Journal of Applied Physiology Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Appl Physiol 99: 699-706, 2005. First published May 26, 2005; doi:10.1152/japplphysiol.00973.2004
8750-7587/05 $8.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
99/2/699    most recent
00973.2004v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (12)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Imray, C. H. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Imray, C. H. E.

Effect of exercise on cerebral perfusion in humans at high altitude

C. H. E. Imray,1 S. D. Myers,2 K. T. S. Pattinson,3 A. R. Bradwell,4 C. W. Chan,4 S. Harris,2 P. Collins,5 A. D. Wright4, the Birmingham Medical Research Expeditionary Society4

1Coventry and Warwickshire County Vascular Unit, University Hospitals Coventry and Warwickshire National Health Service Trust, Coventry; 2QinetiQ, Farnborough; 3Nuffield Department of Anesthetics, University of Oxford, John Radcliffe Hospital, Headley Way, Headington, Oxford; 4The Medical School, University of Birmingham, Birmingham; and 5ScanMed Medical Instruments, Moreton-in-the-Marsh, United Kingdom

Submitted 3 September 2004 ; accepted in final form 1 April 2005


   ABSTRACT
TOP
 ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
The effects of submaximal and maximal exercise on cerebral perfusion were assessed using a portable, recumbent cycle ergometer in nine unacclimatized subjects ascending to 5,260 m. At 150 m, mean (SD) cerebral oxygenation (rSO2%) increased during submaximal exercise from 68.4 (SD 2.1) to 70.9 (SD 3.8) (P < 0.0001) and at maximal oxygen uptake (O2 max) to 69.8 (SD 3.1) (P < 0.02). In contrast, at each of the high altitudes studied, rSO2 was reduced during submaximal exercise from 66.2 (SD 2.5) to 62.6 (SD 2.1) at 3,610 m (P < 0.0001), 63.0 (SD 2.1) to 58.9 (SD 2.1) at 4,750 m (P < 0.0001), and 62.4 (SD 3.6) to 61.2 (SD 3.9) at 5,260 m (P < 0.01), and at O2 max to 61.2 (SD 3.3) at 3,610 m (P < 0.0001), to 59.4 (SD 2.6) at 4,750 m (P < 0.0001), and to 58.0 (SD 3.0) at 5,260 m (P < 0.0001). Cerebrovascular resistance tended to fall during submaximal exercise (P = not significant) and rise at O2 max, following the changes in arterial oxygen saturation and end-tidal CO2. Cerebral oxygen delivery was maintained during submaximal exercise at 150 m with a nonsignificant fall at O2 max, but at high altitude peaked at 30% of O2 max and then fell progressively at higher levels of exercise. The fall in rSO2 and oxygen delivery during exercise may limit exercise at altitude and is likely to contribute to the problems of acute mountain sickness and high-altitude cerebral edema.

maximal oxygen uptake; cerebral oxygenation; cerebral blood flow; cerebrovascular resistance; cerebral oxygen delivery

ALTERED CEREBRAL FUNCTION on ascent to altitude was part of the first description of mountain sickness in 1913 (40), and acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) have been shown to be potentially serious clinical conditions that may occur on acute exposure to altitudes above 2,500–3,000 m. Exercise at altitude causes further decreases in arterial oxygenation and so may exacerbate cerebral hypoxia. However, the fall in arterial saturation that occurs during exercise at high altitude (14) might not affect cerebral oxygenation to the same extent as it does in peripheral tissues due to a compensatory increase in cerebral blood flow (24). Nevertheless, avoidance of strenuous exercise during ascent, and on arrival at altitude, is standard advice for reducing the risk of AMS and HACE. Evidence from clinical studies is conflicting. Higher AMS symptom scores were found in subjects exercising four times a day for 30 min at 50% of their altitude-specific maximal oxygen consumption (O2 max), compared with no exercise, in a chamber study at simulated altitude of 4,800 m (41). Another study of mountaineers, however, showed that physical fitness and exercise intensity during ascent to 4,559 m were of minor importance for the development of AMS (3). It is also possible that other neurological conditions falling outside the usual definition of altitude sickness (2) could be related to exercise.

Near-infrared cerebral spectroscopy and transcranial Doppler measurement of middle cerebral artery (MCA) blood velocity offer continuous noninvasive assessments of cerebral perfusion. Cerebral spectroscopy has been shown to track changes in jugular venous bulb saturations in healthy volunteers under conditions of isocapnic hypoxia (12) and has also been validated by comparison with PET scanning, with 133Xe washout methods and with internal carotid artery stump pressures (54). We have used this technique during dynamic studies of cerebral oxygenation at altitude and assessed the effects of hyperventilation, oxygen therapy, and CO2 supplementation (19, 20) and during assessment of the effects of pressurization in a portable hyperbaric chamber (21). Assessments of cerebral blood flow and cerebral oxygenation during exercise and under field conditions have proven challenging. The standard, upright exercise cycle results in excessive head movement and use of arms, particularly as one approaches maximal exercise. To overcome these difficulties, we built a portable, recumbent exercise ergometer (Alticycle) for undertaking cerebral perfusion measurements in the field.

This study aimed to measure changes in cerebral perfusion at rest and during exercise up to O2 max at altitudes from 150 to 5,260 m to gain further insight into the factors that limit exercise and alter cerebral function on acute exposure to high altitude.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Subjects.   Eleven healthy white Europeans (1 woman; ages 32–65 yr) were studied. All were nonsmokers, normotensive, on no medication, physically fit, living at 50–150 m, with no recent exposure to high altitude, and were familiar with cycle ergometer-based exercise tests. Measurements were recorded at Birmingham, UK (150 m) and during an expedition to Bolivia. The first measurement at high altitude was made 24–36 h after arrival at 3,610 m (La Paz). Two subjects were subsequently excluded from the study because of excessive rises of blood pressure during exercise at this altitude. The group then traveled by road, and repeat measurements were made on the remaining nine subjects 24–36 h after arrival at 4,750 m (Refugio Potosi) and 5,260 m, (ski station, Chacaltaya). All measurements at high altitude were therefore completed within 9 days of arrival in Bolivia. Barometric pressure was obtained from the mean of four portable barometers (Suunto Observer, Helsinki, Finland).

