Angiotensin‐converting enzyme (ACE) activity may be one determinant of adaptability to exercise training, but well‐controlled studies in humans without confounding conditions are lacking. Thus, the ...purpose of the present study was to investigate whether ACE inhibition affects cardiovascular adaptations to exercise training in healthy humans. Healthy participants of both genders (40 ± 7 years) completed a randomized, double‐blind, placebo‐controlled trial. Eight weeks of exercise training combined with placebo (PLA, n = 25) or ACE inhibitor (ACEi, n = 23) treatment was carried out. Before and after the intervention, cardiovascular characteristics were investigated. Mean arterial blood pressure was reduced (p < 0.001) by −5.5 −8.4; −2.6 mmHg in ACEi, whereas the 0.7 −2.0; 3.5 mmHg fluctuation in PLA was non‐significant. Maximal oxygen uptake increased (p < 0.001) irrespective of ACE inhibitor treatment by 13 8; 17 % in ACEi and 13 9; 17 % in PLA. In addition, skeletal muscle endurance increased (p < 0.001) to a similar extent in both groups, with magnitudes of 82 55; 113 % in ACEi and 74 48; 105 % in PLA. In contrast, left atrial volume decreased (p < 0.05) by −9 −16; −2 % in ACEi, but increased (p < 0.01) by 14 5; 23 % in PLA. Total hemoglobin mass was reduced (p < 0.01) by −3 −6; −1 % in ACEi, while a non‐significant numeric increase of 2 −0.4; 4 % existed in PLA. The lean mass remained constant in ACEi but increased (p < 0.001) by 3 2; 4 % in PLA. In healthy middle‐aged adults, 8 weeks of high‐intensity exercise training increases maximal oxygen uptake and skeletal muscle endurance irrespective of ACE inhibitor treatment. However, ACE inhibitor treatment counteracts exercise training‐induced increases in lean mass and left atrial volume. ACE inhibitor treatment compromises total hemoglobin mass.
A high‐intensity endurance exercise training program improves maximal oxygen uptake, whole‐body work capacity, and muscle endurance, with no effect of ACE inhibitor treatment, in normotensive adults. However, ACE inhibitor treatment impairs the exercise‐induced increase in lean mass and left atrial volume and compromises total hemoglobin mass. Results are presented as means with 95% confidence intervals. *p < 0.05, **p < 0.001 for the within‐group change (∆) from baseline from a paired samples t‐test, and #p < 0.05 for the between‐group difference in change from baseline from an independent samples t‐test in participants treated with an angiotensin‐converting enzyme inhibitor (ACEi) or placebo. CMR, cardiovascular magnetic resonance imaging.
We investigated whether immature reticulocyte fraction (IRF) and the immature reticulocytes to red blood cells ratio (IR/RBC) are sensitive and specific biomarkers for microdose recombinant human ...erythropoietin (rHuEPO) and whether the inclusion of reticulocyte percentage (RET%) and the algorithm "abnormal blood profile score (ABPS)" increased the athlete biological passport (ABP) sensitivity compared with hemoglobin concentration (Hb) and the OFF-hr score (Hb-60 × √RET%).
Forty-eight (♀ = 24, ♂ = 24) participants completed a 2-wk baseline period followed by a 4-wk intervention period with three weekly intravenous injections of 9 IU·kg -1 ·bw -1 epoetin β (♀ = 12, ♂ = 12) or saline (0.9% NaCl, ♀ = 12, ♂ = 12) and a 10-d follow-up. Blood samples were collected weekly during baseline and intervention as well as 3, 5, and 10 d after treatment.
The rHuEPO treatment increased Hb (time-treatment, P < 0.001), RET% (time-treatment, P < 0.001), IRF (time-treatment, P < 0.001) and IR/RBC (time-treatment, P < 0.001). IRF and IR/RBC were up to ~58% ( P < 0.001) and ~141% ( P < 0.001) higher compared with placebo, and calculated thresholds provided a peak sensitivity across timepoints of 58% and 54% with ~98% specificity, respectively. To achieve >99% specificity for IRF and IR/RBC, sensitivity was reduced to 46% and 50%, respectively. Across all timepoints, the addition of RET% and ABPS to the ABP increased sensitivity from 29% to 46%. Identification of true-positive outliers obtained via the ABP and IRF and IR/RBC increased sensitivity across all timepoints to 79%.
In summary, IRF, IR/RBC, RET% and ABPS are sensitive and specific biomarkers for microdose rHuEPO in both men and women and complement the ABP.
