A Step Test to Evaluate the Susceptibility to Severe High-Altitude Illness in Field Conditions.

Hermand, Eric, Léo Lesaint, Laura Denis, Jean-Paul Richalet, and François J. Lhuissier. A step test to evaluate the susceptibility to severe high-altitude illness in field conditions. High Alt Med Biol. 00:000-000, 2024.-A laboratory-based hypoxic exercise test, performed on a cycle ergometer, can be used to predict susceptibility to severe high-altitude illness (SHAI) through the calculation of a clinicophysiological SHAI score. Our objective was to design a field-condition test and compare its derived SHAI score and various physiological parameters, such as peripheral oxygen saturation (SpO2), and cardiac and ventilatory responses to hypoxia during exercise (HCRe and HVRe, respectively), to the laboratory test. A group of 43 healthy subjects (15 females and 28 males), with no prior experience at high altitude, performed a hypoxic cycle ergometer test (simulated altitude of 4,800 m) and step tests (20 cm high step) at 3,000, 4,000, and 4,800 m simulated altitudes. According to tested altitudes, differences were observed in O2 desaturation, heart rate, and minute ventilation (p < 0.001), whereas the computed HCRe and HVRe were not different (p = 0.075 and p = 0.203, respectively). From the linear relationships between the step test and SHAI scores, we defined a risk zone, allowing us to evaluate the risk of developing SHAI and take adequate preventive measures in field conditions, from the calculated step test score for the given altitude. The predictive value of this new field test remains to be validated in real high-altitude conditions.

Cardiovascular physiology and pathophysiology at high altitude.

Oxygen is vital for cellular metabolism; therefore, the hypoxic conditions encountered at high altitude affect all physiological functions. Acute hypoxia activates the adrenergic system and induces tachycardia, whereas hypoxic pulmonary vasoconstriction increases pulmonary artery pressure. After a few days of exposure to low oxygen concentrations, the autonomic nervous system adapts and tachycardia decreases, thereby protecting the myocardium against high energy consumption. Permanent exposure to high altitude induces erythropoiesis, which if excessive can be deleterious and lead to chronic mountain sickness, often associated with pulmonary hypertension and heart failure. Genetic factors might account for the variable prevalence of chronic mountain sickness, depending on the population and geographical region. Cardiovascular adaptations to hypoxia provide a remarkable model of the regulation of oxygen availability at the cellular and systemic levels. Rapid exposure to high altitude can have adverse effects in patients with cardiovascular diseases. However, intermittent, moderate hypoxia might be useful in the management of some cardiovascular disorders, such as coronary heart disease and heart failure. The aim of this Review is to help physicians to understand the cardiovascular responses to hypoxia and to outline some recommendations that they can give to patients with cardiovascular disease who wish to travel to high-altitude destinations.

Evaluation of the Lake Louise Score for Acute Mountain Sickness and Its 2018 Version in a Cohort of 484 Trekkers at High Altitude.

Richalet, Jean-Paul, Chantal Julia, and François J. Lhuissier. Evaluation of the Lake Louise Score for acute mountain sickness and its 2018 version in a cohort of 484 trekkers at high altitude. High Alt Med Biol. 22:353-361, 2021. Background: The Lake Louise Score (LLS) is widely used in field studies and chamber studies for the diagnosis of Acute Mountain Sickness (AMS). This score aggregates symptoms that are nonspecific: headache, gastrointestinal symptoms, fatigue, dizziness and sleep disturbance can be due to a variety of causes unrelated to altitude hypoxia. The objectives of this study were to (1) reevaluate the need for a headache score >0 for the diagnosis of AMS, (2) evaluate the role of sleep disturbances, in relation with other symptoms, (3) evaluate the significance of dizziness. Materials and Methods: We analyzed LLS from 484 trekkers at high altitude. Among them, 212 suffered from moderate AMS (mAMS: 3 ≤ LLS < 6) and 115 from severe AMS (sAMS: LLS ≥ 6). Results: Cluster analysis of AMS revealed three main groups presenting the following symptoms: Group 1 includes 254 subjects who had less than 2 symptoms; Group 2 includes 137 subjects who had fatigue, sleep disturbance, and headache, corresponding to mAMS; Group 3 includes 93 subjects who had headache, fatigue, dizziness and sleep disturbance, corresponding to sAMS. A headache score of zero was found in 25% of mAMS and 5% of sAMS subjects. Only the absence of headache associated with the absence of fatigue was specific of absence of sAMS. In subjects with a dizziness score > 1, end-tidal partial pressure of carbon dioxide during a hypoxic exercise test was lower than that in subjects with a dizziness score < 2. Subjects with high ventilatory response to hypoxia may develop dizziness with high altitude exposure. Conclusion: (1) An isolated headache score > 0 should not be mandatory to define AMS, (2) sleep disruption contributes to the diagnosis of AMS, (3) gastrointestinal symptoms and dizziness are weaker contributors to the LLS, (4) dizziness might be linked to a hyperresponsiveness to hypoxia and not to AMS itself.

