Implication of Blood Rheology and Pulmonary Hemodynamics on Exercise-Induced Hypoxemia at Sea Level and Altitude in Athletes.

This study aimed to investigate the changes in blood viscosity, pulmonary hemodynamics, nitric oxide (NO) production, and maximal oxygen uptake (V˙O2max) during a maximal incremental test conducted in normoxia and during exposure to moderate altitude (2,400 m) in athletes exhibiting exercise-induced hypoxemia at sea level (EIH). Nine endurance athletes with EIH and eight without EIH (NEIH) performed a maximal incremental test under three conditions: sea level, 1 day after arrival in hypoxia, and 5 days after arrival in hypoxia (H5) at 2,400 m. Gas exchange and oxygen peripheral saturation (SpO2) were continuously monitored. Cardiac output, pulmonary arterial pressure, and total pulmonary vascular resistance were assessed by echocardiography. Venous blood was sampled before and 3 min after exercise cessation to analyze blood viscosity and NO end-products. At sea level, athletes with EIH exhibited an increase in blood viscosity and NO levels during exercise while NEIH athletes showed no change. Pulmonary hemodynamics and aerobic performance were not different between the two groups. No between-group differences in blood viscosity, pulmonary hemodynamics, and V˙O2max were found at 1 day after arrival in hypoxia. At H5, lower total pulmonary vascular resistance and greater NO concentration were reported in response to exercise in EIH compared with NEIH athletes. EIH athletes had greater cardiac output and lower SpO2 at maximal exercise in H5, but no between-group differences occurred regarding blood viscosity and V˙O2max. The pulmonary vascular response observed at H5 in EIH athletes may be involved in the greater cardiac output of EIH group and counterbalanced the drop in SpO2 in order to achieve similar V˙O2max than NEIH athletes.

Exercise-Induced Hypoxemia in Endurance Athletes: Consequences for Altitude Exposure.

Exercise-induced hypoxemia (EIH) is well-described in endurance-trained athletes during both maximal and submaximal exercise intensities. Despite the drop in oxygen (O2) saturation and provided that training volumes are similar, athletes who experience EIH nevertheless produce the same endurance performance in normoxia as athletes without EIH. This lack of a difference prompted trainers to consider that the phenomenon was not relevant to performance but also suggested that a specific adaptation to exercise is present in EIH athletes. Even though the causes of EIH have been extensively studied, its consequences have not been fully characterized. With the development of endurance outdoor activities and altitude/hypoxia training, athletes often train and/or compete in this stressful environment with a decrease in the partial pressure of inspired O2 (due to the drop in barometric pressure). Thus, one can reasonably hypothesize that EIH athletes can specifically adapt to hypoxemic episodes during exercise at altitude. Although our knowledge of the interactions between EIH and acute exposure to hypoxia has improved over the last 10 years, many questions have yet to be addressed. Firstly, endurance performance during acute exposure to altitude appears to be more impaired in EIH vs. non-EIH athletes but the corresponding physiological mechanisms are not fully understood. Secondly, we lack information on the consequences of EIH during chronic exposure to altitude. Here, we (i) review research on the consequences of EIH under acute hypoxic conditions, (ii) highlight unresolved questions about EIH and chronic hypoxic exposure, and (iii) suggest perspectives for improving endurance training.

Pro-Oxidant/Antioxidant Balance during a Prolonged Exposure to Moderate Altitude in Athletes Exhibiting Exercise-Induced Hypoxemia at Sea-Level.

This study examined to what extent athletes exhibiting exercise-induced hypoxemia (EIH) possess an altered redox status at rest, in response to exercise at sea level (SL) and during moderate altitude exposure. EIH was defined as a fall in arterial O2 saturation of at least 4% during exercise. Nine endurance athletes with EIH and ten without (NEIH) performed a maximal incremental test under three conditions: SL, one (H1) and five (H2) days after arrival to 2400 m. Gas exchange and peripheral capillary oxygen saturation (SpO2) were continuously monitored. Blood was sampled before exercise and after exercise cessation. Advanced oxidation protein products (AOPP), catalase, ferric-reducing antioxidant power, glutathione peroxidase, superoxide dismutase (SOD) and nitric oxide metabolites (NOx) were measured in plasma by spectrophotometry. EIH athletes had higher AOPP and NOx concentrations at pre- and post-exercise stages compared to NEIH at SL, H2 but not at H1. Only the EIH group experienced increased SOD activity between pre- and post-exercise exercise at SL and H2 but not at H1. EIH athletes had exacerbated oxidative stress compared to the NEIH athletes at SL and H2. These differences were blunted at H1. Oxidative stress did not alter the EIH groups' aerobic performance and could lead to higher minute ventilation at H2. These results suggest that higher oxidative stress response EIH athletes could be involved in improved aerobic muscle functionality and a greater ventilatory acclimatization during prolonged hypoxia.

