Physiological Responses to Graded Acute Normobaric Hypoxia Using an Intermittent Walking Protocol
Abstract
Objective
The study aimed to examine the physiological responses to acute normobaric hypoxia during an intermittent walking protocol.
Methods
Twelve active healthy male participants completed a 125-minute test that involved rest and walking (50% ) during normoxic (20.93%O2) and 2 hypoxic conditions (14%O2 and 12%O2). A range of physiological markers were measured throughout the test. Lake Louise Questionnaire scores and Environmental Symptoms Questionnaire cerebral scores were used as a measurement of acute mountain sickness symptoms.
Results
Oxygen saturation, thermal sensation scale, heart rate, perceived thirst, core temperature, rating of perceived exertion, feeling state, and Δbody mass all positively correlated with the highest Lake Louise Questionnaire and Environmental Symptoms Questionnaire cerebral scores (P < .05) and were significantly different between the 3 conditions during the exercise phases.
Conclusion
A range of physiological markers are associated with symptoms of acute mountain sickness following brief periods of hypoxic exposure.
Introduction
The extent of the physiological response to hypoxia is known to vary when traveling above 2500 m.1 In some individuals the decline in the partial pressure of oxygen results in the development of acute mountain sickness (AMS), although this can depend on the ascent style, altitude, prior history of AMS, and an individual's altitude tolerance.1 The Lake Louise Consensus Group2 defined AMS as the presence of headache in an unacclimatized person who has recently arrived at an altitude above 2500 m plus the presence of one or more of the following: gastrointestinal symptoms (anorexia, nausea, or vomiting), insomnia, dizziness, and lassitude or fatigue.
Physiological variables associated with the onset of, and susceptibility to, AMS include hypoxic ventilatory response,3 body temperature,4 peripheral arterial oxygen saturation (SaO2),5 end tidal carbon dioxide concentration,6 peripheral blood O2 content,7 hypoxic cardiac response,7 and lung function.8
Pathophysiological mechanisms of AMS are widely debated. Current thinking centers on the oxidative stress of hypoxia causing hypoventilation, reduced gaseous exchange,9 changes in fluid controlling hormones,10 and possible increased permeability in the central nervous system.11 These mechanisms tend to induce AMS over a period of hours, although Hackett and Roach (2001)12 suggest that AMS symptoms may be seen within 1 hour, whereas others have shown AMS to occur after 1 to 2 hours of arrival to altitudes of approximately 3500 m via plane13 or cable car.14 Research tends to overlook the immediate responses to hypoxic exposure and concentrates on longer term adaptation or, indeed, maladaptation with resulting mountain maladies.
This study aimed to investigate some physiological responses to acute normobaric hypoxia during rest and exercise. Relating physiological changes to subjective AMS symptoms will help develop our understanding of the physiological processes that determine tolerance to acute hypoxia. It was hypothesized that acute physiological changes during an intermittent walking test are sensitive to normoxic and hypoxic conditions. It was also hypothesized that acute physiological responses to a short duration intermittent walking test at simulated altitude may be used to indicate tolerance to acute hypoxia.
Materials and Methods
Participants
Twelve physically active males aged 27 ± 7 years (mean ± SD), height 182 ± 7 cm, weight 85 ± 6 kg, body fat 11.0% ± 1.6%, lactate threshold 27 ± 5.1 mL.kg–1 min–1 and of 54.5 ± 11.3 mL.kg–1 min–1 participated in the study, after giving written informed consent, as approved by the University of Brighton Research Ethics Committee. Participants had not performed exhaustive exercise in the 2 days before each trial and had not consumed alcohol or caffeine during a period of at least 24 hours immediately preceding the study. The participants were nonsmokers and had not spent any time above 2000 m in the preceding 2 months.
Experimental design
The study required participants to attend the laboratory on 4 separate occasions. First, there was a familiarization session involving anthropometric measures and cardiovascular fitness assessment; the next 3 visits involved an intermittent walking test in different conditions (20.93%O2/sea level [NORM], 14%O2/3200 m [HYP1], and 12%O2/4300 m [HYP2]), using a hypoxic tent (Colorado Altitude Training Tent 315, Colorado Altitude Training, Colorado). The order of the tests was randomized, determined by a Latin squares design. Each test was separated by a 7-day “wash out” period.
