacclimatized men (n = 270) and women (n = 123) who spent between 2 h and 7 days at 2,500-4,500 m under well-controlled and standardized experimental conditions. The PV change (ΔPV) was calculated from [Hb] and Hct measurements during a time period when erythrocyte volume is stable. The results are 1) ΔPV decreases rapidly (~6%) after the 1st day at 2,500 m and [Hb] and Hct values increase by 0.5 g/dl and 1.5 points, respectively; 2) ΔPV decreases an additional 1%, and [Hb] and Hct increase an additional 0.1 g/dl and 0.2 points every 500-m increase in elevation above 2,500 m after the 1st day; 3) ΔPV continues to decrease over time at altitude, but the magnitude of this decrease and subsequent increase in [Hb] and Hct levels is dependent on elevation and sex; and 4) individuals with high initial levels of [Hb] and Hct and older individuals hemoconcentrate less at higher elevations. This study provides the first quantitative delineation of ΔPV and hematological responses during the first week of exposure over a wide range of altitudes and demonstrates that absolute altitude and time at altitude, as well as initial hematologic status, sex, and age impact the response.

Acute Mountain Sickness Symptoms Depend on Normobaric versus Hypobaric Hypoxia.

Acute mountain sickness (AMS), characterized by headache, nausea, fatigue, and dizziness when unacclimatized individuals rapidly ascend to high altitude, is exacerbated by exercise and can be disabling. Although AMS is observed in both normobaric (NH) and hypobaric hypoxia (HH), recent evidence suggests that NH and HH produce different physiological responses. We evaluated whether AMS symptoms were different in NH and HH during the initial stages of exposure and if the assessment tool mattered. Seventy-two 8 h exposures to normobaric normoxia (NN), NH, or HH were experienced by 36 subjects. The Environmental Symptoms Questionnaire (ESQ) and Lake Louise Self-report (LLS) were administered, resulting in a total of 360 assessments, with each subject answering the questionnaire 5 times during each of their 2 exposure days. Classification tree analysis indicated that symptoms contributing most to AMS were different in NH (namely, feeling sick and shortness of breath) compared to HH (characterized most by feeling faint, appetite loss, light headedness, and dim vision). However, the differences were not detected using the LLS. These results suggest that during the initial hours of exposure (1) AMS in HH may be a qualitatively different experience than in NH and (2) NH and HH may not be interchangeable environments.

Evidence for cerebral edema, cerebral perfusion, and intracranial pressure elevations in acute mountain sickness.

INTRODUCTION: We hypothesized that cerebral alterations in edema, perfusion, and/or intracranial pressure (ICP) are related to the development of acute mountain sickness (AMS). METHODS: To vary AMS, we manipulated ambient oxygen, barometric pressure, and exercise duration. Thirty-six subjects were tested before, during and after 8 h exposures in (1) normobaric normoxia (NN; 300 m elevation equivalent); (2) normobaric hypoxia (NH; 4400 m equivalent); and (3) hypobaric hypoxia (HH; 4400 m equivalent). After a passive 15 min ascent, each subject participated in either 10 or 60 min of cycling exercise at 50% of heart rate reserve. We measured tissue absorption and scattering via radio-frequency near-infrared spectroscopy (NIRS), optic nerve sheath diameter (ONSD) via ultrasound, and AMS symptoms before, during, and after environmental exposures. RESULTS: We observed significant increases in NIRS tissue scattering of 0.35 ± 0.11 cm(-1) (P = 0.001) in subjects with AMS (i.e., AMS+), consistent with mildly increased cerebral edema. We also noted a small, but significant increase in total hemoglobin concentrations with AMS+, 3.2 ± 0.8 µmolL(-1) (P < 0.0005), consistent with increased cerebral perfusion. No effect of exercise duration was found, nor did we detect differences between NH and HH. ONSD assays documented a small but significant increase in ONSD (0.11 ± 0.02 mm; P < 0.0005) with AMS+, suggesting mildly elevated ICP, as well as further increased ONSD with longer exercise duration (P = 0.005). CONCLUSION: In AMS+, we found evidence of cerebral edema, elevated cerebral perfusion, and elevated ICP. The observed changes were small but consistent with the reversible nature of AMS.