Noninvasive Pulmonary Hemodynamic Evaluation in Athletes With Exercise-Induced Hypoxemia.

BACKGROUND: Pulmonary capillary stress failure is potentially involved in exercise-induced hypoxemia (ie, a significant fall in hemoglobin oxygen saturation [Spo2]) during sea level exercise in endurance-trained athletes. It is unknown whether there are specific properties of pulmonary vascular function in athletes exhibiting oxygen desaturation. METHODS: Ten endurance-trained athletes with exercise-induced hypoxemia (EIH), nine endurance-trained athletes with no exercise-induced hypoxemia (NEIH), and 10 untrained control subjects underwent an incremental exercise stress echocardiography coupled with lung diffusion capacity for carbon monoxide (Dlco) and lung diffusion capacity for nitric oxide (Dlno) testing. Functional adaptation of the pulmonary circulation was evaluated with measurements of mean pulmonary arterial pressure (mPAP), pulmonary capillary pressure, pulmonary vascular resistance (PVR), cardiac output (Qc), and pulmonary vascular distensibility (alpha) mathematically determined from the curvilinearity of the multi-point mPAP/Qc relation. RESULTS: EIH athletes exhibited a lower exercise-induced PVR decrease compared with the untrained and NEIH groups (P < .001). EIH athletes showed higher maximal mPAP compared with NEIH athletes (45.4 ± 0.9 mm Hg vs 41.6 ± 0.9 mm Hg, respectively; P = .003); there was no difference between the NEIH and untrained subjects. Alpha was lower in the EIH group compared with the NEIH group (P < .05). Maximal mPAP, Pcap, and alpha were correlated with the fall of Spo2 during exercise (P < .01, P < .01, and P < .05). Dlno and Dlco increased with exercise in all groups, with no differences between groups. Dlno/Qc was correlated to the exercise-induced Spo2 changes (P < .05). CONCLUSIONS: EIH athletes exhibit higher maximal pulmonary vascular pressures, lower vascular distensibility, or exercise-induced changes in PVR compared with NEIH subjects, in keeping with pulmonary capillary stress failure or intrapulmonary shunting hypotheses.

Muscle and cerebral oxygenation during exercise in athletes with exercise-induced hypoxemia: A comparison between sea level and acute moderate hypoxia.

The objective of the present study was to evaluate the influence of exercise-induced hypoxemia (EIH) on muscle and cerebral oxygenation responses during maximal exercise in normoxia and in acute moderate hypoxia (fraction of inspired oxygen: 15.3%, 2400 m). EIH was defined as a drop in hemoglobin saturation of at least 4% for at least three consecutive minutes during maximal exercise at sea level. Twenty-five athletes performed incremental treadmill tests to assess maximal oxygen consumption (VO2max) in normoxia and in hypoxia. Oxygenation of the vastus lateralis muscle and the left prefrontal cortex of the brain was monitored using near-infrared spectroscopy. During the normoxic test, 15 athletes exhibited EIH; they displayed a larger change in muscle levels of oxyhemoglobin (ΔO2Hb) (p = 0.04) and a greater change in cerebral levels of deoxyhemoglobin (ΔHHb) (p = 0.02) than athletes without EIH (NEIH group). During the hypoxic test, muscle ΔO2Hb was lower in the EIH group than in the NEIH group (p = 0.03). At VO2max, hypoxia was associated with a smaller cerebral ΔO2Hb in both groups, and a greater cerebral ΔHHb compared to normoxia in the NEIH group only (p = 0.02). No intergroup differences in changes in muscle oxygenation were observed. The severity of O2 arterial desaturation was negatively correlated with changes in total muscle hemoglobin in normoxia (r = -0.48, p = 0.01), and positively correlated with the cerebral ΔHHb in normoxia (r = 0.45, p = 0.02). The occurrence of EIH at sea level was associated with specific muscle and cerebral oxygenation responses to exercise under both normoxia and moderate hypoxia.

