Exercise In Acute Hypoxia Research Articles

Systemic blood pressure at exercise in hypoxia in hypertensive and normotensive patients.

The current study aimed to determine whether acute hypoxia exposure in laboratory conditions associated with exercise induces an increase in systemic blood pressure (BP) in normotensive and hypertensive patients, and whether hypertensive patients are more prone to develop severe acute mountain sickness (sAMS). Finally, to determine if BP changes at exercise in acute hypoxia in hypertensive patients are predictive factors for sAMS. From 2012 to 2015, 852 normotensive and 106 hypertensive patients went through an acute hypoxia exercise test before a sojourn at high altitude. A subgroup of 228 normotensive was selected to match age, sex ratio, body weight and BMI and compared with the hypertensive group. In normotensive and hypertensive patients, for a given workload, BP was higher in hypoxia than in normoxia, whereas, for a given heart rate, it was lower in hypoxia than in normoxia. Hypertensive patients treated by beta-blockers showed lower arterial oxygen saturation (vs. other treatments) and blunted cardiac and ventilatory responses to hypoxia at exercise. Based on questionnaires filled out at high altitude, hypertensive patients were not more prone than normotensive patients to develop sAMS. During the laboratory acute hypoxic exercise test, hypertensive patients suffering from sAMS, although taking acetazolamide showed similar BP than hypertensive patients without sAMS and without acetazolamide. We hypothesize that acute hypoxia with exercise in laboratory conditions induces a peripheral vasodilation that balances vasoconstriction and tachycardia centrally induced through the adrenergic system. Hypertensive and normotensive patients behave similarly during exercise in acute hypoxia. Acute hypoxia does not exacerbate the exercise-induced increase in BP. BP variation, during the acute hypoxia exercise test, is not a useful predictor of intolerance to high altitude. Based on laboratory tests in acute hypoxia, hypertensive patients may not be at higher risk to develop sAMS at high altitude.

Heat and Hypoxic Acclimation Increase Monocyte Heat Shock Protein 72 but Do Not Attenuate Inflammation following Hypoxic Exercise.

Acclimation to heat or hypoxic stress activates the heat shock response and accumulation of cytoprotective heat shock proteins (HSPs). By inhibiting the NF-κB pathway HSP72 can preserve epithelial function and reduce systemic inflammation. The aim of this study was to determine the time course of mHSP72 accumulation during acclimation, and to assess intestinal barrier damage and systemic inflammation following hypoxic exercise. Three groups completed 10 × 60-min acclimation sessions (50% normoxic VO2peak) in control (n = 7; 18°C, 35% RH), hypoxic (n = 7; FiO2 = 0.14, 18°C, 35% RH), or hot (n = 7; 40°C, 25% RH) conditions. Tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10), and intestinal fatty acid binding protein (I-FABP) were determined at rest and following a cycling normoxic stress test (NST; ~2 weeks before acclimation), pre-acclimation hypoxic stress test (HST1; FiO2 = 0.14, both at 50% normoxic VO2peak; ~1 week before acclimation) and post-acclimation HST (48 h; HST2). Monocyte HSP72 (mHSP72) was determined before and after exercise on day 1, 3, 5, 6, and 10 of acclimation. Accumulation of basal mHSP72 was evident from day 5 (p < 0.05) of heat acclimation and increased further on day 6 (p < 0.01), and day 10 (p < 0.01). In contrast, basal mHSP72 was elevated on the final day of hypoxic acclimation (p < 0.05). Following the NST, plasma TNF-α (–0.11 ± 0.27 ng.mL−1), IL-6 (+0.62 ± 0.67 ng.mL−1) IL-10 (+1.09 ± 9.06 ng.mL−1) and I-FABP (+37.6 ± 112.8 pg.mL−1) exhibited minimal change. After HST1, IL-6 (+3.87 ± 2.56 ng.mL−1), IL-10 (+26.15 ± 26.06 ng.mL−1) and I-FABP (+183.7 ± 182.1 pg.mL−1) were elevated (p < 0.01), whereas TNF-α was unaltered (+0.08 ± 1.27; p > 0.05). A similar trend was observed after HST2, with IL-6 (+3.09 ± 1.30 ng.mL−1), IL-10 (+23.22 ± 21.67 ng.mL−1) and I-FABP (+145.9 ±123.2 pg.mL−1) increased from rest. Heat acclimation induces mHSP72 accumulation earlier and at a greater magnitude compared to matched work hypoxic acclimation, however neither acclimation regime attenuated the systemic cytokine response or intestinal damage following acute exercise in hypoxia.

Dietary nitrate supplementation increases acute mountain sickness severity and sense of effort during hypoxic exercise.

