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Participation in ultra-endurance running (UER) events continues to grow across ages, including youth athletes. The 50- and 100-km are the most popular distances among youth athletes. Most youth athletes are between 16–18 years; however, some runners younger than 12 years have successfully completed UER events. Parents, athletes, coaches, race directors, and medical professionals often seek advice regarding the safety of youth athletes participating in these events, especially with regard to potential short and long-term health consequences. UER may impact key organ systems during growth and development. We propose a decision-making process, based on current knowledge and the experience of the consensus group that addresses age regulations, medical and psychological well-being, training status and race-specific factors (such as distance, elevation change, remoteness, ambient temperatures, level of medical assistance, and type of provisions provided by the race organizers) to use until evidence of long-term consequences of UER in youth athletes is available. These recommendations are aimed at safe participation in UER events for youth athletes with a proper and individualized assessment.

It is well established that physical activity reduces all-cause mortality and can prolong life. Ultra-endurance running (UER) is an extreme sport that is becoming increasingly popular, and comprises running races above marathon distance, exceeding 6 h, and/or running fixed distances on multiple days. Serious acute adverse events are rare, but there is mounting evidence that UER may lead to long-term health problems. The purpose of this review is to present the current state of knowledge regarding the potential long-term health problems derived from UER, specifically potential maladaptation in key organ systems, including cardiovascular, respiratory, musculoskeletal, renal, immunological, gastrointestinal, neurological, and integumentary systems. Special consideration is given to youth, masters, and female athletes, all of whom may be more susceptible to certain long-term health issues. We present directions for future research into the pathophysiological mechanisms that underpin athlete susceptibility to long-term issues. Although all body systems can be affected by UER, one of the clearest effects of endurance exercise is on the cardiovascular system, including right ventricular dysfunction and potential increased risk of arrhythmias and hypertension. There is also evidence that rare cases of acute renal injury in UER could lead to progressive renal scarring and chronic kidney disease. There are limited data specific to female athletes, who may be at greater risk of certain UER-related health issues due to interactions between energy availability and sex-hormone concentrations. Indeed, failure to consider sex differences in the design of female-specific UER training programs may have a negative impact on athlete longevity. It is hoped that this review will inform risk stratification and stimulate further research about UER and the implications for long-term health.

Background: Sleep disordered breathing (SDB) is a frequent disorder with serious adverse health consequences in people with Down syndrome (DS). This study aims to evaluate and classify sleep and physical activity (PA) characteristics in adults with DS. Methods: Forty participants with DS wore an accelerometer for seven consecutive days to measure physical activity and sleep–wake patterns. The corresponding data were also obtained by survey and polysomnography. The apnea-hypopnea index (AHI) is calculated from the number of apneas and hypopneas per hour of sleep according to international guidelines. Results: Polysomnography showed SDB based on AHI in 95% of adults: 50% had severe SDB, 22.5% presented moderate and 22.5% mild SDB, predominantly in males. They had poor sleep quality (80.1%) and low PA levels. Using statistical classification methods, we observed three clusters with two opposite profiles. Clusters 2 and 3 showed low PA indices (daily steps: 5719 and 5310, respectively) and severe SDB (AHI = 33.6 and 55.5 events/h), high age and high gonial angle. Cluster 1 showed high PA (mean count of daily steps: 6908) and mild to moderate SDB (AHI = 16.8 events/h), low age and low gonial angle. Conclusions: Our findings suggest that there are different profiles (age, gender, obesity, gonial angle) that are associated with SDB in adults with DS. These results suggest that this may represent important factors to consider when planning health promotion and prevention.

International audience; Increased nitric oxide (NO) bioavailability may improve exercise performance and vascular function. It remains unclear whether older adults who experience a decreased NO bioavailability may benefit from chronic NO precursor supplementation. This randomised, double-blind, trial aims to assess the effect of chronic NO precursor intake on vascular function and exercise performance in older adults (60-70 years old). Twenty-four healthy older adults (12 females) performed vascular function assessment and both local (knee extensions) and whole-body (incremental cycling) exercise tests to exhaustion before and after one month of daily intake of a placebo (PLA) or a nitrate-rich salad and citrulline (N+C, 520mg nitrate and 6g citrulline) drink. Arterial blood pressure (BP) and stiffness, post-ischemic, hypercapnic and hypoxic vascular responses were evaluated. Prefrontal cortex and quadriceps oxygenation was monitored by near-infrared spectroscopy. N+C supplementation reduced mean BP (-3.3mmHg; p=0.047) without altering other parameters of vascular function and oxygenation kinetics. N+C supplementation reduced heart rate and oxygen consumption during submaximal cycling and increased maximal power output by 5.2% (p

Background Excessive ventilation (VE) and abnormal gas exchange during exercise are features of chronic thromboembolic pulmonary hypertension (CTEPH). In selected CTEPH patients, balloon pulmonary angioplasty (BPA) improves symptoms and exercise capacity. How BPA affects exercise hyperventilation and gas exchange is poorly understood. Methods In this longitudinal observational study, symptom-limited cardio-pulmonary exercise tests and carbon monoxide lung diffusion (DLCO) were performed before and after BPA (interval, mean (SD): 3.1 (2.4) months) in 36 CTEPH patients without significant cardiac and/or pulmonary comorbidities. Results Peak work rate improved by 20% after BPA whilst VE at peak did not change despite improved ventilatory efficiency (lower VE with respect to CO2 output [VCO2]). At the highest identical work rate pre- and post-BPA (75 (30) watts), VE and the ideal alveolar-arterial oxygen gradient (P(Ai-a)O2) decreased by 17% and 19% after BPA, respectively. The physiological dead space fraction of tidal volume (VD/VT), calculated from measurements of arterial and mixed expired CO2, decreased by 20%. In the meantime, DLCO did not change. The best correlates of P(Ai-a)O2 measured at peak exercise were physiological VD/VT before BPA and DLCO after BPA. Conclusions Ventilatory efficiency, physiological VD/VT and pulmonary gas exchange improved after BPA. The fact that DLCO did not change suggests that the pulmonary capillary blood volume and probably the true alveolar dead space were unaffected by BPA. The correlation between DLCO measured before BPA and P(Ai-a)O2 measured after BPA suggests that DLCO may provide an easily accessible marker to predict the response to BPA in terms of pulmonary gas exchange.

International audience; 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 obtained from 641 subjects in 15 European medical centers before and during a sojourn at high altitude. Depending on the value of SHAI score, advice was given and ACZ was eventually prescribed. The outcome was the occurrence of SHAI at high altitude as a function of 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 years before (23.7%), while life-threatening forms of SHAI (High Altitude Pulmonary and Cerebral Edema) were less frequent (2.6% to 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

International audience; 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 without EE using simple hemostatic tests such as bleeding (BT) and clotting (CT) times. Eighty-one male (43 ± 7 years), permanent residents from La Rinconada (Peru), the highest city in the world (5,100-5,300 m), were evaluated. Thirty-six subjects (44 %) presented with EE. EE subjects compared to non-EE subjects had lower BT (3.6 ± 1.2 vs. 7.0 ± 1.9 min, p < 0.001) and CT (11.7 ± 1.7 vs. 15.1 ± 2.3 min, p < 0.001). These results support the notion that highlanders with EE are in a state of hypercoagulability and call for further hemostasis investigations in this population using more detailed hemostatic methods.

