Beth A. Beidleman

Intermittent altitude exposures reduce acute mountain sickness at 4300 m.

Acute mountain sickness (AMS) commonly occurs at altitudes exceeding 2000-2500 m and usually resolves after acclimatization induced by a few days of chronic residence at the same altitude. Increased ventilation and diuresis may contribute to the reduction in AMS with altitude acclimatization. The aim of the present study was to examine the effects of intermittent altitude exposures (IAE), in combination with rest and exercise training, on the incidence and severity of AMS, resting ventilation and 24-h urine volume at 4300 m. Six lowlanders (age, 23 +/- 2 years; body weight, 77 +/- 6 kg; values are means +/- S.E.M.) completed an Environmental Symptoms Questionnaire (ESQ) and Lake Louise AMS Scoring System (LLS), a resting end-tidal partial pressure of CO2 ( PETCO2) test and a 24-h urine volume collection at sea level (SL) and during a 30 h exposure to 4300 m altitude-equivalent (barometric pressure=446 mmHg) once before (PreIAE) and once after (PostIAE) a 3-week period of IAE (4 h.day(-1), 5 days.week(-1), 4300 m). The previously validated factor score, AMS cerebral score, was calculated from the ESQ and the self-report score was calculated from the LLS at 24 h of altitude exposure to assess the incidence and severity of AMS. During each IAE, three subjects cycled for 45-60 min.day(-1) at 60-70% of maximal O2 uptake (VO2 max) and three subjects rested. Cycle training during each IAE did not affect any of the measured variables, so data from all six subjects were combined. The results showed that the incidence of AMS (%), determined from both the ESQ and LLS, increased (P<0.05) from SL (0 +/- 0) to PreIAE (50 +/- 22) at 24 h of altitude exposure and decreased (P<0.05) from PreIAE to PostIAE (0 +/- 0). The severity of AMS (i.e. AMS cerebral symptom and LLS self-report scores) increased (P<0.05) from SL (0.02 +/- 0.02 and 0.17 +/- 0.17 respectively) to PreIAE (0.49 +/- 0.18 and 4.17 +/- 0.94 respectively) at 24 h of altitude exposure, and decreased (P<0.05) from PreIAE to PostIAE (0.03 +/- 0.02 and 0.83 +/- 0.31 respectively). Resting PETCO2 (mmHg) decreased (i.e. increase in ventilation; P<0.05) from SL (38 +/- 1) to PreIAE (32 +/- 1) at 24 h of altitude exposure and decreased further (P<0.05) from PreIAE to PostIAE (28 +/- 1). In addition, 24-h urine volumes were similar at SL, PreIAE and PostIAE. In conclusion, our findings suggest that 3 weeks of IAE provide an effective alternative to chronic altitude residence for increasing resting ventilation and reducing the incidence and severity of AMS.

Altitude Preexposure Recommendations for Inducing Acclimatization

For many low-altitude (<1500 m) residents, their travel itineraries may cause them to ascend rapidly to high (>2400 m) altitudes without having the time to develop an adequate degree of altitude acclimatization. Prior to departing on these trips, low-altitude residents can induce some degree of altitude acclimatization by ascending to moderate (>1500 m) or high altitudes during either continuous or intermittent altitude preexposures. Generally, the degree of altitude acclimatization developed is proportional to the altitude attained and the duration of exposure. The available evidence suggests that continuous residence at 2200 m or higher for 1 to 2 days or daily 1.5- to 4-h exposures to >4000 m induce ventilatory acclimatization. Six days at 2200 m substantially decreases acute mountain sickness (AMS) and improves work performance after rapid ascent to 4300 m. There is evidence that 5 or more days above 3000 m within the last 2 months will significantly decrease AMS during a subsequent rapid ascent to 4500 m. Exercise training during the altitude preexposures may augment improvement in physical performance. The persistence of altitude acclimatization after return to low altitude appears to be proportional to the degree of acclimatization developed. The subsequent ascent to high altitude should be scheduled as soon as possible after the last altitude preexposure.