Dietary nitrate supplementation enhances sea level performance and may ameliorate hypoxemia at high altitude. However, nitrate may exacerbate acute mountain sickness (AMS), specifically headache. This study investigated the effect of nitrate supplementation on AMS symptoms and exercise responses with 6-h hypoxia. Twenty recreationally active men [age, 22 ± 4 yr, maximal oxygen consumption (V̇o2max), 51 ± 6 ml·min-1·kg-1, means ± SD] completed this randomized double-blinded placebo-controlled crossover study. Twelve participants were classified as AMS- on the basis of Environmental Symptoms Questionnaire [Acute Cerebral Mountain Sickness score (AMS-C)] <0.7 in both trials, and five participants were classified as AMS+ on the basis of AMS-C ≥0.7 on placebo. Five days of nitrate supplementation (70-ml beetroot juice containing ~6.4 mmol nitrate daily) increased plasma NO metabolites by 182 µM compared with placebo but did not reduce AMS or improve exercise performance. After 4-h hypoxia [inspired O2 fraction ([Formula: see text]) = 0.124], nitrate increased AMS-C and headache severity (visual analog scale; whole sample ∆10 [1, 20] mm, mean difference [95% confidence interval]; P = 0.03) compared with placebo. In addition, after 5-h hypoxia, nitrate increased sense of effort during submaximal exercise (∆7 [-1, 14]; P = 0.07). In AMS-, nitrate did not alter headache or sense of effort. In contrast, in AMS+, nitrate increased headache severity (∆26 [-3, 56] mm; P = 0.07), sense of effort (∆14 [1, 28]; P = 0.04), oxygen consumption, ventilation, and mean arterial pressure during submaximal exercise. On the next day, in a separate acute hypoxic exercise test ([Formula: see text] = 0.141), nitrate did not improve time to exhaustion at 80% hypoxic V̇o2max In conclusion, dietary nitrate increases AMS and sense of effort during exercise, particularly in those who experience AMS. Dietary nitrate is therefore not recommended as an AMS prophylactic or ergogenic aid in nonacclimatized individuals at altitude.NEW & NOTEWORTHY This is the first study to identify that the popular dietary nitrate supplement (beetroot) does not reduce acute mountain sickness (AMS) or improve exercise performance during 6-h hypoxia. The consumption of nitrate in those susceptible to AMS exacerbates AMS symptoms (headache) and sense of effort and raises oxygen cost, ventilation, and blood pressure during walking exercise in 6-h hypoxia. These data question the suitability of nitrate supplementation during altitude travel in nonacclimatized people.

Prior Heat or Hypoxic Acclimation Does Not Attenuate the Cytokine Response to Hypoxic Exercise

BACKGROUND: Heat acclimation activates the cellular heat shock response (HSR), inhibiting NF-κB and reducing heat stress-mediated cytokine production and limiting stress-induced inflammation. Hypoxia-mediated intestinal ischemia activates the NF-κB pathway and stimulates pro-inflammatory responses linked to acute mountain sickness and pulmonary and cerebral oedema. The upregulation of the HSR via heat acclimation may therefore reduce inflammatory responses following subsequent hypoxic exercise. PURPOSE: To determine whether prior heat acclimation attenuates the cytokine response following hypoxic exercise. METHODS: Plasma TNF-α, IL-6, IL-10 and IL-1ra were determined at rest and following a 60 minute cycling normoxic stress test (NST) and hypoxic stress test (HST1; FiO2 = 0.14, 50% VO2peak) in 21 men (age 22 ± 5 years; stature 1.76 ± 0.07 m; mass 71.8 ± 7.9 kg; VO2 peak 51 ± 7 mL·kg−1·min−1). Participants formed 3 groups and completed 10 x 60 minute acclimation sessions (50% VO2peak) in control (n = 7; 18 °C, 35% RH), hypoxic (n = 7; FiO2 = 0.14, 18 °C, 35% RH), or hot (n = 7; 40 °C, 25% RH) conditions. A second HST (HST2) was completed 48 hours after the final acclimation session. Cytokine data are presented as mean change in ng·mL−1 with 95% confidence intervals and comparisons made using mixed ANOVA. RESULTS: Following the NST plasma IL-6 (+0.6, 95% CI 0.3 - 0.9 ng·mL-1), IL-10 (+1.1, 95% CI -2.8 - 5.0 ng·mL-1) and IL-1ra (-16.6, 95% CI -60.5 - 27.2 ng·mL-1) exhibited minimal change (p > 0.05). TNF-α was unaltered throughout the study. IL-6 (+3.9, 95% CI 2.8 - 4.9 ng·mL-1), IL-10 (+26.2, 95% CI 15.0 - 37.3 ng·mL-1) and IL-1ra (+1506, 95% CI 746 - 2266 ng·mL-1) were elevated following HST1 (p < 0.01), with no main effect for acclimation group (p > 0.05). A similar trend was observed after acclimation (HST2), with IL-6 (+3.1, 95% CI 2.5 - 3.7 ng·mL-1), IL-10 (+23.2, 95% CI 14.0 - 32.5 ng·mL-1) and IL-1ra (+1237, 95% CI 721 - 1753 ng·mL-1) increased (p < 0.01), and no main effect for trial or acclimation group observed (p > 0.05). CONCLUSIONS: Neither prior heat nor hypoxic acclimation attenuated the systemic cytokine response following acute exercise in hypoxia. Future work investigating the effectiveness of different acclimation modalities on improving inflammatory outcomes to hypoxic stress is recommended.

