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.

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.