One-legged Knee Extension Research Articles

Exercise increases sphingoid base-1-phosphate levels in human blood and skeletal muscle in a time- and intensity-dependent manner.

PurposeSphingosine-1-phosphate (S1P) regulates cardiovascular function and plays an important role in muscle biology. We have previously reported that cycling exercise increased plasma S1P. Here, we investigated the effect of exercise duration and intensity on plasma and skeletal muscle S1P levels.MethodsIn the first experiment, 13 male athletes performed a 60-min exercise at 65 % of VO2max and a graded exercise until exhaustion on a rowing ergometer. Samples of the venous blood were taken, and plasma, erythrocytes and platelets were isolated. In the second experiment, ten male moderately active subjects performed three consecutive periods of one-leg knee extension exercise (at 25, 55 and 85 % of the maximal workload). Muscle biopsies and blood samples from the radial artery and femoral veins were taken.ResultsUnder basal conditions, S1P was released from the leg, as its concentration was lower in the arterial than in the venous plasma (p < 0.01). Exercise until exhaustion increased plasma S1P and sphinganine-1-phosphate (SA1P) concentration (p < 0.05), whereas moderate-intensity exercise elevated only SA1P (p < 0.001). Although knee extension increased muscle S1P content (p < 0.05), it was not released but taken up across the leg during exercise. However, sphingosine was released from both working and resting leg at the highest workload (p < 0.05).ConclusionsPlasma S1P concentration is elevated only by high-intensity exercise which results, at least in part, from increased availability of sphingosine released by skeletal muscle. In addition, exercise markedly affects S1P dynamics across the leg. We speculate that S1P may play an important role in adaptation of skeletal muscle to exercise.Electronic supplementary materialThe online version of this article (doi:10.1007/s00421-014-3080-x) contains supplementary material, which is available to authorized users.

Skeletal muscle oxidative function in vivo and ex vivo in athletes with marked hypertrophy from resistance training

Oxidative function during exercise was evaluated in 11 young athletes with marked skeletal muscle hypertrophy induced by long-term resistance training (RTA; body mass 102.6 ± 7.3 kg, mean ± SD) and 11 controls (CTRL; body mass 77.8 ± 6.0 kg). Pulmonary O2 uptake (Vo2) and vastus lateralis muscle fractional O2 extraction (by near-infrared spectroscopy) were determined during an incremental cycle ergometer (CE) and one-leg knee-extension (KE) exercise. Mitochondrial respiration was evaluated ex vivo by high-resolution respirometry in permeabilized vastus lateralis fibers obtained by biopsy. Quadriceps femoris muscle cross-sectional area, volume (determined by magnetic resonance imaging), and strength were greater in RTA vs. CTRL (by ∼40%, ∼33%, and ∼20%, respectively). Vo2peak during CE was higher in RTA vs. CTRL (4.05 ± 0.64 vs. 3.56 ± 0.30 l/min); no difference between groups was observed during KE. The O2 cost of CE exercise was not different between groups. When divided per muscle mass (for CE) or quadriceps muscle mass (for KE), Vo2 peak was lower (by 15-20%) in RTA vs. CTRL. Vastus lateralis fractional O2 extraction was lower in RTA vs. CTRL at all work rates, during both CE and KE. RTA had higher ADP-stimulated mitochondrial respiration (56.7 ± 23.7 pmol O2·s(-1)·mg(-1) ww) vs. CTRL (35.7 ± 10.2 pmol O2·s(-1)·mg(-1) ww) and a tighter coupling of oxidative phosphorylation. In RTA, the greater muscle mass and maximal force and the enhanced mitochondrial respiration seem to compensate for the hypertrophy-induced impaired peripheral O2 diffusion. The net results are an enhanced whole body oxidative function at peak exercise and unchanged efficiency and O2 cost at submaximal exercise, despite a much greater body mass.

Lifelong physical activity preserves functional sympatholysis and purinergic signalling in the ageing human leg

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 P2Y(2) 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 (WL(max))) 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 VO2 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 P2Y(2) 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 P2Y(2) receptor content.

