[Adaption to chronic hypoxaemia by populations living at high altitude]. / Adaptation à l'hypoxie chronique des populations de haute altitude.

Permanent life at high altitude induces important physiological stresses linked to the exposure to chronic hypoxia. Various strategies have been adopted by diverse populations living in the Andes, Tibet or East Africa. The main mechanism is an increase in red blood cell production, more marked in Andeans than in Tibetans or Ethiopians. Other changes are observed in the cardiovascular or respiratory systems, as well as in the utero-placental circulation. Sometimes, a de-adaptation process to hypoxia develops, when erythrocytosis becomes excessive and leads to haematological, vascular and cerebral complications (Monge's disease or chronic mountain sickness). Pulmonary hypertension may also appear. Therapeutic options are available but not sufficiently used. Genetic studies have recently been undertaken to try to better understand the evolution of the human genome in populations living in various high altitude regions of the world, as well as the genetic risk factors for chronic diseases. A new model has appeared, intermittent chronic hypoxia, due to the development of economic activities (mainly mining) in desert regions of the Altiplano.

Cardiovascular responses during hypoventilation at exercise.

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.

Endothelin receptors blockade blunts hypoxia-induced increase in PAP in humans.

BACKGROUND: Activation of the endothelin-1 (ET-1) pathway may be involved in hypoxia-induced pulmonary vasoconstriction, increase in pulmonary pressure and high altitude pulmonary oedema. Thus, we investigated the effect of the ETA/ETB receptor antagonist, bosentan, on pulmonary artery systolic pressure (PASP) in healthy subjects (n = 10). DESIGN: We used a double-blind, placebo-controlled, randomized, cross-over design to study the effects of a single oral dose of bosentan (250 mg) on PASP after 90-min-exposure to normobaric hypoxia (FiO(2) = 0.12). We measured PASP and cardiac output by echocardiography, systolic arterial blood pressure, arterial O(2) saturation (SaO(2)), and blood gases at rest and during a sub-maximal exercise. RESULTS: PASP in normoxia at rest was 23.5 +/- 2.7 and during exercise 39.8 +/- 11.6 mmHg (P < 0.0001). During the placebo period, hypoxia induced a significant decrease in SaO(2), PaO(2) and PCO(2) and increase in pH. PASP at rest increased significantly: 32.1 +/- 3.5 mmHg (P < 0.001 vs. normoxia). Bosentan significantly blunted the hypoxia-induced increase in PASP: bosentan: 27.0 +/- 3.3 mmHg, P = 0.002 vs. placebo at rest, but not during exercise: bosentan 39.8 +/- 11.6 vs. placebo 43.0 +/- 8.5 mmHg, ns. Bosentan had no effect on the hypoxia-induced changes in blood gases, or on cardiac output and systolic arterial blood pressure, which were not modified by hypoxia. CONCLUSION: A single oral dose of bosentan blunted an acute hypoxia-induced increase in PASP in healthy subjects, without altering cardiac output or systemic blood pressure.

[Lung function prediction equations in Tunisian children: taking into consideration pubertal stage]. / Equations prédictives des variables ventilatoires chez les enfants sains tunisiens : prise en considération du stade pubertaire.

OBJECTIVE: The purpose of this study was to set lung function prediction equations in Tunisian children with standing height and pubertal stage as the independent variables. METHODS: Spirometric values were measured with a Minato portable Spirometer in 684 asymptomatic Tunisian children (351 boys and 333 girls), 8 to 16 years of age. The specific parameters of pulmonary function that were measured included Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 second (FEV(1)), Peak Expiratory Flow (PEF), Maximal Expiratory Flow at 50% of the vital capacity (MEF(50)), and Maximum Mild Expiratory Flow between 25 and 75% (MMEF(25-75)). The pubertal status was assessed for males and females according to the Tanner method. RESULTS: A large variation was observed in the distribution of children's age and height by pubertal stages in both sexes. Multiple regression equations for FVC, FEV(1), MEF(50), MEF(25-75), and PEF for both sexes are presented with standing height and pubertal stage as the independent variables. CONCLUSION: The establishment of validated reference values relevant to the ethnic group of the local population should significantly improve medical surveillance of respiratory diseases in Tunisian children.