Lactate threshold to test
Participants attended the laboratory before hypoxic testing for a familiarization session and assessment of body composition using the Jackson and Pollock15 7-site skinfold body fat assessment, measured by Harpenden callipers (Harpenden, Idass, England). Walking speed, on a 10% gradient at 50% , was predicted using a 10-minute steady state walking test with intensity based on the heart rate:oxygen uptake relationship. Participants then completed a lactate threshold and maximal oxygen uptake test using an incremental running protocol as validated by Weltman et al.16
Intermittent walking test (hypoxic and normoxic)
The intermittent walking test involved testing a range of physiological markers over the 125-minute test duration. The test involved a 35-minute rest followed by three 20-minute exercise phases separated with 5-minute rest intervals and a final 20-minute recovery phase, as shown in Figure 1. Exercise involved participants walking on a treadmill (PP55Sport, Woodway, Germany) at a speed equal to 50% while at a gradient of 10%.
Urine measures
Urine specific gravity was assessed using Combur test sticks (Combur 10 Test, Roche, Manheim, Germany). Urine color was assessed using a urine color chart.17 Urine osmolality was measured using a micro-osmometer (Micro-osmometer 3300, Advanced Instruments Inc, Massachusetts).
Gas measures
Gas samples were collected in Douglas bags over approximately 40 seconds during the rest and exercise periods. Ambient O2 and CO2 values were measured constantly through sample tubing linked to a gas analyzer (Servomex 1400, Servomex Group Ltd, Crowborough, England). SaO2, estimated using a finger pulse oximeter (Nonin 2500, Nonin Medical Inc, Minnesota) was recorded every fifth minute.
Assessment of AMS
A modified 65 question Environmental Symptoms Questionnaire (ESQ),18 with the sleep-based questions extracted, was used. The ESQ change (ΔESQ) was calculated using PRE and POST values. The ESQ cerebral score (ESQc) was calculated using pre (PRE) and post (POST) intermittent walking test values.19 The Lake Louise Questionnaire (LLQ)2 was conducted without the sleep-related question. Symptoms of AMS were calculated using the sum of 4 questions scored 0 to 3, including headache, gastrointestinal upset, fatigue or weakness, dizziness, or lightheadedness. The mean of the 5 LLQ scores over the walking test duration (LLQMEAN) was also calculated. Feeling state was assessed from 4 visual analogue scales, adapted from Roach,20 which included “I feel brilliant” to “I feel awful” (FEEL), “My head is perfect” to “My head is aching severely” (HEAD), “My stomach feels perfect” to “I’m going to be sick” (STOMACH), and “I do not notice my breathing” to “Breathing is hard to cope with” (BREATHE). Thermal sensation,21 perceived thirst,22 and rating of perceived exertion were monitored every fifth minute, using their respective scales.
Blood markers
Finger tip blood samples (Accuchek Softclix Pro, Roche, Lewes, England) were measured in triplicate for hematocrit (Hct), hemoglobin (Hb), blood lactate, and blood glucose. Change in plasma volume (ΔPV%) was calculated from Hct and Hb between each time point using the following equation of Dill and Costill,23 where A was the first blood sample and B was the second:
Physiological strain
Rectal temperature, measured using a probe inserted 10 cm past the anal sphincter (Henleys Medical Supplies Ltd, Welwyn Garden City, England), and heart rate were used to calculate physiological strain index using the equation PSI = 5(Tret – Tre0). (39.5 – Tre0)–1 + 5(HRt – HR0). (180 – HR0)–1, where Tret and HRt were simultaneous measurements taken at any time during the exposure, and Tre0 and HR0 were the initial measurements.24
Blood pressure and lung functions
Blood pressure (Omron R7, Omron, Kyoto, Japan) and lung function (Gold Standard Vitalograph, Vitalograph Ltd, Buckinghamshire, England) were measured.
