Cerebral homeostasis and orthostatic responses in residents of the highest city in the world.

Permanent residence at high-altitude and chronic mountain sickness (CMS) may alter the cerebrovascular homeostasis and orthostatic responses. Healthy male participants living at sea-level (LL; n = 15), 3800 m (HL3800m; n = 13) and 5100 m (HL5100m; n = 17), respectively, and CMS highlanders living at 5100 m (n = 31) were recruited. Middle cerebral artery mean blood flow velocity (MCAv), cerebral oxygen delivery (CDO2), mean blood pressure (MAP), heart rate variability and spontaneuous cardiac baroreflex sensitivity (cBRS) were assessed while sitting, initial 30 s and after 3 min of standing. Cerebral autoregulation index (ARI) was estimated (ΔMCAv%baseline)/ΔMAP%baseline) in response to the orthostatic challenge. Altitude and CMS were associated with hypoxemia and elevated hemoglobin concentration. While sitting, MCAv and LFpower negatively correlated with altitude but were not affected by CMS. CDO2 remained preserved. BRS was comparable across all altitudes, but lower with CMS. Within initial 30 s of standing, altitude and CMS correlated with a lesser ΔMAP while ARI remained unaffected. After 3 min standing, MCAv, CDO2 and cBRS remained preserved across altitudes. The LF/HF ratio increased in HL5100m compared to LL and HL3800m from sitting to standing. In contrary, CMS showed blunted autonomic nervous activation in responses to standing. Despite altitude- and CMS-associated hypoxemia, erythrocytosis and impaired blood pressure regulation (CMS only), cerebral homeostasis remained overall preserved.

Early effects of acetazolamide on hemoglobin mass and plasma volume in chronic mountain sickness at 5100 m.

INTRODUCTION AND OBJECTIVES: Chronic Mountain Sickness (CMS) syndrome, combining excessive erythrocytosis and clinical symptoms in highlanders, remains a public health concern in high-altitude areas, especially in the Andes, with limited therapeutic approaches. The objectives of this study were to assess in CMS-highlanders permanently living in La Rinconada (5100-5300 m, Peru, the highest city in the world), the early efficacy of acetazolamide (ACZ) and atorvastatin to reduce hematocrit (Hct), as well as the underlying mechanisms focusing on intravascular volumes. MATERIALS AND METHODS: Forty-one males (46±8 years of age) permanently living in La Rinconada for 15 [10-20] years and suffering from CMS were randomized between ACZ (250 mg once-daily; N = 13), atorvastatin (20 mg once-daily; N = 14) or placebo (N = 14) uptake in a double-blinded parallel study. Hematocrit (primary endpoint) as well as arterial blood gasses, total hemoglobin mass (Hbmass) and intravascular volumes were assessed at baseline and after a mean (±SD) treatment duration of 19±2 days. RESULTS: ACZ increased PaO2 by +13.4% (95% CI: 4.3 to 22.5%) and decreased Hct by -5.2% (95% CI: -8.3 to -2.2%), whereas Hct remained unchanged with placebo or atorvastatin. ACZ tended to decrease Hbmass (-2.6%, 95% CI: -5.7 to 0.5%), decreased total red blood cell volume (RBCV, -5.3%, 95% CI: -10.3 to -0.3%) and increased plasma volume (PV, +17.6%, 95% CI: 4.9 to 30.3%). Atorvastatin had no effect on intravascular volumes, while Hbmass and RBCV increased in the placebo group (+6.1%, 95% CI: 4.2 to 7.9% and +7.0%, 95%CI: 2.7 to 11.4%, respectively). CONCLUSIONS: Short-term ACZ uptake was effective to reduce Hct in CMS-highlanders living at extreme altitude >5,000 m and was associated with both an increase in PV and a reduction in RBCV.

[Into thin air - Altitude training and hypoxic conditioning: From athlete to patient]. / Into thin air ­ Entraînement en altitude et conditionnement hypoxique : du sportif au malade.

