Charles S. Fulco

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.

Effect of six days of staging on physiologic adjustments and acute mountain sickness during ascent to 4300 meters.

This study determined the effectiveness of 6 days (d) of staging at 2200 m on physiologic adjustments and acute mountain sickness (AMS) during rapid, high-risk ascent to 4300 m. Eleven sea-level (SL) resident men (means +/- SD; 21 +/- 3 yr; 78 +/- 13 kg) completed resting measures of end-tidal CO(2) (Petco(2)), arterial oxygen saturation (Sao(2)), heart rate (HR), and mean arterial pressure (MAP) at SL and within 1 h of exposure to 4300 m in a hypobaric chamber prior to 6 d of staging at 2200 m (preSTG) and on the summit of Pikes Peak following 6 d of staging at 2200 m (postSTG). Immediately following resting ventilation measures, all performed submaximal exercise ( approximately 55% of altitude-specific maximal oxygen uptake) for approximately 2 h on a bicycle ergometer to induce higher levels of AMS. AMS-C, calculated from the Environmental Symptoms Questionnaire, was measured following 4 h and 8 h of exposure at preSTG and postSTG, and the mean was calculated. Resting Petco(2) (mmHg) was unchanged from SL (39.8 +/- 2.6) to preSTG (39.3 +/- 3.0), but decreased (p < 0.05) from preSTG to postSTG (32.8 +/- 2.6). Resting Sao(2) (%) decreased (p < 0.05) from SL (97 +/- 2) to preSTG (80 +/- 4) and increased (p < 0.05) from preSTG to postSTG (83 +/- 3). Resting HR (bpm) and MAP (mmHg) did not change in any of the test conditions. The incidence and severity of AMS-C decreased (p < 0.05) from preSTG (91 +/- 30%; 1.05 +/- 0.56) to postSTG (45 +/- 53%; 0.59 +/- 0.43), respectively. These results suggest that modest physiologic adjustments induced by staging for 6 d at 2200 m reduced the incidence and severity of AMS during rapid, high-risk ascent to 4300 m.

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.

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 Effect of Naproxen on Acute Mountain Sickness and Vascular Responses to Hypoxia

The role of prostaglandins in the pathogenesis of acute mountain sickness and two hypoxia-induced vascular responses was evaluated using the cyclooxygenase inhibitor naproxen. Eleven men spent 24 hours at sea level, followed by 34 hours of decompression to 428 mm Hg while receiving naproxen (N), 250 mg twice daily or placebo (P) in a double-blind crossover trial. Serum naproxen levels measured by high pressure liquid chromatography were not changed by hypoxia. The severity of acute mountain sickness (AMS) by the Environmental Symptom Questionnaire scores and observer assessment were unaffected by drug treatment. Retinal artery diameter measured from projected fundus photographs was increased after 27 hours at altitude (11.4 ± .5 mm) vs. sea level (9.4 ± .5 mm, p < 0.05) during both trials. Upright mean arterial pressure fell after 6 hours at altitude (79 · 3 mm Hg during N and P vs. 92 · 3 at sea level, p < 0.01). Minute ventilation, end expiratory alveolar PO2 and PCO2 did not differ between drug trials. This study suggests vasodilating prostaglandins do not have a major role in the genesis of AMS, hypoxia-induced retinal vasodilatation, or postural blood pressure responses in man.