Copenhagen Muscle Research Center

Copenhagen, Denmark

Copenhagen Muscle Research Center

Copenhagen, Denmark
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Wisen A.G.M.,Lund University | Mao P.,Lund University | Christiansen L.,Bispebjerg Hospital | Saltin B.,Copenhagen Muscle Research Center
European Journal of Physiotherapy | Year: 2015

The purpose of this study was to compare oxygen uptake estimated from submaximal Åstrand tests (VO2est) with measured peak oxygen uptake (VO2peak) from maximal tests, and to compare estimated maximal HR (HRest) with measured HRpeak in obese subjects. Seventy obese subjects performed a maximal exercise test starting with a 4-min period of constant load. VO2peak and HRpeak were measured. VO2est was based on HR at constant load. HRest was calculated by the formula 220-age. The mean± SD of VO2est 2.05 ± 0.39 l/min (20 ± 5 ml/kg/min) was lower than VO2peak 2.42 ± 0.57 l/min (17 ± 4 ml/kg/min) (p < 0.001, p < 0.001, respectively). The mean difference ± 2SD was-0.4 ± 1.22 l/min (-3 ± 10 ml/kg/min) with an uneven distribution of the individual variation. The correlation between the methods was low (r = 0.24, r = 0.38 respectively). The mean± SD of HRest 176 ± 10 bpm was higher than the HRpeak 161 ± 17 bpm (p < 0.001). The mean difference ± 2SD was 15 ± 31.3 bpm with an uneven distribution of the individual variation. The correlation between the methods was low (r = 0.41). The main findings of this study were that estimation of VO2 from the Åstrand test and of HR by the formula 220-age had low validity in obese subjects. Consequently, direct measurements of HRpeak and VO2peak are recommended for accurate prediction of obese individual's exercise capacity. © 2015 Informa Healthcare.

Adser H.,Copenhagen Muscle Research Center | Adser H.,Copenhagen University | Wojtaszewski J.F.P.,Copenhagen Muscle Research Center | Wojtaszewski J.F.P.,Copenhagen University | And 7 more authors.
Acta Physiologica | Year: 2011

Aim: The aim of this study was to test the hypothesis that interleukin (IL)-6 plays a role in exercise-induced peroxisome proliferator-activated receptor γ co-activator (PGC)-1α and tumor necrosis factor (TNF)-α mRNA responses in skeletal muscle and to examine the potential IL-6-mediated AMP-activated protein kinase (AMPK) regulation in these responses. Methods: Whole body IL-6 knockout (KO) and wildtype (WT) male mice (4months of age) performed 1h treadmill exercise. White gastrocnemius (WG) and quadriceps (Quad) muscles were removed immediately (0') or 4h after exercise and from mice not run acutely. Results: Acute exercise reduced only in WT muscle glycogen concentration to 55 and 35% (P<0.05) of resting level in Quad and WG respectively. While AMPK and Acetyl CoA carboxylase (ACC) phosphorylation increased 1.3-fold (P<0.05) in WG and twofold in Quad immediately after exercise in WT mice, no change was detected in WG in IL-6 KO mice. The PGC-1α mRNA content was in resting WG 1.8-fold higher (P<0.05) in WT mice than in IL-6 KO mice. Exercise induced a delayed PGC-1α mRNA increase in Quad in IL-6 KO mice (12-fold at 4h) relative to WT mice (fivefold at 0'). The TNF-α mRNA content was in resting Quad twofold higher (P<0.05) in IL-6 KO than in WT, and WG TNF-α mRNA increased twofold (P<0.05) immediately after exercise only in IL-6 KO. Conclusion: In conclusion, IL-6 affects exercise-induced glycogen use, AMPK signalling and TNF-α mRNA responses in mouse skeletal muscle. © 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.

