This study aimed to determine the cardiovascular responses during a prolonged exercise with voluntary hypoventilation (VH). 7 men performed 3 series of 5-min exercise at 65% of normoxic maximal O (2) uptake under 3 conditions: (1) normal breathing (NB) in normoxia (NB (0.21)), (2) VH in normoxia (VH (0.21)), (3) NB in hypoxia (NB (0.157), inspired oxygen fraction=0.157). In both VH (0.21) and NB (0.157), there was a similar drop in arterial oxygen saturation and arterial O (2) content (CaO (2)) which were lower than in NB (0.21). Heart rate (HR), stroke volume, and cardiac output (-) were higher in VH (0.21) than in NB (0.21) during most parts of exercise whereas there was no difference between NB (0.157) and VH (0.21) or NB (0.21). HR variability analysis suggested an increased sympathetic modulation in VH (0.21) only. O (2) transport and oxygen uptake were generally not different between interventions. Mixed venous O (2) content (C-O (2)) was lower in NB (0.157) than in both VH (0.21) and NB (0.21) and not different between the latter. CaO (2)-C-O (2) was not different between NB (0.157) and NB (0.21) but lower in VH (0.21). This study shows that a prolonged exercise with VH leads to a greater cardiac activity, independent from the hypoxic effect. The greater - in VH compared to normal breathing seems to be the main factor for compensating the drop of arterial oxygen content.

Eight men performed three series of 5-min exercise on a cycle ergometer at 65% of normoxic maximal O(2) consumption in four conditions: (1) voluntary hypoventilation (VH) in normoxia (VH(0.21)), (2) VH in hyperoxia (inducing hypercapnia) (inspired oxygen fraction [F(I)O(2)] = 0.29; VH(0.29)), (3) normal breathing (NB) in hypoxia (F(I)O(2) = 0.157; NB(0.157)), (4) NB in normoxia (NB(0.21)). Using near-infrared spectroscopy, changes in concentration of oxy-(Delta[O(2)Hb]) and deoxyhemoglobin (Delta[HHb]) were measured in the vastus lateralis muscle. Delta[O(2)Hb - HHb] and Delta[O(2)Hb + HHb] were calculated and used as oxygenation index and change in regional blood volume, respectively. Earlobe blood samples were taken throughout the exercise. Both VH(0.21) and NB(0.157) induced a severe and similar hypoxemia (arterial oxygen saturation [SaO(2)] < 88%) whereas SaO(2) remained above 94% and was not different between VH(0.29) and NB(0.21). Arterialized O(2) and CO(2) pressures as well as P50 were higher and pH lower in VH(0.21) than in NB(0.157), and in VH(0.29) than in NB(0.21). Delta[O(2)Hb] and Delta[O(2)Hb - HHb] were lower and Delta[HHb] higher at the end of each series in both VH(0.21) and NB(0.157) than in NB(0.21) and VH(0.29). There was no difference in Delta[O(2)Hb + HHb] between testing conditions. [La] in VH(0.21) was greater than both in NB(0.21) and VH(0.29) but not different from NB(0.157). This study demonstrated that exercise with VH induced a lower tissue oxygenation and a higher [La] than exercise with NB. This was caused by a severe arterial O(2) desaturation induced by both hypoxic and hypercapnic effects.

The purpose of this study was to compare arterial and arterialized blood gases during normoxic and hypoxic exercise. In the same conditions, earlobe pulse oximetry O(2) saturation (Sp(O2)) was compared to arterial oxygen saturation (Sa(O2)). Ten men performed incremental cycle ergometer tests, in normoxia and hypoxia (FI(O2) = 0.127). Blood samples were drawn simultaneously from the radial artery and pre-warmed earlobe capillary blood of subjects at rest, submaximal and near maximal exercise. R(2) between the two samples were 0.99 for P(O2) and S(O2), 0.86 for P(CO2) and 0.97 between Sp(O2) and Sa(O2). Earlobe P(O2) mean was 4.4+/-3.6 mmHg lower than Pa(O2) in normoxia but in hypoxia only 1.1+/-2.2 mmHg low. The mean difference were low in normoxia between Sa(O2) and Sp(O2) and increased in hypoxia, were acceptable for P(CO2), S(O2), pH in all conditions. In conclusion, except for P(O2) in normoxia, pre-warmed earlobe capillary blood is a good substitute to arterial blood to allow measurement of blood gas values in normoxia and hypoxia at rest and exercise.