In response to chronic hypobaric hypoxia, residents at altitude develop physiological adaptations. Despite these adaptations, chronic mountain sickness (CMS) can be observed in 5-33% of individuals residing at high altitude. CMS frequently triggers cardiorespiratory diseases such as pulmonary hypertension and right or left heart failure. Ambient hypoxia further amplifies sleep-related disorders so that sleep disturbance is an important feature of CMS. Our aim was to characterize nocturnal hypoxemia and the associated sleep and ambulatory (A) blood pressure (BP) changes in highlanders. Methods: Cardiorespiratory sleep and 24h ABP monitoring studies were performed in highlanders living in Puno (3800m) and La Rinconada (5100m), Peru. Subjects were divided in groups according to CMS severity scale. Results: 77 males were evaluated (age 43 [34-49] yr, BMI 25 [23-27] kg/m2). Subjects with CMS showed higher 24 h and daytime systolic and diastolic BP than those with no CMS. Highlanders with CMS were characterized by a lower nocturnal oxygen saturation (SpO2) mean, nocturnal SpO2 nadir and a higher oxygen desaturation index than those with no CMS. No difference was found in terms of apnea-hypopnea index. Altitude (β -4.3, p=0.02) and CMS class (β -0.5, p=0.01) were significant predictors of a lower nocturnal SpO2. Conclusions: At altitude lower mean nocturnal SpO2 and frequent desaturations might be implicated in CMS pathogenesis. Moreover, CMS subjects showed higher ABP, which might contribute to their reported worse cardiovascular prognosis as compared with no-CMS highlanders. Further pathophysiological and therapeutic intervention studies are needed for a better management of CMS.

BACKGROUND Sleep‐disordered breathing is associated with a poor prognosis (mortality) in patients with ischemic cardiomyopathy. The understanding of mechanisms linking intermittent hypoxia (IH), the key feature of sleep‐disordered breathing, to ischemic cardiomyopathy progression is crucial for identifying specific actionable therapeutic targets. The aims of the present study were (1) to evaluate the impact of IH on the time course evolution of cardiac remodeling and contractile dysfunction in a rat model of ischemic cardiomyopathy; and (2) to determine the impact of IH on sympathetic activity, hypoxia inducible factor‐1 activation, and endoplasmic reticulum stress in the time course of ischemic cardiomyopathy progression. METHODS AND RESULTS Ischemic cardiomyopathy was induced by a permanent ligature of the left coronary artery in male Wistar rats (rats with myocardial infarction). Rats with myocardial infarction were then exposed to either IH or normoxia for up to 12 weeks. Cardiac remodeling and function were analyzed by Sirius red and wheat germ agglutinin staining, ultrasonography, and cardiac catheterization. Sympathetic activity was evaluated by spectral analysis of blood pressure variability. Hypoxia‐inducible factor‐1α activation and burden of endoplasmic reticulum stress were characterized by Western blots. Long‐term IH exposure precipitated cardiac remodeling (hypertrophy and interstitial fibrosis) and contractile dysfunction during the time course evolution of ischemic cardiomyopathy in rodents. Among associated mechanisms, we identified the early occurrence and persistence of sympathetic activation, associated with sustained hypoxia‐inducible factor‐1α expression and a delayed pro‐apoptotic endoplasmic reticulum stress. CONCLUSIONS Our data provide the demonstration of the deleterious impact of IH on post–myocardial infarction remodeling and contractile dysfunction. Further studies are needed to evaluate whether targeting sympathetic nervous system or HIF‐1 overactivities could limit these effects and improve management of coexisting ischemic cardiomyopathy and sleep‐disordered breathing.

International audience; The development of wearable devices for healthcare monitoring is of primary interest, in particular for homecare applications. But it is challenging to develop an evaluation framework to test and optimize such a device by following a non-invasive protocol. As well established reference devices do exist for capnometry, we propose a protocol to evaluate and compare the performance of the transcutaneous carbon dioxide monitoring wristband that we develop. We present here this protocol, the signal processing pipeline and the data analysis based on signal alignment and intercorrelation study, and the first results on a cohort of 13 healthy subjects. This test allows demonstrating the influence of the device response time and of the carbon dioxide content in the ambient air.Clinical Relevance-The protocol described here allows to test and optimize the new device in clinical conditions simulating hypo and hypercapnia variations on a subject at rest, as it would be the case at home to monitor the health status of chronic respiratory patients, and to compare the performances with reference devices. A strong intercorrelation greater than 0.8 has been observed in 5 healthy subjects out of 13 and factors influencing the intercorrelation are suggested.

Moderate-intensity continuous exercise (MICE) improves fat oxidation. High-intensity intermittent exercise (HIIE) is thought to have a greater potential for fat oxidation but it might be too demanding in the long term for patients. We hypothesized that an initial bout of HIIE could maximize fat oxidation during MICE and the following passive recovery. Eighteen healthy participants performed two acute isocaloric exercise sessions at random. MICE consisted of 45-min cycling at 50% of maximal aerobic power (Pmax). COMB began with five 1-min bouts of HIIE at Pmax (interspaced with 1-min recovery periods) followed by 35-min MICE. Gas exchange allowed substrate oxidation rate assessment.Expressed as a % of energy expenditure, fat oxidation (%) increased during in the passive recovery following COMB (Recovery: 36.0 ± 19.4 vs 23.0 ± 20.3%; ES: 0.66; p 0.0001). An initial bout of HIIE preceding a prolonged moderate-intensity exercise may potentiate fat oxidation during the following recovery. This might be relevant for health management of overweight/obese persons.

International audience; Introduction: Combining exercise training with hypoxic exposure has been recently proposed as a new therapeutic strategy to improve health status of obese individuals. Whether hypoxic exercise training (HET) provides greater benefits regarding body composition and cardiometabolic parameters than normoxic exercise training (NET) remains, however, unclear. We hypothesized that HET would induce greater improvement in exercise capacity and health status than NET in overweight and obese individuals.Methods: Twenty-three subjects were randomized into 8-wk HET (11 men and 1 woman; age, 52 ± 12 yr; body mass index, 31.2 ± 2.4 kg·m) or NET (eight men and three women; age, 56 ± 11 yr; body mass index, 31.8 ± 3.2 kg·m) programs (three sessions per week; constant-load cycling at 75% of maximal heart rate; target arterial oxygen saturation for HET 80%, FiO2 ~0.13, i.e., ~3700 m a.s.l.). Before and after the training programs, the following evaluations were performed: incremental maximal and submaximal cycling tests, measurements of pulse-wave velocity, endothelial function, fasting glucose, insulin and lipid profile, blood NO metabolites and oxidative stress, and determination of body composition by magnetic resonance imaging.Results: Peak oxygen consumption and maximal power output increased significantly after HET only (peak oxygen consumption HET + 10% ± 11% vs NET + 1% ± 10% and maximal power output HET + 11% ± 7% vs NET + 3% ± 10%, P < 0.05). Submaximal exercise responses improved similarly after HET and NET. Except diastolic blood pressure which decreased significantly after both HET and NET, no change in vascular function, metabolic status and body composition was observed after training. Hypoxic exercise training only increased nitrite and reduced superoxide dismutase concentrations.Conclusions: Combining exercise training and hypoxic exposure may provide some additional benefits to standard NET for obese individual health status.

International audience; Introduction: Nitric oxide (NO) precursor supplementation has been shown to increase NO bioavailability and can potentially improve vascular function and exercise performance. It remains unclear whether the combination of NO precursor supplementation and exercise training has synergic effects on exercise performance. This study aims to assess the effect of chronic nitrate and citrulline intake on exercise training adaptations in healthy young individuals.Methods: In this randomized, double-bind trial, 24 healthy young (12 females) subjects performed vascular function assessment (blood pressure, pulse wave velocity, postischemia vasodilation, and cerebrovascular reactivity) and both local (submaximal isometric unilateral knee extension) and whole-body (incremental cycling) exercise tests to exhaustion before and after a 2-month exercise training program and daily intake of a placebo or a nitrate-rich salad and citrulline (N + C, 520 mg nitrate and 6 g citrulline) drink. Prefrontal cortex and quadriceps oxygenation was monitored continuously during exercise by near-infrared spectroscopy.Results: N + C supplementation had no effect on vascular function and muscle and cerebral oxygenation during both local and whole-body exercise. N + C supplementation induced a significantly larger increase in maximal knee extensor strength (+5.1 ± 3.5 vs +0.2 ± 5.5 kg, P = 0.008) as well as a trend toward a larger increase in knee extensor endurance (+35.2 ± 26.1 vs +24.0 ± 10.4 contractions, P = 0.092) than placebo, but no effect on exercise training-induced maximal aerobic performance improvement.Conclusion: These results suggest that chronic nitrate and citrulline supplementation enhances the effect of exercise training on quadriceps muscle function in healthy active young individuals, but this does not translate into improved maximal aerobic performances.

