The World Anti‐Doping Agency prohibit glucocorticoid (GC) administration during competition but allow administration in periods out of competition. However, GC administration may accelerate ...erythropoiesis and resemble blood volume manipulation methods, which are prohibited at all times. Here, we investigated whether a single GC injection accelerate erythropoiesis, increase total hemoglobin mass (Hbmass) and improve exercise performance.
In a randomized, double‐blinded, placebo‐controlled crossover design (3‐month washout), eight trained males (maximal oxygen uptake 60±5 ml O2·min‐1·kg‐1) were injected with 40 mg triamcinolone acetonide (GC group) or saline (PLA group) in the gluteal muscles. Venous blood samples collected before and 7‐10h, 1, 3, 7, 14 and 21 days after treatment were analyzed for Hb and reticulocyte percentage (ret%). Hbmass and mean power output in a 450‐kCal time trial was measured before as well as one and three weeks after treatment.
A 27±28% and 54±41% higher ret% was evident three (P<0.01) and seven (P<0.001) days after the GC administration, respectively, compared with PLA, whereas Hb was similar between groups. Additionally, Hbmass was 20±28g higher (P<0.05) one week after GC administration compared with PLA, but similar after three weeks. The mean power output was similar between groups one (GC: 285±70 W, PLA: 279±69 W) and three (GC: 279±72 W, PLA: 276±71 W) weeks after treatment.
In conclusion, a single intramuscular injection of triamcinolone acetonide was sufficient to accelerate erythropoiesis and increase Hbmass, but did not translate into improved aerobic exercise performance in the present study. Future research should confirm whether anti‐doping authorities should consider glucocorticoid injections as a method of blood volume manipulation.
We investigated the effects of recombinant human erythropoietin (rHuEPO) administration on exercise endurance, maximal aerobic performance, and total hemoglobin mass (tHb). We hypothesized that ...frequent, small intravenous injections of epoetin β would increase time trial performance, peak oxygen uptake (V̇O 2peak ), and tHb in both males and females.
We included 48 healthy, recreational to trained males ( n = 24, mean ± SD V̇O 2peak = 55 ± 5 mL O 2 ·kg -1 ⋅min -1 ) and females ( n = 24; V̇O 2peak of 46 ± 4 mL O 2 ·kg -1 ⋅min -1 ) in a counterbalanced, double-blind, randomized, placebo-controlled study design stratified by sex. Time trial performance, V̇O 2peak , and tHb were determined before and after intravenous injections of either rHuEPO (9 IU·kg bw -1 epoetin β) or saline (0.9% NaCl) three times weekly for 4 wk.
A time-treatment effect ( P < 0.05) existed for time trial performance. Within the rHuEPO group, mean power output increased by 4.1% ± 4.2% ( P < 0.001). Likewise, a time-treatment effect ( P < 0.001) existed for V̇O 2peak , where the rHuEPO group improved V̇O 2peak and peak aerobic power by 4.2% ± 6.1% ( P < 0.001) and 2.9% ± 4.0% ( P < 0.01), respectively. A time-treatment effect ( P < 0.001) existed for tHb, where the rHuEPO group increased tHb by 6.7% ± 3.4% ( P < 0.001). A main effect of "sex" alone was also evident ( P < 0.001), but no sex-specific interactions were found. No changes were observed in the placebo group for mean power output, V̇O 2peak , peak aerobic power, or tHb.
Microdoses with intravenous rHuEPO provide a sufficient erythropoietic stimuli to augment tHb and enhance aerobic-dominated performance in both trained males and females.
With this study we tested the hypothesis that 6 wk 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 6 wk), and Qmax was determined by inert gas rebreathing during cycle ergometer exercise before and after the training period. After the training period, blood volume (determined in duplicates by CO rebreathing) was reestablished to pretraining values by phlebotomy and Qmax was quantified again. Resting echography revealed no structural heart adaptations as a consequence of the training intervention. After 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% after 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 (9 ± 6%) as a consequence of the training intervention, and after normalization of BV by phlebotomy Qmax returned to pretraining values (18.1 ± 2.5 l/min; 12 ± 5% reversal). Thus the exercise training-induced increase in BV is the main mechanism increasing Qmax after 6 wk of endurance training in previously untrained subjects.