INTRODUCTION: Hypoxic exposure should be considered as a continuum, the effects of which depend on the dose and individual response to hypoxia. Hypoxic conditioning (HC) represents an innovative and promising strategy, ranging from improved human performance to therapeutic applications. STATE OF THE ART: With the aim of improving sports performance, the effectiveness of hypoxic exposure, whether natural or simulated, is difficult to demonstrate because of the large variability of the protocols used. In therapeutics, the benefits of HC are described in many pathological conditions such as obesity or cardiovascular pathologies. If the HC benefits from a strong preclinical rationale, its application to humans remains limited. PERSPECTIVES: Advances in training and acclimation will require greater personalization and precise periodization of hypoxic exposures. For patients, the harmonization of HC protocols, the identification of biomarkers and the development and subsequent validation of devices allowing a precise control of the hypoxic stimulus are necessary steps for the development of HC. CONCLUSIONS: From the athlete to the patient, HC represents an innovative and promising field of research, ranging from the improvement of human performance to the prevention and treatment of certain pathologies.

Effects of exercise intensity on clot microstructure and mechanical properties in healthy individuals.

BACKGROUND: Exercise is well established to lead to exercise-induced hypercoagulability, as demonstrated by kinetic coagulation markers. It remains unclear as to whether exercise-induces changes lead in clot development and increased polymerisation. Fractal dimension (df) has been shown to act as a marker of clot microstructure and mechanical properties, and may provide a more meaningful method of determining the relationship between exercise-induced hypercoagulability and potential clot development. METHODS: df was measured in 24 healthy individuals prior to, after 5min of submaximal exercise, following maximal exercise, 45min of passive recovery and following 60min of recovery. Results were compared with conventional markers of coagulation, fibrinolysis and SEM images. RESULTS: Significantly increased df was observed following exercise, returning to resting values following 60min of recovery. The relationship between df and mature clot microstructure was confirmed by SEM: higher df was associated with dense clots formed of smaller fibrin fibres immediately following exercise compared to at rest. Conventional markers of coagulation confirmed findings of previous studies. CONCLUSION: This study demonstrates that df is a sensitive technique which quantifies the structure and properties of blood clots following exercise. In healthy individuals, the haemostatic balance between coagulation and fibrinolysis is maintained in equilibrium following exercise. In individuals with underlying vascular damage who participate in exercise, this equilibrium may be displaced and lead to enhanced clot formation and a prothrombotic state. df may therefore have the potential to not only quantify hypercoagulability, but may also be useful in screening these individuals.

Effects of intermittent hypoxia on erythropoietin, soluble erythropoietin receptor and ventilation in humans.

Erythropoietin (EPO) and soluble EPO receptors (sEPOR) have been proposed to play a central role in the ventilatory acclimatisation to continuous hypoxia in mice. In this study, we demonstrated for the first time in humans (n = 9) that sEPOR is downregulated upon daytime exposure to 4 days of intermittent hypoxia (IH; 6 h·day⁻¹, cycles of 2 min of hypoxia followed by 2 min of reoxygenation; peak end-tidal oxygen tension (P(ET,O2)) 88 Torr, nadir P(ET,O2)) 45 Torr), thereby allowing EPO concentration to rise. We also determined the strength of the association between these haematological adaptations and alterations in the acute hypoxic ventilatory response (AHVR). We observed a nadir in sEPOR on day 2 (-70%), concomitant with the peak in EPO concentration (+50%). Following exposure to IH, tidal volume (V(T)) increased, respiratory frequency remained unchanged, and minute ventilation (V'(E)) was increased. There was a negative correlation between EPO and sEPOR (r = -0.261; p = 0.05), and between sEPOR and V(T) (r = -0.331; p = 0.02). EPO was positively correlated with V'(E) (r = 0.458; p = 0.001). In conclusion, the downregulation of sEPOR by IH modulates the subsequent EPO response. Furthermore, the alterations in AHVR and breathing pattern following IH appear to be mediated, at least in part, by the increase in EPO.

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.

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.

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.