Alticycle.   The Alticycle cycle ergometer has four novel features (Fig. 1). First, the cycling position is fully supine. The body of the subject is held by shoulder straps and a waist belt to the alticycle frame. The head, resting freely in a stable position, is isolated from the main body of the alticycle, and the arms are free. Second, the exercise load is provided by a friction brake applied to a 2-kg flywheel linked through a series of gears that allows it to rotate between 4,000 and 5,000 revolutions/min. This combination provides good inertia for cycling but with minimal weight. Third, power output and cadence are measured via a strain-gauged crank set assessing torque and cadence (Schoberer Rad Me{beta}technik, Jülich, Germany). Power is measured directly in Watts on a second-by-second basis. Fourth, it folds into a self-contained compact backpack-style unit (81x 37x 24 cm, weight 25 kg), allowing it to be carried by a single person.



View larger version (111K):
[in this window]
[in a new window]
  		Fig. 1. A: Alticycle. B: Alticycle in use.

 
Exercise tests.   Subjects completed two tests at each altitude. A O2 max test was undertaken first, followed by a submaximal test on the same day separated by a minimum interval of 4 h. Subjects rested for one-half hour before each test and then exercised gently for 5 min at 50 W to warm up. Subjects maintained a cadence rate of 55 pedal revolutions/min for each test. For the maximal test, starting loads for each subject were estimated to produce a test lasting ~10 min (53). The load was increased by 20-W increments per minute up to volitional exhaustion. In the submaximal test, subjects were required to complete 15 min of cycling comprising three 5-min, consecutive exercise periods at 30, 50, and 70% of the power of the altitude-specific O2 max, respectively.

Expired gas was analyzed breath by breath using a Cosmed K4b2 portable gas-exchange unit (Cosmed, Rome, Italy) for oxygen uptake (O2; photometric gas analyzer), end-tidal CO2 (infrared absorption), and minute volume (turbine flowmeter). The Cosmed K4b2 was chosen for its portability and performance at high altitude (6), which has been confirmed subsequently by the authors (36). Gases were collected via a tight-fitting Cosmed-modified Hans Rudolph facemask. Finger-pulse oximetry (arterial oxygen saturation) was measured using an Ohmeda Biox 3740 Pulse Oximeter (Ohmeda). Continuous beat-to-beat blood pressure was measured using the radial artery tonometry technique with a COLIN CBM-7000 monitor (ScanMed Medical Instruments, Moreton-in-the-Marsh, UK), and mean blood pressure was calculated from the formula mean blood pressure = diastolic blood pressure + 1/3(systolic blood pressure – diastolic blood pressure). Predicted heart rates at O2 max were calculated using the formula 220 – age (yr).

Cerebral hemodynamics.   MCA blood velocity was measured using a 2-MHz, pulsed-wave, range-gated Doppler ultrasound (DWL Multi-Dop T1, DWL Elektronische Systeme, Singen, Germany). The MCA time-averaged mean velocity (cm/s) was recorded electronically. A single, experienced operator performed the measurements by insonating the right MCA through the temporal bone window with the subject at rest. The insonation depth was initially set at 50 mm and then gradually increased to identify the optimal signal. Once found, the position was fixed using a locking headband, which allowed the subject to cycle freely. Occasionally, it was necessary to optimize the signal manually during a test by adjusting the direction but not the depth of the beam.

Cerebral regional oxygenation (rSO2) was measured by continuous, noninvasive, near-infrared cerebral spectroscopy. The Critikon 2020 (Johnson and Johnson Medical, Newport, UK) spectroscope is based on a two-channel sensor and a coupling compensation system. Infrared light is emitted at four wavelengths (776.5, 819.0, 871.4, and 908.7 nm) from a light-emitting diode, and two silicon photodiode detectors are set 10 and 37 mm from the light-emitting diode. The absolute concentrations of oxyhemoglobin (in µM) and deoxyhemoglobin (in µM) are calculated from a modified version of the Beer-Lambert law. The dual detector sensor position was standardized over the right frontoparietal region of the head with sensor margins 3 cm from the midline and 3 cm above the supraorbital crest, taking care to avoid the sagittal and frontal sinus areas (18). The measurement of rSO2 was calculated from the equation rSO2= (oxygenated hemoglobin/total hemoglobin) x 100.

Statistical analyses.   Data was collected continuously by logging it to the DWL Multi-Dop T1. Offline analysis was subsequently undertaken. All data are reported as mean and standard deviation (SD) unless indicated otherwise. Resting measurements were taken immediately before the O2 max test at each altitude. Heart rate, mean blood pressure, arterial saturation, end-tidal PCO2, minute volume, O2, MCA blood velocity, cerebral deoxygenation, cerebral oxygenation, total hemoglobin, and rSO2 were taken from a mean of the three last readings (–20, –10, and 0 s) at each level of exercise. Cerebrovascular resistance (CVRest) was calculated using the formula CVRest = mean arterial blood pressure/MCA blood velocity (26, 44), and cerebral oxygen delivery using the formula cerebral oxygen delivery = arterial oxygen saturation x MCV blood velocity (33).

The significance of changes occurring in resting measurements during ascent and changes in measurements during submaximal exercise were assessed by repeated-measures ANOVA (StatView for Windows, Abacus Concepts, Berkley, CA) with difference located using Tukey's honestly significant different post hoc test. Resting and O2 max data were compared using paired t-tests. P values of <0.05 were considered significant.

The Research and Ethics Committee of the South Birmingham Health Authority granted approval for the studies, and subjects gave their written, informed consent.


   RESULTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
No technical difficulties were experienced with the pulse oximeter or the Alticycle. The signal from the Colin blood pressure monitor occasionally required optimization by adjusting the sensor position over the radial artery, and this was a particular problem with the recordings at 5,260 m. The K4b2 needed to be carefully cleared of condensation before each test. When using an early version of the Alticycle, background rumble interfered with the transcranial Doppler recordings when subjects exercised close to O2 max. Interference was eliminated initially using a 100-MHz filter. Although this was satisfactory, the Alticycle was adapted for all experimental data reported in this paper with a rubber interface placed between the joints of the Alticycle and the subject's head being supported independently of the ergometer by a firm pillow, removing the need for the 100-MHz filter. Good signals from the cerebral spectroscopy probe were maintained by careful cleaning of the forehead and probe with ethanol. Mean (SD) heart rate recorded at O2 max was 90% (SD 7) of predicted of 150 m at 3,610 m, 81% (SD 5) of predicted at 4,750 m, and 74% (SD 4) at 5,260 m.