Statistical methods
Data were checked for normality, and sphericity was adjusted using the Huynh-Feldt method. One-way analysis of variance with repeated measures and Tukey's honestly significantly different post hoc analysis were used to compare between test conditions. Pearson's product moment correlation coefficient was used to determine correlation between selected variables. All data were analyzed using a standard statistical package (SPSS version 14 for Windows, 2005). All data are reported as mean ± SD, with the significance level set at P < .05.
Results
All participants (n = 12) completed NORM and HYP1 trials, although in HYP2 1 participant was extracted from the tent at 40 minutes after briefly losing consciousness. The participant made a full recovery; his data were not used for the analysis. Walking speed, set at 50% ranged between 5.4 km h–1 and 6.2 km h–1.
Power analysis
Power analysis (95% confidence interval) suggested n values of between 8 and 12 for the main physiological markers (LLQ [n = 8], SaO2 [n = 10], heart rate [n = 12], temperature [n = 9]) when comparing between conditions.
AMS markers
The AMS markers, including the highest LLQ score over the test (Figure 2), difference in ESQc (Figure 3), and difference in headache visual analog scale pre- and posttesting increased with greater hypoxia, whereas the highest values were recorded during HYP2 (Table). LLQ and ΔESQc (r = 0.839, P < .001), LLQ and ΔHEAD (r = 0.727, P < .001), and ΔESQc and ΔHEAD (r = 0.903, P < .001) were all found to positively correlate.
Gas exchange measures
and were not found to be different between conditions or correlate with AMS markers. Respiratory exchange ratio and minute ventilation were found to increase with severity of hypoxic conditions during rest (P < .05) and positively correlated with both LLQ and ΔESQc after exercise and recovery (P < .05). SaO2 was found to decrease with hypoxic conditions (Figure 4) and negatively correlated with both LLQ and ΔESQc for all time points during the test (P < .05).
Physiological strain index
Heart rate and core temperature were found to be significantly greater with the more severe hypoxic conditions (P < .05) (Figure 5). Heart rate and core temperature positively correlated with both ESQc and LLQ during exercise and recovery (P < .05). Consequently, physiological strain during rest, exercise, and recovery was found to be greater with further hypoxia and correlated with both LLQ and ESQc (P < .05). Core temperature, heart rate, and physiological strain were found to positively correlate with the corresponding LLQ score during exercise and recovery (P < .05).
Blood markers
Resting and exercise blood lactate values were found to rise with hypoxic conditions (P < .05). There was no significant difference in any of the other blood markers between conditions. Exercising blood lactate values positively correlated with LLQ and ΔESQc (P < .01)
Urine measures
Posttest urine volume and change in urine volume were found to increase with hypoxic conditions (P < .05), but did not correlate with AMS markers. No other urine measures were found to be different between conditions or correlated with the AMS markers.
Perception scales
Perceived thirst and thermal sensation were found to significantly increase with hypoxia during exercise, recovery, and posttest (P < .05). The rating of perceived exertion was significantly increased with hypoxic conditions for all exercise time points (P < .05). Both LLQ and ΔESQc were found to positively correlate with perceived thirst during the third exercise bout and in recovery, with thermal sensation during the final 2 exercise bouts in recovery and posttest, and with all rating of perceived exertion time points (P < .05).
Anthropometrics
Initial anthropometric or cardiovascular fitness markers, including body fat percentage, body mass, body mass index, height, lactate threshold, and , did not correlate with AMS scores. Change in body mass positively correlated with both LLQ (r = 0.681, P < .001) and ESQc (r = 0.667, P < .001) (Figure 6) and was found to increase with more severe hypoxia (P < .05). Lung function values were not found to be different between conditions nor to correlate with any AMS markers.
Discussion
This study aimed to investigate the physiological responses of the human body to acute hypoxia and to determine whether they were associated with the presence of AMS. Physiological strain, thermal sensation scale, heart rate, perceived thirst, core temperature, rating of perceived exertion, feeling state, and Δbody mass increased and SaO2 decreased with the severity of hypoxia. These measures were also found to coincide with the presence of AMS symptoms.
