Low‐volume muscle endurance training prevents decrease in muscle oxidative and endurance function during 21‐day forearm immobilization

Aim: To examine the effects of low‐volume muscle endurance training on muscle oxidative capacity, endurance and strength of the forearm muscle during 21‐day forearm immobilization (IMM‐21d). Methods: The non‐dominant arm (n = 15) was immobilized for 21 days with a cast and assigned to an immobilization‐only group (Imm‐group; n = 7) or an immobilization with training group (Imm+Tr‐group; n = 8). Training comprised dynamic handgrip exercise at 30% of pre‐intervention maximal voluntary contraction (MVC) at 1 Hz until exhaustion, twice a week during the immobilization period. The duration of each exercise session was 51.7 ± 3.4 s (mean ± SE). Muscle oxidative capacity was evaluated by the time constant for phosphocreatine recovery (τ_offPCr) after a submaximal handgrip exercise using ³¹phosphorus‐magnetic resonance spectroscopy. An endurance test was performed at 30% of pre‐intervention MVC, at 1 Hz, until exhaustion. Results: τ _offPCr was significantly prolonged in the Imm‐group after 21 days (42.0 ± 2.8 and 64.2 ± 5.1 s, pre‐ and post‐intervention respectively; P < 0.01) but did not change for the Imm+Tr‐group (50.3 ± 3.0 and 48.8 ± 5.0 s, ns). Endurance decreased significantly for the Imm‐group (55.1 ± 5.1 and 44.7 ± 4.6 s, P < 0.05) but did not change for the Imm+Tr‐group (47.9 ± 3.0 and 51.7 ± 4.0 s, ns). MVC decreased similarly in both groups (P < 0.01). Conclusions: Twice‐weekly muscle endurance training sessions, each lasting approx. 50 s, effectively prevented a decrease in muscle oxidative capacity and endurance; however, there was no effect on MVC decline with IMM‐21d.     

Age‐ and sex‐related differences in muscle phosphocreatine and oxygenation kinetics during high‐intensity exercise in adolescents and adults

The aim of this investigation was to examine the adaptation of the muscle phosphates (e.g. phosphocreatine (PCr) and ADP) implicated in regulating oxidative phosphorylation, and oxygenation at the onset of high intensity exercise in children and adults. The hypotheses were threefold: primary PCr kinetics would be faster in children than adults; the amplitude of the PCr slow component would be attenuated in children; and the amplitude of the deoxyhaemoglobin/myoglobin (HHb) slow component would be reduced in children. Eleven children (5 girls, 6 boys, 13 ± 1 years) and 11 adults (5 women, 6 men, 24 ± 4 years) completed two to four constant work rate exercise tests within a 1.5 T MR scanner. Quadriceps muscle energetics during high intensity exercise were monitored using ³¹P‐MRS. Muscle oxygenation was monitored using near‐infrared spectroscopy. The time constant for the PCr response was not significantly different in boys (31 ± 10 s), girls (31 ± 10 s), men (44 ± 20 s) or women (29 ± 14 s, main effects: age, p = 0.37, sex, p = 0.25). The amplitude of the PCr slow component relative to end‐exercise PCr was not significantly different between children (23 ± 23%) and adults (17 ± 13%, p = 0.47). End‐exercise [PCr] was significantly lower, and [ADP] higher, in females (18 ± 4 mM and 53 ± 16 µM) than males (23 ± 4 mM, p = 0.02 and 37 ± 11 µM, p = 0.02), but did not differ with age ([PCr]: p = 0.96, [ADP]: p = 0.72). The mean response time for muscle tissue deoxygenation was significantly faster in children (22 ± 4 s) than adults (27 ± 7 s, p = 0.01). The results of this study show that the control of oxidative metabolism at the onset of high intensity exercise is adult‐like in 13‐year‐old children, but that matching of oxygen delivery to extraction is more precise in adults. Copyright © 2010 John Wiley & Sons, Ltd.     