Quantitative Model of Sustained Physical Task Duration at Varying Altitudes.

PURPOSE: The objective of this study is to develop a quantitative model that can be used before ascent to altitude (ALT) to predict how much longer a sustained physical task would take for unacclimatized individuals in the early hours of exposure. METHODS: Using multiple linear regression, we analyzed time-trial (TT) performance on 95 unacclimatized men (n = 83) and women (n = 12) at sea level (SL) and at an ALT ranging from 2500 to 4300 m. The TT was initiated within 4 h of ascent to ALT. The independent variables known before ascent were as follows: ALT, age, height, weight, sex, SL peak oxygen uptake, SL task duration time, and body mass index (BMI) classification (normal weight vs overweight). The dependent variable was the percent increase in TT duration from SL to ALT. RESULTS: The most significant factor in the model was ALT (P = 0.0001), followed by BMI classification (P = 0.0009) and the interaction between BMI classification and ALT (P = 0.003). The model is as follows: percent increase in TT duration = [100 + e(-1.517+1.323 (ALT)+3.124 (BMI class)-0.769 (ALT) (BMI class)]. The percent increase in TT duration in overweight individuals was 129% greater than for normal-weight individuals at 3000 m. However, as ALT increased beyond 3000 m, the disparity between groups decreased until 4050 m where the percent increase in TT duration became greater for normal-weight individuals. CONCLUSIONS: This model provides the first quantitative estimates of the percent increase in sustained physical task duration during initial exposure to a wide range of elevations. Because only two easily obtainable factors are required as inputs for the model (ALT and BMI classification), this model can be used by many unacclimatized individuals to better plan their activities at ALT.

Acute Hypobaric Hypoxia Effects on Finger Temperature During and After Local Cold Exposure.

Mountain environments have combined stressors of lower ambient temperature and hypoxia. Cold alone can reduce finger temperature, resulting in discomfort, impaired dexterity, and increased risk of cold injury. Whether hypobaric hypoxia exacerbates these effects is unclear. To examine this, finger temperature responses to two cold water immersion tests were measured at sea level (SL, 99 kPa), 3000 m (70 kPa), and 4675 m (56 kPa) at the same air temperature (22°-23°C). Nine males sat quietly for 30 min, then completed the tests in balanced order. For the cold-induced vasodilation (CIVD) test, middle finger pad temperature was measured during immersion in 4°C water for 30 min. For the Rewarming test, finger temperature was measured for 30 min following a 5 min hand immersion in 16°C water. Average oxygen saturation was 98.6% during SL, 90.7% at 3000 m, and 75.8% at 4657 m. Mean finger temperature during the CIVD test (7.1°C) was similar among trials. There was no difference in CIVD parameters of nadir, apex, or mean finger temperatures; however both onset and apex times were earlier at 3000 m, compared to SL (0.6 min and 1.6 min, respectively). These differences did not persist at 4657 m. Rewarming after hand immersion was similar among trials, reaching 22.7°C after 30 min, compared to an initial finger temperature of 29.3°C. The results of this study provide no evidence that hypobaric hypoxia increases risk of cold injury. Previous findings of blunted finger temperatures at altitude are likely due to the lower ambient temperature that typically occurs at higher elevations.

Hypoxia, Hypobaria, and Exercise Duration Affect Acute Mountain Sickness.