Cerebral AMS symptoms, necessary in the diagnosis of AMS, are suggested to occur after 6 to 12 hours of hypoxic exposure,25,26 with symptoms worsening over a period of days.27 In contrast, 4 participants experienced LLQ scores of >4 (including headache symptoms) at some point in the HYP2 test, whereas 5 participants had an LLQMEAN >3. This may be due to the moderate to high intensity exercise performed, which is known to exacerbate AMS symptoms.20 However, 3 of the participants had LLQ scores of 3 after only 35 minutes of rest. This supports work by Purkayasther et al13 and Erba et al14 who reported AMS in individuals within 1 to 2 hours when exposed to acute altitude. Figures 2 and 3 also highlight the effect greater hypoxic stress has on AMS symptoms, suggesting a hypoxic threshold for AMS symptom development.
SaO2 was found to be the closest correlate of AMS markers during the test duration, supporting previous research.5,28 However, many acute hypoxic studies contradict these findings,29–31 with research at slow ascent rates over a few days finding stronger correlation between SaO2 and the onset of AMS. In the current study, individuals most severely affected by hypoxia had the lowest SaO2 values; the participant withdrawn from HYP2 recorded SaO2 values of 64% during rest, whereas at HYP1 the participant's SaO2 (81–87%) and AMS (LLQ = 2; ESQc = 0.6) values were similar to the other participants.
Heart rate, core temperature, and the physiological strain index correlated well with ΔESQc, the highest LLQ score, and LLQ scores at their respective time points, suggesting physiological strain may be a useful measure in future research. However, the difficulty of measuring physiological strain may outweigh the benefits. Accuracy and reliability of core temperature measurement and calculation at altitude may be impractical.
A rise in core temperature has been shown to be proportional to mountain illness severity, finding a temperature increase of 0.5 ± 0.6°C in individuals with an LLQ score ≤3, 1.2 ± 0.6°C in those with >3, and 1.7 ± 0.6°C in those with cerebral edema.32 Similar studies have also reported AMS sufferers experiencing body temperature increases of ∼1°C.4 The current study recorded significant increases in temperature with severity of hypoxia, which correlated with AMS symptoms. A difference in mean core temperature of ∼0.3°C between HYP1 and HYP2 for all time points during the test suggests the additional hypoxic stress caused greater physiological stress in terms of heat strain, resulting in significantly higher AMS symptom scores for HYP2. The 4 individuals recording the highest LLQMEAN score also recorded the highest average temperature for all time points, suggesting that core body temperature rise may be related to the onset of AMS symptoms.
The heart rate response to hypoxia is widely accepted as an immediate rise with hypoxic exposure,33 with a reduction in resting heart rate over a period of days as oxygen-carrying capacity of the blood improves and pH is reduced toward prealtitude exposure values.34 The current study would support this finding as we observed an immediate rise in resting and exercising heart rate with the heart rate elevated in proportion to the severity of hypoxia, as was found in a similar study29 that found a positive correlation between AMS markers and heart rate (P < .05). The pathophysiological link between heart rate and AMS symptoms is not clear, although an early rise in sympathetic tone due to orthostatic intolerance has been suggested.35 Similarly, in prolonged hypoxic exposure, Krasney36 suggested brain distortion due to a rise in intracranial pressure causes chemoreflexes to increase sympathetic activity. However, the current study found no significant change in blood pressure that would indicate orthostatic intolerance.
A change in body mass was found to be the closest correlate to both ESQc and LLQ. The causal relationship is unclear, although it is thought that greater physiological stress, exacerbated by a poorer response to hypoxia, could cause a greater sweat rate. In contrast, research suggests hypoxia directly suppresses sweat gland function through depressed cholinergic stimulation37 and a decrease in acetylcholine release during hypoxic exposure.38 Insensible water loss through an increase in ventilation with hypoxic severity may also account for these findings.
Posttest urine volume or a change in urine volume did not correlate with ΔESQC or LLQ, similar to other research findings.39 Therefore the study cannot support the hypothesis that hypoxia may influence hormonal orthostatic control. The lack of significant findings may be because of the small participant number and some variation in pretest hydration status. Furthermore, the test protocol did not allow participants to void their bladder until posttest, preventing voluntary diuresis and therefore not recording an individual's urinary response to hypoxia. It is also possible that the short test duration may not have allowed enough time for fluid control to be influenced.