Comparison of oxidative capacity among leg muscles in humans using gated 31P 2‐D chemical shift imaging

In many small animals there are distinct differences in fiber‐type composition among limb muscles, and these differences typically correspond to marked disparities in the oxidative capacities. However, whether there are similar differences in the oxidative capacity among leg muscles in humans is less clear. The purpose of this study was to compare the rate of phosphocreatine (PCr) recovery, a functional in vivo marker of oxidative capacity, in the lateral and medial gastrocnemius, soleus, and the anterior compartment of the leg (primarily the tibialis anterior) of humans. Subjects performed plantar flexion and dorsiflexion gated exercise protocols consisting of 70 sets of three rapid dynamic contractions (<2.86 s) at 20 s intervals (total: 23.3 min). Starting after the sixth set of contractions, ³¹P 2‐D CSI (8 × 8 matrix, 14–16 cm FOV, 3 cm slice, TR 2.86 s) were acquired via a linear transmit/receive surface coil using a GE 3T Excite System. The CSI data were zero‐filled (32 × 32) and a single FID was produced for each time point in the lateral and medial gastrocnemius, soleus, and anterior compartment. The time constant for PCr recovery was calculated from τ = ‐Δt/ln[D/(D + Q)], where Q is the percentage change in PCr due to contraction during the steady‐state portion of the protocol, D the additional drop in PCr from rest, and Δt is the interval between contractions. The τ of PCr recovery was longer (p < 0.05) in the anterior compartment (32 ± 3 s) than in the lateral (23 ± 2 s) and medial gastrocnemius muscles (24 ± 3 s) and the soleus (22 ± 3 s) muscles. These findings suggest that the oxidative capacity is lower in the anterior compartment than in the triceps surae muscles and is consistent with the notion that fiber‐type phenotypes vary among the leg muscles of humans. Copyright © 2009 John Wiley & Sons, Ltd.     

Demonstration of asymmetric muscle perfusion of the back after exercise in patients with adolescent idiopathic scoliosis using intravoxel incoherent motion (IVIM) MRI

The purpose of this work was to quantify muscular perfusion patterns of back muscles after exercise in patients with adolescent idiopathic scoliosis (AIS) using intravoxel incoherent motion (IVIM) MR perfusion imaging. The paraspinal muscles of eight patients with AIS (Cobb angle 35 ± 10°, range [25‐47°]) and nine healthy volunteers were scanned with a 1.5 T MRI, at rest and after performing a symmetric back muscle exercise on a Roman chair. An IVIM sequence with 16 b‐values from 0 to 900 s/mm² was acquired, and the IVIM bi‐exponential signal equation model was fitted in two steps. Perfusion asymmetries were evaluated using the blood flow related IVIM fD* parameter in regions of interest placed within the paraspinal muscles. Statistical significance was assessed using a Student t‐test. The observed perfusion pattern after performing a Roman chair muscle exercise differed consistently in patients with AIS compared with healthy normal volunteers, and consisted of an asymmetrical increase in IVIM fD* [10^?3 mm²/s] above the lumbar convexity from 6.5 ± 5.8 to 28.8 ± 26.8 (p < 0.005), with no increase in the concavity (decrease from 6.5 ± 10.0 to 3.2 ± 1.5 (p = 0.19)), compared with a bilateral symmetric increase in the healthy volunteers (right, increase from 3.3 ± 2.1 to 10.1 ± 4.6 (p < 0.05); left, 6.7 ± 10.7 to 13.3 ± 7.0 (p < 0.05)). In conclusion, patients with AIS exhibit significant asymmetric muscle perfusion over the convexity of the scoliotic curvature after Roman chair exercise.     

