Search

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 (p < 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.

Blood volume (BV) is an important clinical parameter and is usually reported per kg of body mass (BM). When fat mass is elevated, this underestimates BV/BM. One aim was to study if differences in BV/BM related to sex, age, and fitness would decrease if normalized to lean body mass (LBM). The analysis included 263 women and 319 men (age: 10–93 years, body mass index: 14–41 kg/m2) and 107 athletes who underwent assessment of BV and hemoglobin mass (Hbmass), body composition, and cardiorespiratory fitness. BV/BM was 25% lower (70.3 ± 11.3 and 80.3 ± 10.8 mL/kgBM) in women than men, respectively, whereas BV/LBM was 6% higher in women (110.9 ± 12.5 and 105.3 ± 11.2 mL/kgLBM). Hbmass/BM was 34% lower (8.9 ± 1.4 and 11.5 ± 11.2 g/kgBM) in women than in men, respectively, but only 6% lower (14.0 ± 1.5 and 14.9 ± 1.5 g/kgLBM)/LBM. Age did not affect BV. Athlete's BV/BM was 17.2% higher than non-athletes, but decreased to only 2.5% when normalized to LBM. Of the variables analyzed, LBM was the strongest predictor for BV (R2 =.72, p <.001) and Hbmass (R2 =.81, p <.001). These data may only be valid for BV/Hbmass when assessed by CO re-breathing. Hbmass/LBM could be considered a valuable clinical matrix in medical care aiming to normalize blood homeostasis.

Blood volume (BV) is an important clinical parameter and is usually reported per kg of body mass (BM). When fat mass is elevated, this underestimates BV/BM. One aim was to study if differences in BV/BM related to sex, age, and fitness would decrease if normalized to lean body mass (LBM). The analysis included 263 women and 319 men (age: 10–93 years, body mass index: 14–41 kg/m2) and 107 athletes who underwent assessment of BV and hemoglobin mass (Hbmass), body composition, and cardiorespiratory fitness. BV/BM was 25% lower (70.3 ± 11.3 and 80.3 ± 10.8 mL/kgBM) in women than men, respectively, whereas BV/LBM was 6% higher in women (110.9 ± 12.5 and 105.3 ± 11.2 mL/kgLBM). Hbmass/BM was 34% lower (8.9 ± 1.4 and 11.5 ± 11.2 g/kgBM) in women than in men, respectively, but only 6% lower (14.0 ± 1.5 and 14.9 ± 1.5 g/kgLBM)/LBM. Age did not affect BV. Athlete's BV/BM was 17.2% higher than non-athletes, but decreased to only 2.5% when normalized to LBM. Of the variables analyzed, LBM was the strongest predictor for BV (R2 =.72, p <.001) and Hbmass (R2 =.81, p <.001). These data may only be valid for BV/Hbmass when assessed by CO re-breathing. Hbmass/LBM could be considered a valuable clinical matrix in medical care aiming to normalize blood homeostasis.

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, i.e., 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 four 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 oxygen 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.

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.

We examined whether a semi-automated carbon monoxide (CO) rebreathing method accurately detect changes in blood volume (BV) and total hemoglobin mass (tHb). Furthermore, we investigated whether a supine position with legs raised reduced systemic CO dilution time, potentially allowing a shorter rebreathing period. Nineteen young healthy males participated. BV and tHb was quantified by a 10-min CO-rebreathing period in a supine position with legs raised before and immediately after a 900 ml phlebotomy and before and after a 900 ml autologous blood reinfusion on the same day in 16 subjects. During the first CO-rebreathing, arterial and venous blood samples were drawn every 2 min during the procedure to determine systemic CO equilibrium in all subjects. Phlebotomy decreased (P < 0.001) tHb and BV by 166 ± 24 g and 931 ± 247 ml, respectively, while reinfusion increased (P < 0.001) tHb and BV by 143 ± 21 g and 862 ± 250 ml compared to before reinfusion. After reinfusion BV did not differ from baseline levels while tHb was decreased (P < 0.001) by 36 ± 21 g. Complete CO mixing was achieved within 6 min in venous and arterial blood, respectively, when compared to the 10-min sample. On an individual level, the relative accuracy after donation for tHb and BV was 102-169% and 55-165%, respectively. The applied CO-rebreathing procedure precisely detect acute BV changes with a clinically insignificant margin of error. The 10-min CO-procedure may be reduced to 6 min with no clinical effects on BV and tHb calculation. Notwithstanding, individual differences may be of concern and should be investigated further.

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: CaCO3) or ACE inhibitor (ACEi: 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 (nACEi = 23, nPLA = 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 ACEi (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

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.