Acute exposure to hypoxia provokes a decrease in peak oxygen consumption (V˙O2,peak). At and above 4000m, the decrease in V˙O2,peak is greater than expected from the decrease in arterial oxygen content (CaO2) suggesting the participation of other factors. We hypothesized that O2 transfer within the active muscle may play a role. Therefore we used Near Infra Red Spectroscopy (NIRS) to assess oxy (O2Hb) and deoxyhemoglobin (HHb) concentration in the vastus lateralis of trained athletes (TA) and untrained subjects (US) exercising at various inspired oxygen pressure (PIO2=149.4, 131.4, 107.3 and 87.0mmHg). A mathematical model has been developed to compute: (i) the pulmonary (Kp) and muscular (Ktm) O2 diffusion coefficients and (ii) the proportion of arteriolar:capillary:venous blood participating in the NIRS signal at every exercise intensity from rest to peak exercise in the normoxic and various hypoxic conditions. In TA, O2Hb decreased near maximal exercise at 2500 and 4000m, while in US, altitude had no effect. In normoxia O2Hb was higher in TA than in US, the difference disappearing in hypoxia. Ktm increased linearly with workload and altitude and was higher in TA than US while Kp plateaued near maximal exercise, which was consistent with athletes’ greater decrease in CaO2. The greater participation of arterial blood in the NIRS signal in TA at altitudes account for their higher O2Hb values as well as the greater decrease they underwent in hypoxia. At 4000m, athletes loose their advantages of adaptation to training due to a reduced arterial content, and both from NIRS variables and model output, characteristics of O2 transfer of TA converge toward those of US.

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.

Treatment with recombinant human erythropoietin (rhEpo) induces a rise in blood oxygen-carrying capacity (CaO(2)) that unequivocally enhances maximal oxygen uptake (VO(2)max) during exercise in normoxia, but not when exercise is carried out in severe acute hypoxia. This implies that there should be a threshold altitude at which VO(2)max is less dependent on CaO(2). To ascertain which are the mechanisms explaining the interactions between hypoxia, CaO(2) and VO(2)max we measured systemic and leg O(2) transport and utilization during incremental exercise to exhaustion in normoxia and with different degrees of acute hypoxia in eight rhEpo-treated subjects. Following prolonged rhEpo treatment, the gain in systemic VO(2)max observed in normoxia (6-7%) persisted during mild hypoxia (8% at inspired O(2) fraction (F(I)O(2)) of 0.173) and was even larger during moderate hypoxia (14-17% at F(I)O(2) = 0.153-0.134). When hypoxia was further augmented to F(I)O(2) = 0.115, there was no rhEpo-induced enhancement of systemic VO(2)max or peak leg VO(2). The mechanism highlighted by our data is that besides its strong influence on CaO(2), rhEpo was found to enhance leg VO(2)max in normoxia through a preferential redistribution of cardiac output toward the exercising legs, whereas this advantageous effect disappeared during severe hypoxia, leaving augmented CaO(2) alone insufficient for improving peak leg O(2) delivery and VO(2). Finally, that VO(2)max was largely dependent on CaO(2) during moderate hypoxia but became abruptly CaO(2)-independent by slightly increasing the severity of hypoxia could be an indirect evidence of the appearance of central fatigue.