The feasibility of quantitative MRI of extra‐ocular muscles in myasthenia gravis and Graves' orbitopathy

Although quantitative MRI can be instrumental in the diagnosis and assessment of disease progression in orbital diseases involving the extra‐ocular muscles (EOM), acquisition can be challenging as EOM are small and prone to eye‐motion artefacts. We explored the feasibility of assessing fat fractions (FF), muscle volumes and water T2 (T2_water) of EOM in healthy controls (HC), myasthenia gravis (MG) and Graves' orbitopathy (GO) patients. FF, EOM volumes and T2_water values were determined in 12 HC (aged 22‐65 years), 11 MG (aged 28‐71 years) and six GO (aged 28‐64 years) patients at 7 T using Dixon and multi‐echo spin‐echo sequences. The EOM were semi‐automatically 3D‐segmented by two independent observers. MANOVA and t‐tests were used to assess differences in FF, T2_water and volume of EOM between groups (P < .05). Bland–Altman limits of agreement (LoA) were used to assess the reproducibility of segmentations and Dixon scans. The scans were well tolerated by all subjects. The bias in FF between the repeated Dixon scans was ?0.7% (LoA: ±2.1%) for the different observers; the bias in FF was ?0.3% (LoA: ±2.8%) and 0.03 cm³ (LoA: ± 0.36 cm³) for volume. Mean FF of EOM in MG (14.1% ± 1.6%) was higher than in HC (10.4% ± 2.5%). Mean muscle volume was higher in both GO (1.2 ± 0.4 cm³) and MG (0.8 ± 0.2 cm³) compared with HC (0.6 ± 0.2 cm³). The average T2_water for all EOM was 24.6 ± 4.0 ms for HC, 24.0 ± 4.7 ms for MG patients and 27.4 ± 4.2 ms for the GO patient. Quantitative MRI at 7 T is feasible for measuring FF and muscle volumes of EOM in HC, MG and GO patients. The measured T2_water was on average comparable with skeletal muscle, although with higher variation between subjects. The increased FF in the EOM in MG patients suggests that EOM involvement in MG is accompanied by fat replacement. The unexpected EOM volume increase in MG may provide novel insights into underlying pathophysiological processes.     

The role of muscle pump in the development of cardiovascular drift

This study examined the role of muscle pump in the development of cardiovascular drift (CV_drift) during cycling. Twelve healthy males (23.4 ± 0.5 years, mean ± SE) exercised for 90 min with 40 and 80 pedal revolutions per minute (rpm) at the same oxygen consumption, in two separate days. CV_drift was developed in both conditions as indicated by the drop in stroke volume (SV) and the rise in heart rate (HR) from the 20th min onwards (ΔSV = −16.2 ± 2.0 and −17.1 ± 1.0 ml beat⁻¹; ΔHR = 18.3 ± 2.0 and 17.5 ± 3.0 beats min⁻¹ for 40 and 80 rpm, respectively, P < 0.05) but without difference between conditions. Mean cardiac output (CO₂ rebreathing) was 14.7 ± 0.3 l min⁻¹ and 15.0 ± 0.3 l min⁻¹, and mean arterial pressure was 100.0 ± 1.0 mmHg and 96.7 ± 0.8 mmHg for 40 and 80 rpm, respectively, without significant changes over time, and without difference between conditions. Electromyographic activity (iEMG) was lower throughout exercise with 80 rpm (35.6 ± 1.2% and 11.0 ± 1.0% for 40 and 80 rpm, respectively). Similarly, total hemoglobin, determined with near-infrared spectroscopy (NIRS) was 58.0 ± 0.8 (AU) for 40 rpm and 53.0 ± 1.4 (arbitrary units) for 80 rpm, from 30th min onwards (P < 0.05), an indication of lower leg blood volume during the faster pedal rate condition. Thermal status (rectal and mean skin temperature), blood and plasma volume changes, blood lactate concentration, muscle oxygenation (NIRS signal) and the rate of perceived exertion were similar in the two trials. It seems that muscle pump is not an important factor for the development of CV_drift during cycling, at least under the present experimental conditions.     

