[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to investigate the effects of manipulating hematocrit by different methods (acute exercise, training or isovolumic hemodilution) on blood viscosity in high-level aerobic endurance athletes. We hypothesized than increasing hematocrit does not always cause a rise in blood viscosity.
Sixteen endurance athletes underwent maximal exercise before and after 4 weeks of training with (LHTL; n = 10) or without (placebo; n = 6) Live High-Train Low modalities. Total hemoglobin mass was measured before and after training by a carbon monoxide rebreathing technique. After training, subjects performed two maximal exercise bouts separated by isovolumic hemodilution (phlebotomy and/or plasma volume expander) to readjust red blood cell volume and plasma volume to baseline values. Blood samples were obtained before and after exercise to assess hematocrit and blood and plasma viscosity.
Training session (LHTL and placebo) increased hematocrit (Hct) in all subjects but without any significant change in blood viscosity. The decrease in plasma viscosity in all groups may explain this result. Isovolumic hemodilution caused a drop of Hct without any significant change in blood viscosity at rest. Maximal exercise increased Hct, blood and plasma viscosities in both groups, regardless of isovolumic hemodilution. However, peak hemorheological values after exercise were lower after isovolumic hemodilution.
In conclusion, while acute increase in Hct during exercise caused an increase of blood viscosity, the chronic increase of Hct induced by training session did not result in a rise in blood viscosity. The lowering of plasma viscosity during training may compensate for the increase of Hct, hence limiting its impact on blood viscosity.
Full-text · Article · Jan 2016 · Clinical hemorheology and microcirculation
[Show abstract][Hide abstract] ABSTRACT: It is investigated if recombinant human erythropoietin (rHuEPO) treatment for 15 weeks (n = 8) reduces extracellular accumulation of metabolic stress markers such as lactate, H+, and K+ during incremental exhaustive exercise. After rHuEPO treatment, normalization of blood volume and composition by hemodilution preceded an additional incremental test. Group averages were calculated for an exercise intensity ∼80% of pre-rHuEPO peak power output. After rHuEPO treatment, leg lactate release to the plasma compartment was similar to before (4.3 ± 1.6 vs 3.9 ± 2.5 mmol/min) and remained similar after hemodilution. Venous lactate concentration was higher (P < 0.05) after rHuEPO treatment (7.1 ± 1.6 vs 5.2 ± 2.1 mM). Leg H+ release to the plasma compartment after rHuEPO was similar to before (19.6 ± 5.4 vs 17.6 ± 6.0 mmol/min) and remained similar after hemodilution. Nevertheless, venous pH was lower (P < 0.05) after rHuEPO treatment (7.18 ± 0.04 vs 7.22 ± 0.05). Leg K+ release to the plasma compartment after rHuEPO treatment was similar to before (0.8 ± 0.5 vs 0.7 ± 0.7 mmol/min) and remained similar after hemodilution. Additionally, venous K+ concentrations were similar after vs before rHuEPO (5.3 ± 0.3 vs 5.1 ± 0.4 mM). In conclusion, rHuEPO does not reduce plasma accumulation of lactate, H+, and K+ at work rates corresponding to ∼80% of peak power output.
Full-text · Article · Jan 2015 · Scandinavian Journal of Medicine and Science in Sports
[Show abstract][Hide abstract] ABSTRACT: Aims:
To determine the role played by adenosine, ATP and chemoreflex activation on the regulation of vascular conductance in chronic hypoxia.
The vascular conductance response to low and high doses of adenosine and ATP was assessed in ten healthy men. Vasodilators were infused into the femoral artery at sea level and then after 8-12 days of residence at 4559 m above sea level. At sea level, the infusions were carried out while the subjects breathed room air, acute hypoxia (FI O2 = 0.11) and hyperoxia (FI O2 = 1); and at altitude (FI O2 = 0.21 and 1). Skeletal muscle P2Y2 receptor protein expression was determined in muscle biopsies after 4 weeks at 3454 m by Western blot.
At altitude, mean arterial blood pressure was 13% higher (91 ± 2 vs. 102 ± 3 mmHg, P < 0.05) than at sea level and was unaltered by hyperoxic breathing. Baseline leg vascular conductance was 25% lower at altitude than at sea level (P < 0.05). At altitude, the high doses of adenosine and ATP reduced mean arterial blood pressure by 9-12%, independently of FI O2 . The change in vascular conductance in response to ATP was lower at altitude than at sea level by 24 and 38%, during the low and high ATP doses respectively (P < 0.05), and by 22% during the infusion with high adenosine doses. Hyperoxic breathing did not modify the response to vasodilators at sea level or at altitude. P2Y2 receptor expression remained unchanged with altitude residence.