Twin Resemblance in Muscle HIF-1α Responses to Hypoxia and Exercise.

Hypoxia-inducible factor-1 (HIF-1) is a master regulator of myocellular adaptation to exercise and hypoxia. However, the role of genetic factors in regulation of HIF-1 responses to exercise and hypoxia is unknown. We hypothesized that hypoxia at rest and during exercise stimulates the HIF-1 pathway and its downstream targets in energy metabolism regulation in a genotype-dependent manner. Eleven monozygotic twin (MZ) pairs performed an experimental trial in both normoxia and hypoxia (FiO2 10.7%). Biopsies were taken from m. vastus lateralis before and after a 20-min submaximal cycling bout @~30% of sea-level VO2max. Key-markers of the HIF-1 pathway and glycolytic and oxidative metabolism were analyzed using real-time PCR and Western Blot. Hypoxia increased HIF-1α protein expression by ~120% at rest vs. +150% during exercise (p < 0.05). Furthermore, hypoxia but not exercise increased muscle mRNA content of HIF-1α (+50%), PHD2 (+45%), pVHL (+45%; p < 0.05), PDK4 (+1200%), as well as PFK-M (+20%) and PPAR-γ1 (+60%; p < 0.05). Neither hypoxia nor exercise altered PHD1, LDH-A, PDH-A1, COX-4, and CS mRNA expressions. The hypoxic, but not normoxic exercise-induced increment of muscle HIF-1α mRNA content was about 10-fold more similar within MZ twins than between the twins (p < 0.05). Furthermore, in resting muscle the hypoxia-induced increments of muscle HIF-1α protein content, and HIF-1α and PDK4 mRNA content were about 3–4-fold more homogeneous within than between the twins pairs (p < 0.05). The present observations in monozygotic twins for the first time clearly indicate that the HIF-1α protein as well as mRNA responses to submaximal exercise in acute hypoxia are at least partly regulated by genetic factors.

Effect of acute exercise and hypoxia on markers of systemic and mucosal immunity.

PurposeTo determine how immune markers are affected by acute hypoxic exercise at the same relative intensity.MethodsTwelve endurance-trained males (age: 28 ± 4 years, dot{V}O2max: 63.7 ± 5.3 mL/kg/min) cycled for 75 min at 70 % of altitude-specific dot{V}O2max, once in normoxia (N) and once in hypobaric hypoxia equivalent to 2000 m above sea-level (H). Blood and saliva samples were collected pre-, post- and 2 h post-exercise.ResultsParticipants cycled at 10.5 % lower power output in H vs. N, with no significant differences in heart rate (P = 0.10) or rating of perceived exertion (P = 0.21). Post-exercise plasma cortisol was higher in H vs. N [683 (95 % CI 576–810) nmol/l vs. 549 (469–643) nmol/l, P = 0.017]. The exercise-induced decrease in CD4:CD8 ratio was greater in H vs. N (−0.5 ± 0.2 vs. −0.3 ± 0.2, P = 0.019). There were no significant between-trial differences for adrenocorticotropic hormone, plasma cytokines, antigen-stimulated cytokine production, salivary immunoglobulin-A or lactoferrin. However, there was a main trial effect for concentration [F(11) = 5.99, P < 0.032] and secretion [F(11) = 5.01, P < 0.047] of salivary lysozyme, with this being higher in N at every time-point.ConclusionWhether the observed differences between H and N are of sufficient magnitude to clinically impair host defence is questionable, particularly as they are transient in nature and since other immune markers are unaffected. As such, acute hypoxic exercise likely does not pose a meaningful additional threat to immune function compared to exercise at sea level, provided that absolute workload is reduced in hypoxia so that relative exercise intensity is the same.

Effects Of Different Environments On Performance, Reaction Time And Brain-derived Neurotrophic Factor