Maximal voluntary hyperpnoea increases blood lactate concentration during exercise

Ventilatory work during heavy endurance exercise has not been thought to influence systemic lactate concentration. We evaluated the effect of maximal isocapnic volitional hyperpnoea upon arterialised venous blood lactate concentration ([lac⁻]_B) during leg cycling exercise at maximum lactate steady state (MLSS). Seven healthy males performed a lactate minimum test to estimate MLSS, which was then resolved using separate 30 min constant power tests (MLSS=207±8 W, mean ± SEM). Thereafter, a 30 min control trial at MLSS was performed. In a further experimental trial, the control trial was mimicked except that from 20 to 28 min maximal isocapnic volitional hyperpnoea was superimposed on exercise. Over 20–28 min minute ventilation, oxygen uptake, and heart rate during the control and experimental trials were 87.3±2.4 and 168.3±7.0 l min⁻¹ (P<0.01), the latter being comparable to that achieved in the maximal phase of the lactate minimum test (171.9±6.8 l min⁻¹), 3.46±0.20 and 3.83 ± 0.20 l min⁻¹ (P<0.01), and 158.5±2.7 and 166.8±2.7 beats min⁻¹ (P<0.05), respectively. From 20 to 30 min of the experimental trial [lac⁻]_B increased from 3.7±0.2 to 4.7±0.3 mmol l⁻¹ (P<0.05). The partial pressure of carbon dioxide in arterialised venous blood increased approximately 3 mmHg during volitional hyperpnoea, which may have attenuated the [lac⁻]_B increase. These results show that, during heavy exercise, respiratory muscle work may affect [lac⁻]_B. We speculate that the changes observed were related to the altered lactate turnover in respiratory muscles, locomotor muscles, or both.     

Depth‐resolved surface coil MRS (DRESS)‐localized dynamic 31P‐MRS of the exercising human gastrocnemius muscle at 7 T

Dynamic ³¹P‐MRS with sufficiently high temporal resolution enables the non‐invasive evaluation of oxidative muscle metabolism through the measurement of phosphocreatine (PCr) recovery after exercise. Recently, single‐voxel localized ³¹P‐MRS was compared with surface coil localization in a dynamic fashion, and was shown to provide higher anatomical and physiological specificity. However, the relatively long TE needed for the single‐voxel localization scheme with adiabatic pulses limits the quantification of J‐coupled spin systems [e.g. adenosine triphosphate (ATP)]. Therefore, the aim of this study was to evaluate depth‐resolved surface coil MRS (DRESS) as an alternative localization method capable of free induction decay (FID) acquisition for dynamic ³¹P‐MRS at 7 T. The localization performance of the DRESS sequence was tested in a phantom. Subsequently, two dynamic examinations of plantar flexions at 25% of maximum voluntary contraction were conducted in 10 volunteers, one examination with and one without spatial localization. The DRESS slab was positioned obliquely over the gastrocnemius medialis muscle, avoiding other calf muscles. Under the same load, significant differences in PCr signal drop (31.2 ± 16.0% versus 43.3 ± 23.4%), end exercise pH (7.06 ± 0.02 versus 6.96 ± 0.11), initial recovery rate (0.24 ± 0.13 mm /s versus 0.35 ± 0.18 mm /s) and maximum oxidative flux (0.41 ± 0.14 mm /s versus 0.54 ± 0.16 mm /s) were found between the non‐localized and DRESS‐localized data, respectively. Splitting of the inorganic phosphate (Pi) signal was observed in several non‐localized datasets, but in none of the DRESS‐localized datasets. Our results suggest that the application of the DRESS localization scheme yielded good spatial selection, and provided muscle‐specific insight into oxidative metabolism, even at a relatively low exercise load. In addition, the non‐echo‐based FID acquisition allowed for reliable detection of ATP resonances, and therefore calculation of the specific maximum oxidative flux, in the gastrocnemius medialis using standard assumptions about resting ATP concentration in skeletal muscle. Copyright © 2014 John Wiley & Sons, Ltd.     