Exercising in Hypoxia and Other Stimuli: Heart Rate Variability and Ventilatory Oscillations.

Periodic breathing is a respiratory phenomenon frequently observed in patients with heart failure and in normal subjects sleeping at high altitude. However, until recently, periodic breathing has not been studied in wakefulness and during exercise. This review relates the latest findings describing this ventilatory disorder when a healthy subject is submitted to simultaneous physiological (exercise) and environmental (hypoxia, hyperoxia, hypercapnia) or pharmacological (acetazolamide) stimuli. Preliminary studies have unveiled fundamental physiological mechanisms related to the genesis of periodic breathing characterized by a shorter period than those observed in patients (11~12 vs. 30~60 s). A mathematical model of the respiratory system functioning under the aforementioned stressors corroborated these data and pointed out other parameters, such as dead space, later confirmed in further research protocols. Finally, a cardiorespiratory interdependence between ventilatory oscillations and heart rate variability in the low frequency band may partly explain the origin of the augmented sympathetic activation at exercise in hypoxia. These nonlinear instabilities highlight the intrinsic "homeodynamic" system that allows any living organism to adapt, to a certain extent, to permanent environmental and internal perturbations.

Accuracy and Reliability of Pulse O2 Saturation Measured by a Wrist-worn Oximeter.

This study aims to evaluate the accuracy of the Garmin Forerunner 245 heart rate (HR) and pulse O2 saturation (SpO2) sensors compared with electrocardiogram and medical oximeter, from sea level to high altitude. Ten healthy subjects underwent five tests in normoxia and hypoxia (simulated altitudes from 3000 to 5500 m), consisting in a 5-min rest phase, followed by 5-min of mild exercise. Absolute error (±10 bpm for HR and ±3% for SpO2, around criterion) and intraclass correlations (ICC) were calculated. Error rates for HR remained under 10%, except at 3000 m, and ICCs evidenced a good reliability between Garmin and criterion. Overall SpO2 was higher than criterion (P<0.001) with a >50% error rate (>80% above 4800 m), and a poor reliability with criterion. The Garmin device displayed acceptable HR data at rest and exercise for all altitudes, but failed to provide trustworthy SpO2 values, especially at high altitude, where a pronounced arterial O2 desaturation could lead to acute mountain sickness in hypoxia-sensitive subjects, and its life-threatening complications; moreover, readings of overestimated SpO2 values might induce trekkers into further hazardous behavior by pursuing an ascent while being already at risk. Therefore, its use to assess SpO2 should be proscribed in altitude for acclimatization evaluation.

Validation of a Score for the Detection of Subjects with High Risk for Severe High-Altitude Illness.