Environmental measures and subject characteristics for each altitude are listed in Table 1. Body mass did not change significantly during the study. Resting and exercise cardiorespiratory data are shown in Table 2 and cerebral perfusion data in Table 3 and Figs. 2 –5. With increasing altitude, resting heart rate, mean blood pressure, total hemoglobin, and oxyhemoglobin did not change (Table 2). Resting arterial oxygen saturation and end-tidal PCO2 decreased at all altitudes compared with 150 m (P < 0.0001 for both) (Table 2). Resting O2 increased at all altitudes compared with 150 m (P < 0.05). Resting ventilation also increased significantly at 4,750 m (P < 0.05) and 5,260 m (P < 0.001). Resting MCA blood velocity increased from 60.2 cm/s (SD 14.1) at 150 m to 73.4 cm/s (SD 20.4) at 5,260 m (P < 0.05), and resting rSO2 decreased from 68.4% (SD 2.1) at 150 m to 62.4% (SD 3.6) at 5,260 m (P < 0.0001) (Table 3). There was no difference in resting CVRest or cerebral oxygen delivery between the different altitudes (Fig. 2).


View this table:
[in this window]
[in a new window]
  		Table 1. Environmental measurements and subject characteristics for each altitude

 

View this table:
[in this window]
[in a new window]
  		Table 2. Cardiorespiratory data during exercise at different altitudes

 

View this table:
[in this window]
[in a new window]
  		Table 3. Cerebral perfusion data during exercise at different altitudes

 


View larger version (17K):
[in this window]
[in a new window]
  		Fig. 2. Changes in middle cerebral artery blood velocity during exercise at different altitudes ({blacksquare}, 150 m; {blacklozenge}, 3,610 m; {bullet}, 4,750 m; {blacktriangleup}, 5,260 m). Values are means and SE. Velocity at rest increased with increasing altitude (P <0.05). At all altitudes, velocity increased during submaximal exercise (P < 0.05–0.0001) but fell at maximal oxygen uptake (O2 max; P < 0.01–0.0001).

 


View larger version (15K):
[in this window]
[in a new window]
  		Fig. 5. Changes in cerebral oxygen delivery at different altitudes ({blacksquare}, 150 m; {blacklozenge}, 3,610 m; {bullet}, 4,750 m; {blacktriangleup}, 5,260 m). Values are means and SE. Resting values did not change with increasing altitude. Resting and O2 max values were not significantly different at 150 m but fell at 3,610 m (P < 0.01), 4,750 m (P < 0.01), and 5,260 m (P < 0.01).

 
Exercise at 150 m (Tables 2 and 3).   Mean arterial blood pressure did not change significantly during exercise. Oxygen saturation was unchanged during submaximal exercise but fell at O2 max (P < 0.0001). End-tidal CO2 was unchanged during submaximal exercise but was reduced from 36.3 Torr (SD 4.7) resting to 33.1 Torr (SD 5.3) at O2 max (P < 0.05). Ventilation and O2 rose progressively during both submaximal and O2 max tests (P < 0.0001). MCA blood velocity rose initially but fell at the highest workloads with an increase from 60.2 cm/s (SD 4.1) at rest to 65.5 cm/s (SD 12.9) at 70% O2 max (P < 0.05) and a reduction to 50.5 cm/s (SD 22.3) at O2 max (P < 0.01) (Fig. 2). rSO2 increased from 68.4% (SD 2.1) at rest to 70.9% (SD 3.8) during submaximal exercise (P < 0.0001) and to 69.8% (SD 3.1) at O2 max (P < 0.05) (Fig. 3). CVRest and cerebral oxygen delivery were not significantly different between resting and O2 max (Figs. 4 and 5).



View larger version (16K):
[in this window]
[in a new window]
  		Fig. 3. Changes in cerebral oxygenation at different altitudes ({blacksquare}, 150 m; {blacklozenge}, 3,610 m; {bullet}, 4,750 m; {blacktriangleup}, 5,260 m). Values are means and SE. Resting oxygenation decreased with increasing altitude (P < 0.0001). At 150 m, oxygenation increased during submaximal exercise (P < 0.0001) and at O2 max (P <0.05). At higher altitudes, oxygenation was reduced during submaximal exercise and at O2 max (P < 0.01–0.0001).

 


View larger version (15K):
[in this window]
[in a new window]
  		Fig. 4. Changes in cerebrovascular resistance at different altitudes ({blacksquare}, 150 m; {blacklozenge}, 3,610 m; {bullet}, 4,750 m; {blacktriangleup}, 5,260 m). Values are means and SE. Resting values did not change with increasing altitude. Resting and O2 max values were not significantly different at 150 m but rose at 3,610 m (P < 0.05), 4,750 m (not significant), and 5,260 m (P < 0.0001).

 
Exercise at 3,610 m (Table 2 and 3).   Mean arterial blood pressure did not change significantly during exercise. Arterial oxygen saturations were reduced at all levels of exercise compared with baseline (P < 0.0001). End-tidal CO2 during submaximal exercise rose initially but was reduced from 24.9 Torr (SD 1.7) at rest to 21.1 Torr (SD 2.4) at 70% O2 max (P < 0.001) and to 19.3 Torr (SD 1.7) at O2 max (P < 0.0001). Ventilation and O2 rose progressively during the tests (P < 0.0001). MCA blood velocity rose initially and fell with maximal exercise, with an increase from 64.5 cm/s (SD 14.1) at rest to 66.0 cm/s (SD 17.3) at 70% O2 max (P < 0.0001) and a reduction to 50.6 cm/s (SD 21.7) at O2 max (P < 0.0001) (Fig. 2). rSO2 was reduced from 66.2% (SD 2.5) at rest to 62.6% (SD 2.1) during submaximal exercise (P < 0.0001) and to 61.2% (SD 3.3) at O2 max (P < 0.0001) (Fig. 3). There was a rise in CVRest from 1.7 (SD 0.41) at rest to 2.16 (SD 0.57) at O2 max (P < 0.05) (Fig. 4) and a fall in cerebral oxygen delivery from 5,811 (SD 1,419) at rest to 4,665.6 (SD 1,324) at O2 max (P < 0.01) (Fig. 5).