Ex vivo measures of muscle mitochondrial capacity reveal quantitative limits of oxygen delivery by the circulation during exercise

Muscle mitochondrial respiratory capacity measured ex vivo provides a physiological reference to assess cellular oxidative capacity as a component in the oxygen cascade in vivo. In this article, the magnitude of muscle blood flow and oxygen uptake during exercise involving a small-to-large fraction of the body mass will be discussed in relation to mitochondrial capacity measured ex vivo. These analyses reveal that as the mass of muscle engaged in exercise increases from one-leg knee extension, to 2-arm cranking, to 2-leg cycling and x-country skiing, the magnitude of blood flow and oxygen delivery decrease. Accordingly, a 2-fold higher oxygen delivery and oxygen uptake per unit muscle mass are seen in vivo during 1-leg exercise compared to 2-leg cycling indicating a significant limitation of the circulation during exercise with a large muscle mass. This analysis also reveals that mitochondrial capacity measured ex vivo underestimates the maximal in vivo oxygen uptake of muscle by up to ∼2-fold.This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.

Effects of adenosine, exercise, and moderate acute hypoxia on energy substrate utilization of human skeletal muscle

Glucose metabolism increases in hypoxia and can be influenced by endogenous adenosine, but the role of adenosine for regulating glucose metabolism at rest or during exercise in hypoxia has not been elucidated in humans. We studied the effects of exogenous adenosine on human skeletal muscle glucose uptake and other blood energy substrates [free fatty acid (FFA) and lactate] by infusing adenosine into the femoral artery in nine healthy young men. The role of endogenous adenosine was studied by intra-arterial adenosine receptor inhibition (aminophylline) during dynamic one-leg knee extension exercise in normoxia and acute hypoxia corresponding to ∼3,400 m of altitude. Extraction and release of energy substrates were studied by arterial-to-venous (A-V) blood samples, and total uptake or release was determined by the product of A-V differences and muscle nutritive perfusion measured by positron emission tomography. The results showed that glucose uptake increased from a baseline value of 0.2 ± 0.2 to 2.0 ± 2.2 μmol·100 g(-1)·min(-1) during adenosine infusion (P < 0.05) at rest. Although acute hypoxia enhanced arterial FFA levels, it did not affect muscle substrate utilization at rest. During exercise, glucose uptake was higher (195%) during acute hypoxia compared with normoxia (P = 0.058), and aminophylline had no effect on energy substrate utilization during exercise, despite that arterial FFA levels were increased. In conclusion, exogenous adenosine at rest and acute moderate hypoxia during low-intensity knee-extension exercise increases skeletal muscle glucose uptake, but the increase in hypoxia appears not to be mediated by adenosine.

Caffeine intake improves intense intermittent exercise performance and reduces muscle interstitial potassium accumulation

The effect of oral caffeine ingestion on intense intermittent exercise performance and muscle interstitial ion concentrations was examined. The study consists of two studies (S1 and S2). In S1, 12 subjects completed the Yo-Yo intermittent recovery level 2 (Yo-Yo IR2) test with prior caffeine (6 mg/kg body wt; CAF) or placebo (PLA) intake. In S2, 6 subjects performed one low-intensity (20 W) and three intense (50 W) 3-min (separated by 5 min) one-legged knee-extension exercise bouts with (CAF) and without (CON) prior caffeine supplementation for determination of muscle interstitial K(+) and Na(+) with microdialysis. In S1 Yo-Yo IR2 performance was 16% better (P < 0.05) in CAF compared with PLA. In CAF, plasma K(+) at the end of the Yo-Yo IR2 test was 5.2 ± 0.1 mmol/l with no difference between the trials. Plasma free fatty acids (FFA) were higher (P < 0.05) in CAF than PLA at rest and remained higher (P < 0.05) during exercise. Peak blood glucose (8.0 ± 0.6 vs. 6.2 ± 0.4 mmol/l) and plasma NH(3) (137.2 ± 10.8 vs. 113.4 ± 13.3 μmol/l) were also higher (P < 0.05) in CAF compared with PLA. In S2 interstitial K(+) was 5.5 ± 0.3, 5.7 ± 0.3, 5.8 ± 0.5, and 5.5 ± 0.3 mmol/l at the end of the 20-W and three 50-W periods, respectively, in CAF, which were lower (P < 0.001) than in CON (7.0 ± 0.6, 7.5 ± 0.7, 7.5 ± 0.4, and 7.0 ± 0.6 mmol/l, respectively). No differences in interstitial Na(+) were observed between CAF and CON. In conclusion, caffeine intake enhances fatigue resistance and reduces muscle interstitial K(+) during intense intermittent exercise.