PURPOSE: A decision tree based on a clinicophysiological score (severe high-altitude illness (SHAI) score) has been developed to detect subjects susceptible to SHAI. We aimed to validate this decision tree, to rationalize the prescription of acetazolamide (ACZ), and to specify the rule for a progressive acclimatization. METHODS: Data were obtained from 641 subjects in 15 European medical centers before and during a sojourn at high altitude. Depending on the value of the SHAI score, advice was given and ACZ was eventually prescribed. The outcome was the occurrence of SHAI at high altitude as a function of the SHAI score, ACZ prescription, and use and fulfillment of the acclimatization rule. RESULTS: The occurrence of SHAI was 22.6%, similar to what was observed 18 yr before (23.7%), whereas life-threatening forms of SHAI (high-altitude pulmonary and cerebral edema) were less frequent (2.6%-0.8%, P = 0.007). The negative predictive value of the decision tree based was 81%, suggesting that the procedure is efficient to detect subjects who will not suffer from SHAI, therefore limiting the use of ACZ. The maximal daily altitude gain that limits the occurrence of SHAI was established at 400 m. The occurrence of SHAI was reduced from 27% to 12% when the recommendations for ACZ use and 400-m daily altitude gain were respected (P < 0.001). CONCLUSIONS: This multicenter study confirmed the interest of the SHAI score in predicting the individual risk for SHAI. The conditions for an optimized acclimatization (400-m rule) were also specified, and we proposed a rational decision tree for the prescription of ACZ, adapted to each individual tolerance to hypoxia.

Exponential Relationship Between Maximal Apnea Duration and Exercise Intensity in Non-apnea Trained Individuals.

It is well known that the duration of apnea is longer in static than in dynamic conditions, but the impact of exercise intensity on the apnea duration needs to be investigated. The aim of this study was to determine the relationship between apnea duration and exercise intensity, and the associated metabolic parameters. Ten healthy active young non-apnea trained (NAT) men participated in this study. During the first visit, they carried out a maximum static apnea (SA) and a maximal progressive cycle exercise to evaluate the power output achieved at peak oxygen uptake (PVO2peak). During the second visit, they performed four randomized dynamic apneas (DAs) at 20, 30, 40, and 50% of PVO2peak (P20, P30, P40, and P50) preceded by 4 min of exercise without apnea. Duration of apnea, heart rate (HR), arterial oxygen saturation (SpO2), blood lactate concentration [La], rating of perceived exertion (RPE), and subjective feeling were recorded. Apnea duration was significantly higher during SA (68.1 ± 23.6 s) compared with DA. Apnea duration at P20 (35.6 ± 11.7 s) was higher compared with P30 (25.6 ± 6.3 s), P40 (19.2 ± 6.7 s), and P50 (16.9 ± 2.5 s). The relationship between apnea duration and exercise intensity followed an exponential function (y = 56.388e-0.025 x ). SA as DA performed at P20 and P30 induces a bradycardia. Apnea induces an SpO2 decrease which is higher during DA (-10%) compared with SA (-4.4%). The decreases of SPO2 recorded during DA do not differ despite the increase in exercise intensity. An increase of [La] was observed in P30 and P40 conditions. RPE and subjective feeling remained unchanged whatever the apnea conditions might be. These results suggest that the DA performed at 30% of VO2peak could be the best compromise between apnea duration and exercise intensity. Then, DA training at low intensity could be added to aerobic training since, despite the moderate hypoxia, it is sufficient to induce and increase [La] generally observed during high-intensity training.

Effectiveness of a therapeutic multiple-lifestyle intervention taking into account the periconceptional environment in the management of infertile couples: study design of a randomized controlled trial - the PEPCI study.

BACKGROUND: Infertility is defined as the inability to conceive after 12 months of unprotected intercourse. It affects approximately one in six couples seeking pregnancy in France or western countries. Many lifestyle factors of the couples' pre and peri-conceptional environment (weight, diet, alcohol, tobacco, coffee, drugs, physical activity, stress, sleep…) have been identified as risk factors for infertility in both males and females. The high prevalence rates of unhealthy diets and lifestyles in the reproductive population of industrialized countries are worrisome. Nevertheless, adoption of a healthy lifestyle may improve fertility but lifestyle changes are difficult to achieve and to maintain due notably to behavioral factors. METHODS: Consequently, we decided to propose an interventional study aimed at improving the quality of life of infertile couples before the start of assisted reproductive technology treatment. It is a randomized controlled multicentre trial. Both members of the couples are involved in an integrated global care program (PEPCI for "Parcours Environnement PériConceptionnel en Infertilité") vs. usual care. This global intervention not only considers diet and/or physical activity but follows a holistic approach, including a multidisciplinary assessment to address complete physical, psychological and social well-being. According to patient needs, this includes interventions on weight, exercise, diet, alcohol and drugs, mental and social health. DISCUSSION: The main objective of trial is to demonstrate that periconceptional multidisciplinary care has a positive impact on reproductive functions. We will also focus on feasibility, acceptance, compliance and conditions of success of a multifaceted lifestyle intervention. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov, Identifier: NCT02961907 on November 11, 2016.