Short-term residence at altitude increases arterial blood pressure and reduces the vasodilatory responses to adenosine and ATP.
Full-text · Article · Jun 2014 · Acta Physiologica
[Show abstract][Hide abstract] ABSTRACT: The effects of hypoxic training on exercise performance remain controversial. Here we tested the hypotheses that i) hypoxic training possesses ergogenic effects at sea-level and altitude, and ii) the benefits are primarily mediated by improved mitochondrial function of skeletal muscle.
We determined aerobic performance (incremental test to exhaustion and time trial for a set amount of work) in moderately-trained subjects undergoing six weeks of endurance training (3-4 times/week, 60 min/session) in normoxia (placebo, n=8) or normobaric hypoxia (FIO2=0.15; n=9) using a double blind and randomized design. Exercise tests were performed in normoxia and acute hypoxia (FIO2=0.15). Skeletal muscle mitochondrial respiratory capacities and electron coupling efficiencies were measured via high-resolution respirometry. Total hemoglobin mass (Hbmass) was assessed by carbon-monoxide rebreathing.
Skeletal muscle respiratory capacity was not altered by training or hypoxia, however electron coupling control respective to fat oxidation slightly diminished with hypoxic training. Hypoxic training did increase Hbmass more than placebo (8.4 vs 3.3%, p=0.02). In normoxia, hypoxic training had no additive effect on maximal measures of oxygen uptake (VO2peak) or time trial performance. In acute hypoxia, hypoxic training conferred no advantage on VO2peak, but tended to enhance time trial performance more than normoxic training (52 versus 32%, p=0.09).
Our data suggest that, in moderately-trained subjects, six weeks of hypoxic training possess no ergogenic effect at sea-level. It is not excluded that hypoxic training might facilitate endurance capacity at moderate altitude, however this issue is still open and needs to be further examined.
No preview · Article · Mar 2014 · Medicine and science in sports and exercise
[Show abstract][Hide abstract] ABSTRACT: With this study we tested the hypothesis that six weeks of endurance training increases maximal cardiac output (Qmax) relatively more by elevating blood volume (BV) than by inducing structural and functional changes within the heart. Nine healthy but untrained volunteers (VO2max 47 ± 5 ml.min(-1).kg(-1)) underwent supervised training (60 min; 4 times weekly at 65% VO2max for six weeks) and Qmax was determined by inert gas re-breathing during cycle ergometer exercise before and after the training period. After the training period, blood volume (determined in duplicates by CO re-breathing) was re-established to pre-training values by phlebotomy and Qmax was quantified again. Resting echography revealed no structural heart adaptations as a consequence of the training intervention. Following the training period, plasma volume (PV), red blood cell volume (RBCV) and BV increased (p<0.05) by 147 ± 168 (5 ± 5 %), 235 ± 64 (10 ± 3 %) and 382 ± 204 ml (7 ± 4 %), respectively. VO2max was augmented (p<0.05) by 10 ± 7 % following the training period and decreased (p<0.05) by 8 ± 7 % with phlebotomy. Concomitantly, Qmax was increased (p<0.05) from 18.9 ± 2.1 to 20.4 ± 2.3 l.min(-1) (9 ± 6 %) as a consequence of the training intervention, and following normalization of BV by phlebotomy Qmax returned to pre training values (18.1 ± 2.5 l.min(-1); 12 ± 5 % reversal). Thus, the exercise training induced increase in BV is the main mechanism increasing Qmax following six weeks of endurance training in previously untrained subjects.