Exercise at 4,750 m (Tables 2 and 3).   Mean arterial blood pressure increased from 107 mmHg (SD 13) to 128 mmHg (SD 15) during submaximal exercise (P < 0.05) and remained elevated at O2 max compared with resting (P < 0.001). End-tidal CO2 rose initially but was reduced from 23.7 mmHg (SD 2.0) at rest to 20.9 mmHg (SD 2.3) at 70% O2 max (P < 0.0001) and to 19.0 mmHg (SD 2.7) at O2 max (P < 0.0001). Ventilation and O2 rose progressively during the tests (P < 0.0001). MCA blood velocity rose initially and fell at maximal workloads, with an increase from 66.6 cm/s (SD 20.5) at rest to 78.7 cm/s (SD 20.7) at 70% O2 max (P < 0.0001) and a reduction to 58.6 cm/s (SD 19.4) at O2 max (P < 0.0001) (Fig. 2). rSO2 was reduced from 63.0% (SD 2.1) at rest to 58.9% (SD 2.1) during the submaximal exercise test (P < 0.0001) and was reduced to 59.4% (SD 2.6) at O2 max (P < 0.0001) (Fig. 3). The rise in CVRest from 1.75 (SD 0.61) at rest to 2.49 (SD 1.25) at O2 max was not significant (P = 0.057; Fig. 4), but there was a fall in cerebral oxygen delivery from 5,487 (SD 1,688) at rest to 4,270 (SD 1,295) at O2 max (P < 0.01; Fig. 5).

Exercise at 5,260 m (Tables 2 and 3).   Mean arterial blood pressure increased from 108 mmHg (SD 14) at rest to 126 mmHg (SD 12) during submaximal exercise (P < 0.001) but was reduced to 107 mmHg (SD 14) at O2 max compared with resting. Arterial oxygen saturations were reduced compared with resting (P < 0.0001). End-tidal CO2 rose initially but then was reduced from 21.3 Torr (SD 2.9) at rest to 19.4 Torr (SD 1.9) at 70% O2 max (P < 0.001) and to 14.9 Torr (SD 2.0) at O2 max (P < 0.0001). Ventilation and O2 rose progressively during the tests (P < 0.0001). MCA blood velocity rose initially and fell at maximal exercise, with an increase from 73.4 cm/s (SD 20.4) at rest to 81.0 cm/s (SD 19.6) at 70% O2 max (P < 0.001) and a reduction to 67.1 cm/s (SD 16.3) at O2 max (P < 0.0001) (Fig. 2). rSO2 was reduced from 62.4% (SD 3.6) at rest to 61.2% (SD 3.9) during submaximal exercise (P < 0.01) and was reduced to 58.0% (SD 3.0) at O2 max (P < 0.0001) (Fig. 3). There was a rise in CVRest from 1.63 (SD 0.64) at rest to 2.16 (SD 0.7) at O2 max (P < 0.0001) (Fig. 4) and a fall in cerebral oxygen delivery from 6,158 (SD 1,690) at rest to 5,049 (SD 1,264) at O2 max (P < 0.01) (Fig. 5).


   DISCUSSION
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
The cardiopulmonary effects of exercise at altitude have been studied extensively, but the effect of exercise on cerebral perfusion has received limited attention. No comparable studies of cerebral oxygenation at O2 max, or any combined measurements of cerebral oxygenation and MCA blood velocity at O2 max, at high altitude have been reported. Our results showed reductions in cerebral oxygenation and oxygen delivery during submaximal and maximal exercise at altitude.

The major determinants of cerebral blood flow are arterial PO2 (PaO2), arterial PCO2 (PaCO2) (1), and blood pressure, and each of these is altered by both exercise and altitude. Reductions in both PaO2 and PaCO2 on acute exposure to altitude, and during exercise at altitude, will have opposing effects on cerebral blood flow. Furthermore, the effects of these stimuli will be modified and vary with acclimatization. An important part of the respiratory acclimatization to altitude is the change in the hypercapnic ventilatory response, resulting in increased ventilatory sensitivity to CO2 (26). It has been shown that both cerebral blood flow and cerebral oxidative metabolism returns toward baseline by 3 wk at 5,260 m (31). In the present study, the responses observed at 4,750 and 5,260 m probably reflected partial acclimatization since they were performed 4–7 days after arrival at 3,610 m.

Our finding that acute exposure to the three altitudes had no effect on resting mean systemic arterial blood pressure is consistent with other reported studies (50). The rise in mean blood pressure in response to submaximal exercise at each high altitude was similar to that found at 150 m but was only significantly increased at the two highest altitudes. The fall in blood pressure at O2 max is consistent with other reports (50, 51). The changes in blood pressure we observed with exercise at altitude are well above the range at which autoregulation has been shown to occur. Autoregulation maintains a constant cerebral blood flow of 50–60 ml·100 g–1·min–1 over arterial pressures ranging from 60 to 140 mmHg (16). Experience during carotid endarterectomy under loco-regional anesthesia suggests that cerebral blood flow during the cross-clamp phase can be increased with a fairly modest rise in blood pressure, avoiding the need for shunting. A rise in systolic blood pressure of 35–45 mmHg can reverse neurological deficits (46) and is also associated with improved regional cerebral oxygenation (22). The rise in blood pressure may maintain cerebral perfusion during submaximal exercise at altitude, but the fall in blood pressure at O2 max could be a critical factor limiting exercise.