PURPOSE: To examine the isolated and combined effects of severe hypoxia and a mild thermal challenge on performance, physiological measures, reaction time (RT) and serum brain derived neurotrophic factor (BDNF). METHODS: Nine trained male athletes (Age: 23±3y; Wmax: 332.6±45.0W; PL4) completed four experimental trials (CON: 15°C/0m, ALT: 15°C/3800m, TEMP: 25°C/0m, ALT+TEMP: 25°C/3800m) in a randomized, cross-over design. Subjects cycled for 30min in a self-paced test starting at 75%Wmax, their goal was to ‘perform as much work as possible in 30min’. Power output (PO), heart rate, blood lactate, pulse oximetry and core and skin temperature were assessed. Before and after the time trial blood samples were taken for the analysis of BDNF and the psychomotor vigilance task was performed for the determination of RT and RT variability. Two-way (temperature x altitude) and three-way (temperature x altitude x time) ANOVA with repeated measures was used to examine main and interaction effects, paired t-tests were used to identify pair-wise differences. P<.05 was considered significant. RESULTS: Altitude had a detrimental effect on PO (main effect; P<0.001) and a significant interaction effect with time (alt x time; P<0.001). At sea level, in 15°C, subjects produced a mean PO of 243 ± 37W. At altitude, in 15°C, this mean PO was significantly decreased to 170 ± 46W (P<0.001). In 25°C, altitude decreased mean PO in a similar way as in 15°C (TEMP: 236 ± 41W; ALT+TEMP: 167 ± 47W; P<0.05). CONCLUSIONS: Both stressors separately from each other significantly decreased exercise capacity, but we did not observe an interaction effect. Altitude induced an increase in RT and an increase in RT variability, presenting tentative evidence of mental fatigue after exercise in acute hypoxia. Exercise significantly increased BDNF, but no effect of altitude on the BDNF concentration was observed. * BR is funded by the FWO Fund for Scientific Research Flanders, Belgium.

Electrocardiographic Changes During Exercise in Acute Hypoxia and Susceptibility to Severe High-Altitude Illnesses

The goals of this study were to compare ECG at moderate exercise in normoxia and hypoxia at the same heart rate, to provide evidence of independent predictors of hypoxia-induced ECG changes, and to evaluate ECG risk factors of severe high-altitude illness. A total of 456 subjects performed a 20-minute hypoxia exercise test with continuous recording of ECG and physiological measurements before a sojourn above 4000 m. Hypoxia did not induce any conduction disorder, arrhythmias, or change in QRS axis. The amplitude of the P wave in V1 was lower in hypoxia than in normoxia. The amplitudes of the R, S, and T waves and the Sokolow index decreased in hypoxia. Under hypoxia, the amplitude of the ST segment decreased in II and V6 and increased in V1, the ST slope rose in V5 and V6, and the J point was lower in II, V5, and V6. Multivariate regression of hypoxic/normoxic ratios of electrophysiological parameters and clinical characteristics showed a correlation between the decrease in Sokolow index and T-wave amplitude in V5 with desaturation at exercise. Trained status and low body mass index were associated with a smaller decrease in T-wave amplitude in V5 and V6. Comparison of ECG between subjects suffering or not suffering from severe high-altitude illness failed to show any difference. During a hypoxia exercise test, a dose-dependent hypoxia-induced decrease in the amplitude of the P/QRS/T waves was observed. No standard ECG characteristic predicted the risk of developing severe high-altitude illness. Further studies are required to clarify the cause of these electric changes and their potential predictive role in cardiac events.

Systemic oxidative-nitrosative-inflammatory stress during acute exercise in hypoxia; implications for microvascular oxygenation and aerobic capacity.

Exercise performance in hypoxia may be limited by a critical reduction in cerebral and skeletal tissue oxygenation, although the underlying mechanisms remain unclear. We examined whether increased systemic free radical accumulation during hypoxia would be associated with elevated microvascular deoxygenation and reduced maximal aerobic capacity (V̇O2 max ). Eleven healthy men were randomly assigned single-blind to an incremental semi-recumbent cycling test to determine V̇O2 max in both normoxia (21% O2) and hypoxia (12% O2) separated by a week. Continuous-wave near-infrared spectroscopy was employed to monitor concentration changes in oxy- and deoxyhaemoglobin in the left vastus lateralis muscle and frontal cerebral cortex. Antecubital venous blood samples were obtained at rest and at V̇O2 max to determine oxidative (ascorbate radical by electron paramagnetic resonance spectroscopy), nitrosative (nitric oxide metabolites by ozone-based chemiluminescence and 3-nitrotyrosine by enzyme-linked immunosorbent assay) and inflammatory stress biomarkers (soluble intercellular/vascular cell adhesion1 molecules by enzyme-linked immunosorbent assay). Hypoxia was associated with increased cerebral and muscle tissue deoxygenation and lower V̇O2 max (P<0.05 versus normoxia). Despite an exercise-induced increase in oxidative-nitrosative-inflammatory stress, hypoxia per se did not have an additive effect (P>0.05 versus normoxia). Consequently, we failed to observe correlations between any metabolic, haemodynamic and cardiorespiratory parameters (P>0.05). Collectively, these findings suggest that altered free radical metabolism cannot explain the elevated microvascular deoxygenation and corresponding lower V̇O2 max in hypoxia. Further research is required to determine whether free radicals when present in excess do indeed contribute to the premature termination of exercise in hypoxia.

Flow-mediated dilation in the inactive limb following acute hypoxic exercise.