Low-frequency ventilatory oscillations in hypoxia are a major contributor to the low-frequency component of heart rate variability.

PURPOSE: Heart rate variability (HRV) may be influenced by several factors, such as environment (hypoxia, hyperoxia, hypercapnia) or physiological demand (exercise). In this retrospective study, we tested the hypothesis that inter-beat (RR) intervals in healthy subjects exercising under various environmental stresses exhibit oscillations at the same frequency than ventilatory oscillations. METHODS: Spectra from RR intervals and ventilation ([Formula: see text]E) were collected from 37 healthy young male subjects who participated in 5 previous studies focused on ventilatory oscillations (or periodic breathing) during exercise in hypoxia, hyperoxia and hypercapnia. Bland and Altman test and multivariate regressions were then performed to compare respective frequencies and changes in peak powers of the two signals. RESULTS: Fast Fourier analysis of RR and [Formula: see text]E signals showed that RR was oscillating at the same frequency than periodic breathing, i.e., ~ 0.09 Hz (11 s). During exercise, in these various conditions, the difference between minimum and maximum HRV peak power was positively correlated to the same change in ventilation peak power (P < 0.05). Low-frequency (LF) peak power was correlated to tidal volume (P < 0.01) and breathing frequency (P < 0.001). CONCLUSIONS: This study suggests that low-frequency ventilatory oscillations in hypoxia are a major contributor to the LF band power of heart rate variability. CLINICAL TRIAL REG. NO.: NCT02201875.

Effect of dead space on breathing stability at exercise in hypoxia.

Recent studies have shown that normal subjects exhibit periodic breathing when submitted to concomitant environmental (hypoxia) and physiological (exercise) stresses. A mathematical model including mass balance equations confirmed the short period of ventilatory oscillations and pointed out an important role of dead space in the genesis of these phenomena. Ten healthy subjects performed mild exercise on a cycloergometer in different conditions: rest/exercise, normoxia/hypoxia and no added dead space/added dead space (aDS). Ventilatory oscillations (V˙E peak power) were augmented by exercise, hypoxia and aDS (P<0.001, P<0.001 and P<0.01, respectively) whereas V˙E period was only shortened by exercise (P<0.001), with an 11-s period. aDS also increased V˙E (P<0.001), tidal volume (VT, P<0.001), and slightly augmented PETCO2 (P<0.05) and the respiratory frequency (P<0.05). These results confirmed our previous model, showing an exacerbation of breathing instability by increasing dead space. This underlines opposite effects observed in heart failure patients and normal subjects, in which added dead space drastically reduced periodic breathing and sleep apneas. It also points out that alveolar ventilation remains very close to metabolic needs and is not affected by an added dead space. Clinical Trial reg. n°: NCT02201875.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. DISCUSSION AND CONCLUSION: 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.

Ventilatory oscillations at exercise in hypoxia: A mathematical model.

We evaluated the mechanisms responsible for the instability of ventilation control system under simultaneous metabolic (exercise) and environmental (hypoxia) stresses, promoting the genesis of periodic breathing. A model following the main concepts of ventilatory control has been tested, including cardiovascular and respiratory parameters, characteristics of peripheral and central chemoreceptors, at mild exercise in hypoxia (FIO2=0.145). Interaction between O2 and CO2 sensing was introduced following three different modalities. A sensitivity and multivariate regression analyses closely matched with physiological data for magnitude and period of oscillations. Low FIO2 and long circulatory delay from lungs to peripheral chemoreceptors (DeltaTp) lengthen the period of oscillations, while high peripheral and central chemoresponses to O2 and CO2, low FIO2 and high DeltaTp increased their magnitude. Peripheral and central O2/CO2 interactions highlight the role of CO2 on peripheral gain to O2 and the contribution of peripheral afferences on central gain to CO2. Our model supports the key role of peripheral chemoreceptors in the genesis of ventilatory oscillations. Differences in the dynamics of central and peripheral components might be determinant for the system stability.

