Jean-Paul Richalet

Université Paris 13 Nord, · Laboratory "Réponses cellulaires et fonctionnelles à l'hypoxie"

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 perip...

Louis, Alexandre, Charlotte Pröpper, Yann Savina, Corentin Tanne, Guy Duperrex, Paul Robach, Pascal Zellner, Stéphane Doutreleau, Jean-Michel Boulet, Alain Frey, Fabien Pillard, Cristina Pistea, Mathias Poussel, Thomas Thuet, Jean-Paul Richalet, and François Lecoq-Jammes. The impact of COVID-19 on the response to hypoxia. High Alt Med Biol. 00:000-...

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 pathophysiology of High-Altitude Pulmonary Edema is currently attributed to exacerbated heterogenous hypoxic pulmonary vasoconstriction. However, other cellular mechanisms have been hypothesized to be involved but still poorly understood. In this review we focused on cells of acinar area known to be responders to acute hypoxia, notably through...

Hypoxia is a current research topic in biology, physiology, and medicine [...]

Résumé L’exposition à la haute altitude nécessite une acclimatation progressive. Quand elle est prise en défaut, peuvent survenir des pathologies spécifiques dont la forme mineure est le mal aigu des montagnes (céphalées, troubles digestifs, fatigue, insomnie) et les formes compliquées sont l’œdème pulmonaire et l’œdème cérébral de haute altitude q...

Introduction: A lack of knowledge among laypersons about the hazards of high-altitude exposure contributes to morbidity and mortality from acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE) among high-altitude travelers. There are guidelines regarding the recognition, prevention, and treatme...

During a training session for the university diploma of Mountain medicine delivered by University Sorbonne Paris Nord for medical doctors, one of the participants developed signs of maladaptation to high altitude at 3600 m, the severity of which was incorrectly interpreted. Information was sparingly given by the patient (an anesthetist) to several...

Exposure to high altitude induces a decrease in oxygen pressure and saturation in the arterial blood, which is aggravated by exercise. Heart rate (HR) at maximal exercise decreases when altitude increases in prolonged exposure to hypoxia. We developed a simple model of myocardial oxygenation in order to demonstrate that the observed blunting of max...

Erythropoietin (Epo) and its receptor are expressed in central respiratory areas. We hypothesized that chronic Epo deficiency alters functioning of central respiratory areas and thus the respiratory adaptation to hypercapnia. The hypercapnic ventilatory response (HcVR) was evaluated by whole body plethysmography in wild type (WT) and Epo deficient...

NEW FINDINGS • What is the central question of this study? What is the effect of sub-maximal aerobic exercise training on signs and symptoms of chronic mountain sickness (CMS) in Andean highlanders? • What is the main finding and its importance? Aerobic exercise training effectively reduces hematocrit, ameliorates symptoms, and improves aerobic cap...

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. 00: 000-000, 2021.-The Lake Louise Score (LLS) is widely used in field studies and chamber studies for the diagnosis of acute mountain si...

Purpose: The aim of this study was to establish a model to estimate the level of arterial oxygen saturation (SpO2) and help determine the appropriate hypoxic dose in humans exercising in acute hypoxia. Methods: SpO2 values were collected in seven untrained (UTS) and seven endurance-trained male subjects (ETS) who performed six cycle incremental and...

Erythropoietin (Epo) is a pleiotropic cytokine, essential for erythropoiesis. Epo and its receptor (Epo-R) are produced by several tissues and it is now admitted that Epo displays other physiological functions than red blood cell synthesis. Indeed, Epo provides cytoprotective effects, which consist in prevention or fight against pathological proces...

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 i...

Globally, about 400 million people reside at terrestrial altitudes above 1500 m, and more than 100 million lowlanders visit mountainous areas above 2500 m annually. The interactions between the low barometric pressure and partial pressure of O2, climate, individual genetic, lifestyle and socio-economic factors, as well as adaptation and acclimatiza...

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 ph...

Physical exercise may improve haematological conditions in high altitude dwellers by reducing haemoglobin concentration. Therefore, the present study aimed to characterise the effects of one-month exercise training session in a model of rats exposed to chronic hypoxia. Four groups of male rats were studied: normoxic sedentary (NS, n=8), normoxic tr...

Background: A computational proteomic analysis suggested that SARS-CoV-2 might bind to hemoglobin (Hb). The authors hypothesized that this phenomenon could result in a decreased oxygen (O2) binding and lead to hemolytic anemia as well. The aim of this work was to investigate whether the affinity of Hb for O2 was altered during COVID-19. Methods: In...

Background and objective: Chronic intermittent hypoxia (CIH), one of the main features of obstructive sleep apnea (OSA), enhances carotid body-mediated chemoreflex and induces hypertension and breathing disorders. The carbamylated form of erythropoietin (cEpo) may have beneficial effects as it retains its antioxidant/anti-inflammatory and neuropro...

Purpose: A decision tree based on a clinico-physiological score (SHAI score) has been developed to detect subjects susceptible to Severe High Altitude Illness (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 obtain...