Purpose: We evaluated whether or not changes in body composition following moderate hypoxic exposure for 4 weeks were different compared to sea level exposure.Methods: In a randomized crossover design, nine trained participants were exposed to 2320 m of altitude or sea level for 4 weeks, separated by > 3 months. Body fat percentage (BF%), fat mass (FM), and fat-free mass (FFM) were determined before and after each condition by dual X-ray absorptiometry (DXA) and weekly by a bioelectrical impedance scanner to determine changes with a high resolution. Training volume was quantified during both interventions.Results: Hypoxic exposure reduced (P < 0.01) BF% by 2 ± 1 percentage points and increased (P < 0.01) FFM by 2 ± 2% determined by DXA. A tending time × treatment effect existed for FM determined by DXA (P = 0.06), indicating a reduced FM in hypoxia by 8 ± 7% (P < 0.01). Regional body analysis revealed reduced (P < 0.01) BF% and FFM and an increased (P < 0.01) FFM in the truncus area. No changes were observed following sea level. Bioelectrical impedance determined that BF%, FM, and FFM did not reveal any differences between interventions. Urine specific gravity measured simultaneously as body composition was identical. Training volume was similar between interventions (509 ± 70 min/week vs. 432 ± 70 min/week, respectively).Conclusions: Four weeks of altitude exposure reduced BF% and increased FFM in trained individuals as opposed to sea level exposure. The results also indicate that a decrease in FM is greater at altitude compared to sea level. Changes were specifically observed in the truncus area.

Purpose: The World Anti-Doping Agency prohibit 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 accelerate erythropoiesis, increase total hemoglobin mass, and improve exercise performance.Methods: In a counterbalanced, randomized, double-blinded, placebo-controlled crossover design (3-months washout), ten well-trained males (peak oxygen uptake: 60 ± 3 mL O2·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 days after treatment were analyzed for hemoglobin concentration and reticulocyte percentage. Hemoglobin mass and mean power output in a 450-kcal time trial was measured before as well as one and three weeks after treatment.Results: A higher reticulocyte percentage was evident three (19 ± 30 %, P < 0.05) and seven (48 ± 38 %, P < 0.001) days after glucocorticoid administration, compared with placebo, whereas hemoglobin concentration was similar between groups. Additionally, hemoglobin mass was higher (P < 0.05) seven (glucocorticoid: 886 ± 104 g, placebo: 872 ± 103 g) and 21 days (glucocorticoid: 879 ± 111 g, placebo: 866 ± 103 g) after glucocorticoid administration compared with placebo. Mean power output was similar between groups seven (glucocorticoid: 278 ± 64 W, placebo: 275 ± 62 W) and 21 days (glucocorticoid: 274 ± 62 W, placebo: 275 ± 60 W) after treatment.Conclusions: Intramuscular injection of 40 mg triamcinolone acetonide accelerates erythropoiesis and increase hemoglobin mass but does not improve aerobic exercise performan

Dried blood spot (DBS) testing allows fast, easy, and minimally invasive collection of microvolumes of blood. In an anti-doping context, DBS testing has particular relevance for substances prohibited in-competition only such as ephedrine, which is currently detected by urine analysis, since DBS can add information about the blood drug concentrations during the in-competition period. Several collection methods and devices exist for DBS collection from different anatomical sites. Thus, agreements between concentrations of target analytes in DBS samples from different sampling sites, along with between DBS and those in conventional venous plasma samples, need to be evaluated. Herein, we collected matched upper-arm DBS, fingerprick DBS and venous plasma samples from 8 healthy, male subjects in an 8-hour period following oral administrations of 20 mg ('low dose') and 60 mg ('high dose') of ephedrine. We show that the use of alternative sampling sites and matrices are feasible possibilities for ephedrine analysis in doping control. We observed very good agreement between collection sites and that specificity and sensitivity can be upheld despite use of an alternative collection site. However, potential concentration differences between DBS and venous plasma should be considered, and distinct threshold might be necessary if implementing both blood matrices in ephedrine analysis.

Dried blood spot (DBS) testing allows fast, easy and minimally invasive collection of microvolumes of blood. In an anti-doping context, DBS testing has particular relevance for substances prohibited in-competition only such as ephedrine, which is currently detected by urine analysis, because DBS can add information about the blood drug concentrations during the in-competition period. Several collection methods and devices exist for DBS collection from different anatomical sites. Thus, agreements between concentrations of target analytes in DBS samples from different sampling sites, along with between DBS and those in conventional venous plasma samples, need to be evaluated. Herein, we collected matched upper-arm DBS, fingerprick DBS and venous plasma samples from eight healthy male subjects in an 8-h period following oral administrations of 20 mg ('low dose') and 60 mg ('high dose') of ephedrine. We show that the use of alternative sampling sites and matrices is a feasible possibility for ephedrine analysis in doping control. We observed very good agreement between collection sites and that specificity and sensitivity can be upheld despite use of an alternative collection site. However, potential concentration differences between DBS and venous plasma should be considered, and distinct threshold might be necessary if implementing both blood matrices in ephedrine analysis.