The purpose of this study was to elucidate the effect of acute aerobic exercise performed under hypoxic conditions on flow-mediated dilation (FMD) in the inactive limb. Seven males participated in the study. The subjects performed two submaximal leg cycling on a semirecumbent ergometer at the same relative intensity (60% peak oxygen uptake) in normoxia [inspired oxygen fraction (FIO2) = 0·21] and hypoxia (FIO2 = 0·12-0·13) for 30 min. The brachial artery diameter and blood velocity during exercise were measured via ultrasound, and the antegrade and retrograde shear rates were calculated. Before and 5, 30 and 60 min after exercise, brachial artery FMD was measured in normoxia. FMD was estimated as the percentage increase in peak diameter from the baseline diameter at prior occlusion (%FMD) and as the controlling changes in baseline diameter (the corrected-%FMD). No difference in antegrade shear rate during exercise was detected between the normoxic and hypoxic conditions, whereas the retrograde shear rate was larger during hypoxic exercise. The %FMD decreased significantly at 5 min after exercise in both normoxia and hypoxia, and it returned to pre-exercise levels within 60 min of recovery. Significant decreases in FMD at 5 min after exercise had disappeared when the baseline diameter was controlled using an analysis of covariance (the corrected-%FMD). No significant differences were observed between the normoxic and hypoxic trials in the %FMD and corrected-%FMD following exercise. These results suggest that hypoxia has no impact on endothelial function in the inactive limb following acute aerobic exercise.

Acute hypoxic exercise does not alter post-exercise iron metabolism in moderately trained endurance athletes.

This study measured the influence of acute hypoxic exercise on Interleukin-6 (IL-6), hepcidin, and iron biomarkers in athletes. In a repeated measures design, 13 moderately trained endurance athletes performed 5 × 4 min intervals at 90 % of their peak oxygen consumption velocity (vVO2peak) in both normoxic [NORM, fraction of inspired oxygen (F IO2) = 0.2093, 15.3 ± 1.7 km h(-1)] and simulated hypoxic (HYP, F IO2 = 0.1450, 13.2 ± 1.5 km h(-1)) conditions. Venous blood samples were obtained pre-, post-, and 3 h post-exercise, and analysed for serum hepcidin, IL-6, ferritin, iron, soluble transferrin receptor (sTfR), and transferrin saturation. Peak heart rate was significantly lower in HYP compared with NORM (p = 0.01); however, the rating of perceived exertion was similar between trials (p = 0.24). Ferritin (p = 0.02), transferrin (p = 0.03), and IL-6 (p = 0.01) significantly increased immediately post-exercise in both conditions, but returned to baseline 3 h later. Hepcidin levels significantly increased in both conditions 3 h post-exercise (p = 0.05), with no significant differences between trials. A significant treatment effect was observed between trials for sTfR (p = 0.01), but not iron and transferrin saturation. Acute exercise in hypoxia did not influence post-exercise IL-6 production, hepcidin activity or iron metabolism compared with exercise at the same relative intensity in normoxia. Hence, acute exercise performed at the same relative intensity in hypoxia poses no further risk to an athlete's iron status, as compared with exercise in normoxia.

AltitudeOmics: exercise-induced supraspinal fatigue is attenuated in healthy humans after acclimatization to high altitude

We asked whether acclimatization to chronic hypoxia (CH) attenuates the level of supraspinal fatigue that is observed after locomotor exercise in acute hypoxia (AH). Seven recreationally active participants performed identical bouts of constant-load cycling (131 ± 39 W, 10.1 ± 1.4 min) on three occasions: (i) in normoxia (N, PI O2 , 147.1 mmHg); (ii) in AH (FI O2 , 0.105; PI O2 , 73.8 mmHg); and (iii) after 14 days in CH (5260 m; PI O2 , 75.7 mmHg). Throughout trials, prefrontal-cortex tissue oxygenation and middle cerebral artery blood velocity (MCAV) were assessed using near-infrared-spectroscopy and transcranial Doppler sonography. Pre- and post-exercise twitch responses to femoral nerve stimulation and transcranial magnetic stimulation were obtained to assess neuromuscular and corticospinal function. In AH, prefrontal oxygenation declined at rest (Δ7 ± 5%) and end-exercise (Δ26 ± 13%) (P < 0.01); the degree of deoxygenation in AH was greater than N and CH (P < 0.05). The cerebral O2 delivery index (MCAV × Ca O2 ) was 19 ± 14% lower during the final minute of exercise in AH compared to N (P = 0.013) and 20 ± 12% lower compared to CH (P = 0.040). Maximum voluntary and potentiated twitch force were decreased below baseline after exercise in AH and CH, but not N. Cortical voluntary activation decreased below baseline after exercise in AH (Δ11%, P = 0.014), but not CH (Δ6%, P = 0.174) or N (Δ4%, P = 0.298). A twofold greater increase in motor-evoked potential amplitude was evident after exercise in CH compared to AH and N. These data indicate that exacerbated supraspinal fatigue after exercise in AH is attenuated after 14 days of acclimatization to altitude. The reduced development of supraspinal fatigue in CH may have been attributable to increased corticospinal excitability, consequent to an increased cerebral O2 delivery.

