Fabienne Durand

Effects of erythropoietin administration in training athletes and possible indirect detection in doping control

PURPOSE This study investigated the effects of repeated subcutaneous injection of rHuEpo (50 IU x kg(-1)) in athletes and proposes a method based on the measurement in blood samples of the sTfR/serum protein ratio to determine if the observed values of this marker are related to rHuEpo abuse. METHODS Serum erythropoietin concentrations, and hematological and biochemical parameters were evaluated, during treatment and for 25 d posttreatment in nine training athletes. Moreover, the effect of rHuEpo administrations on the maximum oxygen uptake (VO2max) and ventilatory threshold (VT) of these athletes was also studied. Threshold values for sTfr and the sTfr/serum protein ratio were determined from 233 subjects (185 athletes, 15 athletes training at moderately high altitude, and 33 subjects living at >3000 m). RESULTS Significant changes in reticulocytes, hemoglobin (Hb) concentration, hematocrit (Hct), sTfr, and sTfr/serum proteins were observed during and after rHuEpo treatment. The maximal heart rate of 177 beats x min(-1) at the beginning of the study was significantly higher than the value of 168 beats x min(-1) after 26 d of rHuEpo administration. Compared with the values measured at baseline, the VT measured after rHuEpo administration occurred at a statistically significant high level of oxygen uptake. CONCLUSIONS When oxygen uptake measured at the VT was expressed as a percentage of V02 max, the values obtained were also significantly higher. The increased values of Tfr and sTfr/serum proteins, respectively, above 10 microg x mL(-1) and 153, indicated the probable intake of rHuEpo.

Exercise-Induced Arterial Hypoxaemia in Athletes

AbstractDuring exercise, healthy individuals are able to maintain arterial oxygenation, whereas highly-trained endurance athletes may exhibit an exercise-induced arterial hypoxaemia (EIAH) that seems to reflect a gas exchange abnormality. The effects of EIAH are currently debated, and different hypotheses have been proposed to explain its pathophysiology. For moderate exercise, it appears that a relative hypoventilation induced by endurance training is involved. For high-intensity exercise, ventilation/perfusion (V̇A/Q̇) mismatching and/or diffusion limitation are thought to occur. The causes of this diffusion limitation are still under debate, with hypotheses being capillary blood volume changes and interstitial pulmonary oedema. Moreover, histamine is released during exercise in individuals exhibiting EIAH, and questions persist as to its relationship with EIAH and its contribution to interstitial pulmonary oedema. Further investigations are needed to better understand the mechanisms involved and to determine the long term consequences of repetitive hypoxaemia in highly trained endurance athletes.

Evidence for an inadequate hyperventilation inducing arterial hypoxemia at submaximal exercise in all highly trained endurance athletes.

PURPOSE The majority of highly trained endurance athletes with a maximal oxygen uptake greater than 60 mL x min(-1) x kg(-1) develop exercise-induced hypoxemia (EIH). Yet some of them apparently do not. The pathophysiology of EIH seems to be multifactorial, and one explanatory hypothesis is a relative hypoventilation. Nevertheless, conflicting results have been reported concerning its contribution to EIH. The aim of this study was to compare the cardiorespiratory responses to maximal exercise of highly trained endurance athletes demonstrating the same aerobic capacity without EIH (N athletes) and with EIH (H athletes). METHODS Ten N athletes and twelve H athletes performed an incremental exercise test. Measurements of arterial blood gases and cardiorespiratory parameters were performed at rest and during exercise. RESULTS All athletes presented a significant decrease in PaO2 (P < 0.05) from rest up to 80% VO2max associated with an increase in PaCO2, both findings consistent with a relative hypoventilation. Then the H athletes, who had a greater training volume per week and a higher second ventilatory threshold than the N athletes (respectively, 17 +/- 1.1 vs 13.1 +/- 0.7 h x wk(-1); 91.8 +/- 1.7 vs 86.1 +/- 1.8% VO2max), presented a continuous PaO2 decrease up to VO2max. This was associated with a widening (Ai-a)DO2. CONCLUSION This study showed that a relative hypoventilation, probably induced by a high level of endurance training, induced hypoxemia in all athletes. However, a nonventilatory mechanism, perhaps related to the volume of training, seemed to affect gas exchanges beyond the second ventilatory threshold in the H athletes, thereby enhancing EIH.

Interleukins 1-beta, -8, and histamine increases in highly trained, exercising athletes.