The World Anti-Doping Agency prohibits glucocorticoid administration in competition but not in periods out of competition. Glucocorticoid usage is controversial as it may improve performance, albeit ...debated. A hitherto undescribed but performance-relevant effect of glucocorticoids in healthy humans is accelerated erythropoiesis. We investigated whether a glucocorticoid injection accelerates erythropoiesis, increases total hemoglobin mass, and improves exercise performance.
In a counterbalanced, randomized, double-blinded, placebo-controlled crossover design (3 months washout), 10 well-trained males (peak oxygen uptake, 60 ± 3 mL O 2 ·min -1 ·kg -1 ) were injected with 40 mg triamcinolone acetonide (glucocorticoid group) or saline (placebo group) in the gluteal muscles. Venous blood samples collected before and 7-10 h, 1, 3, 7, 14, and 21 d after treatment were analyzed for hemoglobin concentration and reticulocyte percentage. Hemoglobin mass and mean power output in a 450-kcal time trial were measured before as well as 1 and 3 wk after treatment.
A higher reticulocyte percentage was evident 3 d (19% ± 30%, P < 0.05) and 7 d (48% ± 38%, P < 0.001) after glucocorticoid administration, compared with placebo, whereas hemoglobin concentration was similar between groups. Additionally, hemoglobin mass was higher ( P < 0.05) 7 d (glucocorticoid, 886 ± 104 g; placebo, 872 ± 103 g) and 21 d (glucocorticoid, 879 ± 111 g; placebo, 866 ± 103 g) after glucocorticoid administration compared with placebo. Mean power output was similar between groups 7 d (glucocorticoid, 278 ± 64 W; placebo, 275 ± 62 W) and 21 d (glucocorticoid, 274 ± 62 W; placebo, 275 ± 60 W) after treatment.
Intramuscular injection of 40 mg triamcinolone acetonide accelerates erythropoiesis and increases hemoglobin mass but does not improve aerobic exercise performance in the present study. The results are important for sport physicians administering glucocorticoids and prompt a reconsideration of glucocorticoid usage in sport.
Contemporary blood doping—Performance, mechanism, and detection Breenfeldt Andersen, Andreas; Nordsborg, Nikolai Baastrup; Bonne, Thomas Christian ...
Scandinavian journal of medicine & science in sports,
January 2024, 2024-Jan, 2024-01-00, 20240101, Letnik:
34, Številka:
1
Journal Article
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Blood doping is prohibited for athletes but has been a well‐described practice within endurance sports throughout the years. With improved direct and indirect detection methods, the practice has ...allegedly moved towards micro‐dosing, that is, reducing the blood doping regime amplitude. This narrative review evaluates whether blood doping, specifically recombinant human erythropoietin (rhEpo) treatment and blood transfusions are performance‐enhancing, the responsible mechanism as well as detection possibilities with a special emphasis on micro‐dosing. In general, studies evaluating micro‐doses of blood doping are limited. However, in randomized, double‐blinded, placebo‐controlled trials, three studies find that infusing as little as 130 ml red blood cells or injecting 9 IU × kg bw−1 rhEpo three times per week for 4 weeks improve endurance performance ~4%–6%. The responsible mechanism for a performance‐enhancing effect following rhEpo or blood transfusions appear to be increased O2‐carrying capacity, which is accompanied by an increased muscular O2 extraction and likely increased blood flow to the working muscles, enabling the ability to sustain a higher exercise intensity for a given period. Blood doping in micro‐doses challenges indirect detection by the Athlete Biological Passport, albeit it can identify ~20%–60% of the individuals depending on the sample timing. However, novel biomarkers are emerging, and some may provide additive value for detection of micro blood doping such as the immature reticulocytes or the iron regulatory hormones hepcidin and erythroferrone. Future studies should attempt to validate these biomarkers for implementation in real‐world anti‐doping efforts and continue the biomarker discovery.