Dynamic multivoxel‐localized 31P MRS during plantar flexion exercise with variable knee angle

Exercise studies investigating the metabolic response of calf muscles using ³¹P MRS are usually performed with a single knee angle. However, during natural movement, the distribution of workload between the main contributors to force, gastrocnemius and soleus is influenced by the knee angle. Hence, it is of interest to measure the respective metabolic response of these muscles to exercise as a function of knee angle using localized spectroscopy. Time‐resolved multivoxel ³¹P MRS at 7 T was performed simultaneously in gastrocnemius medialis and soleus during rest, plantar flexion exercise and recovery in 12 healthy volunteers. This experiment was conducted with four different knee angles. PCr depletions correlated negatively with knee angle in gastrocnemius medialis, decreasing from 79±14 % (extended leg) to 35±23 %(～40°), and positively in soleus, increasing from 20±21 % to 36±25 %; differences were significant. Linear correlations were found between knee angle and end‐exercise PCr depletions in gastrocnemius medialis (R²=0.8) and soleus (R²=0.53). PCr recovery times and end‐exercise pH changes that correlated with PCr depletion were consistent with the literature in gastrocnemius medialis and differences between knee angles were significant. These effects were less pronounced in soleus and not significant for comparable PCr depletions. Maximum oxidative capacity calculated for all knee angles was in excellent agreement with the literature and showed no significant changes between different knee angles. In conclusion, these findings confirm that plantar flexion exercise with a straight leg is a suitable paradigm, when data are acquired from gastrocnemius only (using either localized MRS or small surface coils), and that activation of soleus requires the knee to be flexed. The present study comprises a systematic investigation of the effects of the knee angle on metabolic parameters, measured with dynamic multivoxel ³¹P MRS during muscle exercise and recovery, and the findings should be used in future study design.     

Effects of muscle damage on 31phosphorus magnetic resonance spectroscopy indices of energetic status and sarcolemma integrity in young mdx mice

³¹Phosphorus magnetic resonance spectroscopy (³¹P-MRS) has been shown to detect altered energetic status (e.g. the ratio of inorganic phosphate to phosphocreatine: Pi/PCr), intracellular acid–base status, and free intracellular magnesium ([Mg²⁺]) in dystrophic muscle compared with unaffected muscle; however, the causes of these differences are not well understood. The purposes of this study were to examine ³¹P-MRS indices of energetic status and sarcolemma integrity in young mdx mice compared with wild-type and to evaluate the effects of downhill running to induce muscle damage on ³¹P-MRS indices in dystrophic muscle. In vivo ³¹P-MRS spectra were acquired from the posterior hindlimb muscles in young (4–10 weeks of age) mdx (C57BL/10ScSn-DMDmdx) and wild-type (C57BL/10ScSnJ) mice using an 11.1-T MR system. The flux of phosphate from PCr to ATP was estimated by ³¹P-MRS saturation transfer experiments. Relative concentrations of high-energy phosphates were measured, and intracellular pH and [Mg²⁺] were calculated. ¹H₂O-T₂ was measured using single-voxel ¹H-MRS from the gastrocnemius and soleus using a 4.7-T MR system. Downhill treadmill running was performed in a subset of mice. Young mdx mice were characterized by elevated ¹H₂O-T₂ (p < 0.01)_, Pi/PCr (p = 0.02), PCr to ATP flux (p = 0.04) and histological inflammatory markers (p < 0.05) and reduced (p < 0.01) [Mg²⁺] compared with wild-type. Furthermore, 24 h after downhill running, an increase (p = 0.02) in Pi/PCr was observed in mdx and wild-type mice compared with baseline, and a decrease (p < 0.001) in [Mg²⁺] and a lower (p = 0.048) intracellular [H⁺] in damaged muscle regions of mdx mice were observed, consistent with impaired sarcolemma integrity. Overall, our findings demonstrate that ³¹P-MRS markers of energetic status and sarcolemma integrity are altered in young mdx compared with wild-type mice, and these indices are exacerbated following downhill running.     