Exercise responses after altitude acclimatization are retained during reintroduction to altitude.

Following 2 to 3 wk of altitude acclimatization, ventilation is increased and heart rate (HR), plasma volume (PV), and lactate accumulation ([La]) are decreased during submaximal exercise. The objective of this study was to determine whether some degree of these exercise responses associated with acclimatization would be retained upon reintroduction to altitude (RA) after 8 d at sea level (SL). Six male lowlanders (X +/- SE; 31 +/- 2 yr, 82.4 +/- 4.6 kg) exercised to exhaustion at the same relative percentages of peak oxygen uptake (VO2peak) at SL, on acute altitude (AA) exposure, after a 16-d chronic altitude (CA) exposure on Pikes Peak (4,300 m), and during a 3- to 4-h RA in a hypobaric chamber (4,300 m; 446 mm Hg) after 8 d at SL. The submaximal exercise to exhaustion time (min) was the same at SL (66.0 +/- 1.6), AA (67.7 +/- 7.3), CA (79.9 +/- 6.2), and RA (67.9 +/- 1.9). At 75% VO2peak: (1) arterial oxygen saturation (SaO2) increased from AA to CA (67.0 +/- 1.5 vs 78.5 +/- 1.8%; P < 0.05) and remained increased at RA (77.0 +/- 2.0%); (2) HR decreased from SL to CA (171 +/- 6 vs 152 +/- 9 beats x min-1; P < 0.05) and remained decreased at RA (157 +/- 5 beats x min-1); (3) calculated PV decreased 6.9 +/- 10.0% at AA, 21.3 +/- 11.1% at CA, and 16.7 +/- 5.4% at RA from SL baseline values, and (4) [La] decreased from AA to CA (5.1 +/- 0.9 vs 1.9 +/- 0.4 mmol x L-1; P < 0.05) and remained decreased at RA (2.6 +/- 0.6 mmol x L-1). Upon RA after 8 d at SL, the acclimatization responses were retained 92 +/- 9% for SaO2, 74 +/- 8% for PV, and 58 +/- 3% for [La] at 75% VO2peak. In conclusion, although submaximal exercise to exhaustion time is not improved upon reintroduction to altitude after 8 d at sea level, retention of beneficial exercise responses associated with altitude acclimatization is likely in individuals whose work, athletic competition, or recreation schedules involve intermittent sojourns to high elevations.

Effect of hypohydration and altitude exposure on aerobic exercise performance and acute mountain sickness

Hypoxia often causes body water deficits (hypohydration, HYPO); however, the effects of HYPO on aerobic exercise performance and prevalence of acute mountain sickness (AMS) at high altitude (ALT) have not been reported. We hypothesized that 1) HYPO and ALT would each degrade aerobic performance relative to sea level (SL)-euhydrated (EUH) conditions, and combining HYPO and ALT would further degrade performance more than one stressor alone; and 2) HYPO would increase the prevalence and severity of AMS symptoms. Seven lowlander men (25 ± 7 yr old; 82 ± 11 kg; mean ± SD) completed four separate experimental trials. Trials were 1) SL-EUH, 2) SL-HYPO, 3) ALT-EUH, and 4) ALT-HYPO. In HYPO, subjects were dehydrated by 4% of body mass. Subjects maintained hydration status overnight and the following morning entered a hypobaric chamber (at SL or 3,048 m, 27°C) where they completed 30 min of submaximal exercise immediately followed by a 30-min performance time trial (TT). AMS was measured with the Environmental Symptoms Questionnaire-Cerebral Score (AMS-C) and the Lake Louise Scoring System (LLS). The percent change in TT performance, relative to SL-EUH, was -19 ± 12% (334 ± 64 to 278 ± 87 kJ), -11 ± 10% (334 ± 64 to 293 ± 33 kJ), and -34 ± 22% (334 ± 64 to 227 ± 95 kJ), for SL-HYPO, ALT-EUH, and ALT-HYPO, respectively. AMS symptom prevalence was 2/7 subjects at ALT-EUH for AMS-C and LLS and 5/7 and 4/7 at ALT-HYPO for AMS-C and LLS, respectively. The AMS-C symptom severity score (AMS-C score) tended to increase from ALT-EUH to ALT-HYPO but was not significant (P = 0.07). In conclusion, hypohydration at 3,048 m 1) degrades aerobic performance in an additive manner with that induced by ALT; and 2) did not appear to increase the prevalence/severity of AMS symptoms.