Near infrared cerebral spectroscopy measures changes in cerebral tissue oxygenation, which is dependent on blood flow, arterial oxygenation, cerebral metabolism, and arterial/venous partitioning (the relative proportion in either the arterial or venous vascular beds). The fall in arterial oxygen saturation at rest with increasing altitude was the most likely cause of the decrease in resting cerebral oxygenation and the increase in resting MCA blood velocity. Similar rises in MCA blood velocity have previously been reported and appear to be most marked on acute ascent, gradually returning toward normal over the following days to weeks (14, 23, 31). The small rise in cerebral oxygenation during submaximal exercise at 150 m could have occurred as a result of an increase in oxygen delivery induced by a gradual fall of cerebral vascular resistance and a matching increase in MCA velocity; but an alternative explanation for the observed rise in cerebral oxygenation could be decreased cerebral oxygen consumption. Similar changes in MCA blood velocity and cerebral oxygenation during submaximal exercise have been reported (17, 18, 34). At O2 max at 150 m, there was a rise in CVRest and an associated fall in MCA velocity. Despite this, near infrared cerebral oxygenation remained higher than the resting levels. This may be attributable to decreased O2, which has been described previously during exhaustive exercise at sea level (9).

In contrast, at the high altitudes studied, cerebral oxygenation (rSO2) fell progressively during submaximal exercise, with a further fall at maximal exercise. There was an increase in cerebral deoxygenated hemoglobin with both altitude and exercise. Saito and colleagues (42) showed similar changes in cerebral oxygenation at sea level and a fall at 2,700 and 3,700 m during submaximal exercise, which was equivalent to our level of 50% of O2 max. However, we found that although cerebral oxygen delivery was sustained to 70% O2 max at sea level, at the high altitudes studied, oxygen delivery peaked at 30% O2 max and thereafter fell. With partial acclimatization, there appeared to be a trend toward improved cerebral oxygen delivery as seen at 5,260 m. The increase in MCA blood velocity during submaximal exercise may have been due to several factors, the most important of which would appear to be increases in mean blood pressure, because there were only small changes in end-tidal CO2. Our finding of a gradual fall of cerebral oxygenation during submaximal exercise and O2 max at altitude may be attributed in part to the gradual fall in oxygen delivery, but an alternative explanation could be a decrease in cerebral oxygen consumption. We believe the slight differences in cerebral oxygenation during submaximal exercise at the two highest altitudes were due to the relatively small change in altitude and to some acclimatization between the two tests.

It has been shown that, during maximal exercise on a rowing machine in elite athletes (33), arterial oxygen saturation and regional cerebral oxygenation decrease but are maintained at resting levels with moderate hyperoxia (inspired oxygen fraction of 0.3). Exercise performance was also elevated without a change in muscle oxygenation, indicating that the cerebral hypoxia rather than muscle hypoxia appears to be a contributing factor for the limitation of exercise capacity. There was an observed reduction in arterial CO2 at maximal exercise. In a second sea level study by the same group, cerebral perfusion was shown to increase in excess of the increases in the global cerebral metabolic activity during the brain activation associated with exercise and that lactate supplements glucose as energy fuel for the brain when the plasma lactate level is elevated. Furthermore, as evidenced by mean MCA velocity determined by transcranial Doppler, cerebral perfusion was enhanced and cerebral oxygenation determined by near-infrared spectroscopy suggested flow increased to a larger extent than the corresponding metabolic oxygen demand (17).

We found no difference in resting CVRest between the different altitudes, although there was a nonsignificant reduction of resting CVRest with increasing altitude. CVRest appeared to change in two distinct phases with exercise. Up to 50% of O2 max, there was a tendency for a small reduction in CVRest, which was associated with a fall in arterial oxygen saturation and a rise in end-tidal CO2. These changes would tend to increase cerebral blood flow, and this was reflected in the rise in cerebral oxygen delivery observed at all altitudes at 30% submaximal exercise. There appeared to be a second phase between 70% O2 max and O2 max. In this phase, there was a marked rise in CVRest at all altitudes, and this is associated with falls in end-tidal CO2 and small rises in arterial oxygen saturation. Both of these changes would tend to decrease cerebral perfusion, and again this was reflected in the reduction of cerebral oxygen delivery observed at all altitudes at O2 max. Somewhat surprisingly, we found no direct correlation between end-tidal CO2 and CVRest. However, CVRest is a product of the complex dynamic interrelationship between all variables mentioned above as well as changes in hypoxic and hypercapnic ventilatory responses and cerebrovascular responsiveness to CO2.

The factors limiting exercise at altitude may be different from those that limit exercise at sea level and may include diffusion limitation of O2 in the alveolus, the work of ventilation, respiratory muscle fatigue, and the possible steal of blood from limb locomotor muscles to respiratory muscles (8, 10, 30). The perception of dyspnea is also increased during exercise at altitude (5), which may lead to the premature ending of exercise. At altitude, O2 in the lung is diffusion limited (52), and this is further exacerbated by exercise. Our results do not support a diffusion limit of CO2 at O2 max at altitudes up to 5,260 m, but further studies are required with measurements of PaCO2. Assessment of other vascular beds, such as exercising muscle, using near-infrared techniques could be used to determine whether there were significant steals of blood either to or from the cerebral circulation at O2 max. These techniques have been successfully used by Nielsen and colleagues at sea level (33).

Our findings of reduced cerebral oxygen delivery and increased CVRest during exercise above 50% of maximum exercise at altitude may relate to the pathogenesis of AMS and HACE. Exercise is likely to exacerbate AMS through increased hypoxia and sodium retention (55), and our results confirm that the brain is subjected to increasing hypoxia during exercise. Our results may explain the deterioration seen in the accuracy of marksmanship caused by acute exposure to altitude and independent of exercise (47) as well as transient and focal neurological deficits occurring at altitude (2, 32). The large rises in blood pressure observed on exercising close to or at O2 max could explain some of the focal and global transient and permanent neurological events observed at high altitude. Clinical examination at a later time point might miss the period of profound hypertension. It is also of interest that the standard formula of 220 – age (yr) used to predict maximal heart rate provided a good estimate at 150 m but increasingly underestimated maximal heart rate at each of the high altitudes. This finding has implications for studies using this formula for predicting energy expenditure or work rate during exercise at altitude.