Cardiac function and arteriovenous oxygen difference during exercise in obese adults

The purpose of this study was to assess cardiac function and arteriovenous oxygen difference (a-vO₂ difference) at rest and during exercise in young, normal-weight (n = 20), and obese (n = 12) men and women who were matched for age and fitness level. Participants were assessed for body composition, peak oxygen consumption (VO_2peak), and cardiac variables (thoracic bioimpedance)—cardiac index (CI), cardiac output (Q), stroke volume (SV), heart rate (HR), and ejection fraction (EF)—at rest and during cycling exercise at 65% of VO_2peak. Differences between groups were assessed with multivariate ANOVA and mixed-model ANOVA with repeated measures controlling for sex. Absolute VO_2peak and VO_2peak relative to fat-free mass (FFM) were similar between normal-weight and obese groups (Mean ± SEE 2.7 ± 0.2 vs. 3.3 ± 0.3 l min⁻¹, p = 0.084 and 52.4 ± 1.5 vs. 50.9 ± 2.3 ml kg FFM⁻¹ min⁻¹, p = 0.583, respectively). In the obese group, resting Q and SV were higher (6.7 ± 0.4 vs. 4.9 ± 0.1 l min⁻¹, p < 0.001 and 86.8 ± 4.3 vs. 65.8 ± 1.9 ml min⁻¹, p < 0.001, respectively) and EF lower (56.4 ± 2.2 vs. 65.5 ± 2.2%, p = 0.003, respectively) when compared with the normal-weight group. During submaximal exercise, the obese group demonstrated higher mean CI (8.8 ± 0.3 vs. 7.7 ± 0.2 l min⁻¹ m⁻², p = 0.007, respectively), Q (19.2 ± 0.9 vs. 13.1 ± 0.3 l min⁻¹, p < 0.001, respectively), and SV (123.0 ± 5.6 vs. 88.9 ± 4.1 ml min⁻¹, p < 0.001, respectively) and a lower a-vO₂ difference (10.4 ± 1.0 vs. 14.0 ± 0.7 ml l00 ml⁻¹, p = 0.002, respectively) compared with controls. Our study suggests that the ability to extract oxygen during exercise may be impaired in obese individuals.     

Role of adenosine in exercise‐induced human skeletal muscle vasodilatation

The role of adenosine in exercise‐induced human skeletal muscle vasodilatation remains unknown. We therefore evaluated the effect of theophylline‐induced adenosine receptor blockade in six subjects and the vasodilator potency of adenosine infused in the femoral artery of seven subjects. During one‐legged, knee‐extensor exercise at ～48% of peak power output, intravenous (i.v.) theophylline decreased (P < 0.003) femoral artery blood flow (F_aBF) by ～20%, i.e. from 3.6 ± 0.5 to 2.9 ± 0.5 L min^?1, and leg vascular conductance (VC) from 33.4 ± 9.1 to 27.7 ± 8.5 mL min^?1 mmHg^?1, whereas heart rate (HR), mean arterial pressure (MAP), leg oxygen uptake and lactate release remained unaltered (P = n.s.). Bolus injections of adenosine (2.5 mg) at rest rapidly increased (P < 0.05) F_aBF from 0.3 ± 0.03 L min^?1 to a 15‐fold peak elevation (P < 0.05) at 4.1 ± 0.5 L min^?1. Continuous infusion of adenosine at rest and during one‐legged exercise at ～62% of peak power output increased (P < 0.05) F_aBF dose‐dependently to level off (P = ns) at 8.3 ± 1.0 and 8.2 ± 1.4 L min^?1, respectively. One‐legged exercise alone increased (P < 0.05) F_aBF to 4.7 ± 1.7 L min^?1. Leg oxygen uptake was unaltered (P = n.s.) with adenosine infusion during both rest and exercise. The present findings demonstrate that endogenous adenosine controls at least ～20% of the hyperaemic response to submaximal exercise in skeletal muscle of humans. The results also clearly show that arterial infusion of exogenous adenosine has the potential to evoke a vasodilator response that mimics the increase in blood flow observed in response to exercise.     

