Influence of prolonged physical exercise on the erythropoietin concentration in blood (original) (raw)
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Effects of recombinant human erythropoietin injections on physical self in endurance athletes
2006
This review describes some of the physiological effects of recombinant human erythropoietin (EPO) in healthy humans. At the blood level EPO increases the arterial O 2 content not only by increasing red blood cell volume, but also by an equally important decrease in plasma volume. Well before that, EPO causes a prompt decrease in plasma levels of renin and aldosterone. Renal clearance studies suggest that EPO decreases renal proximal tubular reabsorption rate leading to activation of the tubuloglomerular feedback mechanism and a fall in glomerular filtration rate. Thus, treatment with EPO may result in suppression of endogenous EPO production through a decrease in intrarenal oxygen consumption. EPO elevates the arterial blood pressure even in healthy subjects. The receptor for EPO is present in many tissues. However, the functional effects of EPO in the skeletal muscle seem limited, and although it has been speculated that non-erythropoietic effects of EPO (angiogenesis, shift in muscle fibre types, cognitive effects) may be responsible for the increase in exercise performance, this has not been confirmed. EPO-induced haemodynamic effects call for careful monitoring during the administration period. The metabolic, hormonal and renal effects of EPO do not seem to range beyond physiologically acceptable limits and are reversible. Taken together, EPO seems safe to use for experimental purposes in healthy volunteers.
European Journal of Applied Physiology
Purpose Recombinant human erythropoietin (rHuEPO) is known to increase thrombotic risk in patients and might have similar effects in athletes abusing the drug. rHuEPO is prohibited by anti-doping legislation, but this risk has not been investigated thoroughly. This analysis was designed to evaluate whether rHuEPO impacts hemostatic profile and endothelial and platelet activation markers in trained subjects, and whether the combination with exercise affects exercise induced alterations. Methods This double-blind, randomized, placebo-controlled trial enrolled healthy, trained male cyclists aged 18-50 years. Participants were randomly allocated (1:1) to receive subcutaneous injections of rHuEPO (epoetin-β; mean dose 6000 IU per week) or placebo (0.9% NaCl) for 8 weeks. Subjects performed five maximal exercise tests and a road race, coagulation and endothelial/platelet markers were measured at rest and directly after each exercise effort. Results rHuEPO increased P-selectin (+ 7.8% (1.5-14.5), p = 0.02) and E-selectin (+ 8.6% (2.0-15.7), p = 0.01) levels at rest. Maximal exercise tests significantly influenced all measured coagulation and endothelial/platelet markers, and in the rHuEPO group maximal exercise tests led to 15.3% ((7.0-24.3%), p = 0.0004) higher E-selectin and 32.1% ((4.6-66.8%), p = 0.0207) higher Platelet factor 4 (PF4) levels compared to the placebo group. Conclusion In conclusion, rHuEPO treatment resulted in elevated E-and P-selectin levels in trained cyclists, indicating enhanced endothelial activation and/or platelet reactivity. Exercise itself induces hypercoagulability, and the combination of rHuEPO and exercise increased E-selectin and PF4 levels more than either intervention alone. Based on this, exercise potentially increases thrombotic risk, a risk that might be enhanced in combination with rHuEPO use.
Hemorheological and cardiovascular effects of erythropoietin in a rat model of sports doping
2010
Recombinant human erythropoietin (rhEPO) has been therapeutically used for correction of anaemia. However, due to the increase in circulating red blood cells (RBCs) it promotes, thus increasing oxygen delivery to muscles and improving performance in sport, it has been also illegally used as sports doping. Besides the well known increase of hematocrit and blood viscosity; which might cause serious complications for the athletes, other disturbances could occur, whose mechanisms remain to be fully elucidated. This study aimed to ...