Full-text · Article · Mar 2014 · AJP Regulatory Integrative and Comparative Physiology
[Show abstract][Hide abstract] ABSTRACT: This study investigated the changes in cerebral near-infrared spectroscopy (NIRS) signals, cerebrovascular and ventilatory responses to hypoxia and CO2 during altitude exposure. At sea level (SL), after 24 hours and 5 days at 4,350 m, 11 healthy subjects were exposed to normoxia, isocapnic hypoxia, hypercapnia, and hypocapnia. The following parameters were measured: prefrontal tissue oxygenation index (TOI), oxy- (HbO2), deoxy- and total hemoglobin (HbTot) concentrations with NIRS, blood velocity in the middle cerebral artery (MCAv) with transcranial Doppler and ventilation. Smaller prefrontal deoxygenation and larger ΔHbTot in response to hypoxia were observed at altitude compared with SL (day 5: ΔHbO2-0.6±1.1 versus -1.8±1.3 μmol/cmper mm Hg and ΔHbTot 1.4±1.3 versus 0.7±1.1 μmol/cm per mm Hg). The hypoxic MCAv and ventilatory responses were enhanced at altitude. Prefrontal oxygenation increased less in response to hypercapnia at altitude compared with SL (day 5: ΔTOI 0.3±0.2 versus 0.5±0.3% mm Hg). The hypercapnic MCAv and ventilatory responses were decreased and increased, respectively, at altitude. Hemodynamic responses to hypocapnia did not change at altitude. Short-term altitude exposure improves cerebral oxygenation in response to hypoxia but decreases it during hypercapnia. Although these changes may be relevant for conditions such as exercise or sleep at altitude, they were not associated with symptoms of acute mountain sickness.Journal of Cerebral Blood Flow & Metabolism advance online publication, 25 September 2013; doi:10.1038/jcbfm.2013.167.
Full-text · Article · Sep 2013 · Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Hemoglobin mass (Hbmass) is commonly assessed using the CO re-breathing method with the subject in the seated position. This may lead to an underestimation of Hbmass as blood in lower extremity veins while seated may not be tagged with carbon monoxide (CO) during the re-breathing period.
To test this hypothesis, CO re-breathing was performed on four occasions in nine male subjects, twice in the seated position and twice in combination with light cycle ergometer exercise (1 W/kg body-weight) intending to accelerate blood circulation and thereby potentially allowing for a better distribution of CO throughout the circulation as compared to in the seated position. Blood samples were drawn from an antecubital vein and the saphenous magna vein following the re-breathing procedure.
In the seated position, CO re-breathing increased the percent carboxyhemoglobin (%HbCO) in the antecubital vein to 8.9 % (7.8-10.7) [median (min-max)], but less (P = 0.017) in the saphenous magna vein [7.8 % (5.0-9.9)]. With exercise, no differences in %HbCO were observed between sampling sites. As a result, CO re-breathing in combination with exercise revealed a ~3 % higher (P = 0.008) Hbmass, i.e., 936 g (757-1,018) as compared to 908 g (718-940) at seated rest.
This study suggests an uneven distribution of CO in the circulation if the CO re-breathing procedure is performed at rest in the seated position and therefore can underestimate Hbmass.
[Show abstract][Hide abstract] ABSTRACT: Inhibition of hepcidin expression by erythropoietic signals is of great physiological importance, however the inhibitory pathways remain poorly understood. To investigate i) the direct effect of erythropoietin (Epo) and ii) the contribution of putative mediators on hepcidin repression, healthy volunteers were injected with a single dose of Epo, either low (63 IU/kg, n=8) or high (400 IU/kg, n=6). Low-dose Epo provoked hepcidin down-modulation within 24 hours; the effect was not immediate since hepcidin circadian variations were still present following injection. High-dose Epo induced no additional effect on the hepcidin response, i.e. hepcidin diurnal fluctuations were not abolished in spite of extremely high Epo levels. We did not find significant changes in putative mediators of hepcidin repression, such as transferrin saturation, soluble transferrin receptor, or growth differentiation factor 15. Furthermore, the potential hepcidin inhibitor, soluble hemojuvelin, was found unaltered by Epo stimulation. This finding was consistent with the absence of signs of iron deficiency observed at the level of skeletal muscle tissue. Our data suggest that hepcidin repression by erythropoietic signals in humans may not be controlled directly by Epo but mediated by a still undefined factor. This article is protected by copyright. All rights reserved.