Is the stress test still part of the useful examinations in the detection of risk heart disease in sports subjects? Should we continue to use it as a surveillance examination in coronary sports patients? Meta-analysis, considering a ST subshift of more than 1mm as a criterion for positivity, underline the low prevalence of abnormal examinations and a significant rate of false-positives. But for the diagnosis of coronary artery disease, it is mainly the evolution of the ST segment to effort or recovery and the occurrence of stress arrhythmias that detect true positivity. When coronary risk is more important (presence of risk factors, resumption of sport, intense and prolonged efforts), it seems lawful to recommend such a review on a regular basis among men over 40 years of age with two risk factors but Also among veterans taking up sport after a period of prolonged inactivity. For the asymptomatic coronary athlete the stress test remains at the centre of the final decision for the resumption of a sport in competition irrespective of the method of revascularization. Of course the stress test, even inevitable, remains flawed in the detection of coronary artery disease in the asymptomatic athlete. However, it provides additional information on the condition of being maximal, and attaching importance to arrhythmias, the tensional profile and the maximum power developed in addition to the ST segment's only study.

In this study, we hypothesized that adding CO2 to an inhaled hypoxic gas mixture will limit the rise of pulmonary artery pressure (PAP) induced by a moderate exercise. Eight 20-year-old males performed four constant-load exercise tests on cycle at 40% of maximal oxygen consumption in four conditions: ambient air, normobaric hypoxia (12.5% O2), inhaled CO2 (4.5% CO2), and combination of hypoxia and inhaled CO2. Doppler echocardiography was used to measure systolic (s)PAP, cardiac output (CO). Total pulmonary resistance (TPR) was calculated. Arterialized blood pH was 7.40 at exercise in ambient and hypoxia conditions, whereas CO2 inhalation and combined conditions showed acidosis. sPAP increases from rest in ambient air to exercise ranged as follows: ambient + 110%, CO2 inhalation + 135%, combined + 184%, hypoxia + 217% (p

Central nervous system diseases are among the most disabling in the world. Neuroprotection and brain recovery from either acute or chronic neurodegeneration still represent a challenge in neurology and neurorehabilitation as pharmacology treatments are often insufficiently effective. Conditioning the central nervous system has been proposed as a potential non-pharmacological neuro-therapeutic. Conditioning refers to a procedure by which a potentially deleterious stimulus is applied near to but below the threshold of damage to the organism to increase resistance to the same or even different noxious stimuli given above the threshold of damage. Hypoxic conditioning has been investigated in several cellular and preclinical models and is now recognized as inducing endogenous mechanisms of neuroprotection. Ischemic, traumatic, or chronic neurodegenerative diseases can benefit from hypoxic conditioning strategies aiming at preventing the deleterious consequences or reducing the severity of the pathological condition (preconditioning) or aiming at inducing neuroplasticity and recovery (postconditioning) following central nervous system injury. Hypoxic conditioning can consist in single (sustained) or cyclical (intermittent, interspersed by short period of normoxia) hypoxia stimuli which duration range from few minutes to several hours and that can be repeated over several days or weeks. This mini-review addresses the existing evidence regarding the use of hypoxic conditioning as a potential innovating neuro-therapeutic modality to induce neuroprotection, neuroplasticity and brain recovery. This mini-review also emphasizes issues which remain to be clarified and future researches to be performed in the field. Impact statement Neuroprotection and brain recovery from either acute or chronic neurodegeneration still represent a challenge in neurology and neurorehabilitation. Hypoxic conditioning may represent a harmless and efficient non-pharmacological new therapeutic modality in the field of neuroprotection and neuroplasticity, as supported by many preclinical data. Animal studies provide clear evidence for neuroprotection and neuroplasticity induced by hypoxic conditioning in several models of neurological disorders. These studies show improved functional outcomes when hypoxic conditioning is applied and provides important information to translate this intervention to clinical practice. Some studies in humans provide encouraging data regarding the tolerance and therapeutic effects of hypoxic conditioning strategies. The main issues to address in future research include the definition of the appropriate hypoxic dose and pattern of exposure, the determination of relevant physiological biomarkers to assess the effects of the treatment and the evaluation of combined strategies involving hypoxic conditioning and other pharmacological or non-pharmacological treatments.

Summary Background The new North American guidelines for participation in competitive sport in patients with coronary artery disease (CAD) are less restrictive than previous guidelines. Aim To evaluate the incidence of major adverse cardiac events (MACE) in men with CAD who practise intensive physical activity after a stenting procedure. MACE included in-stent restenosis (SR), stent thrombosis (ST), new coronary stenosis (NCS), myocardial infarction, heart failure, cardiac arrest or cardiac death. Methods Asymptomatic men with CAD and a coronary stent who practised regular (>4 h/week) sport were included in this retrospective multicentre observational study. All patients presented with left ventricular ejection fraction ≥ 50%, no residual stenosis, and no inducible ischaemia or arrhythmias. Three groups were compared: those undertaking moderate leisure-time sport (MLS), intensive leisure-time sport (ILS) or competitive sport (CS). During follow-up, all patients had a yearly routine cardiology evaluation. Results A total of 108 men with CAD (57.3 ± 9.1 years) were included: 29 MLS, 58 ILS, and 21 CS. During follow-up (57.6 ± 46.0 months) the incidence of MACE was 15.7% (SR = 5, SR + NCS = 4, ST = 4, NCS = 4) and occurred during physical exertion in 59% of patients. ST was more frequent in the CS (n = 3) than in the MLS (n = 1) or ILS (n = 0) groups, especially in patients with bare-metal stents. Conclusions The incidence of MACE was 15.7%, and only ST was significantly more frequent in CS patients than in MLS or ILS patients. Our data support the new US guidelines for exercise eligibility in men with CAD.

Background: While millions of people are living permanently at high altitude (>2500m) worldwide, the mechanisms underlying their tolerance to chronic hypoxia and those responsible for the occurrence of chronic mountain sickness (CMS) remain to be elucidated. Excessive erythrocytosis (EE) is thought to be the main mechanism responsible for CMS symptoms and is included in the definition of CMS but the precise interplay between EE and CMS has been poorly described. Methods: The present study benefits from an exceptional dataset coming from 1594 dwellers of La Rinconada, the highest city in the world (5100-5300m). Based on individual clinical characteristics, subjects were categorized according to i) the presence of EE, ii) CMS symptoms severity and iii) CMS diagnosis based on current guidelines. Findings: The prevalence of EE (44%) and CMS diagnosis (26%) was high compared to other highlander populations. Individuals with EE reported few symptoms while symptomatic individuals had lower hematocrit compared to asymptomatic counterparts. Multivariable analysis revealed that age and sex are the main factors associated with EE while age, hematocrit and number of years living at La Rinconada are factors associated with CMS symptoms. Interpretation: High hematocrit values may be required to reside in La Rinconada with limited symptoms. These results might question the classical definition of CMS in such high altitude population. Funding Statement: This work was supported by the ‘‘Fonds de dotation AGIR pour les maladies chroniques’’ and by the French National Research Agency (ANR-12-TECS-0010) in the framework of the ‘‘Investissements d’avenir’’ program (ANR-15-IDEX-02). Declaration of Interests: All authors have no conflict of interest related to the present work to disclose. Ethics Approval Statement: The study was approved by the ethics committees of Inter-region Rhone-Alpes-Auvergne (IRB-5891) and Universidad Nacional Mayor de San Marcos (CIEI-2019-002).

