Effect of caffeine on submaximal exercise performance at altitude.

The purpose of this study was to determine if caffeine (CAF) could enhance exercise performance at high altitude (HA). Eight males (17 to 24 years) performed two submaximal endurance tests to exhaustion (ETX) while cycling at approximately 80% of their altitude-specific maximal aerobic power during each of three phases: 1) sea level (SL); 2) after 1 h (acute) at 4,300 m; and 3) after 2 weeks (chronic) at 4,300 m. Subjects received either CAF (4 mg.kg-1) or a placebo drink 1 h prior to each ETX bout at each phase in a double-blind crossover design. ETX was little affected during CAF treatment at SL (26.33 to 27.51 min, p = 0.21) but was increased by 54% (22.77 to 35.10 min, p = 0.004) during acute HA exposure and tended to improve (24%, 30.52 to 38.63 min, p = 0.084) during chronic HA exposure. The change in ETX during acute ALT could not be accounted for by differences in substrate metabolism, Q, diet, or RPE, but may have been due to either a CAF-induced increase in tidal volume or to a lessening of an ALT-induced impairment in muscular force production during submaximal exercise.

Effects of altitude acclimatization on fluid regulatory hormone response to submaximal exercise.

To determine the effect of altitude acclimatization on plasma levels of atrial natriuretic peptide (ANP) during submaximal exercise and its relationship with renin and aldosterone, seven male volunteers aged 17-23 yr exercised to exhaustion on a cycle ergometer at 80-85% of their maximum O2 uptake at sea level (SL; 50 m), during 1 h in a hypobaric chamber [acute altitude (AA); 4,300 m], and after 14 or 16 days of residence on the summit of Pikes Peak, CO [chronic altitude (CA); 4,300 m]. Plasma samples taken before exercise, 10 min after the start of exercise, and 5 min postexercise were analyzed for ANP, plasma renin activity (PRA), and aldosterone (ALDO). ANP showed a progressive increase from rest to postexercise [7.49 +/- 1.63 to 11.32 +/- 1.80 (SE) pmol/ml and 6.05 +/- 2.55 to 10.38 +/- 7.20 pmol/ml; P = 0.049, exercise] at SL and AA, respectively, but not at CA (P = 0.039, altitude). Similarly, PRA and ALDO rose from rest to postexercise (P < 0.001, exercise), but the rise in ALDO with exercise was less during AA than during SL and CA (P = 0.002, phase). The decreased ANP levels during exercise after altitude acclimatization, with no change in PRA and ALDO, suggest that ANP has little effect on PRA and ALDO under these conditions.

Hypobaric hypoxia (380 Torr) decreases intracellular and total body water in goats.

The effects of prolonged hypoxia on body water distribution was studied in four unanesthetized adult goats (Capra lircus) at sea level and after 16 days in a hypobaric chamber [(380 Torr, 5,500 m, 24 +/- 1 degrees C); arterial PO2 = 27 +/- 2 (SE) Torr]. Total body water (TBW), extracellular fluid volume (ECF), and plasma volume (PV) were determined with 3H2O, [14C]inulin, and indocyanine green dye, respectively. Blood volume (BV) [BV = 100PV/(100 - hematocrit)], erythrocyte volume (RCV) (RCV = BV - PV), and intracellular fluid (ICF) (ICF = TBW - ECF) and interstitial fluid (ISF) (ISF = ECF - PV) volumes were calculated. Hypoxia resulted in increased pulmonary ventilation and arterial pH and decreased arterial PCO2 and PO2 (P less than 0.05). In addition, body mass (-7.1%), TBW (-9.1%), and ICF volume (-14.4%) all decreased, whereas ECF (+11.7%) and ISF (+27.7%) volumes increased (P less than 0.05). The decrease in TBW accounted for 89% of the loss of body mass. Although PV decreased significantly (-15.3%), BV was unchanged because of an offsetting increase in RCV (+39.5%; P less than 0.05). We conclude that, in adult goats, prolonged hypobaric hypoxia results in decreases in TBW volume, ICF volume, and PV, with concomitant increases in ECF and ISF volumes.

Plasma changes in beta-endorphin to acute hypobaric hypoxia and high intensity exercise.