Blunting effect of hypoxia on the proliferation and differentiation of human primary and rat L6 myoblasts is not counteracted by Epo.

OBJECTIVES: The aim of this study was to evaluate whether hypoxia and/or erythropoietin would be able to modulate proliferation/differentiation processes of rat and human myoblasts. MATERIALS AND METHODS: Rat L6 and primary human myoblasts were grown in 21% or 1% O(2) in the presence or absence of recombinant human erythropoietin (RhEpo). Presence of erythropoietin receptors (EpoR) was assayed using RT-PCR and Western blotting techniques. Cell proliferation was evaluated by determining the doubling time and kinetics of cultures by counting cells. Cell differentiation was analysed by determining myogenic fusion index using antibodies against the myosin heavy chain. Expression of myogenin and myosin heavy chain (MHC) proteins were evaluated using the Western blotting technique. RESULTS: After 96 h culture in growth medium for 2.5 and 9 h, doubling time of L6 and human primary myoblasts respectively, had increased in 1% O(2) conditions (P < 0.01). Kinetics of culture showed alteration in proliferation at 72 h in L6 myoblast cultures and at 4 days in human primary myoblasts. The myogenic fusion index had reduced by 30% in L6 myoblasts and by 20% in human myoblasts (P < 0.01). Expression of myogenin and MHC had reduced by around 50%. Despite presence of EpoR mRNA and protein, RhEpo did not counteract the effects of hypoxia either in L6 cells or in human myoblasts. CONCLUSIONS: The data show that exposure to hypoxic conditions (1% O(2)) of rat and human myoblasts altered their proliferation and differentiation processes. They also show that Epo is not an efficient growth factor to counteract this deleterious effect.

Combining hypoxic methods for peak performance.

New methods and devices for pursuing performance enhancement through altitude training were developed in Scandinavia and the USA in the early 1990s. At present, several forms of hypoxic training and/or altitude exposure exist: traditional 'live high-train high' (LHTH), contemporary 'live high-train low' (LHTL), intermittent hypoxic exposure during rest (IHE) and intermittent hypoxic exposure during continuous session (IHT). Although substantial differences exist between these methods of hypoxic training and/or exposure, all have the same goal: to induce an improvement in athletic performance at sea level. They are also used for preparation for competition at altitude and/or for the acclimatization of mountaineers. The underlying mechanisms behind the effects of hypoxic training are widely debated. Although the popular view is that altitude training may lead to an increase in haematological capacity, this may not be the main, or the only, factor involved in the improvement of performance. Other central (such as ventilatory, haemodynamic or neural adaptation) or peripheral (such as muscle buffering capacity or economy) factors play an important role. LHTL was shown to be an efficient method. The optimal altitude for living high has been defined as being 2200-2500 m to provide an optimal erythropoietic effect and up to 3100 m for non-haematological parameters. The optimal duration at altitude appears to be 4 weeks for inducing accelerated erythropoiesis whereas <3 weeks (i.e. 18 days) are long enough for beneficial changes in economy, muscle buffering capacity, the hypoxic ventilatory response or Na(+)/K(+)-ATPase activity. One critical point is the daily dose of altitude. A natural altitude of 2500 m for 20-22 h/day (in fact, travelling down to the valley only for training) appears sufficient to increase erythropoiesis and improve sea-level performance. 'Longer is better' as regards haematological changes since additional benefits have been shown as hypoxic exposure increases beyond 16 h/day. The minimum daily dose for stimulating erythropoiesis seems to be 12 h/day. For non-haematological changes, the implementation of a much shorter duration of exposure seems possible. Athletes could take advantage of IHT, which seems more beneficial than IHE in performance enhancement. The intensity of hypoxic exercise might play a role on adaptations at the molecular level in skeletal muscle tissue. There is clear evidence that intense exercise at high altitude stimulates to a greater extent muscle adaptations for both aerobic and anaerobic exercises and limits the decrease in power. So although IHT induces no increase in VO(2max) due to the low 'altitude dose', improvement in athletic performance is likely to happen with high-intensity exercise (i.e. above the ventilatory threshold) due to an increase in mitochondrial efficiency and pH/lactate regulation. We propose a new combination of hypoxic method (which we suggest naming Living High-Training Low and High, interspersed; LHTLHi) combining LHTL (five nights at 3000 m and two nights at sea level) with training at sea level except for a few (2.3 per week) IHT sessions of supra-threshold training. This review also provides a rationale on how to combine the different hypoxic methods and suggests advances in both their implementation and their periodization during the yearly training programme of athletes competing in endurance, glycolytic or intermittent sports.