Evolution of blood rheology and its relationship to pulmonary hemodynamic during the first days of exposure to moderate altitude.

Blood rheology and hemodynamic parameters have never been explored together during acclimatization to altitude. This study aimed to investigate changes in blood rheology parameters and pulmonary hemodynamics during the first days of real moderate altitude exposure.Seventeen athletes were tested at sea-level, 20 hours after their arrival at 2,400 meters of altitude (H1) and five days later (H2). Blood was sampled to analyze red blood cell (RBC) aggregation, blood viscosity and hematocrit. Pulmonary arterial pressure (PAP), pulmonary capillary pressure (Pcap) and pulmonary vascular resistance (PVR) were assessed by echocardiography.We observed a rise in hematocrit, blood viscosity, RBC aggregation, PAP, Pcap and PVR between sea-level and H1. In H2, RBC aggregation, hematocrit, PAP, Pcap and PVR remained different compared to sea-level and no difference was observed between H1 and H2. Blood viscosity decreased in H2 and returned to sea-level values.Our results suggest that hemoconcentration occurring within the first hours of altitude exposure increased blood viscosity, which contributed to the changes in pulmonary hemodynamic. When blood viscosity decreased in H2, no change occurred in pulmonary hemodynamic parameters suggesting that hypoxic pulmonary vasoconstriction was still present. The elevated RBC aggregation observed after in H2 could participate in the increase of Pcap.

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, 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⋅min, P < 0.001, and CaO2 to 16.5 ± 1.7 mL·dL, 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.

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.

Heart rate variability to assess ventilatory threshold in ski-mountaineering.

The capacity to predict the heart rate (HR) and speed at the first (VT1) and second (VT2) ventilatory thresholds was evaluated during an incremental ski-mountaineering test using heart rate variability (HRV). Nine skiers performed a field test to exhaustion on an alpine skiing track. VT1 and VT2 were individually determined by visual analysis from gas exchanges (VT1V and VT2V) and time-varying spectral HRV analysis (VT1fH, VT2fH and VT2H). VT1 could not be determined with the HRV methods used. On the contrary, the VT2 was determined in all skiers. No significant difference between HR and speed at VT2H and VT2V was observed (174.3 ± 5.6 vs. 174.3 ± 5.3 bpm, and 6.3 ± 0.9 and 6.3 ± 0.9 km h(-1), respectively). Strong correlations were obtained for HR (r = 0.91) and speed (r = 0.92) at VT2H and VT2V with small limits of agreement (±3.6 bpm for HR). Our results indicated that HRV enables determination of HR and speed at VT2 during a specific ski-mountaineering incremental test. These findings provide practical applications for skiers in order to evaluate and control specific training loads, at least when referring to VT2.

Nutritional and metabolic determinants of blood rheology differ between trained and sedentary individuals.

Body composition and nutrition have been reported to be correlated with blood rheology. However, in sedentary and in physically active individuals these relationships seem to be not exactly similar. This study investigated whether exercise training status influences these relationships. 32 athletes (ATH) (age: 25 ± 0.7 yr; body mass index (BMI): 23.75 ± 0.23 kg/m2) were compared to 21 sedentary subjects (SED) (age: 45.19 ± 2.90; BMI = 33.41 ± 1.33) with nutritional assessment (autoquestionnaire), bioelectrical impedancemetry, viscometry at high shear rate (MT90) and Myrenne aggregometer. Subjects differ according to age, weight and adiposity parameters. Their eating behavior is different: ATH eat a higher percentage of protein (p < 0.005), a lower percentage of lipid (p < 0.05), and a higher total amount of carbohydrate (+31% p < 0.02). Their viscosity factors are similar except plasma viscosity which is higher in SED than ATH (1.51 ± 0.03 vs 1.43 ± 0.02 mPa.s, p < 0.05). In both ATH and SED, abdominal obesity (waist-to-hip ratio or WHR) is associated with impairments in blood rheology, but not exactly the same. In ATH, WHR is associated with an increase in hematocrit (r = 0.647; p = 0.009), plasma viscosity (r = 0.723; p = 0.002), and caloric (and CHO) intake moderately increase RBC rigidity (r = 0.5405; p = 0.0251) and aggregability (r = 0.3366 p = 0.0596). In SED the picture is different, adiposity increases hematocrit (r = 0.460; p = 0.048), abdominal fatness increases blood viscosity independent of hematocrit, and CHO intake is associated with lower RBC aggregability (r = -0.493; p = 0.0319).