Effectiveness of Preacclimatization Strategies for High-Altitude Exposure

Acute mountain sickness (AMS) and large decrements in endurance exercise performance occur when unacclimatized individuals rapidly ascend to high altitudes. Six altitude and hypoxia preacclimatization strategies were evaluated to determine their effectiveness for minimizing AMS and improving performance during altitude exposures. Strategies using hypobaric chambers or true altitude were much more effective overall than those using normobaric hypoxia (breathing, <20.9% oxygen).

Intermittent Hypoxic Exposure Does Not Improve Endurance Performance at Altitude

PURPOSE This study examined the effect of 1 wk of normobaric intermittent hypoxic exposure (IHE) combined with exercise training on endurance performance at a 4300-m altitude (HA). METHODS Seventeen male lowlanders were divided into an IHE (n = 11) or SHAM (n = 6) group. Each completed cycle endurance testing consisting of two 20-min steady state (SS) exercise bouts (at 40% and 60% V O2peak) followed by a 10-min break and then a 720-kJ cycle time trial at HA before IHE or SHAM treatment (Pre-T). IHE treatment consisted of a 2-h rest at a PO2 of 90 mm Hg followed by two 25-min bouts of exercise at approximately 80% of peak HR at a PO2 of 110 mm Hg for 1 wk in a hypoxia room. SHAM treatment was identical except that the PO2 was 148 mm Hg for both rest and exercise. After IHE or SHAM treatment (Post-T), all completed a second cycle endurance test at HA. HR, arterial oxygen saturation (SaO2), and RPE were obtained from the 10th to the 15th minute during the two SS exercise bouts and every 5 min during the time trial. RESULTS Seven volunteers in the IHE group could not finish the 720-kJ time trial either at Pre-T or at Post-T. Time trial analysis was limited, therefore, to the time to reach 360 kJ (halfway point) for all volunteers. From Pre-T to Post-T, there was no improvement in time trial performance (min +/- SE) in the IHE (62.0 +/- 4.8 to 63.7 +/- 5.2) or SHAM (60.9 +/- 6.3 to 54.2 +/- 6.8) group. There was no change from Pre-T to Post-T in HR, SaO2, and RPE during the two SS exercise bouts or time trial in either group. CONCLUSIONS One week of IHE combined with exercise training does not improve endurance performance at a 4300-m altitude in male lowlanders.

Substrate oxidation is altered in women during exercise upon acute altitude exposure

PURPOSE The purpose of this study was to determine whether substrate oxidation during submaximal exercise in women is affected by an acute exposure to 4300-m altitude and menstrual cycle phase. METHODS Eight female lowlanders (mean +/- SD; 33 +/- 3 yr, 58 +/- 6 kg, 163 +/- 8 cm) completed a peak oxygen uptake (VO2peak) and submaximal exercise to exhaustion (EXH) test at 70% of their altitude-specific VO2peak at sea level (SL) and during an acute altitude (AA) exposure to 4300 m in a hypobaric chamber (446 mm Hg) in their early-follicular and midluteal menstrual cycle phase. The respiratory exchange ratio (RER) was calculated from oxygen uptake and carbon dioxide output measurements made during the EXH tests, and used to estimate the percent contribution of fat and carbohydrate to energy metabolism. Blood samples were taken at rest and every 15 min during the EXH tests. Blood samples were evaluated for glucose, lactate, glycerol, free fatty acids, insulin, growth hormone, cortisol, glucagon, epinephrine, norepinephrine, estradiol, and progesterone concentrations. RESULTS Despite increased (P < 0.05) estradiol and progesterone levels in the midluteal phase, substrate oxidation, energy substrates, and metabolic hormones were not affected by cycle phase at SL or AA. However, free fatty acids and cortisol were increased (P < 0.05) whereas RER was decreased (P < 0.05) during exercise upon AA exposure compared with SL in both cycle phases. CONCLUSIONS These data suggest that substrate oxidation is altered in women during exercise at AA compared with SL but is not affected by cycle phase. Whether increased fat or protein oxidation accounts for the lower RER values during the AA exposure cannot be determined from this study but warrants further investigation.