Steding-Ehrenborg K.,Copenhagen Muscle Research Center | Steding-Ehrenborg K.,Hvidovre Hospital | Jablonowski R.,Lund University | Arvidsson P.M.,Lund University | And 3 more authors.
Journal of Cardiovascular Magnetic Resonance | Year: 2013

Background: The effects on left and right ventricular (LV, RV) volumes during physical exercise remains controversial. Furthermore, no previous study has investigated the effects of exercise on longitudinal contribution to stroke volume (SV) and the outer volume variation of the heart. The aim of this study was to determine if LV, RV and total heart volumes (THV) as well as cardiac pumping mechanisms change during physical exercise compared to rest using cardiovascular magnetic resonance (CMR). Methods. 26 healthy volunteers (6 women) underwent CMR at rest and exercise. Exercise was performed using a custom built ergometer for one-legged exercise in the supine position during breath hold imaging. Cardiac volumes and atrio-ventricular plane displacement were determined. Heart rate (HR) was obtained from ECG. Results: HR increased during exercise from 60±2 to 94±2 bpm, (p<0.001). LVEDV remained unchanged (p=0.81) and LVESV decreased with -9±18% (p<0.05) causing LVSV to increase with 8±3% (p<0.05). RVEDV and RVESV decreased by -7±10% and -24±14% respectively, (p<0.001) and RVSV increased 5±17% during exercise although not statistically significant (p=0.18). Longitudinal contribution to RVSV decreased during exercise by -6±15% (p<0.05) but was unchanged for LVSV (p=0.74). THV decreased during exercise by -4±1%, (p<0.01) and total heart volume variation (THVV) increased during exercise from 5.9±0.5% to 9.7±0.6% (p<0.001). Conclusions: Cardiac volumes and function are significantly altered during supine physical exercise. THV becomes significantly smaller due to decreases in RVEDV whilst LVEDV remains unchanged. THVV and consequently radial pumping increases during exercise which may improve diastolic suction during the rapid filling phase. © 2013 Steding-Ehrenborg et al.; licensee BioMed Central Ltd.

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.

Jorgensen S.B.,St. Vincent's Institute | Jorgensen S.B.,Novo Nordisk AS | O'Neill H.M.,St. Vincent's Institute | O'Neill H.M.,McMaster University | And 14 more authors.
Diabetes | Year: 2013

Obesity is associated with chronic low-grade inflammation that contributes to defects in energy metabolism and insulin resistance. Suppressor of cytokine signaling (SOCS)-3 expression is increased in skeletal muscle of obese humans. SOCS3 inhibits leptin signaling in the hypothalamus and insulin signal transduction in adipose tissue and the liver. Skeletal muscle is an important tissue for controlling energy expenditure and whole-body insulin sensitivity; however, the physiological importance of SOCS3 in this tissue has not been examined. Therefore, we generated mice that had SOCS3 specifically deleted in skeletal muscle (SOCS MKO). The SOCS3 MKO mice had normal muscle development, body mass, adiposity, appetite, and energy expenditure compared with wild-type (WT) littermates. Despite similar degrees of obesity when fed a high-fat diet, SOCS3 MKO mice were protected against the development of hyperinsulinemia and insulin resistance because of enhanced skeletal muscle insulin receptor substrate 1 (IRS1) and Akt phosphorylation that resulted in increased skeletal muscle glucose uptake. These data indicate that skeletal muscle SOCS3 does not play a critical role in regulating muscle development or energy expenditure, but it is an important contributing factor for inhibiting insulin sensitivity in obesity. Therapies aimed at inhibiting SOCS3 in skeletal muscle may be effective in reversing obesity-related glucose intolerance and insulin resistance. © 2013 by the American Diabetes Association.

Hellsten Y.,Copenhagen Muscle Research Center | Hellsten Y.,Copenhagen University | Nyberg M.,Copenhagen Muscle Research Center | Nyberg M.,Copenhagen University | And 2 more authors.
Journal of Physiology | Year: 2012

The regulation of blood flow to skeletal muscle involves a complex interaction between several locally formed vasodilators that are produced both in the skeletal muscle interstitium and intravascularly. The gas nitric oxide (NO) and the purines ATP and adenosine, are potent vasodilators that are formed by multiple cell types and released into the skeletal muscle interstitium and in plasma in response to muscle contraction. Cellular sources of ATP and NO in plasma are erythrocytes and endothelial cells, whereas interstitial sources are skeletal muscle cells and endothelial cells. Adenosine originates primarily from extracellular degradation of ATP. During exercise the concentrations of ATP and adenosine increase markedly in the interstitium with smaller increases occurring in plasma, and thus the interstitial concentration during exercise is severalfold higher than in plasma. The concentration of NO metabolites (NOx) in interstitium and plasma does not change during exercise and is similar in the two compartments. Adenosine and NO have been shown to contribute to exercise hyperaemia whereas the role of ATP remains unclear due to lack of specific purinergic receptor blockers. The relative role of intravascular versus interstitial vasodilators is not known but evidence suggests that both compartments are important. In cardiovascular disease, a reduced capacity to form adenosine in the muscle interstitium may be a contributing factor in increased peripheral vascular resistance. © 2012 The Authors. The Journal of Physiology © 2012 The Physiological Society.