PURPOSE Exercise-induced hypoxemia (EIH) in highly trained athletes is associated with an increase in histamine release (%H) during exercise. Certain cytokines, known as histamine-releasing factors, are capable of interacting with basophils and/or mast cells to cause the release of histamine. The aim of this study was to determine whether the increased histamine release in highly trained athletes is related to a high plasma level in interleukin-1 beta (IL-1beta), IL-3, or IL-8 in arterial blood. METHODS These parameters were measured in 11 endurance athletes (23.2 +/- 1.2 yr (mean +/- SEM)) known to develop exercise-induced hypoxemia and 11 control subjects (25.0 +/- 1.1 yr) at rest, during an incremental exhaustive exercise test, and at the fifth minute of recovery. RESULTS Histamine release increased between rest and maximal exercise in the athletes (P < 0.01), showing a strong correlation with EIH (r = 0.76, P < 0.01) and was unchanged in the controls. IL-3 plasma concentration was not altered with training and/or with exercise. Circulating IL-8 levels were not different between trained and untrained subjects at any testing level and increased at maximal exercise in both groups (P < 0.01). IL-1beta plasma levels were higher in athletes than in controls (P < 0.05) at each testing level and increased during exercise only in the athletes (P < 0.05). CONCLUSION An elevated concentration of IL-1beta in plasma and its association with increased IL-8 levels during exercise may partly explain the increase in %H associated with EIH in highly trained athletes. Histamine, IL-8, and IL-1beta releases during exercise reflect an inflammatory reaction, which is probably involved in EIH.

Implication of xanthine oxidase in muscle oxidative stress in COPD patients

Objective: The aim of this study was to determine the implication of xanthine oxidase (XO) in the exercise-induced muscle oxidative stress and muscle dysfunction of these patients. Methods: A randomized, crossover and double-blind study was conducted in nine severe COPD patients, who performed a localized quadriceps endurance test after oral treatment with allopurinol, a XO inhibitor or placebo. Redox status was studied in arterial and venous femoral blood before and after the endurance test. Results: In placebo condition, muscle exercise resulted in a significant increase in AOPP and isoprostanes, with a significant increase in the venoarterial difference (v-a) in isoprostanes after exercise as compared with before (p<0.05). In contrast, allopurinol treatment prevented the elevation in AOPP levels and v-a isoprostanes after exercise. However, no significant improvement in quadriceps muscle endurance was observed, but allopurinol treatment seemed to preserve muscle strength properties. Conclusion: This study demonstrates that XO is implicated in the exercise-induced muscle oxidative stress of COPD patients. Allopurinol administration seemed to improve only some muscle properties. Therefore other sources of muscle oxidative stress should be implicated in muscle dysfunction observed in these patients.

Exercise-Induced Hypoxaemia Developed at Sea-Level Influences Responses to Exercise at Moderate Altitude

Purpose The aim of this study was to investigate the impact of exercise-induced hypoxaemia (EIH) developed at sea-level on exercise responses at moderate acute altitude. Methods Twenty three subjects divided in three groups of individuals: highly trained with EIH (n = 7); highly trained without EIH (n = 8) and untrained participants (n = 8) performed two maximal incremental tests at sea-level and at 2,150 m. Haemoglobin O2 saturation (SpO2), heart rate, oxygen uptake (VO2) and several ventilatory parameters were measured continuously during the tests. Results EIH athletes had a drop in SpO2 from 99 ± 0.8% to 91 ± 1.2% from rest to maximal exercise at sea-level, while the other groups did not exhibit a similar decrease. EIH athletes had a greater decrease in VO2max at altitude compared to non-EIH and untrained groups (-22 ± 7.9%, -16 ± 5.3% and -13 ± 9.4%, respectively). At altitude, non-EIH athletes had a similar drop in SpO2 as EIH athletes (13 ± 0.8%) but greater than untrained participants (6 ± 1.0%). EIH athletes showed greater decrease in maximal heart rate than non-EIH athletes at altitude (8 ± 3.3 bpm and 5 ± 2.9 bpm, respectively). Conclusion EIH athletes demonstrated specific cardiorespiratory response to exercise at moderate altitude compared to non-EIH athletes with a higher decrease in VO2max certainly due to the lower ventilator and HRmax responses. Thus EIH phenomenon developed at sea-level negatively impact performance and cardiorespiratory responses at acute moderate altitude despite no potentiated O2 desaturation.