Frontiers in Physiology, 2020
Erythropoietin (EPO) boosts exercise performance through increase in oxygen transport capacity following regular administration of EPO but preclinical study results suggest that single high dose of EPO also may improve exercise capacity. Twenty-nine healthy subjects (14 males/15 females; age: 25 ± 3 years) were included in a randomized, double-blind, placebo-controlled crossover study to assess peak work load and cardiopulmonary variables during submaximal and maximal cycling tests following a single dose of 60.000 IU of recombinant erythropoietin (EPO) or placebo (PLA). Submaximal exercise at 40%/60% of peak work load revealed no main effect of EPO on oxygen uptake (27.9 ± 8.7 ml min −1 •kg −1 / 37.1 ± 13.2 ml min −1 •kg −1) versus PLA (25.2 ± 3.7 ml min −1 •kg −1 / 33.1 ± 5.3 ml min −1 •kg −1) condition (p = 0.447/p = 0.756). During maximal exercise peak work load (PLA: 3.5 ± 0.6 W•kg −1 vs. EPO: 3.5 ± 0.6 W kg −1 , p = 0.892) and peak oxygen uptake (PLA: 45.1 ± 10.4 ml•min −1 kg −1 vs. EPO: 46.1 ± 14.2 ml•min −1 kg −1 , p = 0.344) reached comparable values in the two treatment conditions. Other cardiopulmonary variables (ventilation, cardiac output, heart rate) also reached similar levels in the two treatment conditions. An interaction effect was found between treatment condition and sex resulting in higher peak oxygen consumption (p = 0.048) and ventilation (p = 0.044) in EPO-treated males. In conclusion, in a carefully conducted study using placebo-controlled design the present data failed to support the hypothesis that a single high dose of EPO has a measurable impact on work capacity in healthy subjects.
Erythropoietin Doping: Cardiovascular Effects in Athletes
2020
The total mass of hemoglobin (Hbmass) correlates with the rate of maximal O2 uptake (VO2max). Recombinant human erythropoietin (rhEpo) and other erythropoiesis stimulating agents (ESAs) increase the number of circulating red blood cells (RBCs), Hbmass and hematocrit (Hct). ESAs are misused by cheating athletes to increase Hbmass. The World Anti-Doping Agency (WADA) has prohibited the misuse of ESAs. VO2max is also dependent on the cardiac output and the rate of peripheral O2 extraction. Preclinical studies purported non-erythropoietic cytoprotective effects of ESAs in the cardiovascular system. However, none or very little Epo receptor protein (EpoR) is expressed by normal cardiovascular tissues. Placebo-controlled clinical trials have failed to confirm beneficial health effects of ESAs in patients with cardiac diseases other than increases in Hb levels. High-dose rhEpo treatment did not improve clinical outcomes of patients with heart failure, coronary syndrome, acute myocardial in...
Experimental physiology, 2014
The aim was to investigate the ability of an erythropoiesis-stimulating agent (ESA), alone or in combination with endurance training, to induce changes in human skeletal muscle fibre and vascular morphology. In a comparative study, 36 healthy untrained men were randomly dispersed into the following four groups: sedentary-placebo (SP, n = 9); sedentary-ESA (SE, n = 9); training-placebo (TP, n = 10); or training-ESA (TE, n = 8). The ESA or placebo was injected once weekly. Training consisted of progressive bicycling three times per week for 10 weeks. Before and after the intervention period, muscle biopsies and magnetic resonance images were collected from the thigh muscles, blood was collected, body composition measured and endurance exercise performance evaluated. The ESA treatment (SE and TE) led to elevated haematocrit, and both ESA treatment and training (SE, TP and TE) increased maximal O2 uptake. With regard to skeletal muscle morphology, TP alone exhibited increases in whole-m...
Erythropoietin on cycling performance – Authors' reply
The Lancet Haematology
Besides, the standing records of the EPO-era cannot be discarded so easily. Sanguinely, further research will lead to medical use of EPO for its performance-enhancing and cytoprotective properties. And, of course, cycling should be clean. We declare no competing interests.
Erythrocytic system under the influence of physical exercise and training
Sports medicine (Auckland, N.Z.), 1990
It is obvious that physical performance, endurance capacity and resistance to fatigue in humans are dependent upon many different factors. One factor, the oxygen carrying capacity of blood, seems to be of particular importance. This factor is mainly determined by haemoglobin concentration, number of circulating erythrocytes and the efficiency of their functions. A single bout of physical effort and, even more, repeated exercise may change the morphological indices of blood and influence the erythropoietic processes in the bone marrow. That is why there is so great an interest now attached to the effects of physical exercise on the erythrocytic system. Although in recent years many papers have been published on the subjects their findings pertaining to the effects of single bouts of exercise and systematic training on the erythrocytic system are often contradictory. The haematological parameters in some top-class athletes, particularly those performing in endurance disciplines are lo...
MONITORING ERYTHROPOIETIN ABUSE IN ATHLETES
British Journal of Haematology, 1999
In conclusion, deferiprone and DFO therapy on alternate days may improve compliance with chelation therapy. A negative iron balance can be achieved with this regimen and it may well be cost-effective. A larger prospective randomized study evaluating this model over a longer period of time seems necessary.