The reduction in cerebral oxygenation we demonstrated at submaximal exercise is relevant for normal climbing at O2 of 50–75% O2 max (39). The finding that mountaineers with a more vigorous ventilatory response to hypoxia have more residual neurobehavioral impairment may be a result of reduced cerebral oxygen delivery (13). The hypercapnic vasoconstriction and subsequent reduced cerebral oxygenation might be due to a hypocapnic-driven reduction in cerebral blood flow (13). Schoene and colleagues (44) showed that the fall in arterial saturation on exercise at altitude was actually greater in subjects with a low hypoxic ventilatory drive. The observed reduction of cerebral oxygen delivery during exercise may be more important than absolute altitude in determining the development of AMS. At any given altitude, arterial and cerebral oxygenations are a dynamic variable dependent on absolute altitude, oxygen delivery, and O2. A resting individual at a higher altitude may have the same cerebral oxygenation as an exercising individual at a lower altitude. Both subjects are at the same "virtual" altitude. Assessing cumulative hypoxic insult (time at a virtual altitude) over a 24-h period might more accurately predict the hypoxic stress an individual has experienced.

The limitations of the near-infrared cerebral spectroscopy method have been reviewed (43, 37). The two-sensor technique eliminates the contribution from the scalp and skull, thereby giving a measurement of tissue oxygenation at a depth of 2.5–5.0 cm. Concerns over contamination of the intracerebral readings with scalp blood flow have been raised in the past. Providing the spacing between the scalp detectors is adequate, scalp flow makes no significant contribution. This was demonstrated using laser Doppler velocimetry and occlusion of scalp flow using a pneumatic tourniquet (35). Near-infrared spectroscopy provides a measure of the proportion of blood that is oxygenated. It does not distinguish how much is in the arterial or venous part of the vascular bed. The proportion of total blood in the brain has been estimated to be 28% arterial and 72% venous (29). In this study, we assumed that neither hypoxia nor exercise affects the arteriovenous partitioning. However, partitioning of the arterial and venous volumes in the brain under hypoxic conditions at rest has been modeled (56), and it is possible that further changes could occur with exercise.

The transcranial Doppler technique is operator dependent and requires careful focusing of the ultrasound probe on the MCA. We standardized this as far as possible by using one experienced operator (28). We cannot be certain whether arterial diameter remained constant during the exercise tests at altitude, but other studies at sea level found no changes with either decreases or increases in PaCO2 (45) or during hypocapnia alone (49). Jorgensen and colleagues (24) showed that the increase in regional cerebral perfusion during exercise at sea level occurred in the MCA territory, with increases in mean MCA blood velocities of 19–32%. However, it has been suggested that much of the increase in MCA blood velocity in response to exercise could arise as an artifact from the increase in amplitude and frequency of the arterial pressure waveform used in Doppler ultrasound studies (38). Nevertheless, cerebral blood flow measured by 133Xe clearance increased by 31% during submaximal exercise at sea level (48). Our finding of a 15% increase in MCA blood velocity was similar to the 14% reported by Hellstroem and colleagues (11), who combined duplex ultrasonography and transcranial Doppler ultrasonography. Our results are also comparable to those reported by Huang and colleagues (15), who, on acute exposure to 4,300 m, recorded increases in internal carotid flow velocity of 15–33% on exercising at 45 and 72% O2 max. Hellstroem and colleagues (11) performed a study at sea level in which a reduction in MCA blood velocity was found at 80–90% of maximal exercise. This was associated with a reduction of PaCO2, again similar to our findings at 150 m. When exercising at 96% O2 max at high altitude, Huang and colleagues (15) noted a small fall in internal carotid flow velocity, but flow remained higher than resting levels in contrast to our study.

Our results are consistent with the hypothesis that cerebral blood flow provides an important signal to the central nervous system and may become a factor limiting exercise at altitude, rather than cardiorespiratory capacity and muscle fatigue (25). Our finding of considerable reductions in cerebral oxygen delivery and cerebral oxygenation during exercise at altitude suggest that these may provide the critical signals. The reduction of cerebral oxygenation during exercise, if it persists during altitude acclimatization, may explain why O2 max is reduced despite normalization of arterial oxygen content (7). Reduction in cerebral oxygenation during exercise may exacerbate the neurological features of AMS and contribute to the development of HACE and other neurological deficits. Our results lend credence to the time-honored advice to avoid strenuous exercise on arrival at high altitude.


   GRANTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
ACKNOWLEDGMENTS
 REFERENCES
 
The work was supported by the Mount Everest Foundation.


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
REFERENCES
 
We are grateful to QinetiQ staff for assistance in the design and construction of Alticycle. The pulse oximeter was loaned by Freelance Surgical, Bristol, UK, and the COLIN CBM-7000 monitor by ScanMed Medical Instruments, Moreton in the Marsh, UK. Margaret Richards provided invaluable secretarial assistance.


   FOOTNOTES
 

Address for reprint requests and other correspondence: C. H. E. Imray, Coventry and Warwickshire County Vascular Unit, Univ. Hospitals Coventry and Warwickshire NHS Trust, Coventry, CV2 2DX, UK (E-mail: chrisimray{at}aol.com)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 