International audience; Purpose: The aim of this study was to assess the acute cardiorespiratory as well as muscle and cerebral tissue oxygenation responses to submaximal constant-load (CL) and high-intensity interval (HII) cycling exercise performed in normoxia and in hypoxia at similar intensity, reproducing whole-body endurance exercise training sessions as performed in sedentary and clinical populations.Methods: Healthy subjects performed two CL (30 min, 75% of maximal heart rate, n = 12) and two HII (15 times 1-min high-intensity exercise-1-min passive recovery, n = 12) cycling exercise sessions in normoxia and in hypoxia [mean arterial oxygen saturation 76 ± 1% (clamped) during CL and 77 ± 5% (inspiratory oxygen fraction 0.135) during HII]. Cardiorespiratory and near-infrared spectroscopy parameters as well as the rate of perceived exertion were continuously recorded.Results: Power output was 21 ± 11% and 15% (according to protocol design) lower in hypoxia compared to normoxia during CL and HII exercise sessions, respectively. Heart rate did not differ between normoxic and hypoxic exercise sessions, while minute ventilation was higher in hypoxia during HII exercise only (+ 13 ± 29%, p < 0.05). Quadriceps tissue saturation index did not differ significantly between normoxia and hypoxia (CL 60 ± 8% versus 59 ± 5%; HII 59 ± 10% versus 56 ± 9%; p > 0.05), while prefrontal cortex deoxygenation was significantly greater in hypoxia during both CL (66 ± 4% versus 56 ± 6%) and HII (58 ± 5% versus 55 ± 5%; p < 0.05) sessions. The rate of perceived exertion did not differ between normoxic and hypoxic CL (2.4 ± 1.7 versus 2.9 ± 1.8) and HII (6.9 ± 1.4 versus 7.5 ± 0.8) sessions (p > 0.05).Conclusion: This study indicates that at identical heart rate, reducing arterial oxygen saturation near 75% does not accentuate muscle deoxygenation during both CL and HII exercise sessions compared to normoxia. Hence, within these conditions, larger muscle hypoxic stress should not be expected.

Background Appropriate advice for the practice of sport in patients with a cardiomyopathy is a challenging issue. Recent evolution towards more comprehensive and tailored recommendations may facilitate the clinical practice. However, neither their application in real life has been evaluated nor the concordance within clinicians. Methods We submitted six cases from real life to an expert panel of eighteen clinicians (7 cardiomyopathy experts, 7 arrhythmia experts, 4 sport physicians). The six athletes had Hypertrophic (HCM, n = 3), Dilated (DCM, n = 2), Right ventricular arythmogenic (ARVC, n = 1) cardiomyopathy. Advice for the practice of sport (competitive or recreational, globally or regarding the main usual activity of the athlete or according to detailed sports classification) was collected through a structured questionnaire. Results Experts authorize the practice of the usual sport in 28% of total cases. Global concordance within experts is significant but low (Kendall W = 0.34, P Conclusions Divergent advices were observed between experts regarding sports activity that can be authorized in athletes with a cardiomyopathy. Advices were also frequently discordant with recent European recommendations. These results underline difficulties for athletes’ personalized recommendation and the need for large prospective studies to progress towards optimal management.

INTRODUCTION The goal of this study was to compare the effects of downhill (DH), uphill (UH), and UH-DH exercise training, at the same metabolic rate, on exercise capacity and skeletal muscle mitochondrial function. METHODS Thirty-two Wistar rats were separated into a control and 3 trained groups. The trained groups exercised for 4 weeks, 5 times per week at the same metabolic rate, either in UH, DH, or combined UH-DH. Twenty-four hours after the last training session, the soleus, gastrocnemius, and vastus intermedius muscles were removed for assessment of mitochondrial respiration. RESULTS Exercise training, at the same metabolic rate, improved maximal running speed without specificity for exercise modalities. Maximal fiber respiration was enhanced in soleus and vastus intermedius in the UH group only. CONCLUSIONS Exercise training, performed at the same metabolic rate, improved exercise capacity, but only UH-trained rats enhanced mitochondrial function in both soleus and vastus intermedius skeletal muscle. Muscle Nerve 54: 925-935, 2016.

Introduction Living in high altitude is challenging for the cardiovascular system, and some of highlanders develop a chronic mountain sickness (CMS). Only few data are available above the altitude of 4380 m. La Rinconada is the highest mining city in the world at an altitude of 5100 m. Objective To describe heart remodeling and pulmonary hemodynamic and study the relationship with CMS. Method Rest and exercise echocardiography were performed in Lima (sea level, n = 18), Puno (3810 m, n = 23) and La Rinconada (n = 55). Results Age and BMI were higher in La Rinconada (30 ± 2; 32 ± 3; 43 ± 2 years and 24 ± 1; 25.4 ± 0.8 and 25.9 ± 0.4 kg.m-2 in Lima, Puno and La Rinconada respectively). Mean arterial pressure were normal and comparable regardless of altitude. As expected, hematocrit significantly (P Fig. 1 ). Conclusion These are the first data of a population living permanently above 5100 m. Eccentric LV remodeling, larger right cavities, lowering myocardial strain in both ventricle are the main findings. The higher rest and exercise TVR in altitude are only related to the hematocrit level.

Background The importance of exercise electrocardiogram (ECG) has been controversial in the prevention of cardiac events among sportsmen. The aim of this study was to determine the frequency of silent myocardial ischemia (SMI) from an exercise ECG and its relationship with induced coronary angiographic assessment and potentially preventable cardiac events. Methods This prospective cohort study included leisure time asymptomatic sportsmen over 35years old, referred from 2011 to 2014 in the Sports Medicine Unit of the University Hospital of Saint-Etienne. Results Of the cohort of 1500 sportsmen (1205 men; mean age 50.7±9.4years; physical activity level 32.8±26.8MET-h/week), 951 (63%) had at least one cardiovascular disease (CVD) risk factor. Family history, medical examination and standard resting 12-lead were collected. A total of 163 exercise ECGs (10.9%) were defined as positive, most of them due to SMI (n=129, 8.6%). SMI was an indication for coronary angiography in 23 cases, leading to 17 documented SMIs (1.1%), including 11 significant stenoses requiring revascularization. In multivariate logistic regression analysis, a high risk of CVD (OR=2.65 [CI 95%: 1.33–5.27], p = 0.005 ) and an age >50years (OR=2.71 [CI 95%: 1.65–4.44], p 0.0001 ) were independently associated with confirmed SMI. Conclusions The association of positive exercise ECG with significant coronary stenosis was stronger among sportsmen with CVD risk factors and older than 50years. Screening by exercise ECG can lower the risk of cardiac events in middle-aged and older sportsmen. One hundred tests would be enough to detect one silent myocardial ischemia at risk for cardiac event.

Background— Pathological T-wave inversion (PTWI) is rarely observed on the ECG of healthy athletes, whereas it is common in patients with certain cardiac diseases. All ECG interpretation guidelines for use within athletes state that PTWI (except in leads aVR, III and V1 and in V1–V4 when preceded by domed ST segment in asymptomatic Afro-Caribbean athletes only) cannot be considered a physiological adaptation. The aims of the present study were to prospectively determine the prevalence of cardiac pathology in athletes presenting with PTWI, and to examine the efficacy of cardiac magnetic resonance in the work-up battery of further examinations. Methods and Results— Athletes presenting with PTWI (n=155) were investigated with clinical examination, ECG, echocardiography, exercise testing, 24h Holter ECG, and cardiac magnetic resonance. Cardiac disease was established in 44.5% of athletes, with hypertrophic cardiomyopathy (81%) the most common pathology. Echocardiography was abnormal in 53.6% of positive cases, and cardiac magnetic resonance identified a further 24 athletes with disease. Five athletes (7.2%) considered normal on initial presentation subsequently expressed pathology during follow-up. Familial history of sudden cardiac death and ST-segment depression associated with PTWI were predictive of cardiac disease. Conclusions— PTWI should be considered pathological in all cases until proven otherwise, because it was associated with cardiac pathology in 45% of athletes. Despite echocardiography identifying pathology in half of these cases, cardiac magnetic resonance must be considered routine in athletes presenting with PTWI with normal echocardiography. Although exclusion from competitive sport is not warranted in the presence of normal secondary examinations, annual follow-up is essential to ascertain possible disease expression.