The purpose of this study was to examine the immediate post-exercise effects of acute exposure to a simulated altitude of 4,300 m on plasma concentrations of beta-endorphin (beta-EP) and associated changes of adrenocorticotropin (ACTH), and cortisol to high intensity cycle exercise (i.e., stages of 90 and 100% peak Vo2). Exercise intensities were assigned relative to peak O2 uptake both under sea level conditions and under acute hypobaric hypoxic conditions. Plasma beta-EP concentrations significantly increased from pre- to immediately post-exercise at both 90 and 100% peak Vo2 in both the sea level and acute hypobaric hypoxic trials. No associated exercise-induced changes were observed for ACTH or cortisol pre- to immediately post-exercise at either sea level or during hypoxic conditions. Exercise at acute hypobaric hypoxia elicited no significantly different responses in plasma beta-EP, ACTH, or cortisol than those elicited by the same relative exercise intensities under normobaric normoxic conditions. Additionally, no changes in the beta-EP/ACTH molar ratio for exercise or between conditions were observed. These data indicate that acute simulated high altitude exposure neither diminishes nor augments the physiological stimuli involved with high relative exercise intensity activation mechanisms of these hormones.

Alterations in human upper extremity motor function during acute exposure to simulated altitude.

We tested the hypothesis that mild motor dysfunction was associated with Acute Mountain Sickness (AMS) by measuring arm movement characteristics in 14 subjects at sea level and at the end of a 30-h simulated altitude exposure (4,600 m). A computerized upper extremity movement analyzer (UEMA) was used to quantitate arm movements between a "start" position and randomly-generated targets on a large digitizing tablet by measuring selected speed parameters and error indices. The UEMA results were compared with the results of the Environmental Symptoms Questionnaire (ESQ) and with neurologic examinations. When compared with sea-level values, the mean values for all the speed-related parameters measured at the end of the 30-h exposure significantly declined by 20% to 32%. The error indices were not different. The declines in the speed-related parameters were significantly correlated with the severity of AMS symptoms as measured by the ESQ (R = 0.82). The neurologic abnormalities were limited to changes in mental status items. These results demonstrate that subclinical alterations in upper extremity speed are associated with mild, reversible AMS and provide evidence that hypoxia may produce supraspinal inhibition of motor pathways.

Operation Everest II: comparison of four instruments for measuring blood O2 saturation.

The bias and precision of four different methods for determining O2 saturation (SO2) were evaluated during a study of hypobaric hypoxia conducted with seven male subjects exposed progressively over a 40-day period to simulated altitudes from sea level (760 Torr) to 8,840 m (240 Torr). SO2 of arterial and mixed venous blood samples were measured with the Instrumentation Laboratory 282 CO-oximeter (CO-OX), the Radiometer ABL-300 (ABL), and the Lex-O2-Con-K (LEX). Noninvasive measurements of arterial SO2 were made with a Hewlett-Packard 47201A ear oximeter (EAR-OX). The CO-OX method was used as a secondary standard for comparison with the other methods because it has been validated against the classical Van Slyke method over a wide physiological range (Maas et al., Clin. Chim. Acta 29: 303-309, 1970). The LEX results most closely approximated but consistently underestimated those of the CO-OX: LEX = 0.93 CO-OX -0.86, standard error of the estimate (SEE) = 5.17, r = 0.98, n = 670. The ABL method appeared to combine two linear trends: for SO2 greater than 75%, ABL = 0.84 CO-OX +14.4, SEE = 1.77, r = 0.97, n = 369; less than 75%, ABL = 0.98 CO-OX +5.9, SEE = 4.44, r = 0.97, n = 486. The EAR-OX results were found to approximate those of the CO-OX at SO2 values only greater than 65%: EAR-OX = 1.07 CO-OX -6.12, SEE = 7.71, r = 0.98, n = 326.(ABSTRACT TRUNCATED AT 250 WORDS)

Propranolol and the compensatory circulatory responses to orthostasis at high altitude.