Sports officials around the world are facing incredible challenges due to the unfair means of practices performed by the athletes to improve their performance in the game. It includes the intake of hormonal based drugs or transfusion of blood to increase their strength and the result of their training. However, the current direct test of detection of these cases includes the laboratory-based method, which is limited because of the cost factors, availability of medical experts, etc. This leads us to seek for indirect tests. With the growing interest of Artificial Intelligence in healthcare, it is important to propose an algorithm based on blood parameters to improve decision making. In this paper, we proposed a statistical and machine learning-based approach to identify the presence of doping substance rhEPO in blood samples.

Objectives: To investigate whether recombinant human erythropoietin (rHuEPO) injections during an altitude training camp impact heart function.Methods: Thirty (12 women) moderately trained subjects stayed at 2320 m altitude for 4 weeks while training. Subjects were randomized to placebo (isotonic saline) or rHuEPO (20 IU/kg body weight) i.v. injections. Transthoracic echocardiography imaging was acquired 3 days after arrival to altitude and prior to the first placebo or rHuEPO injection as well as one day after the last rHuEPO injection three weeks later.Results: rHuEPO did not alter cardiovascular morphology parameters, systolic or diastolic function. In the placebo group, altitude exposure improved left ventricle (LV) systolic function due to an increased twist angle but rHuEPO had no additional effects. Pulmonary arterial systolic pressure was unaffected in either group. Notably, rHuEPO hampered LV untwist rate without affecting LV early filling.Conclusion: rHuEPO provided during mild altitude exposure does not cause any major effects on heart function. The observed alteration in LV untwist induced by rHuEPO is unlikely to have a meaningful clinical effect. Trial registration: Registered on www.clinicaltrials.gov (NCT04227665).

Objectives: To investigate whether recombinant human erythropoietin (rHuEPO) injections during an altitude training camp impact heart function.Methods: Thirty (12 women) moderately trained subjects stayed at 2320 m altitude for 4 weeks while training. Subjects were randomized to placebo (isotonic saline) or rHuEPO (20 IU/kg body weight) i.v. injections. Transthoracic echocardiography imaging was acquired 3 days after arrival to altitude and prior to the first placebo or rHuEPO injection as well as one day after the last rHuEPO injection three weeks later.Results: rHuEPO did not alter cardiovascular morphology parameters, systolic or diastolic function. In the placebo group, altitude exposure improved left ventricle (LV) systolic function due to an increased twist angle but rHuEPO had no additional effects. Pulmonary arterial systolic pressure was unaffected in either group. Notably, rHuEPO hampered LV untwist rate without affecting LV early filling.Conclusion: rHuEPO provided during mild altitude exposure does not cause any major effects on heart function. The observed alteration in LV untwist induced by rHuEPO is unlikely to have a meaningful clinical effect. Trial registration: Registered on www.clinicaltrials.gov (NCT04227665).

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

Dried blood spot (DBS) testing allows fast, easy, and minimally invasive collection of microvolumes of blood. In an anti-doping context, DBS testing has particular relevance for substances prohibited in-competition only such as ephedrine, which is currently detected by urine analysis, since DBS can add information about the blood drug concentrations during the in-competition period. Several collection methods and devices exist for DBS collection from different anatomical sites. Thus, agreements between concentrations of target analytes in DBS samples from different sampling sites, along with between DBS and those in conventional venous plasma samples, need to be evaluated. Herein, we collected matched upper-arm DBS, fingerprick DBS and venous plasma samples from 8 healthy, male subjects in an 8-hour period following oral administrations of 20 mg ('low dose') and 60 mg ('high dose') of ephedrine. We show that the use of alternative sampling sites and matrices are feasible possibilities for ephedrine analysis in doping control. We observed very good agreement between collection sites and that specificity and sensitivity can be upheld despite use of an alternative collection site. However, potential concentration differences between DBS and venous plasma should be considered, and distinct threshold might be necessary if implementing both blood matrices in ephedrine analysis.

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

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.