Brassard P.,Copenhagen Muscle Research Center | Brassard P.,Copenhagen University | Zaar M.,Copenhagen Muscle Research Center | Zaar M.,Copenhagen University | And 5 more authors.
Critical Care Medicine | Year: 2016

Objective: Sympathetic vasoconstriction regulates peripheral circulation and controls blood pressure, but sepsis is associated with hypotension. We evaluated whether apparent loss of sympathetic vasoconstrictor responsiveness relates to distended smooth muscles or to endotoxemia and/or hypoxia. Design: Prospective descriptive study. Setting: Hospital research laboratory. Subjects: Ten healthy young men (age [mean ± SD], 31 ± 8 yr; body weight, 83 ± 10 kg) participated in the study. Interventions: Leg blood flow and mean arterial pressure were determined, whereas leg vascular conductance was calculated during 1) adenosine infusion (vasodilator control), 2) hypoxia (FIO2 = 10%), 3) endotoxemia, and 4) endotoxemia + hypoxia. Leg sympathetic vasoconstrictor responsiveness (reduction in leg vascular conductance) was evaluated by femoral artery tyramine infusion. Measurements and Main Results: Endotoxemia increased body temperature from 36.9 ± 0.4°C to 38.6 ± 0.5°C (p < 0.01) and plasma tumor necrosis factor-α from 6 pg/mL (3-8 pg/mL) to 391 pg/mL (128-2258 pg/mL) (p < 0.01; median [range]). Mean arterial pressure decreased similarly during endotoxemia (-11% ± 16%) and endotoxemia + hypoxia (-10% ± 15%; both p < 0.05). Leg blood flow and leg vascular conductance were not affected by endotoxemia, whereas both were elevated by adenosine infusion (leg blood flow, +94% ± 61%; leg vascular conductance, +97% ± 57%), hypoxia (leg blood flow: +93% ± 58%; leg vascular conductance, +100% ± 115%), and endotoxemia + hypoxia (leg blood flow, +67% ± 120%; leg vascular conductance, +65% ± 57%; p < 0.05). Endotoxemia lessened the tyramine-induced reduction in leg vascular conductance (-28% ± 13%) compared with the reduction during adenosine infusion (-47% ± 5%; p < 0.05). Also, endotoxemia + hypoxia (-17% ± 21%) attenuated the tyramine-induced reduction in leg vascular conductance compared with both adenosine infusion and hypoxia (-45% ± 13%; p < 0.05). Conclusions: Both endotoxemia and combined hypoxia and endotoxemia blunted sympathetic vasoconstrictor responsiveness. Furthermore, tyramine normalized the doubled leg vascular conductance during administration of adenosine, suggesting that distension of vascular smooth muscles does not explain blunted sympathetic vasoconstrictor responsiveness during endotoxemia. © 2016 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Iwasaki K.-I.,University of Texas Southwestern Medical Center | Iwasaki K.-I.,Nihon University | Zhang R.,University of Texas Southwestern Medical Center | Zuckerman J.H.,University of Texas Southwestern Medical Center | And 3 more authors.
Journal of Cerebral Blood Flow and Metabolism | Year: 2011

Cerebral blood flow (CBF) increases and dynamic cerebral autoregulation is impaired by acute hypoxia. We hypothesized that progressive hypocapnia with restoration of arterial oxygen content after altitude acclimatization would normalize CBF and dynamic cerebral autoregulation. To test this hypothesis, dynamic cerebral autoregulation was examined by spectral and transfer function analyses between arterial pressure and CBF velocity variabilities in 11 healthy members of the Danish High-Altitude Research Expedition during normoxia and acute hypoxia (10.5% O2) at sea level, and after acclimatization (for over 1 month at 5,260 m at Chacaltaya, Bolivia). Arterial pressure and CBF velocity in the middle cerebral artery (transcranial Doppler), were recorded on a beat-κBy-κBeat basis. Steady-state CBF velocity increased during acute hypoxia, but normalized after acclimatization with partial restoration of SaO2 (acute, 78%±2%; chronic, 89%±1%) and progression of hypocapnia (end-tidal carbon dioxide: acute, 342 mm Hg; chronic, 211 mm Hg). Coherence (0.40±0.05 Units at normoxia) and transfer function gain (0.77±0.13 cm/s per mm Hg at normoxia) increased, and phase (0.86±0.15 radians at normoxia) decreased significantly in the very-low-frequency range during acute hypoxia (gain, 141%±24%; coherence, 136%±29%; phase, 25%±22%), which persisted after acclimatization (gain, 136%±36%; coherence, 131%±50%; phase, 42%±13%), together indicating impaired dynamic cerebral autoregulation in this frequency range. The similarity between both acute and chronic conditions suggests that dynamic cerebral autoregulation is impaired by hypoxia even after successful acclimatization to an extreme high altitude. © 2011 ISCBFM All rights reserved.