We assessed the ability of the oxygen uptake efficiency slope, whether calculated on 100 and 80% of maximal exercise test duration (OUES100 and OUES80), to identify the change in cardiorespiratory capacities in response to hypoxia in subjects with a broad range of V˙O2peak. Four maximal exercise tests were performed in trained (T) and untrained subjects (UT) in normoxia and at 1000, 2500 and 4500 m. The mean reductions in maximal exercise capacities at 4500 m were the same in T subjects for V˙O2peak (−30%), OUES80 (−26%) and OUES100 (−26%) whereas in UT subjects only OUES100 (−14%), but not OUES80 (−20%), was lower compared with V˙O2peak (−21%, p < 0.05). OUES100 and OUES80 were correlated with V˙O2peak and the ventilatory anaerobic threshold in both groups. Multiple regression analyses showed that V˙O2peak, OUES100 and OUES80 were significantly linked to O2 arterial-venous difference. The OUES80 could be considered as an interesting sub-maximal index of cardiorespiratory fitness in normal or hypoxemic subjects unable to reach V˙O2peak.

This study investigated the effects of training with voluntary hypoventilation (VH) at low pulmonary volumes. Two groups of moderately trained runners, one using hypoventilation (HYPO, n=7) and one control group (CONT, n=8), were constituted. The training consisted in performing 12 sessions of 55 min within 4 weeks. In each session, HYPO ran 24 min at 70% of maximal O(2) consumption ( [V(02max)) with a breath holding at functional residual capacity whereas CONT breathed normally. A V(02max) and a time to exhaustion test (TE) were performed before (PRE) and after (POST) the training period. There was no change in V(O2max), lactate threshold or TE in both groups at POST vs. PRE. At maximal exercise, blood lactate concentration was lower in CONT after the training period and remained unchanged in HYPO. At 90% of maximal heart rate, in HYPO only, both pH (7.36+/-0.04 vs. 7.33+/-0.06; p<0.05) and bicarbonate concentration (20.4+/-2.9 mmolL(-1) vs. 19.4+/-3.5; p<0.05) were higher at POST vs. PRE. The results of this study demonstrate that VH training did not improve endurance performance but could modify the glycolytic metabolism. The reduced exercise-induced blood acidosis in HYPO could be due to an improvement in muscle buffer capacity. This phenomenon may have a significant positive impact on anaerobic performance.

We aimed to evaluate 1) the altitude where maximal heart rate (HR (max)) decreases significantly in both trained and untrained subjects in moderate acute hypoxia, and 2) if the HR (max) decrease could partly explain the drop of V.O (2max). Seventeen healthy males, nine trained endurance athletes (TS) and eight untrained individuals (US) were studied. Subjects performed incremental exercise tests at sea level and at 5 simulated altitudes (1000, 1500, 2500, 3500, 4500 meters). Power output (PO), heart rate (HR), arterial oxygen saturation (SaO (2)), oxygen uptake (V.O (2)), arterialized blood pH and lactate were measured. Both groups showed a progressive reduction in V.O (2max). The decrement in HR (max) (DeltaHR (max)) was significant from 1000 m for TS and 2500 m for US and more important in TS than US (at 1500 m and 3500 m). At maximal exercise, TS had a greater reduction in SaO (2) (DeltaSaO (2)) at each altitude. DeltaHR (max) observed in TS was correlated with DeltaSaO (2). When the two groups were pooled, simple regressions showed that DeltaV.O (2max) was correlated with both DeltaSaO (2) and DeltaHR (max). However, a multiple regression analysis demonstrated that DeltaSaO (2) alone may account for DeltaV.O (2max). Furthermore, in spite of a greater reduction in SaO (2) and HR (max) in TS, no difference was evidenced in relative DeltaV.O (2max) between groups. Thus, in moderate acute hypoxia, the reduction in SaO (2) is the primary factor to explain the drop of V.O (2max) in trained and untrained subjects.