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 (n=39) were randomly assigned to 20 IU·kg body wt-1 rHuEPO or placebo injections every second day for 3 wk during the two intervention periods. Venous blood was collected weekly. Altitude increased ERFE (P ≤ 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 (P < 0.05) and hepcidin levels (P < 0.05), demonstrating the impact of accelerated erythropoiesis and not of other hypoxia-induced mechanisms. Compared to altitude alone, concurrent rHuEPO treatment and altitude exposure induced additive changes in hepcidin (P < 0.05) and ERFE (P ≤ 0.001) parallel with increases in hematocrit (P < 0.001), demonstrating a relevant range of both hepcidin and ERFE. A poor but significant correlation between hepcidin and ERFE was found (R2 = 0.13, P < 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 anti-doping context. Clinical trial registration: Clinical trials identifier, NCT04227665

Some have questioned the evidence for performance-enhancing effects of several substances included on the World Anti-Doping Agency's Prohibited List due to the divergent or inconclusive findings in randomized controlled trials (RCTs). However, inductive statistical inference based on RCTs-only may result in biased conclusions because of the scarcity of studies, inter-study heterogeneity, too few outcome events, or insufficient power. An abductive inference approach, where the body of evidence is evaluated beyond considerations of statistical significance, may serve as a tool to assess the plausibility of performance-enhancing effects of substances by also considering observations and facts not solely obtained from RCTs. Herein, we explored the applicability of an abductive inference approach as a tool to assess the performance-enhancing effects of substances included on the Prohibited List. We applied an abductive inference approach to make inferences on debated issues pertaining to the ergogenic effects of recombinant human erythropoietin (rHuEPO), beta2-agonists and anabolic androgenic steroids (AAS), and extended the approach to more controversial drug classes where RCTs are limited. We report that an abductive inference approach is a useful tool to assess the ergogenic effect of substances included on the Prohibited List - particularly for substances where inductive inference is inconclusive. Specifically, a systematic abductive inference approach can aid researchers in assessing the effects of doping substances, either by leading to suggestions of causal relationships or identifying the need for additional research.

We investigated whether immature reticulocyte fraction (IRF) and immature reticulocytes to red blood cells ratio (IR/RBC) are sensitive biomarkers for low-dose recombinant human erythropoietin (rhEpo) treatment at sea-level (SL) and moderate altitude (AL) and whether multi (FACS) or single (Sysmex-XN) fluorescence flow cytometry is superior for IRF and IR/RBC determination. Thirty-nine participants completed two interventions, each containing a four-week baseline, a four-week SL or AL (2,230m) exposure and a four-week follow-up. During exposure, rhEpo (20 IU·kg-1) or placebo (PLA) was injected at SL (SLrhEpo n = 25, SLPLA n = 9) and AL (ALrhEpo n = 12, ALPLA n = 27) every second day for three weeks. Venous blood was collected weekly. Sysmex measurements revealed that IRF and IR/RBC was up to ~70% (P < 0.01) and ~190% (P < 0.001) higher in SLrhEpo than SLPLA during treatment and up to ~45% (P < 0.001) and ~55% (P < 0.01) lower post-treatment, respectively. Compared with ALPLA, IRF and IR/RBC was up to ~20% (P < 0.05) and ~45% (P < 0.001) lower post-treatment in SLrhEpo, respectively. In ALrhEpo, IRF and IR/RBC was up to ~40% (P < 0.05) and ~110% (P < 0.001) higher during treatment and up to ~25% (P < 0.05) and ~40% (P < 0.05) lower post-treatment, respectively, compared with ALPLA. Calculated thresholds provided ~90% sensitivity for both biomarkers at SL and 33% (IRF) and 66% (IR/RBC) at AL. Specificity was >99%. Single-fluorescence flow cytometry coefficient of variation was >twofold higher at baseline (P < 0.001), and provided larger or similar changes compared to multi-fluorescence, albeit with smaller precision. In conclusion, IRF and IR/RBC were sensitive and specific biomarkers for low-dose rhEpo misuse at SL and AL.

The SHFT device is a novel running wearable consisting of two pods connected to your smartphone issuing several running metrics based on accelerometer and gyroscope technology. The purpose of this study was to investigate the reliability and validity of the power output (PO) metric produced by the SHFT device. To assess reliability, 12 men ran on an outdoor track at 10.5 km·h-1 and 12 km·h-1 on two consecutive days. To assess validity, oxygen uptake (VO2) and SHFT data from eight men and seven women were collected during incremental submaximal running tests on an indoor treadmill on one to four separate days (34 tests in total). SHFT reliability on the outdoor track was strong with coefficients of variance (CV) of 1.8% and 2.4% for 10.5 and 12 km·h-1, respectively. We observed a very strong linear relationship between PO and VO2 (r2 = 0.54) within subjects, and a very strong linear relationship within each subject within each treadmill test (r2 = 0.80). We conclude that SHFT provides a reliable running power estimate and that a very strong relationship between SHFT-Power and metabolic rate exists, which places SHFT as one of the leading commercially available running power meters.