Further research could identify the influence of fluid or orthostatic control on acute physiological responses and development of AMS symptoms. Further validation of the intermittent walking test using greater sample sizes is also necessary. A comparison of this test against longer hypoxic or altitude-based research is needed to ascertain true AMS diagnosis.
Conclusion
An acute normobaric hypoxic intermittent walking protocol may be used to determine the short term physiological responses to hypoxia. Measures of physiological stress related with symptoms of AMS, increasing with severity of hypoxia and exercise.
Footnote
* Previously presented as a poster at Altitude 2006, Birmingham, UK, November 24, 2006.
References
1. Bartsch P., Bailey D.M., Berger M.M., Knauth M., Baumgartner R.W. Acute mountain sickness controversies and advances. High Alt Med Biol 2004; 5, 110–124.
2. Roach R.C., Bartsch P., Hackett P.H., Oelz O. The Lake Louise acute mountain sickness scoring system. in: Hypoxia and Molecular Medicine. Burlington Vermont: Queens City Press, 1993: 272–274.
3. Bartsch P., Swenson E.R., Paul A., Julg B., Hohenhaus E. Hypoxic ventilatory response, ventilation, gas exchange and fluid balance in acute mountain sickness. High Alt Med Biol 2002; 3, 361–376.
4. Roggla G., Moser B., Wagner A., Roggla M. Correlation between raised body temperature and acute mountain sickness score at moderate altitude. Wien Klin Wochenschr 2000; 112, 290–292.
5. Burtscher M., Flatz M., Faulhaber M. Prediction of susceptibility to acute mountain sickness by SaO2 values during short term exposure to hypoxia. High Alt Med Biol 2004; 5, 335–340.
6. Reeves J.T., McCullough R.E., Moore L.G. Sea level PO2 relates to ventilatory acclimatisation at 4300m. JAP 1993; 75, 1117–1122.
7. Savourey G., Launay J., Besnard Y. et al. Normo or hypobaric hypoxic tests: propositions for the determination of the individual susceptibility to altitude illnesses. EJAP 2007; 100, 193–205.
8. Ge R.L., Matsuzawa Y., Takeoka M., Kubo K., Sekiguchi M., Kobayashi T. Low pulmonary diffusing capacity in subjects with acute mountain sickness. Chest 1997; 111, 58–64.
9. Burtscher M., Szubski C., Faulhaber M. Prediction of the susceptibility to AMS in simulated altitude. Sleep and Breathing 2008; 12, 103–108.
10. Loeppky J.A., Icenogle M., Maes D., Riboni K., Hinghofer-Szalkay H., Roach R.C. Early fluid retention and severe acute mountain sickness. JAP 2005; 98, 591–597.
11. Bailey M., Kleger G., Holzgraefe M., Ballmer P.E.B., Bartsch P. Pathophysiological significance of peroxidative stress, neuronal damage, and membrane permeability in acute mountain sickness. JAP 2004; 96, 1459–1463.
12. Hackett P.H., Roach R.C. High-altitude illness. NEJM 2001; 345, 107–114.
13. Purkayastha S.S., Ray U.S., Arora B.S.et al Acclimatization at high altitude in gradual and acute induction. J Appl Physiol 1995; 79, 487–492.
14. Erba P., Anastasi S., Senn O., Maggiorini M., Bloch K.E. Acute mountain sickness is related to nocturnal hypoxemia but not to hypoventilation. Eur Respir J 2004; 24, 303–308.
15. Jackson A.S., Pollock M.L. Generalized equations for predicting body density of men. Brit J Nutr 1978; 40, 497–504.
16. Weltman A., Snead D., Stein P.et al Reliability and validity of a continuous incremental treadmill protocol for the determination of lactate threshold, fixed blood lactate concentrations, and VO2max. Int J Sports Med 1990; 11, 26–32.