INTRODUCTION: This study simultaneously quantified the effects of normobaric hypoxia (NH), hypobaric hypoxia (HH), exercise duration, and exposure time on acute mountain sickness severity (AMS-C). METHODS: Thirty-six subjects (27.7 ± 7.8 yr) participated in a partial repeated measures study, completing two of six conditions: normobaric normoxia (NN: 300 m/984 ft equivalent), NH or HH (Po2 = 91 mmHg; 4400 m/14,436 ft equivalent), combined with moderate intensity cycling for 10 or 60 min. Subjects completed the Environmental Symptoms Questionnaire and oxygen saturation (Spo2) was measured before, 1.5 h, 4 h, and 6.5 h into an 8-h exposure, and 1.5 h post-exposure. We fit multiple linear regression models with cluster adjusted standard errors on the exposure times using NH, HH, and long exercise as indicator variables, and AMS-C as the outcome variable. The Spo2and pre-exposure AMS-C score were used as covariates. RESULTS: NH and HH led to substantial and progressively increasing AMS-C, but NN did not. The effect of HH on AMS-C was significantly different from NH, with AMS-C in HH being 1.6 times higher than in NH. HH led to significantly increasing AMS-C, regardless of the exercise duration, while NH only did so in combination with longer exercise. DISCUSSION: Increases in AMS-C were each independently related to NH, HH, and long duration exercise, with HH affecting AMS-C more severely. This suggests that hypobaria may affect AMS development above the level induced by hypoxia alone. This further suggests that NH and HH may not be interchangeable for studying AMS and that exercise duration may impact physiological responses.

Cycling performance decrement is greater in hypobaric versus normobaric hypoxia.

BACKGROUND: The purpose of this study was to determine whether cycling time trial (TT) performance differs between hypobaric hypoxia (HH) and normobaric hypoxia (NH) at the same ambient PO2 (93 mmHg, 4,300-m altitude equivalent). METHODS: Two groups of healthy fit men were matched on physical performance and demographic characteristics and completed a 720-kJ time trial on a cycle ergometer at sea level (SL) and following approximately 2 h of resting exposure to either HH (n = 6, 20 ± 2 years, 75.2 ± 11.8 kg, mean ± SD) or NH (n = 6, 21 ± 3 years, 77.4 ± 8.8 kg). Volunteers were free to manually increase or decrease the work rate on the cycle ergometer. Heart rate (HR), arterial oxygen saturation (SaO2), and rating of perceived exertion (RPE) were collected every 5 min during the TT, and the mean was calculated. RESULTS: Both groups exhibited similar TT performance (min) at SL (73.9 ± 7.6 vs. 73.2 ± 8.2), but TT performance was longer (P < 0.05) in HH (121.0 ± 12.1) compared to NH (99.5 ± 18.1). The percent decrement in TT performance from SL to HH (65.1 ± 23.6%) was greater (P < 0.05) than that from SL to NH (35.5 ± 13.7%). The mean exercise SaO2, HR, and RPE during the TT were not different in HH compared to NH. CONCLUSION: Cycling time trial performance is impaired to a greater degree in HH versus NH at the same ambient PO2 equivalent to 4,300 m despite similar cardiorespiratory responses.

Evaluating the molecular basis for acute mountain sickness: hypoxia response gene expression patterns in warfighters and murine populations.

Acute mountain sickness (AMS) is an illness that affects many individuals at altitudes above 2,400 m (8,000 ft) resulting in decreased performance. Models that provide quantitative estimates of AMS risk are expanding, but predictive genetic models for AMS susceptibility are still under investigation. Thirty-four male U.S. Army Soldier volunteers were exposed to baseline, 3,000 m, 3,500 m, or 4,500 m altitude conditions in a hypobaric chamber and evaluated for onset of AMS symptoms. In addition, mice were evaluated at extreme hypoxia conditions equivalent to 7,600 m. Real-time polymerase chain reaction hypoxia response array was used to identify 15 genes that were activated in Soldiers and 46 genes that were activated in mice. We identified angiopoietin-like 4 (ANGPTL4) as a gene that is significantly activated in response to hypoxia (5.8-fold upregulated at 4,500 m in humans). The role of ANGPTL4 in high-altitude response has not been explored. Pretreatment of mice with fenofibrate, an ANGPTL4-activating pharmaceutical, had a considerable effect on overall hypoxia response gene expression and resulted in significantly decreased cerebral edema following exposure to hypoxia. Activation of ANGPTL4 may protect against cerebral edema by inhibiting vascular endothelial growth factor and therefore serve as a potential target for AMS prevention.