We investigated whether hepcidin and erythroferrone (ERFE) could complement the Athlete Biological Passport (ABP) in indirectly detecting a 130 mL packed red blood cells (RBCs) autologous blood ...transfusion. Endurance performance was evaluated.
Forty-eight healthy men (n = 24) and women (n = 24) participated. Baseline samples were collected weekly followed by randomization to a blood transfusion (BT, n = 24) or control group (CON, n = 24). Only the BT group donated 450 mL whole blood from which 130 mL RBCs was reinfused four weeks later. Blood samples were collected 3, 7, 14, 21 and 28 days after donation, and 3, 6, and 24 hours and 2, 3, and 6 days following reinfusion. In the CON group samples were collected with the same frequency. Endurance performance was evaluated by a 650-kCal time trial (n = 13) before and one and six days after reinfusion.
A time×treatment effect existed (P < 0.05) for hepcidin and ERFE. Hepcidin was increased (P < 0.01) ~110 and 89% six and 24 hours after reinfusion. Using an individual approach (99% specificity, e.g. allowing 1:100 false-positive), sensitivities, i.e. true positives, of 30% and 61% was found for hepcidin and ERFE, respectively. For the ABP, the most sensitive marker was Off-hr score (Hb (g/L) - 60 × √RET%) (P < 0.05) with a maximal sensitivity of ~58% and ~ 9% following donation and reinfusion, respectively. Combining the findings for hepcidin, ERFE and the ABP yielded a sensitivity across all time-points of 83% following reinfusion in BT. Endurance performance increased 24 hours (+6.4%, P < 0.01) and six days following reinfusion (+5.8%, P < 0.01).
Hepcidin and ERFE may serve as biomarkers in an anti-doping context following an ergogenic, small-volume blood transfusion.
Current markers of iron deficiency (ID), such as ferritin and hemoglobin, have shortcomings, and hepcidin and erythroferrone (ERFE) could be of clinical relevance in relation to early assessment of ...ID. Here, we evaluate whether exposure to altitude-induced hypoxia (2,320 m) alone, or in combination with recombinant human erythropoietin (rHuEPO) treatment, affects hepcidin and ERFE levels before alterations in routine ID biomarkers and stress erythropoiesis manifest. Two interventions were completed, each comprising a 4-wk baseline, a 4-wk intervention at either sea level or altitude, and a 4-wk follow-up. Participants (
= 39) were randomly assigned to 20 IU·kg body wt
rHuEPO or placebo injections every second day for 3 wk during the two intervention periods. Venous blood was collected weekly. Altitude increased ERFE (
≤ 0.001) with no changes in hepcidin or routine iron biomarkers, making ERFE of clinical relevance as an early marker of moderate hypoxia. rHuEPO treatment at sea level induced a similar pattern of changes in ERFE (
< 0.05) and hepcidin levels (
< 0.05), demonstrating the impact of accelerated erythropoiesis and not of other hypoxia-induced mechanisms. Compared with altitude alone, concurrent rHuEPO treatment and altitude exposure induced additive changes in hepcidin (
< 0.05) and ERFE (
≤ 0.001) parallel with increases in hematocrit (
< 0.001), demonstrating a relevant range of both hepcidin and ERFE. A poor but significant correlation between hepcidin and ERFE was found (
= 0.13,
< 0.001). The findings demonstrate that hepcidin and ERFE are more rapid biomarkers of changes in iron demands than routine iron markers. Finally, ERFE and hepcidin may be sensitive markers in an antidoping context.
The present case report aimed to investigate the effects of exercise training in temperate ambient conditions while wearing a heat suit on hemoglobin mass (Hbmass).