Maximal aerobic capacity is a strong health predictor and peak oxygen consumption (V′O2peak) is considered a reflection of total body health. No systematic reviews or meta-analyses to date have synthesised the existing data regardingV′O2peakin patients with obstructive sleep apnoea (OSA).A systematic review of English and French articles using PubMed/MEDLINE and Embase included studies assessingV′O2peakin OSA patients either in mL·kg−1·min−1compared with controls or in % predicted. Two independent reviewers analysed the studies, extracted the data and assessed the quality of evidence.MeanV′O2peakexpressed in mL·kg−1·min−1was significantly lower in patients with OSA than in controls (mean difference −2.7 mL·kg−1·min−1; pV′O2peakwas found to be larger in non-obese patients (body mass index −2). MeanV′O2peak% pred was 89.9% in OSA patients (n=643).OSA patients have reduced maximal aerobic capacity, which can be associated with increased cardiovascular risks and reduced survival in certain patient subgroups. Maximal exercise testing can be useful to characterise functional limitation and to evaluate health status in OSA patients.

A systematic review of English and French articles using Pubmed/Medline and Embase included studies assessing objective physical activity levels of obstructive sleep apnea (OSA) patients and exploring the effects of exercise training on OSA severity, body mass index (BMI), sleepiness, and cardiorespiratory fitness [peak oxygen consumption (VO2peak)]. Two independent reviewers analyzed the studies, extracted the data, and assessed the quality of evidence. For objective physical activity levels, eight studies were included. The mean number of steps per day across studies was 5,388 (95% CI: 3,831–6,945; p

Background: The prevalence of obstructive sleep apnea (OSA) in heart failure (HF) patients ranges from 12 to 53% and is independently associated with a poor prognosis. Chronic Intermittent hypoxia (IH), a hallmark feature of OSA, is associated with sympathetic activation (SA) and could therefore aggravate post-ischemic HF. Purpose: To determine the time course evolution of cardiac remodeling and contractile dysfunction in post-ischemic HF rats exposed 1 to 12 weeks of IH.Methods: Wistar male rats with permanent occlusion of left coronary artery were exposed to IH (21–5% FiO2, 60s cycle, 8h/day) or normoxia (N) for 1, 4 and 12 weeks. A longitudinal follow-up of rat left ventricular (LV) dimensions and function was performed by cardiac ultrasonography. At the end of IH or N exposure, blood pressure (BP) was recorded for power spectral analysis and a pressure-volume conductance catheter system was used to evaluate LV parameters. Results: Although cardiac structure seems to be preserved during the first weeks of IH exposure (lesser LV dilation and posterior wall thinning, p Conclusion: Chronic IH magnifies LV contractile dysfunction in a post-ischemic heart failure model, possibly through exaggerated SA.

Nitric oxide (NO) is implicated in vasomotor control mechanisms altering the diameter of the vessels under various physiological and pathological conditions. There are 2 main NO production pathways, 1 NO synthase (NOS) independent (nitrate–nitrite–NO) and the other is NOS dependent (citrulline–arginine–NO). The objective of the study was to evaluate the effect of acute nitrate and citrulline supplementation on post-ischemic vascular response in healthy subjects. Fourteen subjects performed 2-leg vascular occlusion tests, 3 days apart. They were randomly assigned to consume a drink containing 1200 mg (19.4 mmol) of nitrate and 6 g of citrulline (N+C) or a placebo (Pl). Changes in total hemoglobin (Hbtot) and oxyhemoglobin (HbO2) concentrations were recorded by near-infrared spectroscopy on the thigh and calf muscles. No differences between N+C and Pl were observed during the ischemic period. Hbtot increased to a larger extent during the reperfusion period for the thigh (e.g., area under the curve, 821 ± 324 vs. 627 ± 381 mmol·s−1, p = 0.003) and the calf (515 ± 285 vs. 400 ± 275 mmol·s−1, p = 0.029) in the N+C versus Pl conditions. Similar results were found regarding HbO2 for the thigh (e.g., area under the curve, 842 ± 502 vs. 770 ± 491 mmol·s−1, p = 0.077) and the calf (968 ± 536 vs. 865 ± 275 mmol·s−1, p = 0.075). The larger postocclusive Hbtot and HbO2 responses observed after N+C intake suggests a greater post-ischemic vasodilation, which may be due to increased NO availability, via the activation of the 2 main NO production pathways.

Summary Background Cardiovascular events related to high-intensity sport practice are rare but dramatic. Coronary artery disease (CAD) is the leading cause of these events after the age of 35 years. The value of a maximal exercise test (ET) for detection of athletes at risk remains a matter of debate. Aim The aim of this prospective multicentre study was to clarify the medical value and cost-effectiveness of an ET in middle-aged white asymptomatic athletes who participate in high-intensity sport. Methods All athletes had a physical examination, assessment of cardiovascular risk factors, a resting electrocardiogram and an ET. In case of abnormal ET, complementary cardiovascular evaluation was performed, when requested, to detect potential cardiovascular disease. Results 1361 asymptomatic athletes (mean age 50.4 ± 9.6 years; mean training 5.1 ± 3.2 h/week; 10.4% women) with a normal resting electrocardiogram and without cardiovascular disease were consecutively included. An abnormal ET was reported in 144 subjects (94% men); this was positively related to the subject's age and cardiovascular risk level. Cardiac arrhythmias (48%) and CAD symptoms (33.3%) were mainly reported. Cardiovascular disease was confirmed in 24 cases (1.7% from the whole population; 16.7% from those with an abnormal ET) – mainly CAD (n = 12) and arterial hypertension (n = 8). Seventy athletes presented significant unexplained arrhythmias. The cost was approximately €8450 for every confirmed case of cardiovascular disease. Conclusions In this multicentre study in middle-aged athletes, a systematic ET was abnormal in 10.6% of cases. About 2% of subjects had cardiovascular disease, mainly arrhythmias and CAD. From these results, it seems that in a trained population aged >35 years, ET should be targeted at men with at least two cardiovascular risk factors, with acceptable cost-effectiveness.

Introduction: The effect of eccentric (ECC) versus concentric (CON) training on metabolic properties in skeletal muscle is understood poorly. We determined the responses in oxidative capacity and mitochondrial H2O2 production after eccentric (ECC) versus concentric (CON) training performed at similar mechanical power. Methods: Forty-eight rats performed 5- or 20-day eccentric (ECC) or concentric (CON) training programs. Mitochondrial respiration, H2O2 production, citrate synthase activity (CS), and skeletal muscle damage were assessed in gastrocnemius (GAS), soleus (SOL) and vastus intermedius (VI) muscles. Results: Maximal mitochondrial respiration improved only after 20 days of concentric (CON) training in GAS and SOL. H2O2 production increased specifically after 20 days of eccentric ECC training in VI. Skeletal muscle damage occurred transiently in VI after 5 days of ECC training. Conclusions: Twenty days of ECC versus CON training performed at similar mechanical power output do not increase skeletal muscle oxidative capacities, but it elevates mitochondrial H2O2 production in VI, presumably linked to transient muscle damage. Muscle Nerve 50: 803–811, 2014

International audience; Physical performance relies on the concerted action of myriad responses, many of which are under circadian clock control. Little is known, however, regarding the time-dependent effect on exercise performance at the molecular level. We found that both mice and humans exhibit daytime variance in exercise capacity between the early and late part of their active phase. The daytime variance in mice was dependent on exercise intensity and relied on the circadian clock proteins PER1/2. High-throughput gene expression and metabolic profiling of skeletal muscle revealed metabolic pathways that are differently activated upon exercise in a daytime-dependent manner. Remarkably, we discovered that ZMP, an endogenous AMPK activator, is induced by exercise in a time-dependent manner to regulate key steps in glycolytic and fatty acid oxidation pathways and potentially enhance exercise capacity. Overall, we propose that time of day is a major modifier of exercise capacity and associated metabolic pathways.