Exercise training induces similar elevations in the activity of oxoglutarate dehydrogenase and peak oxygen uptake in the human quadriceps muscle

During exercise involving a small muscle mass, peak oxygen uptake is thought to be limited by peripheral factors, such as the degree of oxygen extraction from the blood and/or mitochondrial oxidative capacity. Previously, the maximal activity of the Krebs cycle enzyme oxoglutarate dehydrogenase has been shown to provide a quantitative measure of maximal oxidative metabolism, but it is not known whether the increase in this activity after a period of training reflects the elevation in peak oxygen consumption. Fourteen subjects performed one-legged knee extension exercise for 5-7 weeks, while the other leg remained untrained. Thereafter, the peak oxygen uptake by the quadriceps muscle was determined for both legs, and muscle biopsies were taken for assays of maximal enzyme activities (at 25°C). The peak oxygen uptake was 26% higher in the trained than in the untrained muscle (395 vs. 315 ml min(-1) kg(-1), respectively; P<0.01). The maximal activities of the Krebs cycle enzymes in the trained and untrained muscle were as follows: citrate synthase, 22.4 vs. 18.2 μmol min(-1) g(-1) (23%, P<0.05); oxoglutarate dehydrogenase, 1.88 vs. 1.54 μmol min(-1) g(-1) (22%, P<0.05); and succinate dehydrogenase, 3.88 vs. 3.28 μmol min(-1) g(-1) (18%, P<0.05). The difference between the trained and untrained muscles with respect to peak oxygen uptake (80 ml min(-1) kg(-1)) corresponded to a flux through the Krebs cycle of 1.05 μmol min(-1) g(-1), and the corresponding difference in oxoglutarate dehydrogenase activity (at 38°C) was 0.83 μmol min(-1) g(-1). These parallel increases suggest that there is no excess mitochondrial capacity during maximal exercise with a small muscle mass.

Does Extreme Muscle Hypertrophy Determine an Impairment of Skeletal Muscle Oxidative Metabolism?

PURPOSE: The purpose was to evaluate the effects of marked skeletal muscle hypertrophy induced by chronic resistance training on skeletal muscle oxidative function. METHODS: Eleven male resistance-trained athletes (RTA, age: 25.4±1.8 [mean±SE] years) and eleven active control subjects (CTRL) were evaluated. Quadriceps femoris muscle volume was determined by magnetic resonance imaging. During incremental cycle ergometer (CE) and one-leg knee-extension (KE) exercise we determined: pulmonary O2 uptake (V'O2); skeletal muscle (vastus lateralis) fractional O2 extraction, as estimated from concentration changes in deoxygenated hemoglobin+myoglobin (delta[deoxy(Hb+Mb)]), determined by near-infrared spectroscopy and expressed as a percentage of the maximal values obtained by a transient limb ischemia. Mitochondrial respiration was evaluated by high-resolution respirometry in permeabilized ("skinned") vastus lateralis fibers obtained by biopsy. RESULTS: Body mass and quadriceps femoris muscle mass were higher in RTA (102.6±2.2 kg and 3.14±0.13 kg, respectively) vs. CTRL (77.7±1.8 and 2.36±0.08). Peak O2 uptake (V'O2peak) was lower in RTA vs. CTRL both during CE (39.6±1.6 mL/min/kg BM vs. 45.9±0.9, respectively) and KE (49.2±2.3 mL/min/100g of quadriceps muscle mass vs. 61.4±3.3). Delta[deoxy(Hb+Mb)]peak was lower in RTA vs. CTRL both in CE (52±3% vs. 72±3) and in KE (51±3% vs. 73±4). On the other hand, rather surprisingly, maximal ADP-stimulated mitochondrial respiration was higher in RTA (56.7±7.1 pmolO2/s/mg wet weight) vs. CTRL (35.7±3.1), also after the values were normalized per citrate synthase activity. CONCLUSIONS: Peak oxidative function in vivo was impaired in RTA, also after eliminating, by the adopted KE protocol, constraints related to cardiovascular O2 delivery. This finding may appear to be in contradiction with the higher maximal ADP-stimulated mitochondrial respiration observed in isolated fibers. The main limitation to oxidative function in RTA in vivo may reside in peripheral O2 diffusion. Financial support by ASI - OSMA Contract I/007/06/0, Workpackage 1B-31-1 is acknowledged.