Purpose: The hypoxic exercise test is used to predict the susceptibility to severe High Altitude Illness (SHAI). In the present study, we aimed to use this test to predict the changes in performance and the physiological responses to moderate altitude in elite swimmers. Methods: Eighteen elite swimmers performed a hypoxic exercise test at sea le...

A 36-year-old woman with no medical history participated in a trekking in Ladakh up to 5300 m of altitude. She was well acclimatized and presented no previous sign of acute mountain sickness, high altitude pulmonary edema or high altitude cerebral edema. After an intense effort to catch up with her group, she became breathless and complained of vis...

Introduction: Tolerance to high altitude in women might be influenced by hormonal status since female hormones modulate ventilation. Methods: Our objectives were (i) to explore in 1060 women, the influence of the phase of menstrual cycle, oral contraception, and menopause with or without hormonal treatment, on hypoxic ventilatory response at exerc...

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...

Chronic mountain sickness (CMS) is a pathological condition resulting from chronic exposure to high-altitude hypoxia. While its prevalence is high in native Andeans (>10%), little is known about the genetic architecture of this disease. Here, we performed the largest genome-wide association study (GWAS) of CMS (166 CMS patients and 146 controls liv...

Tolerance to high altitude in women might be influenced by hormonal status since female hormones are known to modulate ventilation. We explored the influence of 1) the phase of menstrual cycle, 2) oral contraception, 3) menopause with or without hormonal treatment, on ventilatory (HVRe) and cardiac (HCRe) responses to hypoxia at exercise in 1060 wo...

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 sam...

This study aimed to determine whether acute hypoxia associated with exercise induces an increase in systemic blood pressure (SBP) in normotensive and hypertensive subjects, and whether hypertensive subjects are more prone to develop Severe High Altitude Illnesses (SHAI). Finally, to determine if SBP and ECG changes at exercise in hypoxia in hyperte...

Chronic mountain sickness (CMS) is a pathological condition resulting from the loss of adaptation to high altitude. The syndrome is characterized by an excessive number of red blood cells (Excessive Erythropoiesis) associated with a high concentration of hemoglobin, hypoxemia and sometimes pulmonary hypertension. In the Peruvian Andes, the estimate...

Obstructive sleep apnea (OSA) is the most common form of sleep disordered breathing and is associated with wide array of cardiovascular morbidities. It has been proposed that during OSA, the respiratory control center (RCC) is affected by exaggerated afferent signals coming from peripheral/central chemoreceptors which leads to ventilatory instabili...

The measurement of plasma volume (Vp) in humans and animals is frequently performed by the Evans blue dye dilution method. However, after injection of Evans blue into the circulation, no steady state is observed because of delayed mixing and progressive leakage of dye out of vascular space. Various methods of calculation have been proposed, either...

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...

Previous studies suggest that chronic erythropoietin (Epo) deficiency in male mice does not alter normoxic/hypoxic ventilation. As effects of Epo are sex specific and as progesterone could be a respiratory stimulant, we evaluated the impact of Epo deficiency and its possible interaction with progesterone in ventilatory control in female mice during...

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 ph...

The decrease in O 2 pressure in hypoxia, either at high altitude or in disease, induces physiological responses mediated through oxygen sensing systems. Among those responses, chemoreflexes play a major role, especially during the initial phase of exposure to hypoxia. Peripheral chemoreceptors (carotid bodies) and central receptors (retrotrapezoid...

EFFECTS OF HYPOVENTILATION TRAINING AT SUPRAMAXIMAL INTENSITY IN SWIMMING Woorons, X.1, Mucci, P.1, Richalet, J.P.2, Pichon, A.3 1: URePSSS (University of Lille, France), 2: Laboratory ’Hypoxia & Lung’ (University Paris 13, France), 3: MOVE (University of Poitiers, France) Introduction Recently it was demonstrated that swimmers could train unde...

The adrenergic system is part of a full array of mechanisms allowing the human body to adapt to the hypoxic environment. Triggered by the stimulation of peripheral chemoreceptors, the adrenergic centers in the medulla are activated in acute hypoxia and augment the adrenergic drive to the organs, especially to the heart, leading to tachycardia. With...

to the editor: We followed with great interest the recent exchanges between Drs. Teppema and Berendsen ([4][1]) on one hand and Dr. Swenson on the other hand regarding the mechanisms of effects of acetazolamide (AZ) in the prevention of Acute Mountain Sickness (AMS) ([3][2]). One of the essential

Many studies seek to identify and map the brain regions involved in specific physiological regulations. The proto-oncogene c-fos, an immediate early gene, is expressed in neurons in response to various stimuli. The protein product can be readily detected with immunohistochemical techniques leading to the use of c-FOS detection to map groups of neur...

Despite its well-known role in red blood cell production, it is now accepted that erythropoietin (Epo) has other physiological functions. Epo and its receptors are expressed in many tissues such as brain or heart. The presence of Epo/Epo-R in these organs suggests other roles than those usually assigned to this protein. Thus, the aim of this review...