Ventilatory oscillations at exercise: effects of hyperoxia, hypercapnia, and acetazolamide.

Periodic breathing has been found in patients with heart failure and sleep apneas, and in healthy subjects in hypoxia, during sleep and wakefulness, at rest and, recently, at exercise. To unravel the cardiorespiratory parameters liable to modulate the amplitude and period of ventilatory oscillations, 26 healthy subjects were tested under physiological (exercise) and environmental (hypoxia, hyperoxia, hyperoxic hypercapnia) stresses, and under acetazolamide (ACZ) treatment. A fast Fourier transform spectral analysis of breath-by-breath ventilation (V˙E) evidenced an increase in V˙E peak power under hypercapnia (vs. normoxia and hyperoxia, P < 0.001) and a decrease under ACZ (vs. placebo, P < 0.001), whereas it was not modified in hyperoxia. V˙E period was shortened by exercise in all conditions (vs. rest, P < 0.01) and by hypercapnia (vs. normoxia, P < 0.05) but remained unchanged under ACZ (vs. placebo). V˙E peak power was positively related to cardiac output (Q˙c) and V˙E in hyperoxia (P < 0.01), in hypercapnia (P < 0.001) and under ACZ (P < 0.001). V˙E period was negatively related to Q˙c and V˙E in hyperoxia (P < 0.01 and P < 0.001, respectively), in hypercapnia (P < 0.05 and P < 0.01, respectively) and under ACZ (P < 0.05 and P < 0.01, respectively). Total respiratory cycle time was the main factor responsible for changes in V˙E period. In conclusion, exercise, hypoxia, and hypercapnia increase ventilatory oscillations by increasing Q˙c and V˙E, whereas ACZ decreases ventilatory instability in part by a contrasting action on O2 and CO2 sensing. An intrinsic oscillator might modulate ventilation through a complex system where peripheral chemoreflex would play a key role.

Aging, Tolerance to High Altitude, and Cardiorespiratory Response to Hypoxia.

Richalet, Jean-Paul, and François J. Lhuissier. Aging, tolerance to high altitude, and cardiorespiratory response to hypoxia. High Alt Med Biol. 16:117-124, 2015.--It is generally accepted that aging is rather protective, at least at moderate altitude. Some anecdotal reports even mention successful ascent of peaks over 8000 m and even Everest by elderly people. However, very few studies have explored the influence of aging on tolerance to high altitude and prevalence of acute high altitude related diseases, taking into account all confounding factors such as speed of ascent, altitude reached, sex, training status, and chemo-responsiveness. Changes in physiological responses to hypoxia with aging were assessed through a cross-sectional 20-year study including 4675 subjects (2789 men, 1886 women; 14-85 yrs old) and a longitudinal study including 30 subjects explored at a mean 10.4-year interval. In men, ventilatory response to hypoxia increased, while desaturation was less pronounced with aging. Cardiac response to hypoxia was blunted with aging in both genders. Similar results were found in the longitudinal study, with a decrease in cardiac and an increase in ventilatory response to hypoxia with aging. These adaptive responses were less pronounced or absent in post-menopausal untrained women. In conclusion, in normal healthy and active subjects, aging has no deleterious effect on cardiac and ventilatory responses to hypoxia, at least up to the eighth decade. Aging is not a contraindication for high altitude, as far as no pathological condition interferes and physical fitness is compatible with the intensity of the expected physical demand of one's individual. Physiological evaluation through hypoxic exercise testing before going to high altitude is helpful to detect risk factors of severe high altitude-related diseases.

Electrocardiographic changes during exercise in acute hypoxia and susceptibility to severe high-altitude illnesses.

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Periodic breathing in healthy humans at exercise in hypoxia.