Moderate loading of the human osteoarthritic knee joint leads to lowering of intraarticular cartilage oligomeric matrix protein

The non-pharmacological treatment of osteoarthritis (OA) includes exercise therapy; however, little is known about the specific effect of exercise on the joint per se. The purpose of the present study was to investigate the direct effects of a load-bearing exercise upon cartilage in a single, human osteoarthritic joint determined by biochemical markers of cartilage turnover and inflammation in the synovial fluid (SF), serum and urine. Eleven subjects with OA of the knee(s), but with no other joint- or inflammatory disorders, volunteered for the study and had samples of blood, urine and synovial fluid drawn both at baseline and following 30-min one-legged knee-extension exercise. Workload: 60% of 1 RM (Repetition Maximum). Determination of cartilage oligomeric matrix protein (COMP), aggrecan, C-terminal collagen II peptide (CTX-II) and interleukin (IL)-6 were performed in synovial fluid (SF), serum and urine. A significant decrease was found in SF concentration of COMP following exercise, whereas aggrecan, CTX-II and IL-6 remained unchanged. No differences in any of the tested markers were found in serum and urine between baseline and post-exercise. Thirty minutes of mechanical loading of a single knee joint in human subjects with knee OA resulted in a reduced COMP concentration in SF.

Perfusion heterogeneity does not explain excess muscle oxygen uptake during variable intensity exercise

The association between muscle oxygen uptake (VO(2)) and perfusion or perfusion heterogeneity (relative dispersion, RD) was studied in eight healthy male subjects during intermittent isometric (1 s on, 2 s off) one-legged knee-extension exercise at variable intensities using positron emission tomography and a-v blood sampling. Resistance during the first 6 min of exercise was 50% of maximal isometric voluntary contraction force (MVC) (HI-1), followed by 6 min at 10% MVC (LOW) and finishing with 6 min at 50% MVC (HI-2). Muscle perfusion and O(2) delivery during HI-1 (26 +/- 5 and 5.4 +/- 1.0 ml 100 g(-1) min(-1)) and HI-2 (28 +/- 4 and 5.8 +/- 0.7 ml 100 g(-1) min(-1)) were similar, but both were higher (P<0.01) than during LOW (15 +/- 3 and 3.0 +/- 0.6 ml 100 g(-1) min(-1)). Muscle VO(2) was also higher during both HI workloads (HI-1 3.3 +/- 0.4 and HI-2 4.1 +/- 0.6 ml 100 g(-1) min(-1)) than LOW (1.4 +/- 0.4 ml 100 g(-1) min(-1); P<0.01) and 25% higher during HI-2 than HI-1 (P<0.05). O(2) extraction was higher during HI workloads (HI-1 62 +/- 7 and HI-2 70 +/- 7%) than LOW (45 +/- 8%; P<0.01). O(2) extraction tended to be higher (P = 0.08) during HI-2 when compared to HI-1. Perfusion was less heterogeneous (P<0.05) during HI workloads when compared to LOW with no difference between HI workloads. Thus, during one-legged knee-extension exercise at variable intensities, skeletal muscle perfusion and O(2) delivery are unchanged between high-intensity workloads, whereas muscle VO(2) is increased during the second high-intensity workload. Perfusion heterogeneity cannot explain this discrepancy between O(2) delivery and uptake. We propose that the excess muscle VO(2) during the second high-intensity workload is derived from working muscle cells.

Carotid chemoreceptor modulation of muscle blood flow during leg‐extension exercise in healthy humans