AltitudeOmics: on the consequences of high-altitude acclimatization for the development of fatigue during locomotor exercise in humans

The development of muscle fatigue is oxygen (O2)-delivery sensitive [arterial O2 content (CaO2) × limb blood flow (QL)]. Locomotor exercise in acute hypoxia (AH) is, compared with sea level (SL), associated with reduced CaO2 and exaggerated inspiratory muscle work (Winsp), which impairs QL, both of which exacerbate fatigue individually by compromising O2 delivery. Since chronic hypoxia (CH) normalizes CaO2 but exacerbates Winsp, we investigated the consequences of a 14-day exposure to high altitude on exercise-induced locomotor muscle fatigue. Eight subjects performed the identical constant-load cycling exercise (138 ± 14 W; 11 ± 1 min) at SL (partial pressure of inspired O2, 147.1 ± 0.5 Torr), in AH (73.8 ± 0.2 Torr), and in CH (75.7 ± 0.1 Torr). Peripheral fatigue was expressed as pre- to postexercise percent reduction in electrically evoked potentiated quadriceps twitch force (ΔQtw,pot). Central fatigue was expressed as the exercise-induced percent decrease in voluntary muscle activation (ΔVA). Resting CaO2 at SL and CH was similar, but CaO2 in AH was lower compared with SL and CH (17.3 ± 0.5, 19.3 ± 0.7, 20.3 ± 1.3 ml O2/dl, respectively). Winsp during exercise increased with acclimatization (SL: 387 ± 36, AH: 503 ± 53, CH: 608 ± 67 cmH2O·s(-1)·min(-1); P < 0.01). Exercise at SL did not induce central or peripheral fatigue. ΔQtw,pot was significant but similar in AH and CH (21 ± 2% and 19 ± 3%; P = 0.24). ΔVA was significant in both hypoxic conditions but smaller in CH vs. AH (4 ± 1% vs. 8 ± 2%; P < 0.05). In conclusion, acclimatization to severe altitude does not attenuate the substantial impact of hypoxia on the development of peripheral fatigue. In contrast, acclimatization attenuates, but does not eliminate, the exacerbation of central fatigue associated with exercise in severe AH.

The effect of acute exercise in hypoxia on flow-mediated vasodilation

The purpose of this study was to clarify the effect of acute exercise in hypoxia on flow-mediated vasodilation (FMD). Eight males participated in this study. Two maximal exercise tests were performed using arm cycle ergometry to estimate peak oxygen uptake [Formula: see text] while breathing normoxic [inspired O(2) fraction (FIO(2))=0.21] or hypoxic (FIO(2)=0.12) gas mixtures. Next, subjects performed submaximal exercise at the same relative exercise intensity [Formula: see text] in normoxia or hypoxia for 30min. Before (Pre) and after exercise (Post 5, 30, and 60min), brachial artery FMD was measured during reactive hyperemia by ultrasound under normoxic conditions. FMD was estimated as the percent (%) rise in the peak diameter from the baseline value at prior occlusion at each FMD measurement (%FMD). The area under the curve for the shear rate stimulus (SR(AUC)) was calculated in each measurement, and each %FMD value was normalized to SR(AUC) (normalized FMD). %FMD and normalized FMD decreased significantly (P<0.05) immediately after exercise in both condition (mean±SE, FMD, normoxic trial, Pre: 8.85±0.58%, Post 5: -0.01±1.30%, hypoxic trial, Pre: 8.84±0.63%, Post 5: 2.56±0.83%). At Post 30 and 60, %FMD and normalized FMD returned gradually to pre-exercise levels in both trials (FMD, normoxic trial, Post 30: 1.51±0.68%, Post 60: 2.99±0.79%; hypoxic trial, Post 30: 4.57±0.78%, Post 60: 6.15±1.20%). %FMD and normalized FMD following hypoxic exercise (at Post 5, 30, and 60) were significantly (P<0.05) higher than after normoxic exercise. These results suggest that aerobic exercise in hypoxia has a significant impact on endothelial-mediated vasodilation.

