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Copenhagen, Denmark

Lundby C.,Copenhagen Muscle Research Center | Robach P.,Departement Medical
European Journal of Applied Physiology | Year: 2010

The purpose of the study was to reveal erythropoietin (epo) doping. It was recently suggested that the assessment of total haemoglobin mass (tHb) by means of the carbon monoxide re-breathing technique should be implemented in anti-doping work. Since epo may increase the haemoglobin concentration [Hb] simply by reducing plasma volume we injected eight human subjects with epo for 15 weeks and directly tested the feasibility hereof. Epo treatment increased [Hb] in all subjects at all time points (range 3.8-18.8%). In approximately half the subjects this was mainly the consequence of an increased tHb, but in the remaining subjects the change was the result of a decrease in the plasma volume. After the initial epo "boosting" period the assessment of tHb could not detect epo injections in 50% of the subjects in the remaining "maintenance" period. In our opinion the variability observed over time when assessing tHb is not justifiable in an anti-doping setting. © 2009 Springer-Verlag. Source


Mortensen S.P.,University of Southern Denmark | Saltin B.,Copenhagen Muscle Research Center
Experimental Physiology | Year: 2014

New Findings: What is the topic of this review? This review highlights recent advances in our knowledge about the control of skeletal muscle blood flow during exercise in humans. What advances does it highlight? In recent years, it has become evident that the control of skeletal muscle blood flow is an interaction between various vasodilator agents, including nitric oxide, prostaglandins and adenosine. Adenosine triphosphate could play multiple roles by inducing local vasodilatation, overriding local sympathetic vasoconstriction and stimulating the exercise pressor reflex. In humans, skeletal muscle blood flow is regulated by an interaction between several locally formed vasodilators, including NO and prostaglandins. In plasma, ATP is a potent vasodilator that stimulates the formation of NO and prostaglandins and, very importantly, can offset local sympathetic vasoconstriction. Adenosine triphosphate is released into plasma from erythrocytes and endothelial cells, and the plasma concentration increases in both the feed artery and the vein draining the contracting skeletal muscle. Adenosine also stimulates the formation of NO and prostaglandins, but the plasma adenosine concentration does not increase during exercise. In the skeletal muscle interstitium, there is a marked increase in the concentration of ATP and adenosine, and this increase is tightly coupled to the increase in blood flow. The sources of interstitial ATP and adenosine are thought to be skeletal muscle cells and endothelial cells. In the interstitium, both ATP and adenosine stimulate the formation of NO and prostaglandins, but ATP has also been suggested to induce vasoconstriction and stimulate afferent nerves that signal to increase sympathetic nerve activity. Adenosine has been shown to contribute to exercise hyperaemia, whereas the role of ATP remains uncertain due to lack of specific purinergic receptor blockers for human use. The purpose of this review is to address the interaction between vasodilator systems and to discuss the multiple proposed roles of ATP in human skeletal muscle blood flow regulation. © 2014 The Authors. Source


Nordsborg N.B.,Copenhagen University | Lundby C.,Copenhagen Muscle Research Center | Leick L.,Copenhagen University | Pilegaard H.,Copenhagen University
Medicine and Science in Sports and Exercise | Year: 2010

Introduction: The hypothesis that brief intermittent exercise-induced increases in human skeletal muscle metabolic mRNA is dependent on relative workload was investigated. Methods: Trained (n = 10) and untrained (n = 8) subjects performed exhaustive intermittent cycling exercise (4 × 4 min at 85% of V̇O2peak, interspersed by 3 min). Trained subjects also performed the intermittent exercise at the same absolute workload as the untrained subjects, corresponding to 70% of V̇O2peak (n = 6). Results: Exercise at 85% of V̇O2peak elevated (P < 0.001) venous plasma lactate to 10.1 ± 0.4 and 10.8 ± 0.5 mM in the trained and untrained subjects, respectively. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) mRNA expression was increased (P < 0.001) approximately four-to fivefold for several hours after exercise in both groups. After exercise at 70% of V̇O2peak, venous plasma lactate was less (P < 0.001) elevated (3.1 ± 0.7 mM) and PGC-1α mRNA content was less (P < 0.05) increased (approximately threefold) than after exercise at 85% of V̇O2peak. Likewise, pyruvate dehydrogenase kinase 4 and hexokinase II mRNA expressions were increased (P < 0.05) only after exercise performed at 85% of V̇O2peak in the trained subjects. Hypoxia-inducible factor 2α mRNA only increased (P < 0.05) 3 h into recovery in trained subjects, with no difference between the 70% and 85% of V̇O2peak trial. No change in hypoxia-inducible factor 1α, phosphofructokinase, citrate synthase, or lactate dehydrogenase, heart and muscle isoforms, mRNA expressions was detected after any of the exercise trials. Conclusions: The relative intensity of brief intermittent exercise is of major importance for the exercise-induced increase of several mRNA, including PGC-1α. © 2010 by the American College of Sports Medicine. Source