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 (n=39) were randomly assigned to 20 IU·kg body wt-1 rHuEPO or placebo injections every second day for 3 wk during the two intervention periods. Venous blood was collected weekly. Altitude increased ERFE (P ≤ 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 (P < 0.05) and hepcidin levels (P < 0.05), demonstrating the impact of accelerated erythropoiesis and not of other hypoxia-induced mechanisms. Compared to altitude alone, concurrent rHuEPO treatment and altitude exposure induced additive changes in hepcidin (P < 0.05) and ERFE (P ≤ 0.001) parallel with increases in hematocrit (P < 0.001), demonstrating a relevant range of both hepcidin and ERFE. A poor but significant correlation between hepcidin and ERFE was found (R2 = 0.13, P < 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 anti-doping context. Clinical trial registration: Clinical trials identifier, NCT04227665

Some have questioned the evidence for performance-enhancing effects of several substances included on the World Anti-Doping Agency's Prohibited List due to the divergent or inconclusive findings in randomized controlled trials (RCTs). However, inductive statistical inference based on RCTs-only may result in biased conclusions because of the scarcity of studies, inter-study heterogeneity, too few outcome events, or insufficient power. An abductive inference approach, where the body of evidence is evaluated beyond considerations of statistical significance, may serve as a tool to assess the plausibility of performance-enhancing effects of substances by also considering observations and facts not solely obtained from RCTs. Herein, we explored the applicability of an abductive inference approach as a tool to assess the performance-enhancing effects of substances included on the Prohibited List. We applied an abductive inference approach to make inferences on debated issues pertaining to the ergogenic effects of recombinant human erythropoietin (rHuEPO), beta2-agonists and anabolic androgenic steroids (AAS), and extended the approach to more controversial drug classes where RCTs are limited. We report that an abductive inference approach is a useful tool to assess the ergogenic effect of substances included on the Prohibited List - particularly for substances where inductive inference is inconclusive. Specifically, a systematic abductive inference approach can aid researchers in assessing the effects of doping substances, either by leading to suggestions of causal relationships or identifying the need for additional research.

We investigated whether immature reticulocyte fraction (IRF) and immature reticulocytes to red blood cells ratio (IR/RBC) are sensitive biomarkers for low-dose recombinant human erythropoietin (rhEpo) treatment at sea-level (SL) and moderate altitude (AL) and whether multi (FACS) or single (Sysmex-XN) fluorescence flow cytometry is superior for IRF and IR/RBC determination. Thirty-nine participants completed two interventions, each containing a four-week baseline, a four-week SL or AL (2,230m) exposure and a four-week follow-up. During exposure, rhEpo (20 IU·kg-1) or placebo (PLA) was injected at SL (SLrhEpo n = 25, SLPLA n = 9) and AL (ALrhEpo n = 12, ALPLA n = 27) every second day for three weeks. Venous blood was collected weekly. Sysmex measurements revealed that IRF and IR/RBC was up to ~70% (P < 0.01) and ~190% (P < 0.001) higher in SLrhEpo than SLPLA during treatment and up to ~45% (P < 0.001) and ~55% (P < 0.01) lower post-treatment, respectively. Compared with ALPLA, IRF and IR/RBC was up to ~20% (P < 0.05) and ~45% (P < 0.001) lower post-treatment in SLrhEpo, respectively. In ALrhEpo, IRF and IR/RBC was up to ~40% (P < 0.05) and ~110% (P < 0.001) higher during treatment and up to ~25% (P < 0.05) and ~40% (P < 0.05) lower post-treatment, respectively, compared with ALPLA. Calculated thresholds provided ~90% sensitivity for both biomarkers at SL and 33% (IRF) and 66% (IR/RBC) at AL. Specificity was >99%. Single-fluorescence flow cytometry coefficient of variation was >twofold higher at baseline (P < 0.001), and provided larger or similar changes compared to multi-fluorescence, albeit with smaller precision. In conclusion, IRF and IR/RBC were sensitive and specific biomarkers for low-dose rhEpo misuse at SL and AL.

Objectives: Optimized concurrent training regimes are warranted in physical training of military-, law enforcement- and rescue-personnel. This study investigated if four 15-min endurance training sessions weekly improve aerobic capacity and performance more than one 60-min endurance session weekly during the initial phase of a Basic Military Training program.Design: A randomized training intervention study with functional and physiological tests before and after the intervention.Methods: Military conscripts (n=290) were randomly allocated to three groups completing 9 weeks training. Weekly training consisted of four endurance and four strength training sessions lasting 15min each ('Micro-training': MIC); one strength and one endurance session lasting 60min each ('Classical-training': CLA) or two 60min sessions of standard military training ('Control-training': CON).Results: Both 12-min (∼7-10%) and shuttle run performance (∼35-42%) improved (P≤0.001) similarly in all groups. Likewise, functional 2-min maximal repetition exercise capacity increased (P≤0.05) similarly in all groups (Lunges ∼17-24 %; PushUp ∼10-20%; AbdominalFlexions∼21-23%). Peak oxygen uptake changes depended on group (P≤0.05) with increases (P≤0.01) in MIC (7±7%, n=23) and CON (12±18%, n=17) and no changes in CLA. Maximal m. vastus lateralis citrate synthase activity decreased 14±26% (P≤0.001, n=18) in CLA. Likewise, maximal m. vastus lateralis 3-hydroxyacyl-CoA dehydrogenase activity decreased 8±17% in MIC (n=28) and 14±24% in CLA (n=18).Conclusions: Four 15-min endurance training sessions weekly improves running performance and strength-endurance similarly to one 60min session. Peak oxygen uptake only increases with more than one endurance session weekly and leg muscle oxidative capacity appears reduced after basic military training.