Pulmonary vascular function and aerobic exercise capacity at moderate altitude

Purpose There has been suggestion that a greater “pulmonary vascular reserve” defined by a low pulmonary vascular resistance (PVR) and a high lung diffusing capacity (DL) allow for a superior aerobic exercise capacity. How pulmonary vascular reserve might affect exercise capacity at moderate altitude is not known. Methods Thirty-eight healthy subjects underwent an exercise stress echocardiography of the pulmonary circulation, combined with measurements of DL for nitric oxide (NO) and carbon monoxide (CO) and a cardiopulmonary exercise test at sea level and at an altitude of 2250 m. Results At rest, moderate altitude decreased arterial oxygen content (CaO2) from 19.1 ± 1.6 to 18.4 ± 1.7 mL·dL−1, P < 0.001, and slightly increased PVR, DLNO, and DLCO. Exercise at moderate altitude was associated with decreases in maximum O2 uptake (V˙O2max), from 51 ± 9 to 43 ± 8 mL·kg−1⋅min−1, P < 0.001, and CaO2 to 16.5 ± 1.7 mL·dL−1, P < 0.001, but no different cardiac output, PVR, and pulmonary vascular distensibility. DLNO was inversely correlated to the ventilatory equivalent of CO2 (V˙E/V˙CO2) at sea level and at moderate altitude. Independent determinants of V˙O2max as determined by a multivariable analysis were the slope of mean pulmonary artery pressure–cardiac output relationship, resting stroke volume, and resting DLNO at sea level as well as at moderate altitude. The magnitude of the decrease in V˙O2max at moderate altitude was independently predicted by more pronounced exercise-induced decrease in CaO2 at moderate altitude. Conclusion Aerobic exercise capacity is similarly modulated by pulmonary vascular reserve at moderate altitude and at sea level. Decreased aerobic exercise capacity at moderate altitude is mainly explained by exercise-induced decrease in arterial oxygenation.

The impact of moderate altitude on exercise metabolism in recreational sportsmen: a nuclear magnetic resonance metabolomic approach

Although it is known that altitude impairs performance in endurance sports, there is no consensus on the involvement of energy substrates in this process. The objective of the present study was to determine whether the metabolomic pathways used during endurance exercise differ according to whether the effort is performed at sea level or at moderate altitude (at the same exercise intensity, using proton nuclear magnetic resonance, 1H NMR). Twenty subjects performed two 60-min endurance exercise tests at sea level and at 2150 m at identical relative intensity on a cycle ergometer. Blood plasma was obtained from venous blood samples drawn before and after exercise. 1H NMR spectral analysis was then performed on the plasma samples. A multivariate statistical technique was applied to the NMR data. The respective relative intensities of the sea level and altitude endurance tests were essentially the same when expressed as a percentage of the maximal oxygen uptake measured during the corresponding incremental maximal exercise test. Lipid use was similar at sea level and at altitude. In the plasma, levels of glucose, glutamine, alanine, and branched-chain amino acids had decreased after exercise at altitude but not after exercise at sea level. The decrease in plasma glucose and free amino acid levels observed after exercise at altitude indicated that increased involvement of the protein pathway was necessary but not sufficient for the maintenance of glycaemia. Metabolomics is a powerful means of gaining insight into the metabolic changes induced by exercise at altitude.

Does Prior Training Affect Acute O2 Supply Responses During Exercise in Desaturator COPD Patients

Background: This study investigated the effects of a prior individualized training program (TP) on the response to acute oxygen supply during exercise in chronic obstructive pulmonary disease (COPD) patients showing exercise-induced desaturation. Methods: Twenty-two COPD patients (mean [SD] FEV1 = 52.1 [3]% predicted) who desaturated on exercise participated in a TP. Exercise tolerance while breathing compressed air or oxygen was assessed using a walking test (WT) before and after TP. Oxygen flow was individualized. Results: Before TP, acute oxygen supply improved mean exercise tolerance. But this response was heterogeneous as only 8 patients increased their walking distance with oxygen. TP improved exercise tolerance in the entire population. However, a greater affect of oxygen administration during exercise was not observed after TP. The response to oxygen again showed great disparity as only 6 patients increased their walking distance with oxygen after TP. Conclusion: The response to oxygen supply during exercise varied among COPD patients. Moreover, despite the clinical benefits of TP, no cumulative effect of TP and oxygen supply was observed during exercise performance.