The goal of this study was to assess the effects of a prolonged expiration (PE) carried out down to the residual volume (RV) during a submaximal exercise and consider whether it would be worth including this respiratory technique in a training programme to evaluate its effects on performance. Ten male triathletes performed a 5-min exercise at 70% of maximal oxygen consumption in normal breathing (NB(70)) and in PE (PE(70)) down to RV. Cardiorespiratory parameters were measured continuously and an arterialized blood sampling at the earlobe was performed in the last 15s of exercise. Oxygen consumption, cardiac frequency, end-tidal and arterial carbon dioxide pressure, alveolar-arterial difference for O(2) (PA(O2) - Pa(O2)) and P(50) were significantly higher, and arterial oxygen saturation (87.4+/-3.4% versus 95.0+/-0.9%, p<0.001), alveolar (PA(O2)) or arterial oxygen pressure, pH and ventilatory equivalent were significantly lower in PE(70) than NB(70). There was no difference in blood lactate between exercise modalities. These results demonstrate that during submaximal exercise, a prolonged expiration down to RV can lead to a severe hypoxemia caused by a PA(O2) decrement (r=0.56; p<0.05), a widened PA(O2) - Pa(O2) (r=-0.85; p<0.001) and a right shift of the oxygen dissociation curve (r=-0.73; p<0.001).

The factors determining maximal oxygen consumption were explored in eight endurance trained subjects (TS) and eight untrained subjects (US) exposed to moderate acute normobaric hypoxia. Subjects performed maximal incremental tests at sea level and simulated altitudes (1,000, 2,500, 4,500 m). Heart rate (HR), stroke volume (SV), cardiac output \({(\dot{{Q}})},\) arterialized oxygen saturation \({(\hbox{Sa}^{\prime}\hbox{O}_2)},\) oxygen uptake \({(\dot{{V}}\hbox{O}_{\rm 2max})},\) ventilation (\({\dot{{V}}{E}},\) expressed in normobaric conditions) were measured. At maximal exercise, ventilatory equivalent \({(\dot{{V}}{E}/\dot{{V}}\hbox{O}_{\rm 2max}),\, \hbox{O}_2}\) transport \({(\dot{{Q}}\hbox{aO}_{\rm 2max})}\) and O2 extraction (O2ERmax) were calculated. In TS, \({\dot{{Q}}_{\rm max}}\) remained unchanged despite a significant reduction in \({\hbox{HR}_{\rm max}}\) at 4,500 m. SVmax remained unchanged. \({\dot{{V}}{E}_{\rm max}}\) decreased in TS at 4,500 m, \({\dot{{V}}{E}/\dot{{V}}\hbox{O}_{\rm 2max}}\) was lower in TS and greater at 4,500 m vs. sea level in both groups. Sa′O2max decreased at and above 1,000 m in TS and 2,500 m in US, O2ERmax increased at 4,500 m in both groups. \({\dot{{Q}}\hbox{aO}_{\rm 2max}}\) decreased with altitude and was greater in TS than US up to 2,500 m but not at 4,500 m. \({\dot{{V}}\hbox{O}_{\rm 2max}}\) decreased with altitude but the decrement \({(\Delta \dot{{V}}\hbox{O}_{\rm 2max})}\) was larger in TS at 4,500 m. In both groups \({\Delta \dot{{V}}\hbox{O}_{\rm 2max}}\) in moderate hypoxia was correlated with \({\Delta \dot{{Q}}\hbox{aO}_{\rm 2max}}.\) Several differences between the two groups are probably responsible for the greater \({\Delta \dot{{V}}\hbox{O}_{\rm 2max}}\) in TS at 4,500 m : (1) the relative hypoventilation in TS as shown by the decrement in \({\dot{{V}}{E}_{\rm max}}\) at 4,500 m (2) the greater \({\dot{{Q}}\hbox{aO}_{\rm 2max}}\) decrement in TS due to a lower Sa′O2max and unchanged \({\dot{{Q}}_{\rm max}}\) 3) the smaller increase in O2ERmax in TS, insufficient to compensate the decrease in \({\dot{{Q}}a\hbox{O}_{\rm 2max}}.\)