Summary Hepatopulmonary syndrome (HPS) is of prognostic value in patients awaiting for orthotopic liver transplantation (OLT), but little is known about the effect of cirrhotic cardiomyopathy (CCM). The aim of the present study was to estimate the prevalence and possible relation between respiratory and cardiac abnormalities in a same series of patients awaiting OLT. Special attention was paid to the prognostic value of CCM in comparison to HPS. Eighty-three patients were included (19 females, 64 males; 52.1 ± 10.0 yrs). All had lung function testing with arterial blood gases and echocardiographic evaluation at rest with a contrast echocardiography in case of arterial oxygenation defect. To estimate the presence of CCM, patients underwent a complete left and right echocardiography and Doppler examination. Complete echocardiographic assessment could be obtained in 64 of the 83 patients of the study. HPS was observed in 16.9% (14/83) and CCM in 23.4% (15/64) of patients. There was a tendency of more serious adverse events before and after OLT in patients with HPS in comparison to others but CCM was not of prognostic value. HPS and CCM were frequent in these patients awaiting OLT but both abnormalities were not found in the same patients. CCM was neither related to death before OLT nor to death or serious adverse events after OLT.

BACKGROUND Echocardiography (ECHO) plays a key role in both the diagnosis and prognosis of pulmonary hypertension (PH). Many equations have been published to assess right heart hemodynamics using ECHO. The objective of this study was to test the accuracy and precision of different echocardiographic equations in comparison with the right heart catheterization. METHODS AND RESULTS Complete right heart hemodynamic assessments were prospectively obtained from 115 individuals (mean age 66±1 years; 57 males) who had known or suspected PH. Several equations were tested for the estimation of right atrial pressure, mean and systolic pulmonary artery pressure (MPAP), cardiac output, pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance (PVR). The accuracy of ECHO was good, with a mean difference

It was previously shown that dehydroepiandrosterone (DHEA) reverses chronic hypoxia-induced pulmonary hypertension (PH) in rats, but whether DHEA can improve the clinical and hemodynamic status of patients with PH associated to chronic obstructive pulmonary disease (PH-COPD) has not been studied whereas it is a very severe poorly treated disease.Eight patients with PH-COPD were treated with DHEA (200mg daily orally) for 3 months. The primary end-point was the change in the 6-minute walk test (6-MWT) distance. Secondary end-points included pulmonary hemodynamics, lung function tests and tolerance of treatment.The 6-MWT increased in all cases, from 333m (median [IQR]) (257; 378) to 390m (362; 440) (P0.05). Mean pulmonary artery pressure decreased from 26mmHg (25; 27) to 21.5mmHg (20; 25) (P0.05) and pulmonary vascular resistance from 4.2UI (3.5; 4.4) to 2.6UI (2.5; 3.8) (P0.05). The carbon monoxide diffusing capacity of the lung (DLCO % predicted) increased significantly from 27.4% (20.1; 29.3) to 36.4% (14.6; 39.6) (P0.05). DHEA treatment did not change respiratory parameters of gas exchange and the 200mg per day of DHEA used was perfectly tolerated with no side effect reported.DHEA treatment significantly improves 6-MWT distance, pulmonary hemodynamics and DLCO of patients with PH-COPD, without worsening gas exchange, as do other pharmacological treatments of PH (trial registration NCT00581087).

Background: Increased brain natriuretic peptide (BNP) in cardiovascular disease is thought to be a compensatory protective mechanism allowing to delay the occurrence of terminal heart failure. Heart transplantation should normalize the neuroendocrine balance but BNP remains elevated in stable heart-transplant recipients (Htx). Such increase has been related to persistent endothelial and cardiac dysfunctions. The purpose of this study was to determine whether selected Htx, presenting with normal hemodynamic and cardiac systolic and diastolic functions on both side of the heart, show a normalization of their BNP plasma values. Methods: Of a cohort of well-being 26 Htx, we selected 12 patients with normal hemodynamics and left and right heart systolic and diastolic functions and compared their circulating BNP, cyclic guanosine monophosphate (cGMP) (the BNP second messenger) and endothelin-1 (ET) values with that of 12 age-, body mass index- and mean arterial pressure-matched controls. Cardiac function determination by echodoppler included cardiac filling pressures assessment using tissue Doppler imaging. Blood samples for biological and hormonal determinations were drawn at rest, within 15 min before echocardiography. Results: As selected, hemodynamic and left and right heart systolic and diastolic functions were located in the normal range in Htx. Plasma ET value was also similar in Htx and controls (20.7 ± 0.9 vs. 19.6 ± 0.9 fmol/mL). However, circulating BNP, like cGMP, was still significantly increased after heart transplantation, when compared with controls (33.8 ± 8.5 vs. 4.0 ± 0.9 pg/mL, p = 0.002 and 8.2 ± 1.1 vs. 4.4 ± 0.3 nmol/L, p = 0.003) for BNP and cGMP, respectively, in Htx and controls. Interestingly, the sole correlation observed was between BNP and cGMP (r = 0.85, p

Improvement of exercise capacity by continuous (CT) versus interval training (IT) remains debated. We tested the hypothesis that CT and IT might improve peripheral and/or central adaptations, respectively, by randomly assigning 10 healthy subjects to two periods of 24 trainings sessions over 8 weeks in a cross-over design, separated by 12 weeks of detraining. Maximal oxygen uptake (VO2max), cardiac output (Qmax) and maximal arteriovenous oxygen difference (Da-vO2max) were obtained during an exhaustive incremental test before and after each training period. VO2max and Qmax increased only after IT (from 26.3 +/- 1.6 to 35.2 +/- 3.8 ml min(-1) kg(-1) and from 17.5 +/- 1.3 to 19.5 +/- 1.8 l min(-1), respectively; P < 0.01). Da-vO2max increased after both protocols (from 11.0 +/- 0.8 to 12.7 +/- 1.0; P < 0.01 and from 11.0 +/- 0.8 to 12.1 +/- 1.0 ml 100 ml(-1), P < 0.05 in CT and IT, respectively). At submaximal intensity a significant rightward shift of the Q/Da-vO2 relationship appeared only after CT. These results suggest that in isoenergetic training, central and peripheral adaptations in oxygen transport and utilization are training-modality dependant. IT improves both central and peripheral components of Da-vO2max whereas CT is mainly associated with greater oxygen extraction.

Metabolic demand and muscle mechanical tension are closely coupled during exercise, making their respective drives to the circulatory response difficult to establish. This coupling being altered in eccentric cycling, we implemented an experimental design featuring eccentric vs. concentric constant-load cycling bouts to gain insights into the control of the exercise-induced circulatory response in humans. Heart rate (HR), stroke volume (SV), cardiac output (Q̇), oxygen uptake (V̇o2), and electromyographic (EMG) activity of quadriceps muscles were measured in 11 subjects during heavy concentric (heavy CON: 270 ± 13 W; V̇o2 = 3.59 ± 0.20 l/min), heavy eccentric (heavy ECC: 270 ± 13 W, V̇o2 = 1.17 ± 0.15 l/min), and light concentric (light CON: 70 ± 9 W, V̇o2 = 1.14 ± 0.12 l/min) cycle bouts. Using a reductionist approach, the circulatory responses observed between heavy CON vs. light CON (difference in V̇o2 and power output) was ascribed either to metabolic demand, as estimated from heavy CON vs. heavy ECC (similar power output, different V̇o2), or to muscle mechanical tension, as estimated from heavy ECC vs. light CON (similar V̇o2, different power output). 74% of the Q̇ response was determined by the metabolic demand, also accounting for 65% and 84% of HR and SV responses, respectively. Consequently, muscle mechanical tension determined 26%, 35%, and 16% of the Q̇, HR, and SV responses, respectively. Q̇ was significantly related to V̇o2 ( r2 = 0.83) and EMG activity ( r2 = 0.82; both P < 0.001). These results suggest that the exercise-induced circulatory response is mainly under metabolic control and support the idea that the level of muscle activation plays a role in the cardiovascular regulation during cycle exercise in humans.