Previously, we have shown that transient carotid chemoreceptor (CC) inhibition causes vasodilation in limb muscle in exercising dogs, and a reduction in muscle sympathetic nerve activity during handgrip exercise in humans. The purpose of the present investigation was to determine if CC inhibition causes an increase in exercising muscle blood flow during leg‐extension exercise in humans. Healthy subjects (N = 5) breathed hyperoxic gas (FIO2 = 1.0) for 2 minutes at rest and during submaximal one‐legged knee‐extension exercise. Femoral arterial blood flow data was obtained from continuous Doppler recordings at rest and during exercise. Leg‐extension exercise increased heart rate (64 vs. 87 beats · min−1), mean blood pressure (84 vs. 96 mmHg), muscle blood flow (0.37 vs. 1.60 L · min−1) and muscle conductance (4.75 vs. 16.82 units). Transient hyperoxia had no effect on muscle blood flow or conductance at rest. In contrast, during exercise both muscle blood flow and muscle conductance were increased with hyperoxia. The mean peak increase in muscle blood flow and conductance was 30 +/− 6% and 30 +/− 8%, respectively, above steady state normoxic values. Blood pressure was unchanged with hyperoxia at rest or during exercise. These preliminary findings suggest that the CC plays a role in muscle blood flow control during exercise in healthy humans.

On the mechanisms that limit oxygen uptake during exercise in acute and chronic hypoxia: role of muscle mass

Peak aerobic power in humans (VO2,peak) is markedly affected by inspired O2 tension (FIO2). The question to be answered in this study is what factor plays a major role in the limitation of muscle peak VO2 in hypoxia: arterial O2 partial pressure (Pa,O2) or O2 content (Ca,O2)? Thus, cardiac output (dye dilution with Cardio-green), leg blood flow (thermodilution), intra-arterial blood pressure and femoral arterial-to-venous differences in blood gases were determined in nine lowlanders studied during incremental exercise using a large (two-legged cycle ergometer exercise: Bike) and a small (one-legged knee extension exercise: Knee)muscle mass in normoxia, acute hypoxia (AH) (FIO2 = 0.105) and after 9 weeks of residence at 5260 m (CH). Reducing the size of the active muscle mass blunted by 62% the effect of hypoxia on VO2,peak in AH and abolished completely the effect of hypoxia on VO2,peak after altitude acclimatization. Acclimatization improved Bike peak exercise Pa,O2 from 34 +/- 1 in AH to 45 +/- 1 mmHg in CH(P <0.05) and Knee Pa,O2 from 38 +/- 1 to 55 +/- 2 mmHg(P <0.05). Peak cardiac output and leg blood flow were reduced in hypoxia only during Bike. Acute hypoxia resulted in reduction of systemic O2 delivery (46 and 21%) and leg O2 delivery (47 and 26%) during Bike and Knee, respectively, almost matching the corresponding reduction in VO2,peak. Altitude acclimatization restored fully peak systemic and leg O(2) delivery in CH (2.69 +/- 0.27 and 1.28 +/- 0.11 l min(-1), respectively) to sea level values (2.65 +/- 0.15 and 1.16 +/- 0.11 l min(-1), respectively) during Knee, but not during Bike. During Knee in CH, leg oxygen delivery was similar to normoxia and, therefore, also VO2,peak in spite of a Pa,O2 of 55 mmHg. Reducing the size of the active mass improves pulmonary gas exchange during hypoxic exercise, attenuates the Bohr effect on oxygen uploading at the lungs and preserves sea level convective O2 transport to the active muscles. Thus, the altitude-acclimatized human has potentially a similar exercising capacity as at sea level when the exercise model allows for an adequate oxygen delivery (blood flow x Ca,O2), with only a minor role of Pa,O2 per se, when Pa,O2 is more than 55 mmHg.

Is the balance between skeletal muscular metabolic capacity and oxygen supply capacity the same in endurance trained and untrained subjects?

We attempted to test whether the balance between muscular metabolic capacity and oxygen supply capacity in endurance-trained athletes (ET) differs from that in a control group of normal physically active subjects by using exercises with different muscle masses. We compared maximal exercise in nine ET subjects [Maximal oxygen uptake (VO(2)max) 64 ml kg(-1) min(-1) +/- SD 4] and eight controls (VO(2)max 46 +/- 4 ml kg(-1) min(-1)) during one-legged knee extensions (1-KE), two-legged knee extensions (2-KE) and bicycling. Maximal values for power output (P), VO(2)max, concentration of blood lactate ([La(-)]), ventilation (VE), heart rate (HR), and arterial oxygen saturation of haemoglobin (SpO(2)) were registered. P was 43 (2), 89 (3) and 298 (7) W (mean +/- SE); and VO(2)max: 1,387 (80), 2,234 (113) and 4,115 (150) ml min(-1)) for controls in 1-KE, 2-KE and bicycling, respectively. The ET subjects achieved 126, 121 and 126% of the P of controls (p < 0.05) and 127, 124, and 117% of their VO(2)max (p < 0.05). HR and [La(-)] were similar for both groups during all modes of exercise, while VE in ET was 147 and 114% of controls during 1-KE and bicycling, respectively. For mass-specific VO(2)max (VO(2)max divided by the calculated active muscle mass) during the different exercises, ET achieved 148, 141, and 150% of the controls' values, respectively (p < 0.05). During bicycling, both groups achieved 37% of their mass-specific VO(2) during 1-KE. Finally we conclude that ET subjects have the same utilization of the muscular metabolic capacity during whole body exercise as active control subjects.