Periodic breathing is frequent in heart failure or ventilatory disorders during sleep, and common during sleep at high altitude, but has been rarely studied in wakefulness and during exercise. A retrospective analysis of ventilation from hypoxia exercise tests was realized in 82 healthy subjects separated into two groups with either high or low ventilatory response to hypoxia at exercise (HVRe). A fast Fourier transform spectral analysis of the breath-by-breath ventilation (V̇e) signal, O2 saturation, and end-tidal PCO2 evidenced a periodic pattern with a period of 11.1 to 12.0 s. The peak power of the V̇e spectrum was higher in the high HVRe group (P < 0.001). A prospective study (25 subjects) was performed to evaluate the influence of cardiorespiratory factors on the amplitude and period of oscillations in various conditions of exercise (20 to 40% maximal aerobic power) and hypoxia (0 to 4,000 m altitude). The period of V̇e was shorter at exercise (vs. rest, P < 0.001) and hypoxia (vs. normoxia, P < 0.001), and inversely related with cardiac output and V̇e (P < 0.001). V̇e peak power was higher at exercise (P < 0.001) and hypoxia (P < 0.001), and was positively related with cardiac output and V̇e (P < 0.001). V̇e peak power in hypoxia was positively related with the ventilatory response to CO2 (HCVR). This novel observation suggests that healthy subjects demonstrate a spontaneous periodic breathing, not clearly observable at rest and in normoxia, but triggered by hypoxic exercise. The periodic pattern is enhanced in subjects with high HVRe and high HCVR, suggesting that oxygen and CO2 play synergistic roles in the modulation of these oscillations.

Ageing and cardiorespiratory response to hypoxia.

The risk of severe altitude-induced diseases is related to ventilatory and cardiac responses to hypoxia and is dependent on sex, age and exercise training status. However, it remains unclear how ageing modifies these physiological adaptations to hypoxia. We assessed the physiological responses to hypoxia with ageing through a cross-sectional 20 year study including 4675 subjects (2789 men, 1886 women; 14-85 years old) and a longitudinal study including 30 subjects explored at a mean 10.4 year interval. The influence of sex, training status and menopause was evaluated. The hypoxia-induced desaturation and the ventilatory and cardiac responses to hypoxia at rest and exercise were measured. In men, ventilatory response to hypoxia increased (P < 0.002), while desaturation was less pronounced (P < 0.001) with ageing. Cardiac response to hypoxia was blunted with ageing in both sexes (P < 0.001). Similar results were found in the longitudinal study, with a decrease in cardiac and an increase in ventilatory response to hypoxia with ageing. These adaptive responses were less pronounced or absent in post-menopausal women (P < 0.01). At exercise, desaturation was greater in trained subjects but cardiac and ventilatory responses to hypoxia were preserved by training, especially in elderly people. In conclusion, respiratory response to hypoxia and blood oxygenation improve with ageing in men while cardiac response is blunted with ageing in both sexes. Training aggravates desaturation at exercise in hypoxia, improves the ventilatory response and limits the ageing-induced blunting of cardiac response to hypoxia. Training limits the negative effects of menopause in cardiorespiratory adaptations to hypoxia.

Ventilatory and cardiac responses to hypoxia at submaximal exercise are independent of altitude and exercise intensity.

The hypoxic exercise test combining a 4,800-m simulated altitude and a cycloergometer exercise at 30% of normoxic maximal aerobic power (MAP) is used to evaluate the individual chemosensitivity to hypoxia in submaximal exercise conditions. This test allows the calculation of three main parameters: the decrease in arterial oxygen saturation induced by hypoxia at exercise (ΔSa(e)) and the ventilatory (HVR(e)) and cardiac (HCR(e)) responses to hypoxia at exercise. The aim of this study was to determine the influence of altitude and exercise intensity on the values of ΔSa(e), HVR(e), and HCR(e). Nine subjects performed hypoxic tests at three simulated altitudes (3,000 m, 4,000 m, and 4,800 m) and three exercise intensities (20%, 30%, and 40% MAP). ΔSa(e) increased with altitude and was higher for 40% MAP than for 20% or 30% (P < 0.05). For a constant heart rate, the loss in power output induced by hypoxia, relative to ΔSa(e), was independent of altitude (4,000-4,800 m) and of exercise intensity. HVR(e) and HCR(e) were independent of altitude (3,000-4,800 m) and exercise intensity (20%-40% MAP). Moreover, the intraindividual variability of responses to hypoxia was lower during moderate exercise than at rest (P < 0.05 to P < 0.001). Therefore, we suggest that HVR(e) and HCR(e) are invariant parameters that can be considered as intrinsic physiological characteristics of chemosensitivity to hypoxia.