Polar Activity Watch 200: a new device to accurately assess energy expenditure.

OBJECTIVES: Energy expenditure (EE) based on movement detection is calculated by a new device, the Activity Watch 200 (AW200). The aim of this study was to validate EE measured by this device against indirect calorimetry (IC) and to assess the reproducibility of AW200 measurements. DESIGN: EE was assessed during a 9.7 km hike. 10 men and 10 women in the age range 35-45 years, and 5 men and 6 women in the age range 50-55 years were tested. One in five participants of each age- and sex-matched group was equipped with a portable metabograph (Oxycon Mobil) for IC measurements. Data were collected every 30 min during the hike, and IC was extrapolated for the remaining four other participants of the group. RESULTS: During the total hike, there was a high correlation between EE obtained from the AW200 and the IC calculation (r = 0.987, p<0.001). Identical values of EE were calculated by both methods during the first 90 min of the hike. However, EE calculated by the AW200 at 120 min and at the end of the hike was lower (p<0.05). Bland-Altman analysis showed limits of agreements between 105 and 279 kJ after 30 and 120 min, respectively. EE measured by the AW200 was well correlated with IC measurements, and limits of agreement between devices were below 10% of the measured values for hike durations longer than 60 min. CONCLUSION: The AW200 appears to be a very useful and accurate device for measuring EE during exercise in recreational hikers and provides a useful tool for keeping track of personal EE.

Interchangeability between heart rate and photoplethysmography variabilities during sympathetic stimulations.

Photoplethysmography variability (PPGV) is currently considered to be a good surrogate to heart rate variability (HRV) measurements using the time between two pulse waves instead of RR intervals. Nevertheless, the interchangeability between HRV and PPGV has never been evaluated in situations with severe alterations in the autonomic nervous system (ANS). We aimed to identify the conditions for a correct utilization of PPGV in evaluating the consequences of sympathetic stimulations. Nine subjects performed three tests: active orthostatic test, slow walk and moderate and exhaustive cycling exercises in the supine position. Pulse waves at the fingertip and RR intervals were recorded at the same time. We used correlations and the Bland and Altman method to compare and evaluate interchangeability between several HRV indices. Bland and Altman analysis highlighted small discrepancies between PPGV and HRV for all HRV indices in the supine position and for LF(ms)(2), HF(ms)(2), LF(peak) and RMSSD in the upright position. During the slow walk, it was impossible to detect properly PPG peaks. We observed large differences between the two methods during the cycling exercise. In conclusion, PPGV can be used instead of HRV without reserve in the supine position but only for some HRV indices in the upright position and not during slow walk and cycling exercise.

[Determining factors of pulmonary function in healthy Tunisian children]. / Déterminants de la fonction pulmonaire chez l'enfant sain en Tunisie.