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.

Postural instability and acute mountain sickness during exposure to 24 hours of simulated altitude (4300 m).

Short exposures to severe or moderate hypoxia can have detrimental effects on postural stability. We hypothesized that continuous 24-h exposure to simulated 4300-m altitude (446 mmHg) would adversely affect postural stability and that this change in postural stability would be related to the severity of acute mountain sickness (AMS). On two different studies with similar experimental designs, postural instability was measured after approximately 3 and approximately 24 h of exposure using a computer-controlled unstable platform system in a total of 19 volunteers on three consecutive, 30-sec tests: eyes open (EO), eyes closed (EC), and a dynamic test involving tracking a circular moving object. Compared to baseline sea-level results, increases in postural instability were obtained with the EO test after 2 to 3 h (30%, p = 0.002) and 23 to 24 h (21%, p = 0.036) of altitude exposure. Similar increases were obtained on the EC test: 2 to 3 h (25%, p < 0.001) and 23 to 24 h (31%, p < 0.001). Although absolute instability values were higher on the EC test, the ratio EC/EO and the relative temporal changes with altitude exposure were similar. There were no significant altitude-stability effects on the target-tracking task. Sixty-three percent of the subjects (12 of 19) exhibited significant AMS (> 0.7 ESQ-C score) at some point during the 24-h exposure. No statistically significant correlations were obtained between the ESQ-C and any of the postural instability tests. These results indicate that postural stability is adversely affected during a 24-h exposure to 4300 m; however, there does not appear to be a correlation with the incidence or severity of AMS.

The impact of moderate-altitude staging on pulmonary arterial hemodynamics after ascent to high altitude.

Staged ascent (SA), temporary residence at moderate altitude en route to high altitude, reduces the incidence and severity of noncardiopulmonary altitude illness such as acute mountain sickness. To date, the impact of SA on pulmonary arterial pressure (PAP) is unknown. We tested the hypothesis that SA would attenuate the PAP increase that occurs during rapid, direct ascent (DA). Transthoracic echocardiography was used to estimate mean PAP in 10 healthy males at sea level (SL, P(B) approximately 760 torr), after DA to simulated high altitude (hypobaric chamber, P(B) approximately 460 torr), and at 2 times points (90 min and 4 days) during exposure to terrestrial high altitude (P(B) approximately 460 torr) after SA (7 days, moderate altitude, P(B) approximately 548 torr). Alveolar oxygen pressure (Pao(2)) and arterial oxygenation saturation (Sao(2)) were measured at each time point. Compared to mean PAP at SL (mean +/- SD, 14 +/- 3 mmHg), mean PAP increased after DA to 37 +/- 8 mmHg (Delta = 24 +/- 10 mmHg, p < 0.001) and was negatively correlated with both Pao(2) (r(2) = 0.57, p = 0.011) and Sao(2) (r(2) = 0.64, p = 0.005). In comparison, estimated mean PAP after SA increased to only 25 +/- 4 mmHg (Delta = 11 +/- 6 mmHg, p < 0.001), remained unchanged after 4 days of high altitude residence (24 +/- 5 mmHg, p = not significant, or NS), and did not correlate with either parameter of oxygenation. SA significantly attenuated the PAP increase associated with continuous direct ascent to high altitude and appeared to uncouple PAP from both alveolar hypoxia and arterial hypoxemia.