We are pleased to address questions raised by Wheeler and colleagues concerning the identified high prevalence of hypertrophic cardiomyopathy (HCM) in our recent publication.1 The aim of our study was to prospectively determine the prevalence of cardiac pathology in athletes presenting with pathological T-wave inversion (PTWI), and to examine the efficacy of cardiac magnetic resonance in the further examination workup. Although Wheeler et al consider a PTWI prevalence of 2.4% high, it is nearly identical (2.3%) to that reported from a large, unselected population of 32 652 individuals.2 Indeed, ethnicity is known to impact T-wave inversion (TWI) rates, with black athletes and controls demonstrating TWI rates of 4.1% and 3.4% in the lateral leads only.3 Wheeler et al request outcome data in athletes with lone PTWI (ie, without ST …

Summary Background Eccentric exercise training has been shown to improve muscle force strength without excessive cardiovascular stress. Such an exercise modality deserves to be tested in pulmonary arterial hypertension. Aim We aimed to assess the effects of an eccentric training modality on cardiac function and survival in an experimental monocrotaline-induced model of pulmonary arterial hypertension with right ventricular dysfunction. Methods Forty rats were randomly assigned to one of four groups: 40 mg/kg monocrotaline-injected sedentary rats; 40 mg/kg monocrotaline-injected eccentric-trained rats; sedentary control rats; or eccentric-trained control rats. Eccentric exercise training consisted of downhill running on a treadmill with a −15° slope for 30 minutes, 5 days a week for 4 weeks. Training tolerance was assessed by echocardiography, right ventricle catheterization and the rats’ maximal eccentric speed. Results Survival in monocrotaline-injected eccentric-trained rats was not different from that in monocrotaline-injected sedentary rats. Monocrotaline-injected eccentric-trained rats tolerated this training modality well, and haemodynamic status did not deteriorate further compared with monocrotaline-injected sedentary rats. The eccentric maximal speed decline was less pronounced in trained compared with sedentary pulmonary arterial hypertension rats. Conclusions Eccentric exercise training had no detrimental effects on right heart pressure, cardiac function and survival in rats with stable monocrotaline-induced pulmonary hypertension.

In middle-aged persons, moderate physical activity energy expenditure (PAEE) has been shown to be associated with increased vagal-related heart rate variability (HRV) indexes and better health status. The purpose of this study was to determine whether a very high PAEE has greater effect on vagal-related HRV indexes and self-estimates of well-being in middle-aged subjects having distinct long-term physical activity profiles. Forty-four subjects were divided into three groups on the basis of the sport score of the Modified Baecke Questionnaire for Older Adults: sedentary (SED, n = 15), moderately-trained (MT, n = 16), and highly-trained subjects (HT, n = 13). PAEE was estimated by triaxial accelerometry during one week. Time and frequency domain HRV indexes were determined during quiet periods in the morning on 5-min R-R interval segments under controlled breathing. Quality of life was evaluated using the SF-36 health survey questionnaire. PAEE was significantly different for each group (374.5 +/- 13.8, 616.8 +/- 22.4, and 1086.6 +/- 43.2 kcal . day (-1) for SED, MT, and HT, respectively, p < 0.001). MT presented significantly higher vagal-related HRV indexes than SED and HT (p < 0.05). None of the HRV indexes was significantly greater in HT than in SED. MT and HT had similar health status scores, which were significantly higher than for SED. These results indicate that in middle-aged subjects, habitual moderate PAEE is associated with greater vagal tone and self-estimates of well-being compared to low PAEE. In contrast, very high PAEE is associated with similar vagal-related indexes as low PAEE, despite better overall health status.

The purpose of the study was to determine the potential beneficial effect of six weeks oral L-arginine supplementation (LAS) on endurance exercise, an important determinant of daily-life activity in patients with chronic stable heart failure (CHF). After an initial incremental maximal exercise test, CHF patients performed an identical thirty-minute interval endurance exercise test before and after six weeks with (L-arginine group; ARG) or without LAS (control group; CTL). Hemodynamic, respiratory, and metabolic parameters were determined at rest, during exercise, and during recovery. Mean heart rate decreased throughout exercise and recovery after LAS (- 8.2 +/- 1.4 b x min(-1); p = 0.003 and - 6.7 +/- 1.6 b x min(-1); p < 0.001, respectively), systemic blood pressure and respiratory parameters remaining unchanged. Resting L-argininaemia increased from 102 +/- 11 to 181 +/- 37 micromol x l(-1) (p < 0.004) and exercise-induced peak increase in plasma lactate was blunted after LAS (4.13 +/- 0.75 vs. 3.13 +/- 0.39 mmol x l(-1); p = 0.02). No significant change was observed in the control group. In heart failure patients, six weeks oral LAS enhances endurance exercise tolerance, reducing both heart rate and circulating lactates. This suggests that chronic LAS might be useful as a therapeutic adjuvant in order to improve the patient's physical fitness.

This study investigates whether a 6-wk intermittent hypoxia training (IHT), designed to avoid reductions in training loads and intensities, improves the endurance performance capacity of competitive distance runners. Eighteen athletes were randomly assigned to train in normoxia [Nor group; n = 9; maximal oxygen uptake (V̇o2 max) = 61.5 ± 1.1 ml·kg−1·min−1] or intermittently in hypoxia (Hyp group; n = 9; V̇o2 max= 64.2 ± 1.2 ml·kg−1·min−1). Into their usual normoxic training schedule, athletes included two weekly high-intensity (second ventilatory threshold) and moderate-duration (24–40 min) training sessions, performed either in normoxia [inspired O2fraction (FiO2) = 20.9%] or in normobaric hypoxia (FiO2= 14.5%). Before and after training, all athletes realized 1) a normoxic and hypoxic incremental test to determine V̇o2 maxand ventilatory thresholds (first and second ventilatory threshold), and 2) an all-out test at the pretraining minimal velocity eliciting V̇o2 maxto determine their time to exhaustion (Tlim) and the parameters of O2uptake (V̇o2) kinetics. Only the Hyp group significantly improved V̇o2 max(+5% at both FiO2, P < 0.05), without changes in blood O2-carrying capacity. Moreover, Tlimlengthened in the Hyp group only (+35%, P < 0.001), without significant modifications of V̇o2kinetics. Despite similar training load, the Nor group displayed no such improvements, with unchanged V̇o2 max(+1%, nonsignificant), Tlim(+10%, nonsignificant), and V̇o2kinetics. In addition, Tlimimprovements in the Hyp group were not correlated with concomitant modifications of other parameters, including V̇o2 maxor V̇o2kinetics. The present IHT model, involving specific high-intensity and moderate-duration hypoxic sessions, may potentialize the metabolic stimuli of training in already trained athletes and elicit peripheral muscle adaptations, resulting in increased endurance performance capacity.