Performance during simple and complex military psychomotor tasks at various altitudes.

BACKGROUND: The purposes were to determine the following: 1) the threshold between 2500-4300 m at which simple and complex military task performance is degraded; 2) whether the degree of degradation, if any, is related to changes in altitude illness, fatigue, or sleepiness at a given altitude; and 3) whether the level of hypoxemia, independent of altitude, affects simple and complex military task performance. METHODS: There were 57 lowlanders (mean +/- SD; 22 +/- 3 yr; 79 +/- 12 kg) who were exposed to either 2500 m (N = 17), 3000 m (N = 12), 3500 m (N = 11), or 4300 m (N = 17). Disassembly and reassembly of a weapon (DsAs, simple), rifle marksmanship (RM, complex), acute mountain sickness (AMS), fatigue, sleepiness, and arterial oxygen saturation (SaO2) were measured at sea level (SL), and after 8 h (HA8) and 30 h (HA30) of exposure to each altitude. RESULTS: DsAs did not change from SL to HA8 or HA30 at any altitude. RM speed (target/min) decreased from SL (20 +/- 1.5) to HA8 (17 +/- 1.5) and HA30 (17 +/- 3) only at 4300 m. AMS, fatigue, and sleepiness were increased and SaO2 was decreased at 2500 m and above. Increased sleepiness was the only variable associated with decreased RM speed at 4300 m (r = -0.67; P = 0.004). Greater hypoxemia, independent of altitude, was associated with greater decrements in RM speed (r = 0.27; P = 0.04). CONCLUSIONS: Simple psychomotor performance was not affected by exposures between 2500-4300 m; however, complex psychomotor performance (i.e., RM speed) was degraded at 4300 m most likely due to increased sleepiness. Greater levels of hypoxemia were associated with greater decrements in RM speed.

Efficacy of residence at moderate versus low altitude on reducing acute mountain sickness in men following rapid ascent to 4300 m.

To determine if residence at moderate (~2000 m) compared to low (<50 m) altitude reduces acute mountain sickness (AMS) in men during subsequent rapid ascent to a higher altitude. Nine moderate-altitude residents (MAR) and 18 sea-level residents (SLR) completed the Environmental Symptoms Questionnaire (ESQ) at their respective baseline residence and again at 12, 24, 48, and 72 h at 4300 m to assess the severity and prevalence of AMS. AMS cerebral factor score (AMS-C) was calculated from the ESQ at each time point. AMS was judged to be present if AMS-C was ≥0.7. Resting end-tidal CO2 (PETco2) and arterial oxygen saturation (Sao2) were assessed prior to and at 24, 48, and 72 h at 4300 m. Resting venous blood samples were collected prior to and at 72 h at 4300 m to estimate plasma volume (PV) changes. MAR compared to SLR: 1) AMS severity at 4300 was lower (p<0.05) at 12 h (0.50±0.69 vs. 1.48±1.28), 24 h (0.15±0.19 vs. 1.39±1.19), 48 h (0.10±0.18 vs. 1.37±1.49) and 72 h (0.08±0.12 vs. 0.69±0.70); 2) AMS prevalence at 4300 was lower (p<0.05) at 12 h (22% vs. 72%), 24 h (0% vs. 56%), 48 h (0% vs. 56%), and 72 h (0% vs. 45%); 3) resting Sao2 (%) was lower (p<0.05) at baseline (95±1 vs. 99±1) but higher (p<0.05) at 4300 at 24 h (86±2 vs. 81±5), 48 h (88±3 vs. 83±6), and 72 h (88±2 vs. 83±5); and 4) PV (%) did not differ at 72 h at 4300 m in the MAR (4.5±6.7) but was reduced for the SLR (-8.1±10.4). These results suggest that ventilatory and hematological acclimatization acquired while living at moderate altitude, as indicated by a higher resting Sao2 and no reduction in PV during exposure to a higher altitude, is associated with greatly reduced AMS after rapid ascent to high altitude.

