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Jacobs R.A.,University of Zurich | Boushel R.,University of Zurich | Boushel R.,The Copenhagen Muscle Research Center | Wright-Paradis C.,University of Zurich | And 6 more authors.
Experimental Physiology | Year: 2013

New Findings: • What is the central question of this study? Are the enzymatic alterations in human skeletal muscle observed following 9-11 days of exposure to high altitude reflected in mitochondrial function? • What is the main finding and its importance? The main findings of this study are that the capacity fat oxidation, individualized respiration capacity through mitochondrial complex I and II, and electron coupling efficiency are not greatly affected by 9-11 days of exposure to high altitude. The importance of this data is that high altitude exposure failed to affect integrated measures of mitochondrial functional capacity in skeletal muscle despite significant decrements to enzyme concentrations involved in the tricarboxylic acid (TCA) cycle and oxidative phosphorylation. Studies regarding mitochondrial modifications in human skeletal muscle following acclimatization to high altitude are conflicting, and these inconsistencies may be due to the prevalence of representing mitochondrial function through static and isolated measurements of specific mitochondrial characteristics. The aim of this study, therefore, was to investigate mitochondrial function in response to high-altitude acclimatization through measurements of respiratory control in the vastus lateralis muscle. Skeletal muscle biopsies were obtained from 10 lowland natives prior to and again after a total of 9-11 days of exposure to 4559 m. High-resolution respirometry was performed on the muscle samples to compare respiratory chain function and respiratory capacities. Respirometric analysis revealed that mitochondrial function was largely unaffected, because high-altitude exposure did not affect the capacity for fat oxidation or individualized respiration capacity through either complex I or complex II. Respiratory chain function remained unaltered, because neither coupling nor respiratory control changed in response to hypoxic exposure. High-altitude acclimatization did, however, show a tendency (P= 0.059) to limit mass-specific maximal oxidative phosphorylation capacity. These data suggest that 9-11 days of exposure to high altitude do not markedly modify integrated measures of mitochondrial functional capacity in skeletal muscle despite significant decrements in the concentrations of enzymes involved in the tricarboxylic acid cycle and oxidative phosphorylation. © 2012 The Authors. Experimental Physiology © 2012 The Physiological Society.

Larsen H.B.,The Copenhagen Muscle Research Center | Sheel A.W.,University of British Columbia
Scandinavian Journal of Medicine and Science in Sports | Year: 2015

Today the Kenyan dominance in middle- and long-distance running is so profound that it has no equivalence to any other sport in the world. Critical physiological factors for performance in running include maximal oxygen consumption (VO2max), fractional VO2max utilization and running economy (energetic cost of running). Kenyan and non-Kenyan elite runners seem to be able to reach very high, but similar maximal oxygen uptake levels just as there is some indication that untrained Kenyans and non-Kenyans have a similar VO2max. In addition, the fractional utilization of VO2max seems to be very high but similar in Kenyan and European runners. Similarly, no differences in the proportion of slow muscle fibers have been observed when comparing Kenyan elite runners with their Caucasian counterparts. In contrast, the oxygen cost of running at a given running velocity has been found to be lower in Kenyan elite runners relative to other elite runners and there is some indication that this is due to differences in body dimensions. Pulmonary system limitations have been observed in Kenyan runners in the form of exercise-induced arterial hypoxemia, expiratory flow limitation, and high levels of respiratory muscle work. It appears that Kenyan runners do not possess a pulmonary system that confers a physiological advantage. Additional studies on truly elite Kenyan runners are necessary to understand the underlying physiology which permits extraordinary running performances. © 2015 John Wiley & Sons A/S.

Mortensen S.P.,The Copenhagen Muscle Research Center | Askew C.D.,Queensland University of Technology | Askew C.D.,University of The Sunshine Coast | Walker M.,University of The Sunshine Coast | And 2 more authors.
Journal of Physiology | Year: 2012

Passive leg movement is associated with a ∼3-fold increase in blood flow to the leg but the underlying mechanisms remain unknown. The objective of the present study was to examine the role of nitric oxide (NO) for the hyperaemia observed during passive leg movement. Leg haemodynamics and metabolites of NO production (nitrite and nitrate; NOx) were measured in plasma and muscle interstitial fluid at rest and during passive leg movement with and without inhibition of NO formation in healthy young males. The hyperaemic response to passive leg movement and to ACh was also assessed in elderly subjects and patients with peripheral artery disease. Passive leg movement (60 r.p.m.) increased leg blood flow from 0.3 ± 0.1 to 0.9 ± 0.1 litre min-1 at 20 s and 0.5 ± 0.1 litre min-1 at 3 min (P < 0.05). Mean arterial pressure remained unchanged during the trial. When passive leg movement was performed during inhibition of NO formation (NG-mono-methyl-l-arginine; 29-52 mg min-1), leg blood flow and vascular conductance were increased after 20 s (P < 0.05) and then returned to baseline levels, despite an increase in arterial pressure (P < 0.05). Passive leg movement increased the femoral venous NOx levels from 35 ± 5 at baseline to 62 ± 11 μmol l-1 during passive leg movement (P < 0.05), whereas muscle interstitial NOx levels remained unchanged. The hyperaemic response to passive leg movement were correlated with the vasodilatation induced by ACh (r2= 0.704, P < 0.001) and with age (r2= 0.612, P < 0.001). Leg blood flow did not increase during passive leg movement in individuals with peripheral arterial disease. These results suggest that the hypaeremia induced by passive leg movement is NO dependent and that the source of NO is likely to be the endothelium. Passive leg movement could therefore be used as a non-invasive tool to evaluate NO dependent endothelial function of the lower limb. © 2012 The Authors. The Journal of Physiology © 2012 The Physiological Society.