Purpose: This study aimed to determine whether hypoventilation training at supramaximal intensity could improve swimming performance more than the same training carried out under normal breathing conditions. Methods: Over a 5-week period, sixteen triathletes (12 men, 4 women) were asked to include twice a week into their usual swimming session one...

La pratique de plus en plus fréquente d’activités sportives ou de loisir en haute altitude amène à se poser la question des facteurs de risque de la pathologie engendrée par l’exposition aiguë à l’hypoxie : mal aigu des montagnes, œdème pulmonaire et œdème cérébral de haute altitude. Des études épidémiologiques récentes ont permis d’identifier ces...

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 physiologi...

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, t...

Introduction: Erythropoietin (Epo) is involved in the hypoxic ventilatory response but its effect on the hypercapnic ventilatory response remains to be determined. The objective was therefore to assess the role of Epo on the ventilatory response to hypercapnia (HcVR) and establish if Epo has an effect on peripheral and/or central ventilatory pathwa...

Introduction: Periodic breathing has been found in patients with heart failure and sleep apneas but was rarely studied in wakeful state during exercise in healthy humans. Materials and Methods: We analyzed 82 healthy subjects breath-by-breath ventilation (VE) signals by Fast Fourier Transform, from standardized hypoxia exercise tests. The influence...

Periodic breathing has been rarely studied in wakefulness during exercise in healthy humans. Spectral analyses of 82 healthy subjects breath-by-breath ventilation (VE) signals, from hypoxia exercise tests, evidenced a periodic pattern with a period from 11.1 to 12.0 seconds. VE Peak power was higher in the group 'high ventilatory response to hypo...

Periodic breathing has been rarely studied in wakefulness during exercise in healthy humans. Spectral analyses of 82 healthy subjects breath‐by‐breath ventilation ( V E) signals, from hypoxia exercise tests, evidenced a periodic pattern with a period from 11.1 to 12.0 seconds. V E Peak power was higher in the group 'high ventilatory response to hyp...

-To compare ECG at moderate exercise in normoxia and hypoxia at the same heart rate, to evidence independent predictors of hypoxia-induced ECG changes and evaluate electrocardiographic risk factors of severe high altitude illnesses (SHAI). -456 subjects performed a 20-minute hypoxia exercise test with continuous recording of ECG and physiological m...

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 ven...

Many studies seek to identify and map the brain regions involved in specific physiological regulations. The proto-oncogene c-fos, an immediate early gene, is expressed in neurons in response to various stimuli. The protein product can be readily detected with immunohistochemical techniques leading to the use of c-FOS detection to map groups of neur...

In high altitude conditions, as hypoxia induces pulmonary vasoconstriction and increase in pulmonary arterial pressure, right ventricular (RV) function will be affected. The right ventricular function may be affected directly by the hypoxic challenge or indirectly through a pressure overload due to changes in the pulmonary circulation. Both animal...

Our objective was to determine the nocturnal ventilatory pattern and characterize the effect of oxygen enrichment on nocturnal ventilatory pattern and sleep quality in miners exposed to intermittent hypobaric hypoxia at 4200 m. A total of 16 acclimatized miners were studied. Nocturnal ventilatory pattern (plethysmographic inductance), arterial oxyg...

Background Risk prediction of acute mountain sickness, high altitude (HA) pulmonary or cerebral edema is currently based on clinical assessment. Our objective was to develop a risk prediction score of Severe High Altitude Illness (SHAI) combining clinical and physiological factors. Study population was 1017 sea-level subjects who performed a hypoxi...

Abstract Espinoza, Jose R., Giancarlo Alvarez, Fabiola León-Velarde, Hugo F. Ju Preciado, Jose-Luis Macarlupu, Maria Rivera-Ch, Jorge Rodriguez, Judith Favier, Anne-Paule Gimenez-Roqueplo, and Jean-Paul Richalet. Vascular endothelial growth factor-A is associated with chronic mountain sickness in Andean population. High Alt Med Biol. 15:146-154, 20...

The purposes of this study are to establish the relationships among vertical jumping parameters, aerobic fitness and sprint running performance and to examine the anthropometric and physiological profile in elite Futsal Tunisian players. Twenty-six elite Tunisian Futsal players (age 26 ± 3 years, height 1.77 ± 0.75 m, weight 69.3 ± 8.5 Kg) voluntee...

The N-Methyl-d-Aspartate (NMDA) receptors - neuronal nitric oxide synthase (nNOS) pathway is involved in the ventilatory response to hypoxia. The objective was to assess the possible effect of erythropoietin deficiency and chronic exposure to hypoxia on this pathway during ventilatory response to acute hypoxia. Wild-type (WT) and erythropoietin-def...

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...

Aim: This work aims to study the regulation of the glutathione peroxidase and catalase activities in myoblasts from the L6 line exposed to 21%, 5% and 1% O2 during the cell differentiation. Material and methods: Rat L6 myoblasts were grown in 1%, 5% or 21% O2 in the presence or absence of N-acetyl cysteine. The cell proliferation was evaluated b...