Transient increase in femoral arterial blood flow to the contralateral non-exercising limb during one-legged exercise

We studied the effect of exercise intensity and duration on blood flow to the non-exercising leg during one-legged dynamic knee extension. Femoral arterial blood flow (FBF) to the non-exercising leg, blood pressure (BP), and heart rate (HR) were monitored during one-legged dynamic knee extension exercise at 15, 30, and 45% maximal voluntary contraction (MVC) in seven healthy females. There was an interaction between exercise intensity and duration for FBF and FVC (P < 0.01). During the initial phase of contralateral leg exercise at all intensities, FBF and femoral vascular conductance (FVC) of non-exercising leg increased, and the increase was larger at higher intensities (P < 0.01). After initial vasodilatation, FBF and FVC decreased to baseline, which suggests the vasoconstriction. However, FBF and FVC gradually increased during exercise at 15% MVC. We conclude that transient vasodilatation at the onset of exercise is followed by gradual change to vasoconstriction in non-exercising limb during dynamic one-legged exercise and these changes are exercise intensity- and duration-dependent.

Effect of dexamethasone on skeletal muscle Na+,K+ pump subunit specific expression and K+ homeostasis during exercise in humans

The effect of dexamethasone on Na(+),K(+) pump subunit expression and muscle exchange of K(+) during exercise in humans was investigated. Nine healthy male subjects completed a randomized double blind placebo controlled protocol, with ingestion of dexamethasone (Dex: 2 x 2 mg per day) or placebo (Pla) for 5 days. Na(+),K(+) pump catalytic alpha1 and alpha2 subunit expression was approximately 17% higher (P < 0.05) and the structural beta1 and beta2 subunit expression was approximately 6-8% higher (P < 0.05) after Dex compared with Pla. During one-legged knee-extension for 10 min at low intensity (LI; 18.6 +/- 1.0 W), two moderate intensity (51.7 +/- 2.4 W) exercise bouts (MI(1): 5 min; 2 min recovery; MI(2): exhaustive) and two high-intensity (71.7 +/- 2.5 W) exercise bouts (HI(1): 1 min 40 s; 2 min recovery; HI(2): exhaustive), femoral venous K(+) was lower (P < 0.05) in Dex compared with Pla. Thigh K(+) release was lower (P < 0.05) in Dex compared with Pla in LI and MI, but not in HI. Time to exhaustion in MI(2) tended to improve (393 +/- 50 s versus 294 +/- 41 s; P = 0.07) in Dex compared with Pla, whereas no difference was detected in HI(2) (106 +/- 10 s versus 108 +/- 9 s). The results indicate that an increased Na(+),K(+) pump expression per se is of importance for thigh K(+) reuptake at the onset of low and moderate intensity exercise, but less important during high intensity exercise.

Role of adenosine in regulating the heterogeneity of skeletal muscle blood flow during exercise in humans

Evidence from both animal and human studies suggests that adenosine plays a role in the regulation of exercise hyperemia in skeletal muscle. We tested whether adenosine also plays a role in the regulation of blood flow (BF) distribution and heterogeneity among and within quadriceps femoris (QF) muscles during exercise, measured using positron emission tomography. In six healthy young women, BF was measured at rest and then during three incremental low and moderate intermittent isometric one-legged knee-extension exercise intensities without and with theophylline-induced nonselective adenosine receptor blockade. BF heterogeneity within muscles was calculated from 16-mm(3) voxels in BF images and heterogeneity among the muscles from the mean values of the four QF compartments. Mean BF in the whole QF and its four parts increased, and heterogeneity decreased with workload both without and with theophylline (P < 0.001). Adenosine receptor blockade did not have any effect on mean bulk BF or BF heterogeneity among the QF muscles, yet blockade increased within-muscle BF heterogeneity in all four QF muscles (P = 0.03). Taken together, these results show that BF becomes less heterogeneous with increasing exercise intensity in the QF muscle group. Adenosine seems to play a role in muscle BF heterogeneity even in the absence of changes in bulk BF at low and moderate one-leg intermittent isometric exercise intensities.