17. Armstrong L.E. Performing in Extreme Environments. London: Human Kinetics, 2000.
18. Wright A.D., Jones G.T., Fletcher R.F., Mackintosh J.H., Bradwell A.R. The environmental symptoms questionnaire in acute mountain sickness. Aviat Space Environ Med 1985; 56, 572–575.
19. Sampson J.B., Cymerman A., Burse R.L., Maher J.T., Rock P.B. Procedures for the measurement of acute mountain sickness. Aviat Space Environ Med 1983; 54, 1063–1073.
20. Roach R.C., Maes D., Sandoval D.et al Exercise exacerbates acute mountain sickness at simulated high altitude. JAP 2000; 88, 581–585.
21. Gagge A.P., Stolwijk J.A., Saltin B. Comfort and thermal sensations and associated physiological responses during exercise at various ambient temperatures. Environ Res 1969; 2, 209–229.
22. Engell D.B., Maller O., Sawka M.N., Francesconi R.N., Drolet L., Young A.J. Thirst and fluid intake following graded hypohydration levels in humans. Physiol Behav 1987; 40, 229–236.
23. Dill D.B., Costill D.L. Calculation of percentage changes in volumes of blood, plasma, and red cells in dehydration. JAP 1974; 37, 247–248.
24. Moran D.S., Montain S.J., Pandolf K.B. Evaluation of different levels of hydration using a new physiological strain index. Am J Physiol Reg 1 1998; 275, R854–R860.
25. Houston C.S., Dickinson J. Cerebral form of high-altitude illness. Lancet 1975; 27, 58–761.
26. Singh I., Khanna P.K., Srivastava M.C. et al. Acute mountain sickness. NEJM 1969; 28, 175–184.
27. Ward M.P., Miledge J.S., West J.B. High Altitude Medicine and Physiology. New York: Oxford University Press Inc, 2000.
28. Bircher H.P., Eichenberger U., Maggiorini M., Oelz O., Bartsch P. Relationship of mountain sickness to physical fitness and exercise intensity during ascent. J Wilderness Med 1993; 5, 302–311.
29. O’Connor T., Dubowitz G., Bickler P.E. Pulse oximetry and the diagnosis of acute mountain sickness. High Alt Med Biol 2004; 5, 341–348.
30. Roach R.C., Houston C.S., Honigman B. et al. How well do older persons tolerate moderate altitude?. Western J Med 1995; 162, 32–36.
31. Roeggla G., Roeggla M., Podolsky A., Wagner A., Laggner A.N. How can acute mountain sickness be quantified at moderate altitude. J Roy Soc Med 1996; 89, 359–360.
32. Maggiorini M., Bartsch P., Oelz O. Association between raised body temperature and acute mountain sickness: cross sectional study. BMJ 1997; 315, 403–404.
33. Marshall J.M. Peripheral chemoreceptors and cardiovascular regulation. Physiol Rev 1994; 74, 543–594.
34. Mazzeo R.S., Brooks G.A., Butterfield G.E., Podolin D.A., Wolfel E.E., Reeves J.T. Acclimatization to high altitude increase muscle sympathetic activity both at rest and during exercise. Am J Physiol Reg 1 1995; 269, R201–R207.
35. Loeppky J.A., Icenogle M.V., Maes D., Riboni K., Scotto P., Roach R.C. Body temperature, autonomic responses and acute mountain sickness. High Alt Med Biol 2003; 4, 367–374.
36. Krasney J.A. A neurogenic basis for acute altitude illness. Med Sci Sport Ex 1994; 26, 195–208.
37. Dipasquale D.M., Kolkhorst F.W., Nichols J.F., Buono M.J. Effect of acute normobaric hypoxia on peripheral sweat rate. High Alt Med Biol 2002; 3, 289–292.
38. Elizondo R.S. Local control of eccrine sweat gland function. Fed Proc 1973; 32, 1583–1587.
39. Miledge J.S., Beeley J.M., McArthur A.S., Morice A.H. Atrial natriuretic peptide, altitude and acute mountain sickness. Clin Sci 1989; 77, 509–514.
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Published online: December 1, 2008
Issue published: December 2008
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