Julien V Brugniaux

Université Grenoble Alpes · Department of Sport Sciences

Exposure to chronic hypobaric hypoxia imposes a significant physiological burden to more than 80 million humans living above 2,500 m throughout the world. Among them, 50,000 live in the world’s highest city, La Rinconada, located at 5,000-5,300 m in southern Peru. Expedition 5300 is the first scientific and medical programme led in La Rinconada to...

Background: It is widely recognized that electrical muscle stimulation (EMS) can enhance physical functions, but its impact on cerebral hemodynamic changes is not well understood. Specifically, the changes in cerebral blood flow velocity (CBFv) and oxygenation during EMS have not been thoroughly examined. Thus, the purpose of this study was to inve...

Background: Functional electrical stimulation (FES) used to assist movements, such as pedaling, has proven highly beneficial effects However, its use is limited by the stimulation induced fatigue and discomfort. A challenge is to find a way to produce high force while minimizing muscle fatigue. Sequential stimulation (SEQ) has shown promising resul...

Permanent residence at high-altitude and chronic mountain sickness (CMS) may alter the cerebrovascular homeostasis and orthostatic responses. 15/13/17 healthy participants living at sea-level (LL), 3,800m (HL3800m) and 5,100m (HL5100m), respectively, and 31 additional highlanders with CMS living at 5,100m were recruited. Middle cerebral artery mean...

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...

Introduction Chronic mountain sickness (CMS) is a condition characterized by excessive erythrocytosis in response to chronic hypobaric hypoxia. CMS frequently triggers cardiorespiratory diseases such as pulmonary hypertension and right or left heart failure. Ambient hypoxia might be further amplified night-time by intermittent hypoxia related to sl...

Aims A unique Andean population lives in the highest city of the world (La Rinconada, 5,100 m, Peru) and frequently develops a maladaptive syndrome, termed chronic mountain sickness (CMS). Both extreme altitude and CMS are a challenge for the cardiovascular system. This study aims to evaluate cardiac remodelling and pulmonary circulation at rest an...

Purpose Both prolonged exercise and acute high-altitude exposure are known to induce cardiac changes. We sought to describe the cardiac responses to speed climbing at high-altitude, including left ventricular (LV) performance assessment using the myocardial work index (MWI), a new index derived from 2D speckle tracking echocardiography (STE). Meth...

Chronic mountain sickness (CMS) is a high-altitude (HA) maladaptation syndrome characterised by elevated systemic oxidative-nitrosative stress (OXNOS) due to a free radical-mediated reduction in vascular nitric oxide (NO) bioavailability. To better define underlying mechanisms and vascular consequences, this study compared healthy male lowlanders (...

Purpose The combined effects of acute hypoxia and exercise on cognition remain to be clarified. We investigated the effect of speed climbing to high altitude on reactivity and inhibitory control in elite climbers. Methods Eleven elite climbers performed a speed ascent of the Mont-Blanc (4810 m) and were evaluated pre- (at 1000 m) and immediately p...

High-altitude exposure results in a hyperventilatory-induced respiratory alkalosis followed by renal compensation (bicarbonaturia) to return arterial blood pH(a) toward sea-level values. However, acid-base balance has not been comprehensively examined in both lowlanders and indigenous populations - where the latter are thought to be fully adapted t...

Champigneulle, Benoit, Ivan Hancco, Richard Renan, Stéphane Doutreleau, Emeric Stauffer, Aurélien Pichon, Julien V. Brugniaux, Hélène Péré, Pierre Bouzat, David Veyer, and Samuel Verges. High-altitude environment and COVID-19: SARS-CoV-2 seropositivity in the highest city in the world. High Alt Med Biol. 22: 000-000, 2021. Background: A reduced cor...

Résumé Introduction L’exposition hypoxique est à considérer comme un continuum, dont les effets dépendent de la dose et de la sensibilité individuelle à l’hypoxie. Le conditionnement hypoxique (CH) représente une stratégie innovante et prometteuse, allant de l’amélioration des performances humaines à des applications thérapeutiques. État des conn...

Little is known about hemostasis modifications induced by chronic hypoxic exposure in high-altitude residents, especially in those who develop excessive erythrocytosis (EE, i.e. hemoglobin concentration ≥ 21 g·dL-1 in male and ≥ 19 g·dL-1 in female). The aim of this preliminary study was to assess coagulation alterations in highlanders with or with...

Key points: Highlanders developed unique adaptative mechanisms to chronic hypoxic exposure, including substantial haemoglobin and haematocrit increases. A significant proportion of populations living permanently at high altitude developed however maladaptive features known as chronic mountain sickness (CMS). This study aimed to assess the effects...

Females are more prone to cognitive decline, stroke and neurodegenerative disease, possibly due to more marked reductions in cerebral blood flow and cerebrovascular reactivity to CO2 (CVRCO2HYPER) in later life. To what extent regular exercise confers selective neuroprotection in females remains unestablished. To examine this, 73 adults were prospe...