Effect Of Exercise Intensity On Maximal Fat Oxidation In One-leg Vs. Whole Body Exercise

During whole body exercise maximal fat oxidation occurs at moderate exercise intensity, but it is not clear how exercise intensity will influence fat oxidation during graded one-leg knee extension exercise. PURPOSE: The present study investigated maximal fat oxidation during graded quadriceps muscle exercise and during graded whole body exercise. METHODS: In the overnight fasted state 9 healthy males (age: 27 ± 2 yrs., weight: 82 ± 3 kg, BMI: 24 ± 1 kg m-2, VO2max: 50 ± 2 ml min-1 kg-1) performed one-legged knee extension exercise at 25 % of maximal one-leg workload (Wmax) for 30 minutes followed by exercise at 55 % Wmax for 30 minutes with the other leg and finally exercise at 85 % Wmax for 30 minutes with the first leg. Blood was sampled from a femoral artery and both femoral veins, and blood flow was determined by ultrasound Doppler technique at rest and through exercise. Respiratory Quotient (RQ) was calculated from arterio-venous measurements. On a separate day, again in the overnight fasted state, the subjects performed a graded bicycle exercise test and pulmonary data was analyzed on-line (Achten et al. 2001). RER and RQ data were used to calculate fat oxidation through indirect calorimetry. One-way repeated measurement ANO VA was applied and data are expressed as mean ± SEM. RESULTS: During graded whole body exercise maximal fat oxidation occurred at 48.4 ± 1.8 % of VO2max and averaged 0.44 ± 0.04 g min-1. During graded one-leg knee extension exercise oxygen uptake across the leg (0.03 ± 0.01, 0.23 ± 0.02, 0.35 ±0.03, 0.53 ±0.04l min-1) increased (P<0.05) from rest through exercise at 25, 55 and 85 % Wmax, respectively. The calculated leg RQ (0.76 ± 0.04, 0.86 ± 0.02, 0.87 ±0.01, 0.92 ±0.01) and total leg fat oxidation (0.01 ± 0.01, 0.06 ± 0.01, 0.08 ±0.01, 0.13 ± 0.03 g min-1) also increased (p<0.05) from rest to 85 % Wmax. CONCLUSIONS: During graded one-leg exercise with a limited muscle mass fat oxidation increases with exercise intensity in contrast to whole body exercise where fat oxidation is attenuated at higher exercise intensities. Achten J et al. Determination of the exercise intensity that elicits maximal fat oxidation. MSSE. 2002, 34(1):92-7. Financial support from the Danish National Research Foundation and the Danish Ministry of Culture Committee on Sports Research is gratefully acknowledged

Blood pressure assessment during resistance exercise: comparison between auscultation and Finapres

The objective of this study was to test whether the auscultatory method and Finapres provide similar readings for blood pressure response during two resistance exercise protocols of different intensities, and to gain some insight into whether auscultation can be used to monitor cardiovascular stress during resistance exercise. Fourteen patients performed six and 15 maximum repetitions (six and 15, respectively) of one-leg knee extension on different days. Blood pressure (BP) was measured simultaneously with the two methods at rest and during the last repetition of the protocols. Neither the systolic blood pressure (SBP) nor the diastolic blood pressure (DBP) differed between methods, both at rest and at six maximum repetitions. Conversely, Finapres recorded higher systolic blood pressure at 15 maximum repetitions (168.8+/-21.7 mmHg) than auscultation (147.0+/-14.5 mmHg; P<0.001). In addition, the blood pressure values obtained by both methods in each exercise protocol (six and 15 maximum repetitions, respectively) were ranked in tertiles and also treated by the gamma (gamma) nonparametric correlation. We observed a high probability for patients to be ranked on the same tertile regardless of the method used, at both six maximum repetitions (SBP=0.80, DBP=0.97) and 15 maximum repetitions (SBP=0.88, DBP=0.92). High association between methods was also observed by simple regression when measurements taken at rest and at each intensity were analyzed altogether for both SBP (r=0.95, r adjusted=0.89) and DBP (r=0.79, r adjusted=0.62). Auscultation provides lower BP values than Finapres, especially at the end of a set including 15 maximum repetitions. The former, however, seems appropriate to assess the relative cardiovascular stress imposed by different protocols of resistance exercise.