The SHFT device is a novel running wearable consisting of two pods connected to your smartphone issuing several running metrics based on accelerometer and gyroscope technology. The purpose of this study was to investigate the reliability and validity of the power output (PO) metric produced by the SHFT device. To assess reliability, 12 men ran on an outdoor track at 10.5 km·h-1 and 12 km·h-1 on two consecutive days. To assess validity, oxygen uptake (VO2) and SHFT data from eight men and seven women were collected during incremental submaximal running tests on an indoor treadmill on one to four separate days (34 tests in total). SHFT reliability on the outdoor track was strong with coefficients of variance (CV) of 1.8% and 2.4% for 10.5 and 12 km·h-1, respectively. We observed a very strong linear relationship between PO and VO2 (r2 = 0.54) within subjects, and a very strong linear relationship within each subject within each treadmill test (r2 = 0.80). We conclude that SHFT provides a reliable running power estimate and that a very strong relationship between SHFT-Power and metabolic rate exists, which places SHFT as one of the leading commercially available running power meters.

BACKGROUND Whether arterial stiffness (AS) can be improved by regular exercise in healthy individuals remains equivocal according to cross-sectional and longitudinal studies assessing arterial properties at discrete time points. The purpose of the present study was to pinpoint the time course of training-induced adaptations in central AS. METHODS Aorta characteristic impedance (Zc) and carotid distensibility (CD) were determined with ultrasonography prior to (week 0) and across 8 weeks (weeks 2, 4, and 8) of supervised endurance training (ET) (3 × 60 minutes cycle ergometry sessions per week), in 9 previously untrained healthy normotensive adults (27 ± 4 years) with no history of cardiovascular disease. Exercise capacity was assessed by maximal oxygen consumption (VO2max) elicited by incremental ergometry. RESULTS VO2max increased throughout the ET intervention (+12% from week 0 to week 8, P < 0.001, P for linear trend <0.001). Systolic blood pressure rose with ET (+7% from week 0 to week 8, P = 0.019, P for linear trend <0.001). Aorta Zc augmented from week 0 to week 8 of ET in all individuals (+38%, P = 0.003, P for linear trend = 0.002). CD did not significantly differ among time points (P = 0.196) although a linear decreasing trend was detected (P = 0.016). CONCLUSIONS Central AS augments during a conventional ET intervention that effectively enhances aerobic exercise capacity in young individuals. This suggests that normal, healthy elastic arteries are not amendable to improvement unless impairment is present.