ortenblad N.,University of Southern Denmark | Nielsen J.,University of Southern Denmark | Saltin B.,Copenhagen Muscle Research Center | Holmberg H.-C.,Mid Sweden University
Journal of Physiology | Year: 2011

Little is known about the precise mechanism that relates skeletal muscle glycogen to muscle fatigue. The aim of the present study was to examine the effect of glycogen on sarcoplasmic reticulum (SR) function in the arm and leg muscles of elite cross-country skiers (n= 10, 72 ± 2 ml kg-1 min-1) before, immediately after, and 4 h and 22 h after a fatiguing 1 h ski race. During the first 4 h recovery, skiers received either water or carbohydrate (CHO) and thereafter all received CHO-enriched food. Immediately after the race, arm glycogen was reduced to 31 ± 4% and SR Ca2+ release rate decreased to 85 ± 2% of initial levels. Glycogen noticeably recovered after 4 h recovery with CHO (59 ± 5% initial) and the SR Ca2+ release rate returned to pre-exercise levels. However, in the absence of CHO during the first 4 h recovery, glycogen and the SR Ca2+ release rate remained unchanged (29 ± 2% and 77 ± 8%, respectively), with both parameters becoming normal after the remaining 18 h recovery with CHO. Leg muscle glycogen decreased to a lesser extent (71 ± 10% initial), with no effects on the SR Ca2+ release rate. Interestingly, transmission electron microscopy (TEM) analysis revealed that the specific pool of intramyofibrillar glycogen, representing 10-15% of total glycogen, was highly significantly correlated with the SR Ca2+ release rate. These observations strongly indicate that low glycogen and especially intramyofibrillar glycogen, as suggested by TEM, modulate the SR Ca2+ release rate in highly trained subjects. Thus, low glycogen during exercise may contribute to fatigue by causing a decreased SR Ca2+ release rate. © 2011 The Authors. Journal compilation © 2011 The Physiological Society. Source


Morkeberg J.,Copenhagen Muscle Research Center | Sharpe K.,University of Melbourne | Karstoft K.,Copenhagen University | Ashenden M.J.,Science and Industry Against Blood Doping SIAB Research Consortium
Scandinavian Journal of Medicine and Science in Sports | Year: 2014

The detection of recombinant human erythropoietin (rhEPO) is difficult and becomes more challenging when only microdoses are administered intravenously. Twenty-three subjects were divided into two groups: EPO group (n=7) and CONTROL group (n=16). Seven urine and blood samples per subject were collected at least 5 days apart to determine within- and between-subject standard deviations in the percentage of migrating isoforms by the MAIIA test. Six injections of 50IU/kg bw (boosting dosage) of epoetin beta (Neorecormon, Roche Diagnostics, Hvidovre, Denmark) were performed intravenously during a 3-week period, followed by two microinjections of only 10IU/kg bw. Blood and urine samples were collected 2, 6, 12, and 72h after the microinjection, as well as 72h after the last boosting dose. Sensitivities and specificities of the MAIIA test were examined by absolute and passport thresholds. Sensitivity was 100% for at least 12h after the microinjection, with ~30% of plasma samples still exceeding the 99.9% passport threshold 72h after a microinjection. The specificity was higher for the passport approach compared to the absolute approach, but there were no differences in sensitivities between approaches or between specimens (urine and plasma). We conclude that the MAIIA test shows potential for detecting very small doses of rhEPO. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Source

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