  1. Ainslie PN and Poulin MJ. Ventilatory, cerebrovascular, and cardiovascular interactions in acute hypoxia: regulation by carbon dioxide. J Appl Physiol 97: 149–159, 2004.
  2. Basnyat B, Wu T, and Gertsch JH. Neurological conditions at altitude that fall outside the usual definition of altitude sickness. High Alt Med Biol 5: 171–179, 2004.
  3. Bircher HP, Eichenberger U, Maggiorini M, Oelz O, and Bartsch P. Relationship of mountain sickness to physical fitness and exercise intensity during ascent. J Wilderness Med 5: 302–311, 1994.
  4. Buchfurher MJ, Hansen JE, Robinson TE, Sue DY, Wasserman K, and Whipp BJ. Optimizing the exercise protocol for cardiopulmonary assessment. J Appl Physiol 55: 1558–1564, 1983.
  5. Burki NK, McConnell JW, Ayub M, and Liles RM. Effects of acute prolonged exposure to high-altitude hypoxia on exercise-induced breathlessness. Clin Sci (Lond) 96: 327–333, 1999.
  6. Burtscher M, Bachmann O, Hatzl T, Hotter B, Likar R, Philadelphy M, and Nachbauer W. Cardiopulmonary and metabolic responses in healthy elderly humans during a 1-week hiking programme at high altitude. Eur J Appl Physiol 84: 379–386, 2001.
  7. Calbet JAL, Boushel R, Radegran G, Sondergaard H, Wagner PD, and Saltin B. Why is O2 max after altitude acclimatization still reduced despite normalization of arterial O2 content? Am J Physiol Regul Integr Comp Physiol 284: R304–R316, 2003.
  8. Cibella F, Cuttita G, Romano S, Grassi B, Bonsignore G, and Milic-Emili J. Respiratory energetics during exercise at high altitude. J Appl Physiol 86: 1785–1792, 1999.
  9. Dalsgaard MK, Ogoh S, Dawson EA, Yoshiga CC, Quistorff B, and Secher NH. Cerebral carbohydrate cost of physical exertion in humans. Am J Physiol Regul Integr Comp Physiol 287: R534–R540, 2004.
  10. Gudjonsdottir M, Appendini L, Baderna P, Purro A, Patessio A, Villanis G, Pastorelli M, Sigurdsson SB, and Donner CF. Diaphragm fatigue during exercise at high altitude: the role of hypoxia and workload. Eur Respir J 17: 674–680, 2001.
  11. Hellstroem G, Fischer-Colbrie W, Wahlgren NG, and Jogestrand T. Carotid artery blood flow and middle cerebral artery blood flow velocity during physical exercise. J Appl Physiol 81: 413–418, 1996.
  12. Henson IC, Calalang C, Temp JA, and Ward DS. Accuracy of a cerebral oximeter in healthy volunteers under conditions of isocapnic hypoxia. Anesthesiology 88: 58–65, 1998.
  13. Hornbein TF, Townes BD, Schoene RB, Sutton JR, and Houston CS. The cost to the central nervous system of climbing to extremely high altitude. N Engl J Med 321: 1714–1719, 1989.
  14. Huang SY, Moore LG, McCullough RE, McCullough RG, Micco AJ, Fulco C, Cymerman A, Manco-Johnson M, Weil JV, and Reeves JT. Internal carotid and vertebral arterial flow velocity in men at high altitude. J Appl Physiol 63: 395–400, 1987.
  15. Huang SY, Tawney KW, Bender PR, Groves BM, McCullough RE, McCullough RG, Micco AJ, Manco-Johnson M, Cymerman A, Greene ER, and Reeves JT. Internal carotid flow velocity with exercise before and after acclimatisation to 4,300 m. J Appl Physiol 71: 1469–1476, 1991.
  16. Humphey PRD. Clinical relevance of measurements of cerebral blood flow. Br J Hosp Med 26: 233–241, 1981.
  17. Ide K, Horn A, and Secher NH. Cerebral metabolic response to submaximal exercise. J Appl Physiol 87: 1604–1608, 1999.
  18. Ide K and Secher NH. Cerebral blood flow and metabolism during exercise. Prog Neurobiol 61: 397–414, 2000.
  19. Imray CH, Barnett NJ, Walsh S, Clarke T, Morgan J, Hale D, Hoar H, Mole D, Chesner I, and Wright AD. Near-infrared spectroscopy in the assessment of cerebral oxygenation at high altitude. Wilderness Environ Med 9: 198–203, 1998.
  20. Imray CH, Brearey S, Clarke T, Hale D, Morgan J, Walsh S, and Wright AD. Cerebral oxygenation at high altitude and the response to carbon dioxide, hyperventilation and oxygen. Clin Sci (Colch) 98: 159–164, 2000.
  21. Imray CH, Clarke T, Forster PJ, Harvey TC, Hoar H, Walsh S, and Wright AD. Carbon dioxide contributes to the beneficial effect of pressurization in a portable hyperbaric chamber at high altitude. Clin Sci (Colch) 100: 151–157, 2001.
  22. Imray CH, Mead MK, Thacker AJ, and Dimitri WR. Blood pressure manipulation during loco-regional anaesthetic carotid surgery. Br J Anaesth 88: 303–304, 2002.
  23. Jensen JB, Wright AD, Lassen NA, Harvey TC, Winterborn MH, Raichle ME, and Bradwell AR. Cerebral blood flow in acute mountain sickness. J Appl Physiol 69: 430–433, 1990.
  24. Jorgensen LG, Perko G, and Secher NH. Regional cerebral artery mean flow velocity and blood flow during dynamic exercise in humans. J Appl Physiol 73: 1825–1830, 1992.
  25. Kayser B. Exercise starts and ends in the brain. Eur J Appl Physiol 90: 411–419, 2003.
  26. Kellogg RH. The role of CO2 in altitude acclimatization. In: The Regulation of Human Respiration, edited by Cunningham DJC and Lloyd BB. Oxford, UK: Blackwell Scientific Publications, 1963, p. 374–394.
  27. Lavi S, Egbarya R, Lavi R, and Jacob G. Role of nitric oxide in the regulation of cerebral blood flow in humans: chemoregulation versus mechanoregulation. Circulation 107: 1901–1905, 2003.
  28. Lennard NS, Vijayasekar C, Tiivas C, Chan CWM, Higman DJ, and Imray CHE. Control of emboli in patients with recurrent or crescendo transient ischaemic attacks using preoperative transcranial Doppler-directed Dextran therapy. Br J Surg 90: 166–170, 2003.
  29. McCormick PW, Stewart M, Goetting MG, and Balakrishnan G. Regional cerebrovascular oxygen saturation measured by optical spectroscopy in humans. Stroke 22: 596–602, 1991.
  30. Mognini P, Saibene F, and Veicsteinas A. Ventilatory work during exercise at high altitude. Int J Sports Med 3: 33–36, 1982.
  31. Moller K, Paulson OB, Hornbein TF, Colier WN, Paulson AS, Roach RC, Holm S, and Knudsen GM. Unchanged cerebral blood flow and oxidative metabolism after acclimatization to high altitude. J Cereb Blood Flow Metab 22: 118–126, 2002.