Mortensen S.P.,The Copenhagen Muscle Research Center | Nyberg M.,The Copenhagen Muscle Research Center | Nyberg M.,Copenhagen University | Winding K.,The Copenhagen Muscle Research Center | Saltin B.,The Copenhagen Muscle Research Center
Journal of Physiology | Year: 2012

Ageing is associated with an impaired ability to modulate sympathetic vasoconstrictor activity (functional sympatholysis) and a reduced exercise hyperaemia. The purpose of this study was to investigate whether a physically active lifestyle can offset the impaired functional sympatholysis and exercise hyperaemia in the leg and whether ATP signalling is altered by ageing and physical activity. Leg haemodynamics, interstitial [ATP] and P2Y2 receptor content was determined in eight young (23 ± 1 years), eight lifelong sedentary elderly (66 ± 2 years) and eight lifelong active elderly (62 ± 2 years) men at rest and during one-legged knee extensions (12 W and 45% maximal workload (WLmax)) and arterial infusion of ACh and ATP with and without tyramine. The vasodilatory response to ACh was lowest in the sedentary elderly, higher in active elderly (P < 0.05) and highest in the young men (P < 0.05), whereas ATP-induced vasodilatation was lower in the sedentary elderly (P < 0.05). During exercise (12 W), leg blood flow, vascular conductance and was lower and leg lactate release higher in the sedentary elderly compared to the young (P < 0.05), whereas there was no difference between the active elderly and young. Interstitial [ATP] during exercise and P2Y2 receptor content were higher in the active elderly compared to the sedentary elderly (P < 0.05). Tyramine infusion lowered resting vascular conductance in all groups, but only in the sedentary elderly during exercise (P < 0.05). Tyramine did not alter the vasodilator response to ATP infusion in any of the three groups. Plasma [noradrenaline] increased more during tyramine infusion in both elderly groups compared to young (P < 0.05). A lifelong physically active lifestyle can maintain an intact functional sympatholysis during exercise and vasodilator response to ATP despite a reduction in endothelial nitric oxide function. A physically active lifestyle increases interstitial ATP levels and skeletal muscle P2Y2 receptor content. 2012 The Physiological Society.

Bada A.A.,The Copenhagen Muscle Research Center | Svendsen J.H.,Rigshospitalet | Svendsen J.H.,Danish National Research Foundation Center for Cardiac Arrhythmia | Secher N.H.,The Copenhagen Muscle Research Center | And 2 more authors.
Journal of Physiology | Year: 2012

In dogs, manipulation of heart rate has no effect on the exercise-induced increase in cardiac output. Whether these findings apply to humans remain uncertain, because of the large differences in cardiovascular anatomy and regulation. To investigate the role of heart rate and peripheral vasodilatation in the regulation of cardiac output during steady-state exercise, we measured central and peripheral haemodynamics in 10 healthy male subjects, with and without atrial pacing (100-150 beats min -1) during: (i) resting conditions, (ii) one-legged knee extensor exercise (24 W) and (iii) femoral arterial ATP infusion at rest. Exercise and ATP infusion increased cardiac output, leg blood flow and vascular conductance (P < 0.05), whereas cerebral perfusion remained unchanged. During atrial pacing increasing heart rate by up to 54 beats min -1, cardiac output did not change in any of the three conditions, because of a parallel decrease in stroke volume (P < 0.01). Atrial pacing increased mean arterial pressure (MAP) at rest and during ATP infusion (P < 0.05), whereas MAP remained unchanged during exercise. Atrial pacing lowered central venous pressure (P < 0.05) and pulmonary capillary wedge pressure (P < 0.05) in all conditions, whereas it did not affect pulmonary mean arterial pressure. Atrial pacing lowered the left ventricular contractility index (dP/dt) (P < 0.05) in all conditions and plasma noradrenaline levels at rest (P < 0.05), but not during exercise and ATP infusion. These results demonstrate that the elevated cardiac output during steady-state exercise is regulated by the increase in skeletal muscle blood flow and venous return to the heart, whereas the increase in heart rate appears to be secondary to the regulation of cardiac output. © 2012 The Authors. The Journal of Physiology © 2012 The Physiological Society.

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