Sweat rate and prediction validation during high-altitude treks on Mount Kilimanjaro.

This study measured sweat rates (m(sw)) during high-altitude summer treks on Mt. Kilimanjaro to evaluate the efficacy of a recently developed fuzzy piecewise sweat prediction equation (Pw,sol) for application to high-altitude conditions. We hypothesized that the Pw,sol equation, adjusted for the barometric pressure (Pb) decreasing steadily at high altitude (Pw,sol+Alt), would allow for a more accurate prediction of m(sw) than Pw,sol unadjusted for altitude (Pw,sol(SL)). Fifteen men (43 ± 16 yr; 80 ± 22 kg) and seven women (46 ± 16 yr; 77 ± 18 kg) wearing hiking clothes (clo ∼1.15; clothing evaporative potential = 0.27) and carrying light loads (9 ± 2 kg), were studied during morning and afternoon treks (∼2-3 h) while ascending from 2,829 m to 3,505 m. After each trek, m(sw) was measured with specific biophysical parameters at 15-min intervals. During the trek day, Pb progressively declined (530 to 504 Torr), as solar radiation and ambient temperature (°C) rose transiently. During all treks, m(sw) ranged from 68 to 393 g·m(-2)·h(-1) (0.14 to 0.79 l/h). For each subject, derived Pw,sol(SL) and Pw,sol+Alt model outputs accurately predicted the morning and afternoon average m(sw) within a root mean square error of 0.145 l/h. No differences were found between Pw,sol(SL) and Pw,sol+Alt values. In conclusion, we report the first m(sw) measured during outdoor high-altitude activities and determined that Pw,sol(SL) equation can be used to predict fluid needs during high-altitude activities without alterations for lower Pb. This model prediction provides a valid water planning tool for outdoor activities at high altitude up to 3,500 m.

Predictive models of acute mountain sickness after rapid ascent to various altitudes.

PURPOSE: Despite decades of research, no predictive models of acute mountain sickness (AMS) exist, which identify the time course of AMS severity and prevalence following rapid ascent to various altitudes. METHODS: Using general linear and logistic mixed models and a comprehensive database, we analyzed 1292 AMS cerebral factor scores in 308 unacclimatized men and women who spent between 4 and 48 h at altitudes ranging from 1659 to 4501 m under experimentally controlled conditions (low and high activity). Covariates included in the analysis were altitude, time at altitude, activity level, age, body mass index, race, sex, and smoking status. RESULTS: AMS severity increased (P < 0.05) nearly twofold (i.e., 179%) for every 1000-m increase in altitude at 20 h of exposure, peaked between 18 and 22 h of exposure, and returned to initial levels by 48 h of exposure regardless of sex or activity level. Peak AMS severity scores were 38% higher (P < 0.05) in men compared with women at 20 h of exposure. High active men and women (>50% of maximal oxygen uptake for >45 min at altitude) demonstrated a 72% increase (P < 0.05) in the odds (odds ratio, 1.72; confidence interval, 1.03-3.08) of AMS compared with low active men and women. There was also a tendency (P = 0.10) for men to demonstrate greater odds of AMS (odds ratio, 1.65; confidence interval, 0.84-3.25) compared with women. Age, body mass index, race, and smoking status were not significantly associated with AMS. CONCLUSIONS: These models provide the first quantitative estimates of AMS risk over a wide range of altitudes and time points and suggest that in addition to altitude and time at altitude, high activity increases the risk of developing AMS. In addition, men demonstrated increased severity but not prevalence of AMS.