Supraspinal fatigue after normoxic and hypoxic exercise in humans

Inadequate cerebral O2 availability has been proposed to be an important contributing factor to the development of central fatigue during strenuous exercise. Here we tested the hypothesis that supraspinal processes of fatigue would be increased after locomotor exercise in acute hypoxia compared to normoxia, and that such change would be related to reductions in cerebral O2 delivery and tissue oxygenation. Nine endurance-trained cyclists completed three constant-load cycling exercise trials at ∼80% of maximal work rate: (1) to the limit of tolerance in acute hypoxia; (2) for the same duration but in normoxia (control); and (3) to the limit of tolerance in normoxia. Throughout each trial, prefrontal cortex tissue oxygenation and middle cerebral artery blood velocity (MCAV) were assessed using near-infrared spectroscopy and transcranial Doppler sonography, respectively. Cerebral O2 delivery was calculated as the product of arterial O2 content and MCAV. Before and immediately after each trial, twitch responses to supramaximal femoral nerve stimulation and transcranial magnetic stimulation were obtained to assess neuromuscular and cortical function, respectively. Exercise time was reduced by 54% in hypoxia compared to normoxia (3.6 ± 1.3 vs. 8.1 ± 2.9 min; P < 0.001). Cerebral O2 delivery, cerebral oxygenation and maximum O2 uptake were reduced whereas muscle electromyographic activity was increased in hypoxia compared to control (P < 0.05). Maximum voluntary force and potentiated quadriceps twitch force were decreased below baseline after exercise in each trial; the decreases were greater in hypoxia compared to control (P < 0.001), but were not different in the exhaustive trials (P > 0.05). Cortical voluntary activation was also decreased after exercise in all trials, but the decline in hypoxia (Δ18%) was greater than in the normoxic trials (Δ5–9%) (P < 0.05). The reductions in cortical voluntary activation were paralleled by reductions in cerebral O2 delivery. The results suggest that curtailment of exercise performance in acute severe hypoxia is due, in part, to failure of drive from the motor cortex, possibly as a consequence of diminished O2 availability in the brain.

Sildenafil and Bosentan Improve Arterial Oxygenation During Acute Hypoxic Exercise: A Controlled Laboratory Trial

Sildenafil and, recently, bosentan have been reported to increase arterial saturation and exercise capacity at altitude. The mechanisms behind this are still poorly defined but may be related to attenuation of hypoxic pulmonary vasoconstriction (HPV) and improved gas exchange. This study was designed to examine and compare the effect of sildenafil and bosentan on pulmonary gas exchange during acute hypoxic exercise in a controlled laboratory setting. Sixteen athletic university students (8 males, 8 females) were examined during exercise in a hypoxic chamber (11% oxygen) before and after the administration of either sildenafil (n=10) or bosentan (n=6). Respiratory and metabolic measurements were taken at rest and during increasing exercise intensity (up to 90% of their individual maximal oxygen uptake [VO(2)max]) in concert with arterial blood gas sampling. Both drugs resulted in small, but significant increases in arterial PO(2) (2-3 Torr) and O(2) saturation (3-4%) at rest and during hypoxic exercise, in both men and women. No significant changes in arterial PCO(2) or ventilation were seen at rest or during exercise in hypoxia; however, heart rate (both at rest and during exercise) was increased with both sildenafil and bosentan in both men and women. These data demonstrate that sildenafil and bosentan equally improve arterial oxygenation in acute hypoxia in both men and women, which could account for improved physical performance at altitude.

Impairment Of 3000m Racing Performance At Moderate Altitude Is Influenced By VO2 And SaO2 Maintenance

Athletic competitions involving endurance exercise at moderate altitude are characterized by impaired performances compared to sea level. The decline in maximal oxygen uptake (VO2max) with acute exposure to moderate altitude has been shown to be dependent on both the magnitude of VO2max at sea level, as well as the ability to maintain arterial oxyhemoglobin saturation (SaO2) during exercise. Whether these relationships extend to influence racing performance with acute altitude exposure is unknown. PURPOSE: This study examined if SaO2 and VO2 maintenance during heavy exercise in acute hypoxia are related to the acute decline in racing performance of elite athletes at altitude. METHODS: Twenty-seven elite distance runners (18 M, 9 F, VO2max = 71.8 + 7.2 ml/kg/min) performed a treadmill exercise bout at a constant speed which simulated their 3000m race pace, both in normoxia (elevation 230m) and breathing 16.3 % O2 (simulating 2100m). Separate 3000m time trials were completed on 400m all-weather outdoor tracks at elevations of 230m (SL), 18 hrs prior to exposure to altitude, and 2100m (ALT), 48 hrs after arrival at altitude. Statistical significance was set at P < 0.05. RESULTS: Group 3000m time trial performance was significantly slower at ALT versus SL (D3000m race time = +48.5 + 12.7 s or 9.2%), and the declines in performances were similar in men (+48.4 + 14.6 s) and women (+48.6 + 8.9 s). Athletes grouped as low SaO2 during race pace treadmill running in normoxia (SaO2 < 91%, n = 7) had a significantly larger decline in race pace VO2 in hypoxia (-9.2 + 2.1 ml/kg/min) and slowing of 3000m race time at altitude (+54.0 + 13.7 s) compared to athletes grouped with high SaO2 during race pace running in normoxia (SaO2 > 93%, n = 7, DVO2 = -3.5 + 2.0 ml/kg/min, D3000m race time = +38.9 + 9.7 s). SaO2 during normoxic race pace running was significantly correlated with both the decline in VO2 from normoxia to hypoxia during race pace running (r = -0.68), as well as the decline in 3000m race time at ALT (r = -0.38). CONCLUSION: These results indicate that the degree of arterial oxyhemoglobin desaturation during heavy exercise, already known to influence the decline in VO2max at altitude, also contributes to the magnitude of the decline in racing performance with acute altitude exposure. Supported by a grant from the US Olympic Committee and USA Track and Field