Bloddoping, herunder blodtransfusioner og brug af EPO, er en fortsat udfordring for antidopingmyndighederne, hvorfor det er vigtigt at undersøge og evaluere nye potentielle sporingsmetoder. Denne afhandling har til formål at skabe ny viden relateret til bloddoping og sporingen såvel de fysiologiske effekter heraf. Et aktuelt behov er at evaluere biomarkører relateret til jernmetabolismen og evaluere de nuværende sporingsmetoder i relation til køn, og andre lovlige faktorer som kan nedsætte følsomheden af metoderne samt såkaldte ”mikro-doserings” strategier. Jernmarkører har ikke kun potentiale i en anti-doping sammenhæng, men også for blodbanker verden over der forsøger at optimere gendannelsen af det tappede blod. Potentielle præstationsforbedrende effekter som følge af sidstnævnte er også vigtige at fastslå for at finde den nedre grænse for hvornår det er relevant i en anti-doping sammenhæng. Ét overordnet mål for denne afhandling var at skabe ny viden omkring udviklingen i jernmarkørerne hepcidin og erythroferrone efter en bloddonation på 450 ml og en efterfølgende autolog blodtransfusion af en halv blodpose (~130 ml røde blodlegemer). Hypotesen var at begge hormoner repræsenterede følsomme markører for en ændret jernmetabolisme, relevant i både en klinisk og anti-doping kontekst. Ydermere, blev følsomheden og specificiteten af Atletens Biologiske Pas undersøgt i en kønsspecifik analyse efter både autolog blodtransfusion og en tre ugers behandling med små mængder EPO. Den fremsatte hypotese var at inklusionen af retikulocytprocenten og algoritmen Abnormal Blood Profile Score (ABPS) ville øge følsomheden. En yderligere hypotese var at de anvendte dopingstrategier øgede udholdenhedspræstationen på en tidskørsel. Desuden menes højdeeksponering at blive anvendt til at sløre brugen af EPO. Det blev derfor undersøgt om påvirkningen af højde simultant med en EPO behandling influerede Atletens Biologiske Pas. Hypotesen var at en forøget følsomhed ville være at, As prohibited blood manipulations remains a challenge for anti-doping authorities, it is important to continuously investigate and evaluate new potential detection methods. A current need is to evaluate the potential of iron biomarkers and improve the sensitivity of current detection methodologies following micro-dosing regimes in a sex-specific context as well as evaluate the impact of well-known confounding factors. In addition, specific and sensitive biomarkers relevant in an antidoping context may also have merit in a blood donation context, where a rapid recovery after blood donation is a priority. Finally, it is important to determine the physiological effects of the applied regimes to establish the lower limit of relevance for anti-doping authorities. Specifically, the present thesis investigated to which extent iron regulatory markers was affected by alterations in blood volume following a standard whole blood donation of 450 mL and a subsequent small-volume autologous blood transfusion of half a blood bag (~130 mL red blood cells). It was hypothesized that hepcidin and erythroferrone in conjunction represented clinical and anti-doping relevant markers for altered iron homeostasis. In addition, the sensitivity and specificity of the Athlete Biological Passport was investigated in males and females following both blood donation and reinfusion as well as a micro-dosing strategy of recombinant human erythropoietin (rHuEPO), where it was hypothesized that the inclusion of reticulocyte percentage and the algorithm Abnormal Blood Profile Score (ABPS) would increase sensitivity. It was also hypothesized that both the small-volume blood transfusion and a micro-dosing strategy of recombinant human erythropoietin would improve cycling time trial performance. Furthermore, it was hypothesized that altitude exposure concurrent with rHuEPO treatment would results in reduced specificity of the Athlete Biological Passport although the sensitivity would be increase

Total hemoglobin mass (Hbmass) is routinely assessed in studies by the carbon monoxide (CO) rebreathing. Its clinical application is often hindered due to the consequent rise in carboxyhemoglobin (%HbCO) and the concern of CO toxicity. We tested the reproducibility of the CO rebreathing with a CO dose of 0.5 mL/kg body mass (CO0.5) compared to 1.5 mL/kg (CO1.5) and when shortening the CO rebreathing protocol. Therefore, CO rebreathing was performed 1×/day in eight healthy individuals on four consecutive days. On each day, either CO0.5 (CO0.5-1 and CO0.5-2) or CO1.5 (CO1.5-1 and CO1.5-2) was administered. Venous blood samples to determine %HbCO and quantify Hbmass were obtained prior to, and at 6 (T6), 8 (T8) and 10 min (T10) of CO rebreathing. This protocol was tested at sea level and at 2320 m to investigate the altitude-related measurement error. At sea level, the mean difference (95% limits of agreement) in Hbmass between CO0.5-1 and CO0.5-2 was 26 g (–26; 79 g) and between CO1.5-1 and CO1.5-2, it was 17 g (–18; 52 g). The respective typical error (TE) corresponded to 2.4% (CO0.5) and 1.5% (CO1.5), while it was 6.5% and 3.0% at 2320 m. With CO0.5, shortening the CO rebreathing resulted in a TE for Hbmass of 4.4% (T8 vs. T10) and 14.1% (T6 vs T10) and with CO1.5, TE was 1.6% and 5.8%. In conclusion, the CO dose and rebreathing time for the CO rebreathing procedure can be decreased at the cost of a measurement error ranging from 1.5-14.1%.

This review critically evaluates the magnitude of performance enhancement that can be expected from various autologous blood transfusion (ABT) procedures and the underlying physiological mechanisms. The review is based on a systematic search, and it was reported that 4 of 28 studies can be considered of very high quality, i.e. placebo-controlled, double-blind crossover studies. However, both high-quality studies and other studies have generally reported performance-enhancing effects of ABT on exercise intensities ranging from ~70 to 100% of absolute peak oxygen uptake (VO2peak) with durations of 5-45 min, and the effect was also seen in well-trained athletes. A linear relationship exists between ABT volume and change in VO2peak. The likely correlation between ABT volume and endurance performance was not evident in the few available studies, but reinfusion of as little as 135 mL packed red blood cells has been shown to increase time trial performance. Red blood cell reinfusion increases endurance performance by elevating arterial oxygen content (CaO2). The increased CaO2 is accompanied by reduced lactate concentrations at submaximal intensities as well as increased VO2peak. Both effects improve endurance performance. Apparently, the magnitude of change in haemoglobin concentration ([Hb]) explains the increase in VO2peak associated with ABT because blood volume and maximal cardiac output have remained constant in the majority of ABT studies. Thus, the arterial-venous O2 difference during exercise must be increased after reinfusion, which is supported by experimental evidence. Additionally, it remains a possibility that ABT can enhance repeated sprint performance, but studies on this topic are lacking. The only available study did not reveal a performance-enhancing effect of reinfusion on 4 × 30 s sprinting. The reviewed studies are of importance for both the physiolog