Introduction Pulmonary function parameters are known to vary with age, sex, height and ethnic extraction. No normal values have been reported for pulmonary function in Tunisian children. Moreover, little attention has been paid to the factors affecting the development of lung function in Tunisian healthy children. State of art Birth weight and height, physical activity level, anthropometric, socioeconomic and environmental factors could influence the development of lung function in healthy children. Perspectives The studies conducted by our group have allowed us 1) to set reference values for spirometry in healthy Tunisian children; 2) to indicate that, in Tunisian adolescents, the use of only one morphological parameter such as height, is not sufficient, but the pubertal status could be taken into account to standardize the lung function and 3) to show the main predictive factors for pulmonary development to be the anthropometric factors such as height, weight, maximal inspiratory and expiratory thoracic perimeter, sex and age, and the environmental conditions (type of heating) in our population of healthy Tunisian children. Conclusion These findings should improve medical surveillance of respiratory diseases, stipulation of preventive and therapeutic measures in Tunisian children.

Effects of acute hypoxic exposure on prooxidant/antioxidant balance in elite endurance athletes.

We investigated whether acute hypoxic exposures could modify the pro-oxidant/antioxidant balance in elite endurance athletes, known to have efficient antioxidant status. Forty-one elite athletes were subjected to two hypoxic tests: one at an altitude of 4 800 m during 10-min of mild exercise (4 800 m test) and the second at rest for 3 h at an altitude of 3 000 m (3 000 m test). Plasma levels of advanced oxidation protein products (AOPP), malondialdehydes (MDA), ferric reducing antioxidant power (FRAP) and lipid-soluble antioxidants were measured before and immediately after the 4 800 m test and at the end of the 3 000 m test. The 4 800 m and the 3 000 m tests induced a significant increase in the level of MDA and AOPP (+7.1% and +71.7% for 4 800 m test and +8.6% and +40.9% for 3 000 m test). The changes in plasma MDA and arterial oxygen saturations were significantly correlated (r=0.35) during the 3 000 m test. FRAP values (-13%) and alpha-tocopherol (-21%) were decreased following the 3 000 m test. However, following the 4 800 m test, only alpha-tocopherol was decreased (-16%). These results provide evidence that the highly-trained athletes do not have the antioxidant buffering capacity to counterbalance free radical over-production generated by acute hypoxic exposure, with or without mild exercise.

Effects of the 'live high-train low' method on prooxidant/antioxidant balance on elite athletes.

BACKGROUND/OBJECTIVES: We previously demonstrated that acute exposure to hypoxia (3 h at 3000 m) increased oxidative stress markers. Thus, by using the 'living high-training low' (LHTL) method, we further hypothesized that intermittent hypoxia associated with endurance training alters the prooxidant/antioxidant balance. SUBJECTS/METHODS: Twelve elite athletes from the Athletic French Federation were subjected to 18-day endurance training. They were divided into two groups: one group (control group) trained at 1200 m and lived in hypoxia (2500-3000 m simulated altitude) and the second group trained and lived at 1200 m. The subjects performed an acute hypoxic test (10 min at 4800 m) before and immediately after the training. Plasma levels of advanced oxidation protein products (AOPP), malondialdehydes (MDA), ferric-reducing antioxidant power (FRAP), lipid-soluble antioxidants normalized for triacylglycerols, and cholesterol and retinol were measured before and after the 4800 m tests. RESULTS: After the training, MDA and AOPP concentrations were decreased in response to the 4800 m test only for the control group. Eighteen days of LHTL induced a significant decrease of all antioxidant markers (FRAP, P=0.01; alpha-tocopherol, P=0.04; beta-carotene, P=0.01 and lycopene, P=0.02) for the runners. This imbalance between antioxidant and prooxidant might result from insufficient intakes in vitamins A and E. CONCLUSIONS: The LHTL model characterized by the association of aerobic exercises and intermittent resting hypoxia exposures decreased the antioxidant status whereas the normoxic endurance training induced preconditioning mechanisms in response to the 4800 m test.