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.

Does correction of exercise-induced desaturation by O(2) always improve exercise tolerance in COPD? A preliminary study.

BACKGROUND: This study sought to investigate whether correction of exercise-induced desaturation by oxygen supply (O(2)) systematically improves exercise tolerance and cardiorespiratory adaptations in COPD patients. METHODOLOGY: Twenty-five COPD patients [FEV(1)=52+/-2.5% pred] exhibiting exercise-induced desaturation performed cyclo-ergometer endurance exercise at 60%of their maximal workload in two randomized conditions: air vs. O(2). O(2) was adjusted to ensure 90 < or = SpO(2) < or = 95%. Endurance time (Tlim), dyspnoea, ventilation (V (E)), breathing frequency (fb), tidal volume (V(T)), cardiac output (CO), heart rate (HR) and arterio-venous difference in oxygen (AVD) were compared between conditions. RESULTS: The comparison of whole group performance between conditions revealed no differences, but individual analysis showed that O(2) increased Tlim for 14 patients [+68%; p<0.01; (positive responders)], decreased it for seven [-36%; p<0.05; (negative responders)] and induced no change for four (non-responders). For positive responders, improved performance was supported by reduced dyspnoea, V (E), fb, HR and CO and increased AVD. For negative responders, hyperoxia resulted in increased dyspnoea and fb without change in V (E) or cardiovascular parameters. CONCLUSION: For comparable correction of exercise desaturation, O(2) does not induce similar effects on exercise responses in all patients. These results were confirmed in complementary study with 11 consecutives patients at higher exercise intensity. For R+, we recorded the classic and expected O(2) effects on cardiorespiratory adaptations (i.e. reduced ventilatory demand and cardiac output). In the other group, exercise breathing frequency and dyspnoea were paradoxically increased despite desaturation correction. However, this study must be considered as pilot study, which will need to be confirmed in future studies conducted on a larger case series.

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.

6-minute walk testing is more sensitive than maximal incremental cycle testing for detecting oxygen desaturation in patients with COPD.

STUDY OBJECTIVES: Some respiratory patients exhibit oxygen desaturation during rehabilitative walking but not during maximal cardiopulmonary exercise testing (CPET). We evaluated exercise-induced desaturation during 6-min walk testing (6MWT) in comparison with CPET in patients with COPD and determined the reproducibility of the phenomenon. PATIENTS: We tested 80 consecutive patients with COPD (FEV(1), 62.4 +/- 2% predicted) and 10 patients with supplementary COPD (FEV(1), 59.1 +/- 5% predicted) [mean +/- SEM] to determine the reproducibility. MEASUREMENTS AND RESULTS: First, patients with COPD performed cycle CPET (first CPET [CPET-1]). Three days later, they performed two 6MWTs (first 6MWT [6MWT-1] and second 6MWT [6MWT-2]). Pulse oximetric saturation (SpO(2)) was recorded every minute in both tests. Three groups emerged: desaturation at 6MWT not observed at CPET (DND) [n = 23], desaturation in both tests (n = 16), and no desaturation in either test (n = 41). Second, to evaluate reproducibility, 10 additional subjects with COPD who exhibited desaturation during two successive 6MWTs but not in CPET performed a second CPET (CPET-2) and a single-bout 6MWT (6MWT-3) in a supplementary trial. When two CPETs were performed, lack of O(2) desaturation was noted in both. O(2) desaturation was confirmed in 6MWT-2 and 6MWT-3 (7.4 +/- 1% and 7.4 +/- 1.5%, respectively). CONCLUSION: Twenty-eight percent of patients with COPD presented DND. The phenomenon was reproducible and not protocol dependent, emphasizing the clinical interest of the 6MWT.