Key points: Chronic mountain sickness (CMS) is a maladaptation syndrome encountered at high-altitude (HA) characterised by severe hypoxaemia that carries a higher risk of stroke and migraine and is associated with increased morbidity and mortality. We examined if exaggerated oxidative-nitrosative-inflammatory stress (OXINOS) and corresponding decr...

Key points: In vitro evidence has identified that coagulation is activated by increased oxidative stress, though the link and underlying mechanism in humans have yet to be established. We conducted the first randomised controlled trial in healthy participants to examine if oral antioxidant prophylaxis alters the haemostatic responses to hypoxia an...

Molecular oxygen (O2) is a vital element in human survival and plays a major role in a diverse range of biological and physiological processes. Although normobaric hyperoxia can increase arterial oxygen content (CaO2), it also causes vasoconstriction and hence reduces O2delivery in various vascular beds including the heart, skeletal muscle, and bra...

Antioxidant intake among maladapted highlanders: link to vascular function - Volume 76 Issue OCE4 - T. Filipponi, C.J. Marley, J.V. Brugniaux, C. Murillo Jauregui, M. Villena, C. Sartori, S.F. Rimoldi, U. Scherrer, D.M. Bailey

Post-prandial hyperlipidaemia (PPH) acutely impairs systemic vascular endothelial function, potentially attributable to a free radical-mediated reduction in vascular nitric oxide (NO) bioavailability (oxidative-nitrosative stress). However, it remains to be determined whether this extends to the cerebrovasculature. To examine this, 38 (19 young (≤...

to the editor: The question raised by Wang et al. ([5][1]) in their recent Viewpoint is important inasmuch as apneic events in obstructive sleep apnea (OSA) are associated with both hypoxia and hypercapnia. Given the cerebrovasculature is more sensitive to hypercapnia than hypoxia ([2][2]) it is

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 prop...

Caffeine is one of the most widely consumed psycho-stimulants in the world, yet little is known about its effects on brain oxygenation and metabolism. Using a double-blind, placebo-controlled, randomized cross-over study design, we combined transcranial Doppler ultrasound (TCD) and near-infrared spectroscopy (NIRS) to study caffeine's effect on mid...

Elevated cardiorespiratory fitness improves resting cerebral perfusion, although to what extent this is further amplified during acute exposure to exercise stress and the corresponding implications for cerebral oxygenation remain unknown. To examine this, we recruited 12 moderately active and 12 sedentary healthy males. Middle cerebral artery blood...

Our knowledge of the erythropoietin (Epo) molecule has come a long way since Carnot and Deflandre's landmark observations, over a century ago, attributing the increase in red blood cells to a factor called ‘hemopoietin’. For decades the scientific community thought that the role of Epo was limited to red blood cell production. However, since the mi...

We aimed to develop new equations that predict exercise-induced energy expenditure (EE) more accurately than previous ones during running by including new parameters as fitness level, body composition and/or running intensity in addition to heart rate (HR). Original equations predicting EE were created from data obtained during three running intens...

Age-related impairments in cerebral blood flow and cerebrovascular reactivity to carbon dioxide (CVRCO2) are established risk factors for stroke that respond favorably to aerobic training. The present study examined to what extent cerebral hemodynamics are improved when training is sustained throughout the adult lifespan. Eighty-one healthy males w...

The present study examined to what extent professional boxing compromises cerebral haemodynamic function and its association with CTBI (chronic traumatic brain injury). A total of 12 male professional boxers were compared with 12 age-, gender- and physical fitness-matched non-boxing controls. We assessed dCA (dynamic cerebral autoregulation; thigh-...

We read with interest the study by Fan and colleagues describing how the carbonic anhydrase (CA) inhibitor acetazolamide reduced periodic breathing and accelerated acclimatisation to high altitude in native lowlanders (Fan et al. 2012). Intravenous infusion was shown to increase resting cerebral blood flow (CBF) and cerebrovascular reactivity to ca...

to the editor: First, we would like to thank all the authors who contributed to make this a rigorous and thorough debate (see Ref. [2][1]). As expected, we can note some very strong opinions and diverging points of view among the contributors even from the same institution or within members of the

Nine young normotensive healthy males (24.6± 3.7 years; 75.4± 10.2 kg) MAP = 91 ± 6 mmHg were studied for 1‐hour following an incremental ramp protocol to VO 2peak (56.2± 10.5 ml/kg/min) on an electronically braked cycle ergometer. Blood pressure was assessed via an automated blood pressure monitor (Datex‐Ohmeda, Finland). Regional limb pulse wave...

Dynamic cerebral autoregulation is impaired in subjects who develop acute mountain sickness (AMS), a neurological disorder characterized by headache. The present study examined if the normoxic sea-level measurement of dynamic cerebral autoregulation would predict subsequent susceptibility to AMS during rapid ascent to terrestrial high altitude. A d...