Live and/or sleep high:train low, using normobaric hypoxia.

The increase in oxygen transport elicited by several weeks of exposure to moderate to high altitude is used to increase physical performance when returning to sea level. However, many studies have shown that aerobic performance may not increase at sea level after a training block at high altitude. Subsequently, the concept of living high and training low was introduced in the early 1990s and was further modified to include simulated altitude using hypobaric or normobaric hypoxia. Review is given of the main studies that have used this procedure. Hematological changes are limited to insignificant or moderate increase in red cell mass, depending on the "dose" of hypoxia. Maximal aerobic performance is increased when the exposure to hypoxia is at least over 18 days. Submaximal performance and running economy have been found increased in several, but not all, studies. The tolerance (fatigue, sleep, immunological status, cardiac function) is good when the altitude or simulated altitude is not higher than 3000 m. Virtually no data are available about the effect of this procedure upon anaerobic performance. The wide spread of these techniques deserves further investigations.

Factors affecting the development of lung function in Tunisian children.

We undertook to evaluate the impacts of morphology at birth, physical activity, anthropometric, socioeconomic and environmental factors on lung function in healthy Tunisian children. Pulmonary function parameters were measured with a Minato portable spirometer in a randomized population of 756 healthy children (388 males and 368 females) aged between 6 and 16. The morphology at birth, the gestational age, the physical activity, the socioeconomic status, the type of habitation, and the environmental factors were all assessed by a standard questionnaire. Using univariate analysis, we found that: (1) morphometric parameters (height, weight, maximal inspiratory, and expiratory perimeter), as well as sex were highly associated with pulmonary function parameters; (2) Height at birth showed strong significant relations with FVC, FEV(1), and FEV(1)/FVC; (3) lung function parameters were influenced by physical training of our children, socioeconomic status, indoor pollution, and passive smoking; and (4) we did not observe any association between the gestational age and the weight at their birth and lung function parameters. Using a general linear model analysis, morphometric parameters, age, sex, type of heating, and maximal inspiratory and expiratory perimeters had significant relation with respiratory parameters. In our population of healthy Tunisian children, the main predictive factors of the pulmonary development were the morphological factors such as height, weight, maximal inspiratory, and expiratory thoracic perimeter, sex and age, and the environmental conditions such as type of heating but not morphology at birth, physical activity, or socioeconomic status.

Altitude, heart rate variability and aerobic capacities.

We analyzed the relationship between aerobic capacities and changes in heart rate variability (HRV) in Nordic-skiers during living high-training low (Hi-Lo). Eleven skiers trained for 18 days at 1200 m, sleeping at 1200 m (LL, n = 5) or in hypoxic rooms (HL, n = 6, 3 x 6 days at altitudes of 2500 - 3000 - 3500 m, 11 h . day (-1)). Measurements were performed before, during and two weeks after Hi-Lo. VO(2max), peak power output were not improved in HL nor in LL, whereas VO(2) and power at the respiratory compensation point (VO(2RCP) and PRCP) increased by 7.5 % and 5.0 % only in HL. Significant changes in HRV occurred only in LL, in the standing position, including a 30 % (p < 0.05) increase in resting heart rate (HR), a 50 % (p < 0.05) decrease in total spectral power (TP) and a 77 % (p < 0.05) decrease in high frequency activity (HF). When all the subjects were pooled, the changes in HRV in the supine position were correlated to the changes in aerobic capacities, i.e., HF, LF and TP were correlated to VO(2RCP) and HR, HF and TP were correlated to PRCP. This study confirms the relationship between HRV and changes in aerobic capacity, therefore highlighting the potential value of HRV for monitoring altitude training adaptations.

Brain stem NO modulates ventilatory acclimatization to hypoxia in mice.