The purpose of this study was to evaluate the limiting factors of maximal aerobic performance in endurance trained (TW) and sedentary (UW) women. Subjects performed four incremental tests on a cycle ergometer at sea level and in normobaric hypoxia corresponding to 1000, 2500 and 4500 m. Maximal oxygen uptake decrement (Delta VO2 max) was larger in TW at each altitude. Maximal heart rate and ventilation decreased at 4500 m in TW. Maximal cardiac output remained unchanged. In both groups, arterialized oxygen saturation (Sa'O2 max) decreased at and above 2500 m and maximal O2 transport (QaO2 max) decreased from 1000 m. At 4500 m, there was no more difference in QaO2 max between TW and UW. Mixed venous O2 pressure (PvO2 max) was lower and O2 extraction (O2ERmax) greater in TW at each altitude. The primary determinant factor of VO2 max decrement in moderate acute hypoxia in trained and untrained women is a reduced maximal O2 transport that cannot be compensate by tissue O2 extraction.

During moderate exercise breathing a low inspired O2 fraction (FIO2), arterial O2 desaturation may depend on the fitness level. Seven trained (TM) and seven untrained men (UTM) cycled in normoxia and in hypoxia (FIO2=0.187, 0.173, 0.154, 0.13 and 0.117). We compared TM and UTM at submaximal intensities below the ventilatory threshold. Ventilatory variables were monitored and arterial oxygen saturation was measured by pulse oximetry. O2 saturation was not different between groups at sea level. In hypoxia, O2 saturation was lower in TM than in UTM at FIO2=0.154 (87.3 ± 2.9% vs 90.4 ± 1.5% at 90 W) and below. Both the ventilatory‐equivalent and the end‐tidal O2 pressure were lower in TM at sea level and at every FIO2, with the differences between TM and UTM becoming apparent at lower exercise intensity and increasing in magnitude as the severity of hypoxia increased. O2 saturation was correlated with the ventilatory parameters at every FIO2 and the correlations were stronger in severe hypoxia. These results demonstrate that a moderate exercise carried out in hypoxia, contrary to normoxic conditions, can lead to a greater arterial desaturation in TM compared with UTM. This phenomenon could be partly attributed to a relative hypoventilation in trained subjects.

PURPOSE:The purpose of this study was to determine the physiological responses of sedentary and endurance-trained female subjects during maximal exercise at different levels of acute hypoxia. METHODS:Fourteen women who were sea level residents were divided into two groups according to their level of fitness: 1) endurance-trained women (TW) (N = 7), VO(2max) = 56.3 +/- 4.7 mL.kg(-1).min(-1); and 2) sedentary women (SW) (N = 7), VO(2max) = 34.8 +/- 5.6 mL.kg(-1).min(-1). Subjects performed four maximal cycle ergometer tests in normoxia and under hypoxic conditions (F(I)O(2) = 0.187, 0.154, and 0.117, corresponding to altitudes of 1000, 2500, and 4500 m, respectively). RESULTS:VO(2max) decreased significantly by 3.6 +/- 2.1, 14 +/- 2.5, and 27.4 +/- 3.6% in TW, and by 5 +/- 4, 9.4 +/- 6.4, and 18.7 +/- 7% in SW at 1000, 2500, and 4500 m, respectively. The drop of VO(2max) (DeltaVO(2max)) was greater in TW at and above 2500 m. Arterial O2 saturation (SpO(2)) at maximal exercise was lower in TW at every altitude (1000 m: 90.9 +/- 1.9 vs 94.6 +/- 1.4%; 2500 m: 82.8 +/- 2.8 vs 90.0 +/- 2.1%; 4500 m: 65.0 +/- 4.7 vs 73.6 +/- 4.5%). Maximal heart rate decreased significantly from 1000 m in the two groups. SpO(2) was correlated to DeltaVO(2max) at 4500 m (r = -0.81, P < 0.01) and 2500 m (r = -0.81, P < 0.01), but not below. Furthermore, we noted a relationship between SpO(2) and O2 pulse (VO(2)/HR) at every F(I)O(2). CONCLUSION:These results demonstrate that endurance-trained women show a greater decrement in VO(2max) at high altitudes. This could be explained mainly by a higher arterial desaturation, which is largely caused, according to our results, by diffusion limitation.