  32. Murdoch DR. Focal neurological deficits associated with high altitude. Wilderness Environ Med 7: 79–80, 1996.
  33. Nielsen HB, Boushel R, Madsen P, and Secher NH. Cerebral desaturation during exercise reversed by O2 supplementation. Am J Physiol Heart Circ Physiol 277: H1045–H1052, 1999.
  34. Nielsen HB, Boesen M, and Secher NH. Near-infrared spectroscopy determined brain and muscle oxygenation during exercise with normal and resistive breathing. Acta Physiol Scand 171: 63–70, 2001.
  35. Owen-Reece H, Elwell CE, Wyatt JS, and Delpy DT. The effect of scalp ischaemia on measurement of cerebral blood volume by near-infrared spectroscopy. Physiol Meas 17: 279–286, 1996.
  36. Pattinson K, Myers S, and Gardner-Thorpe C. Problems with capnography at high altitude. Anaesthesia 59: 69–72, 2004.
  37. Pattinson K, Clutton-Brock T, and Imray C. Validity of near-infrared cerebral spectroscopy. Anaesthesia 59: 507–508, 2004.
  38. Poulin MJ, Syed RJ, and Robbins PA. Assessments of flow by transcranial Doppler ultrasound in the middle cerebral artery during exercise in humans. J Appl Physiol 86: 1632–1637, 1999.
  39. Pugh LGCE. Muscular exercise on Mt. Everest. J Physiol 141: 233–261, 1958.
  40. Ravenhill TH. Some experiences of mountain sickness in the Andes. J Trop Med Hyg 16: 313–320, 1913.
  41. Roach RC, Maes D, Sandoval D, Robergs RA, Icenogle M, Hinghofer-Szalkay H, Lium D, and Loeppky JA. Exercise exacerbates acute mountain sickness at simulated high altitude. J Appl Physiol 88: 581–585, 2000.
  42. Saito S, Nishihara F, Takazawa T, Kanai M, Aso C, Shiga T, and Shimada H. Exercise-induced cerebral deoxygenation among untrained trekkers at moderate altitudes. Arch Environ Health 54: 271–276, 1999.
  43. Schindler E, Zickmann B, Muller M, Boldt J, Knoll J, and Hernpelmann G. Cerebral oximetry by infrared spectroscopy in comparison with continuous measurement of oxygen saturation of the jugular vein bulb in intervention of the internal carotid artery. Vasa 24: 168–175, 1995.
  44. Schoene RB, Lahiri S, Hackett PH, Peters RM, Milledge JS, Pizzo CJ, Sarnquist FH, Boyer SJ, Graber DJ, Maret KH, and West JB. Relationship of hypoxic ventilatory response to exercise performance on Mount Everest. J Appl Physiol 56: 1478–1483, 1984.
  45. Serrador JM, Picot PA, Rutt BK, Shoemaker JK, and Bondar RL. MRI measures of middle cerebral artery diameter in conscious humans during simulated orthostasis. Stroke 31: 1672–1678, 2000.
  46. Stoneham MD and Warner O. Blood pressure manipulation during awake carotid surgery to reverse neurological deficit after carotid cross-clamping. Br J Anaesth 87: 641–644, 2001.
  47. Tharion WJ, Hoyt RW, Marlowe BE, and Cymerman A. Effects of high altitude and exercise on marksmanship. Aviat Space Environ Med 63: 114–117, 1992.
  48. Thomas SN, Schroeder T, Secher NH, and Mitchell JH. Cerebral blood flow during submaximal and maximal dynamic exercise in humans. J Appl Physiol 67: 744–748, 1989.
  49. Valdueza JM, Balzer JO, Villringer A, Vogl TJ, Kutter R, and Einhaupl KM. Changes in blood flow velocity and diameter of the middle cerebral artery during hyperventilation: assessment with MR and transcranial Doppler sonography. Am J Neuroradiol 18: 1929–1934, 1997.
  50. Vogel JA and Harris CW. Cardiopulmonary responses of resting man during early exposure to high altitude. J Appl Physiol 22: 1124–1128, 1967.
  51. Vogel JA, Hansen JE, and Harris CW. Cardiovascular responses in man during exhaustive work at sea level and high altitude. J Appl Physiol 23: 531–539, 1967.
  52. West JB, Boyer SJ, Graber DJ, Hackett PH, Maret KH, Milledge JS, Peters RM, Pizzo CJ, Samaja M, Sarnquist FH, Schoene RB, and Winslow RM. Maximal exercise at extreme altitudes on Mount Everest. J Appl Physiol 55: 688–698, 1983.
  53. Whipp BJ, Davis JA, Torres F, and Wasserman K. A test to determine the parameters of aerobic function during exercise. J Appl Physiol 50: 217–221, 1981.
  54. Williams IM, Voha R, Farrel A, Picton AJ, Mortimer AJ, and McCollum CN. Cerebral oxygen saturation, transcranial Doppler ultrasonography and stump pressure in carotid surgery. Br J Surg 81: 960–964, 1994.
  55. Withey WR, Milledge JS, Williams ES, Minty BD, Bryson EI, Luff NP, Older MW, and Beeley JM. Fluid and electrolyte homeostasis during prolonged exercise at altitude. J Appl Physiol 55: 409–412, 1983.
  56. Wolff CB and Imray CHE. Partitioning of arterial and venous volumes in the brain under hypoxic conditions. Adv Exp Med Biol 540: 19–23, 2003.



This article has been cited by other articles:


Home page
 ChestHome page
R. B. Schoene
Illnesses at High Altitude
Chest, August 1, 2008; 134(2): 402 - 416.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
N. H. Secher, T. Seifert, and J. J. Van Lieshout
Cerebral blood flow and metabolism during exercise: implications for fatigue
J Appl Physiol, January 1, 2008; 104(1): 306 - 314.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
A. W. Subudhi, M. C. Lorenz, C. S. Fulco, and R. C. Roach
Cerebrovascular responses to incremental exercise during hypobaric hypoxia: effect of oxygenation on maximal performance
Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H164 - H171.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
A. W. Subudhi, A. C. Dimmen, and R. C. Roach
Effects of acute hypoxia on cerebral and muscle oxygenation during incremental exercise
J Appl Physiol, July 1, 2007; 103(1): 177 - 183.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
L. M. Romer, H. C. Haverkamp, M. Amann, A. T. Lovering, D. F. Pegelow, and J. A. Dempsey
Effect of acute severe hypoxia on peripheral fatigue and endurance capacity in healthy humans
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R598 - R606.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
99/2/699    most recent
00973.2004v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (12)
Right arrow Citing Articles via Google Scholar