The objective of our study was to assess the role of neuronal nitric oxide synthase (nNOS) in the ventilatory acclimatization to hypoxia. We measured the ventilation in acclimatized Bl6/CBA mice breathing 21% and 8% oxygen, used a nNOS inhibitor, and assessed the expression of N-methyl-d-aspartate (NMDA) glutamate receptor and nNOS (mRNA and protein). Two groups of Bl6/CBA mice (n = 60) were exposed during 2 wk either to hypoxia [barometric pressure (PB) = 420 mmHg] or normoxia (PB = 760 mmHg). At the end of exposure the medulla was removed to measure the concentration of nitric oxide (NO) metabolites, the expression of NMDA-NR1 receptor, and nNOS by real-time RT-PCR and Western blot. We also measured the ventilatory response [fraction of inspired O(2) (Fi(O(2))) = 0.21 and 0.08] before and after S-methyl-l-thiocitrulline treatment (SMTC, nNOS inhibitor, 10 mg/kg ip). Chronic hypoxia caused an increase in ventilation that was reduced after SMTC treatment mainly through a decrease in tidal volume (Vt) in normoxia and in acute hypoxia. However, the difference observed in the magnitude of acute hypoxic ventilatory response [minute ventilation (Ve) 8% - Ve 21%] in acclimatized mice was not different. Acclimatization to hypoxia induced a rise in NMDA receptor as well as in nNOS and NO production. In conclusion, our study provides evidence that activation of nNOS is involved in the ventilatory acclimatization to hypoxia in mice but not in the hypoxic ventilatory response (HVR) while the increased expression of NMDA receptor expression in the medulla of chronically hypoxic mice plays a role in acute HVR. These results are therefore consistent with central nervous system plasticity, partially involved in ventilatory acclimatization to hypoxia through nNOS.

Spirometric values in Tunisian children: relationship with pubertal status.

BACKGROUND: Little is known about the effect of pubertal stages on lung function parameters in Tunisian children. AIM: The purpose of this study is to determine the relationship between lung function and pubertal stage in Tunisian children using anthropometric parameters. SUBJECTS AND METHODS: Pulmonary function parameters were measured with a Minato portable spirometer in 684 healthy Tunisian children (351 males and 333 females) aged between 8 and 16. The pubertal status was assessed for males and females according to the Tanner Method. RESULTS: A large variation was observed in the distribution of children's age and height by pubertal stages in both sexes. Height increased with age and pubertal stage in both males and females. The results also showed a significant increase in parameters of lung function (FVC, FEV(1), PEF, MEF(50) and MMEF(25-75)) with pubertal stage in Tunisian children. The analysis of covariance adjusting for anthropometric parameters showed that pubertal status had a significant independent effect on some pulmonary function parameters in both sexes. CONCLUSION: The results indicated that the parameters of pulmonary function for healthy Tunisian school children increased with age, height and pubertal stage. The present study has indicated that the use of only one morphological parameter such as height is not sufficient, but the pubertal status could be taken into account to standardize the lung function.

Role of maximal heart rate and arterial O2 saturation on the decrement of VO2max in moderate acute hypoxia in trained and untrained men.

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.

Moderate exercise in hypoxia induces a greater arterial desaturation in trained than untrained men.

During moderate exercise breathing a low inspired O(2) fraction (F(I)O(2)), arterial O(2) desaturation may depend on the fitness level. Seven trained (TM) and seven untrained men (UTM) cycled in normoxia and in hypoxia (F(I)O(2)=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. O(2) saturation was not different between groups at sea level. In hypoxia, O(2) saturation was lower in TM than in UTM at F(I)O(2)=0.154 (87.3 +/- 2.9% vs 90.4 +/- 1.5% at 90 W) and below. Both the ventilatory-equivalent and the end-tidal O(2) pressure were lower in TM at sea level and at every F(I)O(2), with the differences between TM and UTM becoming apparent at lower exercise intensity and increasing in magnitude as the severity of hypoxia increased. O(2) saturation was correlated with the ventilatory parameters at every F(I)O(2) 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.