Hypoxic exercise training elicits the mobilization of hematopoietic progenitor cells and endothelial precursor cells into the peripheral blood compartment in healthy men

Bone marrow‐derived, circulating endothelial progenitor cells (EPC) is contributing to the maintenance of endothelial function and organ perfusion by mechanisms ranging from endothelial repair to postnatal angiogenesis and vasculogenesis. This study investigates how hypoxic exercise training influences the mobilization of EPC subsets into the peripheral blood compartment. Fifteen sedentary healthy men cycled on an ergometer at about 60% of maximal oxygen consumption under 15%O2 condition for 40 minutes per day, 5 days per week for 5 weeks. Our results indicated that acute 12%O2 exercise increased the mobilization of hematopoietic stem cells (CD34+/KDR+/CD117+), early EPC (CD34+/KDR+/CD133+), and endothelial precursor cells (CEP, CD34+/KDR+/CD133−) into the peripheral blood compartment at pre‐training stage. Moreover, both resting and 12%O2 exercise‐mobilized circulating HSC and CEP levels were significantly elevated following 5 weeks of 15%O2 exercise training. However, no significant changes in circulating (CD34+/KDR+/CD31+) and shedding endothelial cells (KDR+/CD31+/phosphotidylserine+) levels occurred following acute or chronic hypoxic exercise. Hence, we conclude that long‐term moderate‐intensity exercise at 15%O2 environment elicits the mobilization of hematopoietic progenitor cells, especially HSC and CEP, into the peripheral blood compartment, which may facilitate angiogenesis or vasculogenesis in exercising muscles.

Muscle Deoxygenation And Electromyographic Activity During Isolated Muscle Exercise In Hypoxia

It is well known that acute hypoxia significantly increased the rates of development of exercise-induced muscle fatigue. It is hypothesized that muscle deoxygenation is accelerated during exercise in hypoxia, and that this would be related to the rate of increase in electromyographic (EMG) activity as an index of motor unit recruitment. PURPOSE: The aim of the present study was to elucidate the changes in muscle deoxygenation and EMG activity during isolated muscle exercise in hypoxia and the relationship between the changes in deoxygenation and EMG activity. METHODS: Seven healthy male subjects performed intermittent, unilateral, isometric, submaximal quadriceps muscle contractions [60% maximal voluntary contraction (MVC), 5 sec of contraction/5 sec of rest] while breathing normoxic (FIO2=0.21) or hypoxia (FIO2=0.11-0.12) gas mixture. MVC was obtained before and at the end of each minute of submaximal exercise until exhaustion, defined as the inability to exert or maintain 60% of rested MVC. The change in muscle deoxygenation was measured by near-infrared spectroscopy. Surface EMG and muscle deoxygenation were simultaneously recorded from the vastus lateralis muscle. RESULTS: The deoxygenation index (deoxygenated Hb/Mb - oxygenated Hb/Mb) during exercise in hypoxia was larger (P<0.05) than that in normoxia. The rate of increase in iEMG during exercise in hypoxia was greater (P<0.05) than in normoxia. The rate of percent reduction of MVC in hypoxia was larger (P<0.05) than normoxia. To clarify the relationship between parameters during exercise in hypoxia and normoxia, the magnitude of the changes in deoxygenation index and iEMG at end of first three minutes during submaximal exercise were calculated individually as the difference between those obtained in hypoxia and normoxia (delta = hypoxia - normoxia). A significant positive correlation was observed between delta deoxygenation index and delta iEMG at the second (r=0.71, P<0.05) and third (r=0.75, P<0.05) minutes during exercise. CONCLUSIONS: These results suggest that the rates of rise of muscle activity and development of fatigue during submaximal isolated muscle exercise in acute hypoxia are linked to the magnitude of muscle deoxygenation.

Non-invasive evaluation of the capillary recruitment in the human muscle during exercise in hypoxia

This study proposes a non-invasive evaluation of capillary recruitment in human muscle from resting state to maximal exercise while under hypoxic conditions. Our work is based on the analysis of oxygen transport variables measured during incremental exercise in endurance-trained men (n=8) and in their sedentary counterparts (n=8). Maximal exercise tests were performed on a cycloergometer in normoxia and at three simulated normobaric levels of hypoxia (altitude equivalent to 1000, 2500 and 4500 m). We made the assumption that the relationship between the oxygen diffusion coefficient (Kt) and cardiac output (Qc) was: Kt=kQcNc where Nc is the capillary recruitment coefficient during exercise. Our results demonstrate that Nc increases with altitude and that the increase is greater in trained compared with untrained subjects at high altitude (4500 m). Moreover, the venous PO2 threshold beyond which capillary recruitment increases is lower in trained men. Despite their greater increase in capillary recruitment, trained men are not able to compensate for their drastic drop in arterial oxygen content during exercise in acute hypoxia, which results in a greater drop in maximal oxygen consumption than in sedentary men.