As part of their training ...regimens, 5 national-team members of endurance sports (3 males) performed ∼5 weekly heat suit exercise training sessions each lasting 50 minutes for a duration of ∼8 weeks. Two other male athletes acted as controls. After the initial 8-week period, 3 of the athletes continued for 2 to 4 months with ∼3 weekly heat sessions in an attempt to maintain acquired adaptations at a lower cost. Hbmass was assessed in duplicate before and after intervention and maintenance period based on automated carbon monoxide rebreathing.
Heat suit exercise training increased rectal temperature to a median value of 38.7°C (range 38.6°C-39.0°C), and during the initial ∼8 weeks of heat suit training, there was a median increase of 5% (range 1.4%-12.9%) in Hbmass, while the changes in the 2 control athletes were a decrease of 1.7% and an increase of 3.2%, respectively. Furthermore, during the maintenance period, the 3 athletes who continued with a reduced number of heat suit sessions experienced a change of 0.7%, 2.8%, and -1.1%, indicating that it is possible to maintain initial increases in Hbmass despite reducing the weekly number of heat suit sessions.
The present case report illustrates that heat suit exercise training acutely raises rectal temperature and that following 8 weeks of such training Hbmass may increase in elite endurance athletes.
Introduction
Determination of blood volume (BV) using the dual‐isotope (e.g., 99mTc‐labeled red blood cells 99mTc‐RBC and 125I‐labeled human serum albumin 125I‐HSA) injection method is limited in ...medicine due to the long isotope half‐life. However, BV has been determined in laboratory settings for 100 years using the carbon monoxide (CO)‐rebreathing‐based procedure, which allows frequent BV measurements.
Methods
We investigated the reliability and accuracy of a semi‐automated CO‐rebreathing device by comparing it against the dual‐isotope methodology and its ability to detect a known blood removal. In study A, BV was determined three times in ~2 h; twice using the device with rebreathing protocols lasting 2 (CO2min) and 10 min (CO10min) and once with the dual‐isotope technique. In study B, the accuracy of the device was assessed by its ability to detect a 2% removal of BV.
Results
A good correlation was observed between both the CO‐rebreathing protocols (r2 = 0.89–0.98; p < 0.001) and the dual‐isotope approach (r2 = 0.89–0.95; p < 0.001). In absolute terms BV was 425 ± 263 mL and 491 ± 388 mL lower (p < 0.001) when quantified with the dual‐isotope compared to the CO‐rebreathing protocols. When reducing BV by 132 ± 25 mL (2%), the device quantified a lower (p < 0.001) BV of 150 ± 45 mL.
Conclusion
This study emphasizes that the semi‐automated device accurately determines small changes (i.e., 2%) in BV and that a high correlation with the dual‐isotope methodology exists. The findings are clinically relevant owing to the method's simple and fast nature (the absence of radioactive tracers and reduced time requirements, i.e., ~15 min vs. ~180 min) and the possibility for repeated measurements within a single day.
The cumbersome nature of the dual‐isotope (e.g., 99mTc and 125I‐HSA) injection method has limited the widespread use of blood volume (BV) evaluation in medicine. However, BV has been determined in laboratory settings for centuries using a reliable and rapid carbon monoxide (CO)‐rebreathing‐based procedure. Here, the reliability and accuracy of a newly developed semi‐automated CO‐rebreathing device was investigated by comparing it against the dual‐isotope methodology and its ability to detect a known blood removal. In study A, BV was determined three times within a single day; twice with the device with rebreathing protocols lasting 2 (CO2min) and 10 minutes (CO10min) and once with the dual‐isotope technique. In study B, the accuracy of the device was assessed by its ability to detect a 2% removal of BV. A good correlation (r2 = 0.89–0.95; p < 0.001) was observed between both the CO‐rebreathing protocols versus the dual‐isotope approach and between the two CO‐rebreathing protocols (r2 = 0.89–0.98; p < 0.001). However, in absolute terms BV was 425 ± 263 mL and 491 ± 388 mL lower (p < 0.001) when quantified with the dual‐isotope compared to the CO‐rebreathing protocols. When reducing BV by 132 ± 25 mL (2%), the device accurately quantified a lower (p < 0.001) BV and determined this reduction being 150 ± 45 mL. This study emphasizes the high precision and accuracy of the device and a high correlation with the dual‐isotope methodology. The findings are clinically relevant owing to the device simple and fast nature (the absence of radioactive tracers and reduced time requirements, i.e., ~15 min vs. ~180 min) and the possibility for repeated measurements within a single day.