Nyberg M.,Copenhagen University | Christensen P.M.,Copenhagen University | Mortensen S.P.,Copenhagen Muscle Research Center | Mortensen S.P.,University of Southern Denmark | And 2 more authors.
Experimental Physiology | Year: 2014

The present study examined whether an increase in leg blood flow and oxygen delivery at the onset of intense exercise would speed the rate of rise in leg oxygen uptake. Nine healthy men (25 ± 1 years old, mean ± SEM) performed one-leg knee-extensor exercise (62 ± 3 W, 86 ± 3% of incremental test peak power) for 4 min during a control setting (CON) and with infusion of ATP into the femoral artery in order to increase blood flow before and during exercise. In the presence of ATP, femoral arterial blood flow and O2 delivery were higher (P < 0.001) at the onset of exercise and throughout exercise (femoral arterial blood flow after 10 s, 5.1 ± 0.5 versus 2.7 ± 0.3 l min-1; after 45 s, 6.0 ± 0.5 versus 4.1 ± 0.4 l min-1; after 90 s, 6.6 ± 0.6 versus 4.5 ± 0.4 l min-1; and after 240 s, 7.0 ± 0.6 versus 5.1 ± 0.3 l min-1 in ATP and CON conditions, respectively). Leg oxygen uptake was not different in ATP and CON conditions during the first 20 s of exercise but was lower (P < 0.05) in the ATP compared with CON conditions after 30 s and until the end of exercise (30 s, 436 ± 42 versus 549 ± 45 ml min-1; and 240 s, 705 ± 31 versus 814 ± 59 ml min-1 in ATP and CON, respectively). Lactate release was lower after 60, 120 and 180 s of exercise with ATP infusion. These results suggest that O2 delivery is not limiting the rise in skeletal muscle oxygen uptake in the initial phase of intense exercise. © 2014 The Physiological Society.

Dahl R.,Copenhagen Muscle Research Center | Larsen S.,Copenhagen Muscle Research Center | Dohlmann T.L.,Copenhagen Muscle Research Center | Qvortrup K.,Copenhagen Muscle Research Center | And 3 more authors.
Acta physiologica (Oxford, England) | Year: 2015

AIM: Mitochondria undergo continuous changes in shape as result of complex fusion and fission processes. The physiological relevance of mitochondrial dynamics is still unclear. In the field of mitochondria bioenergetics, there is a need of tools to assess cell mitochondrial content. To develop a method to visualize mitochondrial networks in high resolution and assess mitochondrial volume.METHODS: Confocal fluorescence microscopy imaging of mitochondrial network stains in human vastus lateralis single muscle fibres and focused ion beam/ scanning electron microscopy (FIB/SEM) imaging, combined with 3D reconstruction was used as a tool to analyse mitochondrial morphology and measure mitochondrial fractional volume.RESULTS: Most type I and type II muscle fibres have tubular highly interconnected profusion mitochondria, which are thicker and more structured in type I muscle fibres (Fig. 1). In some muscle fibres, profission-isolated ellipsoid-shaped mitochondria were observed. Mitochondrial volume was significantly higher in type I muscle fibres and showed no correlation with any of the investigated molecular and biochemical mitochondrial measurements (Fig. 2). Three-dimensional reconstruction of FIB/SEM data sets shows that some subsarcolemmal mitochondria are physically interconnected with some intermyofibrillar mitochondria (Fig. 3).CONCLUSION: Two microscopy methods to visualize skeletal muscle mitochondrial networks in 3D are described and can be used as tools to investigate mitochondrial dynamics in response to life-style interventions and/or in certain pathologies. Our results question the classification of mitochondria into subsarcolemmal and intermyofibrillar pools, as they are physically interconnected. © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

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