Full-text · Article · Apr 2013 · European Journal Of Haematology
[Show abstract][Hide abstract] ABSTRACT: Changes in cerebral perfusion and CO(2) cerebrovascular reactivity during and immediately after a sojourn at high altitude remain unclear but may be critical for acclimatization. The aim of the present study was to assess the effects of 6days at 4,350m on cerebral perfusion and cerebrovascular reactivity (CVR) to CO(2) by arterial spin labeling (ASL) magnetic resonance imaging at sea level and to compare it with transcranial Doppler (TCD) results at altitude. Eleven healthy male subjects, non-acclimatized to altitude, stayed for 6days at 4,350m (Observatoire Vallot, massif du Mont-Blanc). Prior to the stay and within 6h after returning to sea level, subjects were investigated using pseudo-continuous ASL at 3T during a block-design inhalation paradigm to measure basal cerebral blood flow (CBF) and CO(2) CVR. End-tidal CO(2) (PetCO(2)), respiratory rate, heart rate and oxygen saturation were recorded during the exam. Subjects were also examined using TCD prior to and on day 5 of the stay at altitude to measure blood velocity in the middle cerebral artery (MCAv) and CO(2) CVR. CO(2) CVR was expressed as percent change in ASL CBF or TCD MCAv per mmHg change in PetCO(2). PetCO(2) was significantly decreased during and after altitude. Significant increases in TCD MCAv compared to before altitude measurements were observed on day 5 at altitude (+20.5±15.5 %). Interestingly, ASL CBF remained increased in the MCA and anterior vascular territories (+22.0±24.1 % and 20.5±20.3 %, respectively) after altitude under normoxic conditions. TCD CVR tended to decrease on day 5 at 4,350m (-12.3±54.5 % in the MCA) while the ASL CVR was significantly decreased after altitude (-29.5±19.8 % in the MCA). No correlation was observed between cerebral hemodynamic changes and symptoms of acute mountain sickness at high altitude. In conclusion, prolonged exposure to high altitude significantly increases blood flow during the altitude stay and within 6h after returning to sea level. Decreased CO(2) CVR after prolonged altitude exposure was also observed using ASL. Changes in cerebral hemodynamics with altitude exposure probably involve other mechanisms than the vasodilatory effect of hypoxia only, since it persists under normoxia several hours following the descent.
[Show abstract][Hide abstract] ABSTRACT: It remains unclear by which mechanism 'live high-train low' (LHTL) altitude training increases exercise performance. Haematological and skeletal muscle adaptations have both been proposed. To test the hypotheses that (i) LHTL improves maximal oxygen uptake (VO(2)max) and (ii) this improvement is related to hypoxia-induced increases in total haemoglobin mass (Hb(mass)) and not to improved maximal oxidative capacity of skeletal muscle, we determined VO(2)max before LHTL and after LHTL, before and after the altitude-induced increases in Hb(mass) (measured by carbon-monoxide rebreathing) had been abolished by isovolumic haemodilution. We obtained skeletal muscle biopsies to quantify mitochondrial oxidative capacity and efficiency. Sixteen endurance-trained athletes were assigned (double-blinded, placebo controlled) to ≥16 h/day over 4 weeks to normoxia (placebo, n=6) or normobaric hypoxia equivalent to 3000 m altitude (LHTL, n=10). Four-week LHTL did not increase VO(2)max, irrespective of treatment (LHTL: 1.5%; placebo: 2.0%). Hb(mass) was slightly increased (4.6%) in 5 (of 10) LHTL subjects but this was not accompanied by a concurrent increase in VO(2)max. In the subjects demonstrating an increase in Hb(mass), isovolumic haemodilution elicited a 5.8% decrease in VO(2)max. Cycling efficiency was altered neither with time nor by LHTL. Neither maximal capacity of oxidative phosphorylation nor mitochondrial efficiency was modified by time or LHTL. The present results suggest that LHTL has no positive effect on VO(2)max in endurance-trained athletes because (i) muscle maximal oxidative capacity is not improved following LHTL and (ii) erythrocyte volume expansion after LHTL, if any, is too small to alter O(2) transport.
Full-text · Article · Jul 2012 · British Journal of Sports Medicine
[Show abstract][Hide abstract] ABSTRACT: Hypoxia-stimulated erythropoiesis, such as that observed when red blood cell volume (RCV) increases in response to high-altitude exposure, is well understood while the physiological importance is not. Maximal exercise tests are often performed in hypoxic conditions following some form of RCV manipulation in an attempt to elucidate oxygen transport limitations at moderate to high altitudes. Such attempts, however, have not made clear the extent to which RCV is of benefit to exercise at such elevations. Changes in RCV at sea level clearly have a direct influence on maximal exercise capacity. Nonetheless, at elevations above 3000 m, the evidence is not that clear. Certain studies demonstrate either a direct benefit or decrement to exercise capacity in response to an increase or decrease, respectively, in RCV whereas other studies report negligible effects of RCV manipulation on exercise capacity. Adding to the uncertainty regarding the importance of RCV at high altitude is the observation that Andean and Tibetan high-altitude natives exhibit similar exercise capacities at high altitude (3900 m) even though Andean natives often present with a higher percent haematocrit (Hct) when compared with both lowland natives and Tibetans. The current review summarizes past literature that has examined the effect of RCV changes on maximal exercise capacity at moderate to high altitudes, and discusses the explanation elucidating these seemingly paradoxical observations.