[Extract] Colbert and Schoeller highlight an interesting point of view concerning the potential shift in physical activity (PA) monitoring. While the use of objective measures is highly encouraged, one must still recognize the limitations of such devices and importantly that we don't currently possess or utilize the perfect PA assessment tool.

In humans, cerebrovascular responses to alterations in arterial Pco(2) and Po(2) are well documented. However, few studies have investigated human coronary vascular responses to alterations in blood gases. This study investigated the extent to which the cerebral and coronary vasculatures differ in their responses to euoxic hypercapnia and isocapnic...

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 o...

It has been shown that the antioxidant status was altered by the "live high-train low" (LHTL) method, however, no information is available regarding the antioxidant restoration during the recovery period. We tested the hypothesis that the antioxidant status is impaired by 18 days LHTL in elite athletes and remained altered after 14 days of recovery...

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 (...

Periodic occlusion of the upper airway in patients with obstructive sleep apnea leads to chronic intermittent hypoxia, which increases the acute hypoxic ventilatory response (AHVR). Animal studies suggest that oxidative stress may modulate AHVR by increasing carotid body sensitivity to hypoxia. This has not been shown in humans. To determine whethe...

We investigated the impact of 13 days of "living high-training low" (LHTL) on the antioxidant/prooxidant balance in elite endurance swimmers. Eighteen elite swimmers from the French Swimming Federation were submitted to a 13-day endurance training and divided into two groups: one group trained at 1,200 m and lived in hypoxia (2,500-3,000 m simulate...

We investigated the strength of the association between oxidative stress, hypoxia inducible factor 1 (HIF-1 alpha) and acute hypoxic ventilatory response (AHVR) after hypoxic training in elite runners. Six elite runners were submitted to 18-day of "living high-training low" (LHTL) and six performed the same training in normoxia. AHVR was measured d...

Intermittent hypoxia (IH) is thought to be responsible for many of the long-term cardiovascular consequences associated with obstructive sleep apnoea (OSA). Experimental human models of IH can aid in investigating the pathophysiology of these cardiovascular complications. The purpose of this study was to determine the effects of IH on the cardiovas...

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. EE was assessed during a 9.7 km hike. 10 men and 10 women in the age range 35-4...

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. Twelve elite athletes from the Athletic French Fede...

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...

Periodic occlusion of the upper airway in patients with obstructive sleep apnea (OSA) leads to intermittent hypoxia (IH). IH is characterized by repeated episodes of hypoxia/reoxygenation, which is known to increase the production of reactive oxygen species (ROS). Causal relationships between OSA, IH and oxidative stress have not been established b...

The regulation of cerebral blood flow (CBF) is a complex process that is altered significantly with altitude exposure. Acute exposure produces a marked increase in CBF, in proportion to the severity of the hypoxia and mitigated by hyperventilation-induced hypocapnia when CO(2) is uncontrolled. A number of mediators contribute to the hypoxia-induced...

Without Abstract

The "living high-training low" model (Hi-Lo) may improve aerobic performance in athletes, and the main mechanism of this improvement is thought to be augmented erythropoiesis. A positive effect of Hi-Lo has been demonstrated previously by using altitudes of 2,000-3,000 m. Since the rate of erythropoiesis is altitude-dependent, we tested whether a h...

This study tested the effects of “living high-training low” (Hi–Lo) on aerobic performance and economy of work in elite athletes. Forty endurance athletes (cross-country skiers, swimmers, runners) performed 13–18 consecutive days of training at 1,200 m altitude, by sleeping at 1,200 m (LL, n = 20) or in hypoxic rooms with 5–6 nights at 2,500 m foll...

The “living high–training low” model (LHTL), i.e., training in normoxia but sleeping/living in hypoxia, is designed to improve the athletes performance. However, LHTL efficacy still remains controversial and also little is known about the duration of its potential benefit. This study tested whether LHTL enhances aerobic performance in athletes, and...

The "living high-training low" (LHTL) model is frequently used to enhance aerobic performance. However, the clinical tolerance and acclimatization process to this intermittent exposure needs to be examined. Forty one athletes from three federations (cross-country skiers, n=11; swimmers, n=18; runners, n=12) separately performed a 13 to 18-day train...

The efficiency of "living high, training low" (LHTL) remains controversial, despite its wide utilization. This study aimed to verify whether maximal and/or submaximal aerobic performance were modified by LHTL and whether these effects persist for 15 days after returning to normoxia. Last, we tried to elucidate whether the mechanisms involved were o...

Both training and chronic hypoxia act on the autonomic nervous system. Because trained Andean high-altitude natives could perform a high-altitude marathon (4220 m above sea level) in 02:27:23 h, we hypothesized that living in chronic hypoxia does not limit the training-induced benefits on the autonomic modulation of the heart. Trained (N=13) and se...

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