Tachycardia has been shown to be an important response involved in the maintenance of cardiac output during orthostasis at high altitude. This study was undertaken to determine if tachycardia, mediated by beta-adrenergic sympathetic stimulation, actually represents an essential response. Twelve young, healthy male subjects were administered either 80 mg propranolol (n = 6) or placebo (n = 6), t.i.d. at sea level and for 3 days (d) prior to and during the first 15 d of a 19-d altitude sojourn (On Treatment). Individuals were randomly assigned to each group. Upright tilt tests were performed at sea level and at high altitude during days 2, 7, and 15 On Treatment. Subjects were also tilt-tested at sea level and on day 19 of the altitude exposure without placebo or propranolol administration (Off Treatment). Heart rate, stroke volume, calf blood flow, and blood pressure were obtained during supine rest and after 12 min of 60 degrees tilt. We found no differences between groups in any of the circulatory measurements at sea level and altitude while Off Treatment. During the On Treatment phases at sea level and altitude, propranolol caused reductions in heart rate and blood pressure values in each position (p less than 0.05). Supine and upright cardiac output, however, were found not altered due to compensatory increases in stroke volume (p less than 0.05). We concluded that tachycardia, both at rest and during upright tilt at high altitude is important, but not essential to maintain cardiac output.

Effects of propranolol on acute mountain sickness (AMS) and well-being at 4,300 meters of altitude.

A number of physiological responses and adjustments occur at high altitude to compensate for hypoxia. We hypothesized that interference with one component of the normal compensatory process, the sympathetic nervous system, would hinder altitude acclimatization and thereby exacerbate acute mountain sickness (AMS) and compromise well-being. Twelve young males (21.2 +/- 0.4 years) received either 80 mg propranolol (PRO; n = 6) or placebo (PLA; n = 6), t.i.d. at sea level (SL) and during the first 15 d of a 19-d residence at 4,300 m (HA). Individuals were randomly assigned to each group. The Environmental Symptoms Questionnaire (ESQ) was administered at SL and twice daily (AM and PM) during the entire altitude exposure in order to assess AMS symptoms and subjective feelings of well-being. Supine heart rate (HR) was determined at rest twice at SL and four times at HA. HR in the PLA group increased 40% over SL values (57 +/- 3 to 80 +/- 4 beats/min) by day 7 at HA (p less than 0.01). HR in the PRO group did not increase above SL values during medication at HA. By 4 d after the medication administration was terminated, HR in the PRO group had increased and did not differ from the PLA group. Throughout the entire altitude exposure, ESQ scores for the PRO group were lower than or similar to the PLA group. Furthermore, cessation of PRO treatment did not result in a change in well-being. These findings suggested that interference with the normal acclimatization process by beta-adrenergic blockade did not exacerbate AMS or reduce feelings of well-being.

Dexamethasone as prophylaxis for acute mountain sickness. Effect of dose level.

Rapid exposure of unacclimatized persons to high altitude causes the syndrome acute mountain sickness (AMS). Prophylactic treatment with frequent high doses of dexamethasone has been shown to prevent AMS. To determine whether lower, less frequent doses were effective in preventing AMS, 28 men between the ages of 18 and 32 were exposed to a simulated altitude of 4,570 m for 45 h in a hypobaric chamber on two occasions while taking one of three doses of dexamethasone (4 mg, 1 mg, or .25 mg every 12 h) or a placebo in a double-blind, crossover design. The 4-mg dose of dexamethasone reduced the incidence of AMS symptoms compared with placebo and the other dose levels. Dexamethasone did not alter fluid balance or plasma volume changes, but treatment with 1 mg and 4 mg suppressed cortisol secretion. There was no evidence of adrenal cortical suppression after treatment with dexamethasone or placebo 48 h after discontinuing altitude exposure and drug treatment. The results indicate that 4 mg of dexamethasone twice daily is an effective prophylactic treatment for AMS, while lower doses are relatively ineffective.

Hemodynamic and sympathoadrenal responses to altitude in humans: effect of dexamethasone.

Altitude exposure alters hemodynamics and sympathoadrenal function and elicits acute mountain sickness (AMS). Since dexamethasone prevents AMS and influences responsiveness to catecholamines, we studied hemodynamic and sympathoadrenal responses to 4,570 m simulated altitude in 8 subjects treated with dexamethasone or placebo. Mean pulse rates were less at altitude with dexamethasone (96.1 for placebo and 84.1 for dexamethasone; treatment-altitude interaction, p = 0.0045). Altitude led to a postural decline in mean arterial pressure (posture-altitude interaction, p = 0.0026), but this was not affected by dexamethasone. Dexamethasone reduced urinary epinephrine to a greater extent during altitude exposure (from 9.41 ng.mg-1 creatinine with placebo to 4.16 with dexamethasone) when compared with sea level (from 3.24 to 3.08). Urinary excretion of norepinephrine was unchanged at altitude. We conclude that acute altitude exposure is associated with stimulation of the adrenal medulla and not the sympathetic nervous system. Dexamethasone blocks the adrenal medullary response and blunts the pulse rate increase at altitude.