Effects of exercise and training in hypoxia on antioxidant/pro-oxidant balance.

OBJECTIVE: The aim was to investigate the effects of acute exercise under hypoxic condition and the repetition of such exercise in a 'living low-training high' training on the antioxidant/prooxidant balance. DESIGN: Randomized, repeated measures design. SETTING: Faculté de Médecine, Clermont-Ferrand, France. SUBJECTS: Fourteen runners were randomly divided into two groups. A 6-week endurance training protocol integrated two running sessions per week at the second ventilatory threshold into the usual training. INTERVENTION: A 6-week endurance training protocol integrated two running sessions per week at the second ventilatory threshold into the usual training. The first hypoxic group (HG, n=8) carried out these sessions under hypoxia (3000 m simulated altitude) and the second normoxic group (NG, n=6) in normoxia. In control period, the runners were submitted to two incremental cycling tests performed in normoxia and under hypoxia (simulated altitude of 3000 m). Plasma levels of advanced oxidation protein products (AOPP), malondialdehydes (MDA) and lipid oxidizability, ferric-reducing antioxidant power (FRAP), lipid-soluble antioxidants (alpha-tocopherol and beta-carotene) normalized for triacyglycerols and cholesterol were measured before and after the two incremental tests and at rest before and after training. RESULTS: No significant changes of MDA and AOPP level were observed after normoxic exercise, whereas hypoxic exercise induced a 56% rise of MDA and a 44% rise of AOPP. Plasma level of MDA and arterial oxygen hemoglobin desaturations after the acute both exercises were highly correlated (r=0.73). alpha-Tocopherol normalized for cholesterol and triacyglycerols increased only after hypoxic exercise (10-12%, P<0.01). After training, FRAP resting values (-21%, P<0.05) and alpha-tocopherol/triacyglycerols ratio (-24%, P<0.05) were diminished for HG, whereas NG values remained unchanged. CONCLUSIONS: Intense exercise and hypoxia exposure may have a cumulative effect on oxidative stress. As a consequence, the repetition of such exercise characterizing the 'living low-training high' model has weakened the antioxidant capacities of the athletes. SPONSORSHIP: International Olympic Committee and the Direction Régionale de la Jeunesse et des Sports de la Région Auvergne.

Carvedilol inhibits right ventricular hypertrophy induced by chronic hypobaric hypoxia.

Right ventricular hypertrophy induced by chronic hypoxia is mainly due to a mechanical stress upon the ventricular wall secondary to pulmonary arterial hypertension. However, the hypoxic chronic activation of the sympathetic nervous system can contribute to the development of right ventricular hypertrophy either via myocardial adrenergic receptors and/or a vasoconstriction and remodeling of pulmonary arteries. To highlight the specific role of the sympathetic nervous system on hypoxia-induced right ventricular hypertrophy and particularly the efficiency of carvedilol, our study compared physiological, myocardial, and pulmonary arterial morphometric data in rats treated by alpha-(prazosin), or beta-(propranolol) or alphabeta-(carvedilol) antagonist and exposed to chronic hypobaric hypoxia (2 weeks at 380 mmHg barometric pressure). In chronic hypoxia, both systolic right ventricular pressure and Fulton's ratio (right/(left+septum) ventricular weight) were lower in rats treated by prazosin (-16.7 and -13.6%), propranolol (-28.6 and -12.7%) and carvedilol (-15.9 and -14.3%) respectively when compared to glucose (p<0.05). Surprisingly, prazosin was unable to reduce right ventricular hypertrophy induced by chronic hypoxia, whereas, left ventricular weight increased. Wall thickness index of pulmonary arteries increased in chronic hypoxia and was reduced by carvedilol. In conclusion, the hypoxia-induced activation of the adrenergic system participates in the development of right ventricular hypertrophy. Carvedilol is effective in reducing hypoxia-induced right ventricular hypertrophy, pulmonary arterial hypertension, and muscularization of pulmonary arteries.