Are blood flow and lipolysis in subcutaneous adipose tissue influenced by contractions in adjacent muscles in humans?

Aerobic exercise increases whole body adipose tissue lipolysis, but is lipolysis higher in subcutaneous adipose tissue (SCAT) adjacent to contracting muscles than in SCAT adjacent to resting muscles? Ten healthy, overnight-fasted males performed one-legged knee extension exercise at 25% of maximal workload (W(max)) for 30 min followed by exercise at 55% W(max) for 120 min with the other leg and finally exercised at 85% W(max) for 30 min with the first leg. Subjects rested for 30 min between exercise periods. Femoral SCAT blood flow was estimated from washout of (133)Xe, and lipolysis was calculated from femoral SCAT interstitial and arterial glycerol concentrations and blood flow. In general, blood flow and lipolysis were higher in femoral SCAT adjacent to contracting than adjacent to resting muscle (time 15-30 min; blood flow: 25% W(max) 6.6 +/- 1.0 vs. 3.9 +/- 0.8 ml x 100 g(-1) x min(-1), P < 0.05; 55% W(max) 7.3 +/- 0.6 vs. 5.0 +/- 0.6 ml x 100 g(-1) x min(-1), P < 0.05; 85% W(max) 6.6 +/- 1.3 vs. 5.9 +/- 0.7 ml x 100 g(-1) x min(-1), P > 0.05; lipolysis: 25% W(max) 102 +/- 19 vs. 55 +/- 14 nmol x 100 g(-1) x min(-1), P = 0.06; 55% W(max) 86 +/- 11 vs. 50 +/- 20 nmol x 100 g(-1) x min(-1), P > 0.05; 85% W(max) 88 +/- 31 vs. -9 +/- 25 nmol x 100 g(-1) x min(-1), P < 0.05). In conclusion, blood flow and lipolysis are generally higher in SCAT adjacent to contracting than adjacent to resting muscle irrespective of exercise intensity. Thus specific exercises can induce "spot lipolysis" in adipose tissue.

Effect of acetazolamide on leg endurance exercise at sea level and simulated altitude

Acetazolamide can be taken at sea level to prevent acute mountain sickness during subsequent altitude exposure. Acetazolamide causes metabolic acidosis at sea level and altitude, and increases SaO2 (arterial oxygen saturation) at altitude. The aim of the present study was to determine whether acetazolamide impairs muscle endurance at sea level but not simulated altitude (4300 m for <3 h). Six subjects (20+/-1 years of age; mean+/-S.E.M.) performed exhaustive constant work rate one-leg knee-extension exercise (25+/-2 W) once a week for 4 weeks, twice at sea level and twice at altitude. Each week, subjects took either acetazolamide (250 mg) or placebo orally in a double-blind fashion (three times a day) for 2 days. On day 2, all exercise bouts began approx. 2.5 h after the last dose of acetazolamide or placebo. Acetazolamide caused similar acidosis (pH) in all subjects at sea level (7.43+/-0.01 with placebo compared with 7.34+/-0.01 with acetazolamide; P<0.05) and altitude (7.48+/-0.03 with placebo compared with 7.37+/-0.01 with acetazolamide; P<0.05). However, endurance performance was impaired with acetazolamide only at sea level (48+/-4 min with placebo compared with 36+/-5 min with acetazolamide; P<0.05), but not altitude (17+/-2 min with placebo compared with 20+/-3 min with acetazolamide; P = not significant). In conclusion, lack of impairment of endurance performance by acetazolamide compared with placebo at altitude was probably due to off-setting secondary effects resulting from acidosis, e.g. ventilatory induced increase in SaO2 for acetazolamide compared with placebo (89+/-1 compared with 86+/-1% respectively; P<0.05), which resulted in an increased oxygen pressure gradient from capillary to exercising muscle.