This review critically evaluates the magnitude of performance enhancement that can be expected from various autologous blood transfusion (ABT) procedures and the underlying physiological mechanisms. The review is based on a systematic search, and it was reported that 4 of 28 studies can be considered of very high quality, i.e. placebo-controlled, double-blind crossover studies. However, both high-quality studies and other studies have generally reported performance-enhancing effects of ABT on exercise intensities ranging from ~70 to 100% of absolute peak oxygen uptake (VO2peak) with durations of 5-45 min, and the effect was also seen in well-trained athletes. A linear relationship exists between ABT volume and change in VO2peak. The likely correlation between ABT volume and endurance performance was not evident in the few available studies, but reinfusion of as little as 135 mL packed red blood cells has been shown to increase time trial performance. Red blood cell reinfusion increases endurance performance by elevating arterial oxygen content (CaO2). The increased CaO2 is accompanied by reduced lactate concentrations at submaximal intensities as well as increased VO2peak. Both effects improve endurance performance. Apparently, the magnitude of change in haemoglobin concentration ([Hb]) explains the increase in VO2peak associated with ABT because blood volume and maximal cardiac output have remained constant in the majority of ABT studies. Thus, the arterial-venous O2 difference during exercise must be increased after reinfusion, which is supported by experimental evidence. Additionally, it remains a possibility that ABT can enhance repeated sprint performance, but studies on this topic are lacking. The only available study did not reveal a performance-enhancing effect of reinfusion on 4 × 30 s sprinting. The reviewed studies are of importance for both the physiolog

BACKGROUND Whether arterial stiffness (AS) can be improved by regular exercise in healthy individuals remains equivocal according to cross-sectional and longitudinal studies assessing arterial properties at discrete time points. The purpose of the present study was to pinpoint the time course of training-induced adaptations in central AS. METHODS Aorta characteristic impedance (Zc) and carotid distensibility (CD) were determined with ultrasonography prior to (week 0) and across 8 weeks (weeks 2, 4, and 8) of supervised endurance training (ET) (3 × 60 minutes cycle ergometry sessions per week), in 9 previously untrained healthy normotensive adults (27 ± 4 years) with no history of cardiovascular disease. Exercise capacity was assessed by maximal oxygen consumption (VO2max) elicited by incremental ergometry. RESULTS VO2max increased throughout the ET intervention (+12% from week 0 to week 8, P < 0.001, P for linear trend <0.001). Systolic blood pressure rose with ET (+7% from week 0 to week 8, P = 0.019, P for linear trend <0.001). Aorta Zc augmented from week 0 to week 8 of ET in all individuals (+38%, P = 0.003, P for linear trend = 0.002). CD did not significantly differ among time points (P = 0.196) although a linear decreasing trend was detected (P = 0.016). CONCLUSIONS Central AS augments during a conventional ET intervention that effectively enhances aerobic exercise capacity in young individuals. This suggests that normal, healthy elastic arteries are not amendable to improvement unless impairment is present.

BACKGROUND Whether arterial stiffness (AS) can be improved by regular exercise in healthy individuals remains equivocal according to cross-sectional and longitudinal studies assessing arterial properties at discrete time points. The purpose of the present study was to pinpoint the time course of training-induced adaptations in central AS. METHODS Aorta characteristic impedance (Zc) and carotid distensibility (CD) were determined with ultrasonography prior to (week 0) and across 8 weeks (weeks 2, 4, and 8) of supervised endurance training (ET) (3 × 60 minutes cycle ergometry sessions per week), in 9 previously untrained healthy normotensive adults (27 ± 4 years) with no history of cardiovascular disease. Exercise capacity was assessed by maximal oxygen consumption (VO2max) elicited by incremental ergometry. RESULTS VO2max increased throughout the ET intervention (+12% from week 0 to week 8, P < 0.001, P for linear trend <0.001). Systolic blood pressure rose with ET (+7% from week 0 to week 8, P = 0.019, P for linear trend <0.001). Aorta Zc augmented from week 0 to week 8 of ET in all individuals (+38%, P = 0.003, P for linear trend = 0.002). CD did not significantly differ among time points (P = 0.196) although a linear decreasing trend was detected (P = 0.016). CONCLUSIONS Central AS augments during a conventional ET intervention that effectively enhances aerobic exercise capacity in young individuals. This suggests that normal, healthy elastic arteries are not amendable to improvement unless impairment is present.