Sprint-interval training (SIT) is efficient at improving maximal aerobic capacity and anaerobic fitness at sea-level and may be a feasible training strategy at altitude. Here, it was evaluated if SIT ...intensity can be maintained in mild to moderate hypoxia. It was hypothesized that 6 x 30 s Wingate sprint performance with 2 min active rest between sprints can be performed in hypoxic conditions corresponding to ~3,000 m of altitude without reducing mean power output (MPO). In a single-blinded, randomized crossover design, ten highly-trained male endurance athletes with a maximal oxygen uptake (Formula: see textO2max) of 68 ± 5 mL O2 × min-1 × kg-1 completed 6 x 30 s all-out Wingate cycling sprints separated by two-minute active recovery on four separate days in a hypobaric chamber. The ambient pressure within the chamber on each experimental day was 772 mmHg (~0 m), 679 mmHg (~915 m), 585 mmHg (~ 2,150 m), and 522 mmHg (~3,050 m), respectively. MPO was not different at sea-level and up to ~2,150 m (~1% and ~3% non-significant decrements at ~915 and ~2,150 m, respectively), whereas MPO was ~5% lower (P<0.05) at ~3,050 m. Temporal differences between altitudes was not different for peak power output (PPO), despite a main effect of altitude. In conclusion, repeated Wingate exercise can be completed by highly-trained athletes at altitudes up to ~2,150 m without compromising MPO or PPO. In contrast, MPO was compromised in hypobaric hypoxia corresponding to ~3,050 m. Thus, SIT may be an efficient strategy for athletes sojourning to moderate altitude and aiming to maintain training quality.
Purpose
Angiotensin-converting enzyme (ACE) inhibitor treatment is widely applied, but the fact that plasma ACE activity is a potential determinant of training-induced local muscular adaptability is ...often neglected. Thus, we investigated the hypothesis that ACE inhibition modulates the response to systematic aerobic exercise training on leg and arm muscular adaptations.
Methods
Healthy, untrained, middle-aged participants (40 ± 7 yrs) completed a randomized, double-blinded, placebo-controlled trial. Participants were randomized to placebo (PLA: CaCO
3
) or ACE inhibitor (ACE
i
: enalapril) for 8 weeks and completed a supervised, high-intensity exercise training program. Muscular characteristics in the leg and arm were extensively evaluated pre and post-intervention.
Results
Forty-eight participants (
n
ACEi
= 23,
n
PLA
= 25) completed the trial. Exercise training compliance was above 99%. After training, citrate synthase, 3-hydroxyacyl-CoA dehydrogenase and phosphofructokinase maximal activity were increased in m. vastus lateralis in both groups (all
P
< 0.05) without statistical differences between them (all time × treatment
P
> 0.05). In m. deltoideus, citrate synthase maximal activity was upregulated to a greater extent (time × treatment
P
< 0.05) in PLA (51 33;69 %) than in ACE
i
(28 13;43 %), but the change in 3-hydroxyacyl-CoA dehydrogenase and phosphofructokinase maximal activity was similar between groups. Finally, the training-induced changes in the platelet endothelial cell adhesion molecule-1 protein abundance, a marker of capillary density, were similar in both groups in m. vastus lateralis and m. deltoideus.
Conclusion
Eight weeks of high-intensity whole-body exercise training improves markers of skeletal muscle mitochondrial oxidative capacity, glycolytic capacity and angiogenesis, with no overall effect of pharmacological ACE inhibition in healthy adults.
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