Exposure to high altitude induces pulmonary hypertension that may lead to life-threatening conditions. In a randomized, double-blind, placebo-controlled study, the effects of oral sildenafil on altitude-induced pulmonary hypertension and gas exchange in normal subjects were examined. Twelve subjects (sildenafil [SIL] n = 6; placebo [PLA] n = 6) were exposed for 6 days at 4,350 m. Treatment (3 x 40 mg/day) was started 6 to 8 hours after arrival from sea level to high altitude and maintained for 6 days. Systolic pulmonary artery pressure (echocardiography) increased at high altitude before treatment (+29% versus sea level, p < 0.01), then normalized in SIL (-6% versus sea level, NS) and remained elevated in PLA (+21% versus sea level, p < 0.05). Pulmonary acceleration time decreased by 27% in PLA versus 6% in SIL (p < 0.01). Cardiac output and systemic blood pressures increased at high altitude then decreased similarly in both groups. Pa(O(2)) was higher and alveolar-arterial difference in O(2) lower in SIL than in PLA at rest and exercise (p < 0.05). The altitude-induced decrease in maximal O(2) consumption was smaller in SIL than in PLA (p < 0.05). Sildenafil protects against the development of altitude-induced pulmonary hypertension and improves gas exchange, limiting the altitude-induced hypoxemia and decrease in exercise performance.

Abstract Both acute hypoxia and sildenafil may influence autonomic control through transient cardiovascular effects. In a double-blind study, we investigated whether sildenalfil could interfere with cardiovascular effects of hypoxia. Twelve healthy men (placebo, PLA n = 6; sildenalfil, SIL n = 6) were exposed to 4,350m during six days. Treatment was continuously administered from 6-8 hours after arrival at altitude (3x40mg/day). The autonomic control on the heart was assessed by heart rate variability (HRV) during sleep at sea level (SL), between days 1-2 (D1-2) and days 5-6 (D5-6) in hypoxia. Arterial pressure (AP) and total peripheral resistances (TPR) were obtained during daytime. There were no statistical difference between groups in HRV, AP, and TPR throughout the study. Hypoxia induced a decrease in R-R interval and an increase in AP in both groups. Low frequency/high frequency ratio increased at D1-2 (PLA, P = 0.04; SIL, P = 0.02) and D5-6 (PLA and SIL, P = 0.04) versus SL, while normalized high frequency power decreased only in PLA (

Both acute hypoxia and sildenafil may influence autonomic control through transient cardiovascular effects. In a double-blind study, we investigated whether sildenalfil (Sil) could interfere with cardiovascular effects of hypoxia. Twelve healthy men [placebo (Pla) n = 6; Sil, n = 6] were exposed to an altitude of 4,350 m during 6 days. Treatment was continuously administered from 6 to 8 h after arrival at altitude (3 x 40 mg/day). The autonomic control on the heart was assessed by heart rate variability (HRV) during sleep at sea level (SL) and between day 1-2 and day 5-6 in hypoxia. Arterial pressure (AP) and total peripheral resistances (TPR) were obtained during daytime. There was no statistical difference between groups in HRV, AP, and TPR throughout the study. Hypoxia induced a decrease in R-R interval and an increase in AP in both groups. Low frequency-to-high frequency ratio increased at day 1-2 (Pla, P = 0.04; Sil, P = 0.02) and day 5-6 (Pla and Sil, P = 0.04) vs. SL, whereas normalized high-frequency power decreased only in Pla (P = 0.04, day 1-2 vs. SL). Normalized low-frequency power increased at high altitude (Pla and Sil, P = 0.04, day 5-6 vs. SL). TPR decreased at day 2 in Pla (P = 0.02) and tended to normalize at day 6 (P = 0.07, day 6 vs. day 2). Acute hypoxia induced a decrease in parasympathetic and increase in sympathetic tone, which tended to be reversed with acclimatization. Sil had no deleterious effects on the cardiovascular response to high-altitude exposure and its control by the autonomic nervous system.