Recombinant human erythropoietin (rHuEPO) is ergogenic but micro‐doses remain a challenge for anti‐doping authorities. Here, we investigated the hypothesis that frequent micro‐doses of rHuEPO enhance ...maximal oxygen consumption (VO2max) and time trial performance and that the combination of immature reticulocyte fraction (IRF) and the Athlete's Biological Passport (ABP) would enhance detection compared to the ABP alone. In a randomized, double‐blinded, placebo‐controlled design, 34 trained (VO2max: 52 ± 7 ml×min‐1×kg‐1, mean ± SD) adults received either rHuEPO (rHuEPO: epoetin‐β, 9 IU/kg, n = 16) or placebo (PLA: 0.9% NaCl, n = 18) three times a week for four weeks. Before and after the intervention, VO2max, mean power output during a 400‐kcal time trial and total hemoglobin mass (tHb) were measured. Venous blood samples were collected before, each week during rHuEPO administration, and 3, 5 and 10 days after the last injection. Hematological values were evaluated using dedicated ABP software. VO2max increased by 4.7% (p<0.01) and tHb increased by 6.8% (p<0.001) in the rHuEPO group when compared to the PLA group where no changes were evident. Mean power output during the time trial increased by 4.0% (p<0.01) in the rHuEPO group with no changes observed in the PLA group. Inclusion of IRF thresholds improved ABP sensitivity from 47% to 73%, yielding a peak sensitivity during the first two weeks of the rHuEPO treatment and 10 days after cessation of treatment. In conclusion, these findings show that four weeks of rHuEPO micro‐doses are sufficient to induce considerable ergogenic effects on both VO2max and time trial performance in trained adults. The inclusion of IRF thresholds into the ABP improved sensitivity during treatment and the viability of including IRF into the ABP should be considered although more studies are needed.
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.
PURPOSEThis study tested the hypothesis that autologous blood transfusion (ABT) of ~50% of the red blood cells (RBC) from a standard 450-mL phlebotomy would increase mean power in a cycling time ...trial. In addition, the study investigated whether further ABT of RBC obtained from another 450-mL phlebotomy would increase repeated cycling sprint ability.
METHODSIn a randomized, double-blind, placebo-controlled crossover design (3-month wash-out), nine highly trained male subjects donated two 450-mL blood bags each (BT trial) or were sham phlebotomized (PLA trial). Four weeks later, a 650-kcal time trial (n = 7) was performed 3 d before and 2 h after receiving either ~50% (135 mL) of the RBC or a sham transfusion. On the following day, transfusion of RBC (235 mL) from the second donation or sham transfusion was completed. A 4 × 30-s all-out cycling sprint interspersed by 4 min of recovery was performed 6 d before and 3 d after the second ABT (n = 9).
RESULTSThe mean power was increased in time trials from before to after transfusion (P < 0.05) in BT (213 ± 35 vs 223 ± 38 W; mean ± SD) but not in PLA (223 ± 42 vs 224 ± 46 W). In contrast, the mean power output across the four 30-s sprint bouts remained similar in BT (639 ± 35 vs 644 ± 26 W) and PLA (638 ± 43 vs 639 ± 25 W).
CONCLUSIONSABT of only ~135 mL of RBC is sufficient to increase mean power in a 650-kcal cycling time trial by ~5% in highly trained men. In contrast, a combined high-volume transfusion of ~135 and ~235 mL of RBC does not alter 4 × 30-s all-out cycling performance interspersed with 4 min of recovery.
Duplicate measure of hemoglobin mass by carbon monoxide (CO)-rebreathing is a logistical challenge as recommendations prompt several hours between measures to minimize CO-accumulation. This study ...investigated the feasibility and reliability of performing duplicate CO-rebreathing procedures immediately following one another. Additionally, it was evaluated whether the obtained hemoglobin mass from three different CO-rebreathing devices is comparable. Fifty-five healthy participants (22 males, 23 females) performed 222 duplicate CO-rebreathing procedures in total. Additionally, in a randomized cross-over design 10 participants completed three experimental trials, each including three CO-rebreathing procedures, with the first and second separated by 24 h and the second and third separated by 5-10 min. Each trial was separated by >48 h and conducted using either a glass-spirometer, a semi-automated electromechanical device, or a standard three-way plastic valve designed for pulmonary measurements. Hemoglobin mass was 3 ± 22 g lower (
< 0.05) at the second measure when performed immediately after the first with a typical error of 1.1%. Carboxyhemoglobin levels reached 10.9 ± 1.3%. In the randomized trial, hemoglobin mass was similar between the glass-spirometer and three-way valve, but ∼6% (∼50 g) higher for the semi-automated device. Notably, differences in hemoglobin mass were up to ∼13% (∼100 g) when device-specific recommendations for correction of CO loss to myoglobin and exhalation was followed. In conclusion, it is feasible and reliable to perform two immediate CO-rebreathing procedures. Hemoglobin mass is comparable between the glass-spirometer and the three-way plastic valve, but higher for the semi-automated device. The differences are amplified if the device-specific recommendations of CO-loss corrections are followed.
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