To evaluate the role of central and peripheral contributions to exercise limitation after transplantation, we compared, during exercise, 2 groups of very well-trained heart transplants recipients (HTRs) and kidney transplant recipients (KTRs) with a group of control subjects (CSs), matched for physical level.Nineteen male subjects, 7 HTRs, 6 KTRs and 6 CSs, participated in the study. All transplant patients were in sinus rhythm and were matched for immunosuppressive therapy, none of whom had therapy with chronotropic effects. Exercise capacities were evaluated using a symptom-limited treadmill test. Oxygen consumption (VO2) and heart rate (HR) were measured continuously. Heart rate reserve (HRR) was defined as peak HR minus resting HR; resting HR was the stabilized HR measured in the supine position before the treadmill test.Functional capacities were evaluated for all HTRs, KTRs and CSs, according to maximal VO2 (41.5 +/- 4.0, 52.0 +/- 8.7 and 50.6 +/- 9.0 ml/kg per min, respectively), maximal treadmill speed (9.9 +/- 1.2, 12.7 +/- 1.9 and 15.5 +/- 1.5 km/h) and HRR (65 +/- 17, 101 +/- 12 and 110 +/- 11 beats per minute [bpm]), which were significantly lower in the HTR group (p0.05). Regardless of type of organ transplant, both HTR and KTR patients had a similar VO2/treadmill speed relationship, significantly higher than in the CS group. HRR correlated with maximal VO2 for HTRs (r = 0.72, p0.05).Despite regular training, the decreased mechanical efficiency reflected by an increased VO2/treadmill speed relationship suggests a peripheral limitation in both heart and kidney transplant patients. Furthermore, exercise limitations in HTRs likely arose from both central and peripheral factors, in view of their specific HRR reduction. These factors probably contributed to the decreased speed and VO2 observed in the HTR group.

BUCHHEIT, M., C. SIMON, A. CHARLOUX, S. DOUTRELEAU, F. PIQUARD, and G. BRANDENBERGER. Heart Rate Variability and Intensity of Habitual Physical Activity in Middle-Aged Persons. Med. Sci. Sports Exerc., Vol. 37, No. 9, pp. 1530–1534, 2005. Purpose: In the middle-aged, it has been shown that moderate physical activity is associated with increased global HR variability (HRV) and vagal-related HRV indexes. However, the relative effect of quantity and intensity of physical activity on HRV is still unknown. The purpose of this study was to compare HRV indexes in three groups of subjects presenting different long-term physical activity profiles: sedentary subjects (SED) with low-energy expenditure (PAEE) and two groups of subjects with equivalent moderate PAEE, but differing in terms of intensity of physical activity (active (ACT) and sportive (SP) individuals). Methods: Forty-three middle-aged subjects (61.2 4.3 yr) were divided into the three groups on the basis of a physical activity questionnaire (Modified Baecke Questionnaire for Older Adults). Physical activity was evaluated by accelerometry for 1 wk. Time and frequency domain HRV indexes were determined during quiet periods in the morning on 5-min stationary R–R interval segments under controlled breathing. Quality of life was evaluated using the SF-36 Health Survey Questionnaire. Results: SP spent more time in moderate to very high activities than ACT (2.1 0.1 vs 0.6 0.1 hwk 1 ; P 0.05) and less time in very light to light activities (62.8 2.0 vs 73.7 1.7 hwk 1 ; P 0.05). SP presented higher vagal-related HRV indexes than SED (P 0.05), whereas increases in ACT were less marked. ACT and SP had similar health status scores, which were higher than for SED (P 0.05). Conclusions: In older adults with different lifestyles, habitual moderate PAEE is associated with better self-estimated overall health status and higher vagal-related HRV indexes compared with subjects with low PAEE, especially when moderate- to very high–intensity physical activities are undertaken.

Our objectives were firstly, to study the patterns of the cardiac output (Q(.)) and the arteriovenous oxygen difference [(a-nu(-))O(2)] responses to oxygen uptake (V(.)O(2)) during constant workload exercise (CWE) performed above the respiratory compensation point (RCP), and secondly, to establish the relationships between their kinetics and the time to exhaustion. Nine subjects performed two tests: a maximal incremental exercise test (IET) to determine the maximal V(.)O(2) (V(.)O(2)peak), and a CWE test to exhaustion, performed at p Delta50 (intermediate power between RCP and V(.)O(2)peak). During CWE, V(.)O(2) was measured breath-by-breath, Q(.) was measured beat-by-beat with an impedance device, and blood lactate (LA) was sampled each minute. To calculate ( a-nu(-)O(2), the values of V(.)O(2) and Q(.) were synchronised over 10 s intervals. A fitting method was used to describe the V(.)O(2), Q(.) and ( a-nu(-))O(2) kinetics. The ( a-nu(-)O(2) difference followed a rapid monoexponential function, whereas both V(.)O(2) and Q(.) were best fitted by a single exponential plus linear increase: the time constant (tau) V(.)O(2) [57 (20 s)] was similar to tau ( a-nu(-)O(2), whereas tau for Q(.) was significantly higher [89 (34) s, P0.05] (values expressed as the mean and standard error). LA started to increase after 2 min CWE then increased rapidly, reaching a similar maximal value as that seen during the IET. During CWE, the rapid component of V(.)O(2) uptake was determined by a rapid and maximal ( a-nu(-)O(2) extraction coupled with a two-fold longer Q(.) increase. It is likely that lactic acidosis markedly increased oxygen availability, which when associated with the slow linear increase of Q(.), may account for the V(.)O(2) slow component. Time to exhaustion was larger in individuals with shorter time delay for ( a-nu(-)O(2) and a greater tau for Q(.).

Objectives : Circulating adrenomedullin (ADM), a potent vasorelaxing and natriuretic peptide involved in cardiovascular homeostasis, is increased after cardiac and renal transplantation. ADM is also implicated in hemodynamic abnormalities during liver cirrhosis, but whether ADM is increased late after liver transplantation is unknown. Patients : A total of 18 subjects—10 liver-transplant patients (Ltx) and 8 healthy subjects—were enrolled in the study. Design and measurements : After a 15-min rest period in supine position, heart rate and systemic blood pressure were determined in all subjects. Then, venous blood samples were obtained in order to simultaneously determine the cyclosporine through levels, the biological (cyclosporine, renal and hepatic functions) and hormonal (ADM and atrial natriuretic peptide (ANP)) characteristics of the Ltx. Results : ADM (27.2±4.1 vs. 53.8±6.9 pmol/l, P =0.02), and ANP (5.9±0.9 vs. 12.8±1.4 pmol/l, P =0.001) were significantly increased in late, stable Ltx (35.4±9.6 months after transplantation). Furthermore, increased ADM correlated positively with elevated creatinine ( r =0.76, P =0.01) and ANP ( r =0.64, P =0.04) after liver transplantation. Conclusions : Liver-transplant patients exhibit a sustained increase in circulating ADM. Such an increase likely results from renal impairment associated with volume regulation abnormalities, suggesting a potential role for ADM in volume regulation after liver transplantation.

To investigate the effect of L-arginine supplementation (L-ARG) on physiological and metabolic changes during exercise, we determined in a double-blind study the cardiorespiratory (heart rate, oxygen consumption (VO(2)) and carbon dioxide production (VCO(2)) and the metabolic (lactate and ammonia) responses to maximal exercise after either an intravenous L-ARG hydrochloride salt or placebo load in 8 healthy subjects. Exercise-induced increases in heart rate, VO(2) and VCO(2) were not significantly different after L-ARG or placebo. By contrast, peak plasma ammonia and lactate were significantly decreased after L-ARG load (60.6 +/- 8.2 vs. 73.1 +/- 9.1 micro mol x l(-1), p < 0.01 and 7.1 +/- 0.7 vs. 8.2 +/- 1.1 mmol x l(-1), p < 0.01, for ammonia and lactate, respectively). Plasma L-citrulline increased significantly during exercise only after L-ARG load, despite a concomitant decrease in plasma L-ARG. Furthermore, a significant inverse relationship was observed between changes in lactate and L-citrulline concentrations after L-ARG load (r = -0.84, p = 0.009). These results demonstrate that intravenous L-ARG reduces significantly exercise-induced increase in plasma lactate and ammonia. Taken together, the specific L-citrulline increase and the inverse relationship observed between L-citrulline and plasma lactate after L-ARG might support that L-ARG supplementation enhances the L-arginine-nitric oxide (NO) pathway during exercise.