Altitude acclimatization attenuates plasma ammonia accumulation during submaximal exercise.

This study examined the effects of acclimatization to 4,300 m altitude on changes in plasma ammonia concentrations with 30 min of submaximal [75% maximal O2 uptake (VO2max)] cycle exercise. Human test subjects were divided into a sedentary (n = 6) and active group (n = 5). Maximal uptake (VO2max) was determined at sea level and at high altitude (HA; 4,300 m) after acute (t less than 24 h) and chronic (t = 13 days) exposure. The VO2max of both groups decreased 32% with acute HA when compared with sea level. In the sedentary group, VO2max decreased an additional 16% after 13 days of continuous residence at 4,300 m, whereas VO2max in the active group showed no further change. In both sedentary and active subjects, plasma ammonia concentrations were increased (P less than 0.05) over resting levels immediately after submaximal exercise at sea level as well as during acute HA exposure. With chronic HA exposure, the active group showed no increase in plasma ammonia immediately after submaximal exercise, whereas the postexercise ammonia in the sedentary group was elevated but to a lesser extent than at sea level or with acute HA exposure. Thus postexercise plasma ammonia concentration was decreased with altitude acclimatization when compared with ammonia concentrations following exercise performed at the same relative intensity at sea level or acute HA. This decrease in ammonia accumulation may contribute to enhanced endurance performance and altered substrate utilization with exercise following acclimatization to altitude.

Physiological responses to prolonged upper-body exercise.

To date, investigators have not examined physiological responses to prolonged upper-body exercise. Knowledge of the feasibility of performing this type of exercise and the elicited responses could have application in designing continuous training programs for upper-body muscle groups. Nine males, with a peak oxygen uptake (means +/- SD) of 49 +/- 7 for cycle (CY) and 35 +/- 6 ml X min-1 X kg-1 for arm crank (AC) exercise, completed four 60-min exercise tests. The subjects performed AC and CY exercise at the same absolute (ABS) oxygen uptake (1.6 1 X min-1) and at the same relative (REL) percent of ergometer-specific peak oxygen uptake (60%). During the ABS tests, AC exercise elicited significantly (P less than 0.05) greater heart rate (HR), ventilatory equivalent of oxygen (VE X VO2(-1), blood lactate (La), and percent decrease in plasma volume (PV) than CY exercise. During the REL tests, HR was lower and VE X VO2(-1) was higher for AC than CY exercise; there were no differences between AC and CY exercise in La or PV responses. These data demonstrate that upper-body exercise can be performed for 60 min at a relative intensity which might be sufficient to elicit a cardiovascular training effect. However, because heart rates are lower during upper-than lower-body exercise at the same relative intensity, exercise prescriptions based on heart rate alone may need to be modified for upper-body exercise.

Prevention of acute mountain sickness by dexamethasone.

Acute mountain sickness is a syndrome that occurs when unacclimatized persons ascend rapidly to high altitudes. It is postulated that cerebral edema causes its symptoms. Since dexamethasone is useful in treating some forms of cerebral edema, we investigated its role in the prevention of acute mountain sickness. Using a double-blind crossover design, we exposed eight young men to a simulated altitude of 4570 m (15,000 ft) on two occasions. By random assignment, each subject received dexamethasone (4 mg every 6 hours) or placebo for 48 hours before and throughout the 42-hour exposure. The presence of symptoms of acute mountain sickness was established by two methods: a questionnaire and an interview by a physician. Dexamethasone significantly reduced the symptoms of acute mountain sickness. During dexamethasone treatment, the cerebral-symptom score (mean +/- S.E.) decreased from 1.09 +/- 0.18 to 0.26 +/- 0.08, and the respiratory-symptom score decreased from 0.64 +/- 0.09 to 0.31 +/- 0.06 (both, P less than 0.05). As judged by the interviewing physician, the symptom score decreased from 1.10 +/- 0.11 to 0.28 +/- 0.07 (P = 0.01). We conclude that dexamethasone may be effective in preventing the symptoms of acute mountain sickness.