[Show abstract][Hide abstract] ABSTRACT: Prolonged running is known to induce hemolysis. It has been suggested that hemolysis may lead to a significant loss of red blood cells; however, its actual impact on the erythrocyte pool is unknown. Here, we test the hypothesis that prolonged running with high hemolytic potential decreases total red blood cell volume (RCV). Hemolysis (n = 22) and RCV (n = 19) were quantified in ultra-marathon runners before and after a 166-km long mountain ultra-endurance marathon (RUN) with 9500 m of altitude gain/loss. Assessment of total hemoglobin mass (Hb(mass) ) and RCV was performed using a carbon monoxide rebreathing technique. RUN induced a marked acute-phase response and promoted hemolysis, as shown by a decrease in serum haptoglobin (P < 0.05). Elevated serum erythropoietin concentration and reticulocyte count after RUN were indicative of erythropoietic stimulation. Following RUN, runners experienced hemodilution, mediated by a large plasma volume expansion and associated with a large increase in plasma aldosterone. However, neither Hb(mass) nor RCV were found to be altered after RUN. Our findings indicate that mechanical/physiological stress associated with RUN promotes hemolysis but this has no impact on total erythrocyte volume. We therefore suggest that exercise 'anemia' is entirely due to plasma volume expansion and not to a concomitant decrease in RCV.
Full-text · Article · Jun 2012 · Scandinavian Journal of Medicine and Science in Sports
[Show abstract][Hide abstract] ABSTRACT: Studies regarding mitochondrial modifications in human skeletal muscle following acclimatization to high altitude are conflicting, and these inconsistencies may be due to the prevalence of representing mitochondrial function through static and isolated measurements of specific mitochondrial characteristics. Therefore the aim of this study was to investigate mitochondrial function in response to high altitude acclimatization through measurements of respiratory control in the m. vastus lateralis. Skeletal muscle biopsies were obtained from ten lowland natives prior to and again after a total of 9-11 days of exposure to 4,559 m. High-resolution respirometry was performed on the muscle samples to compare respiratory chain function and respiratory capacities. Respirometric analysis revealed that mitochondrial function was largely unaffected, as high altitude exposure did not affect the capacity for fat oxidation or individualized respiration capacity through either complex I or complex II. Respiratory chain function remained unaltered, as both coupling and respiratory control did not change in response to hypoxic exposure. High altitude acclimatization did, however, show a tendency (p=0.059) to limit mass specific maximal oxidative phosphorylation capacity. This data suggests that 9-11 days of exposure to high altitude does not markedly modify integrated measures of mitochondrial functional capacity in skeletal muscle despite significant decrements to enzyme concentrations involved in the tricarboxylic acid (TCA) cycle and oxidative phosphorylation.
Full-text · Article · May 2012 · Experimental physiology
[Show abstract][Hide abstract] ABSTRACT: It was investigated if athletes subjected to 4 wk of living in normobaric hypoxia (3,000 m; 16 h/day) while training at 800-1,300 m ["live high-train low" (LHTL)] increase muscular and systemic capacity for maintaining pH and K(+) homeostasis as well as intense exercise performance. The design was double-blind and placebo controlled. Mean power during 30-s all-out cycling was similar before and immediately after LHTL (650 ± 31 vs. 628 ± 32 W; n = 10) and placebo exposure (658 ± 22 vs. 660 ± 23 W; n = 6). Supporting the performance data, arterial plasma pH, lactate, and K(+) during submaximal and maximal exercise were also unaffected by the intervention in both groups. In addition, muscle buffer capacity (in mmol H(+)·kg dry wt(-1)·pH(-1)) was similar before and after in both the LHTL (140 ± 12 vs. 140 ± 16) and placebo group (145 ± 2 vs. 140 ± 3). The expression of sarcolemmal H(+) transporters (Na(+)/H(+) exchanger 1, monocarboxylate transporters 1 and 4), as well as expression of Na(+)-K(+) pump subunits-α(1), -α(2), and -β(1) was also similar before and after the intervention. In conclusion, muscular and systemic capacity for maintaining pH and K(+) balance during exercise is similar before and after 4 wk of placebo-controlled normobaric LHTL. In accordance, 30-s all-out sprint ability was similar before and after LHTL.
No preview · Article · Mar 2012 · Journal of Applied Physiology