Effects of endurance training on oxidative capacity and structural composition of human arm and leg muscles

Six healthy subjects performed endurance training of the same duration with legs and arms consecutively. Performance and muscle structure were measured before and after training in lower and upper limbs. Training induced similar increases in maximal oxygen consumption (6 ± 1 vs. 7 ± 2 mL min^?1 kg^?1: legs vs. arms, P > 0.05) and mitochondrial volume in leg and arm muscles (42 ± 12 vs. 31 ± 11%: legs vs. arms, P > 0.05). The gain in mitochondrial volume after training was achieved solely by increasing the fraction of mitochondria (+40 ± 11%, P < 0.05) in the same muscle volume (+2 ± 2%, P > 0.05) in the legs. In contrast, increased muscle volume (+14 ± 3%, P < 0.05), in addition to a tendency for an increase in mitochondrial fraction (+16 ± 11%, P > 0.05), occurred in the arms after training. Thus, similar improvements in muscle oxidative capacity in upper and lower limbs were brought about by different mechanisms. It is suggested that due to infrequent use and a lack of load-bearing function, arm muscle volume is underdeveloped in untrained, sedentary or detrained/injured subjects and that the mode of endurance training used in this study is sufficient to enlarge arm muscle volume as well as aerobic capacity.     

Interrelations of muscle functional MRI,diffusion‐weighted MRI and 31P‐MRS in exercised lower back muscles

Exercise‐induced changes of transverse proton relaxation time (T₂), tissue perfusion and metabolic turnover were investigated in the lower back muscles of volunteers by applying muscle functional MRI (mfMRI) and diffusion‐weighted imaging (DWI) before and after as well as dynamic ³¹P‐MRS during the exercise. Inner (M. multifidus, MF) and outer lower back muscles (M. erector spinae, ES) were examined in 14 healthy young men performing a sustained isometric trunk‐extension. Significant phosphocreatine (PCr) depletions ranging from 30% (ES) to 34% (MF) and Pi accumulations between 95% (left ES) and 120%–140% (MF muscles and right ES) were observed during the exercise, which were accompanied by significantly decreased pH values in all muscles (?pH ≈ –0.05). Baseline T₂ values were similar across all investigated muscles (approximately 27 ms at 3 T), but revealed right–left asymmetric increases (T₂,_inc) after the exercise (right ES/MF: T₂,_inc = 11.8/9.7%; left ES/MF: T₂,_inc = 4.6/8.9%). Analyzed muscles also showed load‐induced increases in molecular diffusion D (p = .007) and perfusion fraction f (p = .002). The latter parameter was significantly higher in the MF than in the ES muscles both at rest and post exercise. Changes in PCr (p = .03), diffusion (p < .01) and perfusion (p = .03) were strongly associated with T_2,inc, and linear mixed model analysis revealed that changes in PCr and perfusion both affect T_2,inc (p < .001). These findings support previous assumptions that T₂ changes are not only an intra‐cellular phenomenon resulting from metabolic stress but are also affected by increased perfusion in loaded muscles. Copyright © 2014 John Wiley & Sons, Ltd.     

Measuring perfusion and bioenergetics simultaneously in mouse skeletal muscle: a multiparametric functional‐NMR approach

A totally noninvasive set‐up was developed for comprehensive NMR evaluation of mouse skeletal muscle function in vivo. Dynamic pulsed arterial spin labeling‐NMRI perfusion and blood oxygenation level‐dependent (BOLD) signal measurements were interleaved with ³¹P NMRS to measure both vascular response and oxidative capacities during stimulated exercise and subsequent recovery. Force output was recorded with a dedicated ergometer. Twelve exercise bouts were performed. The perfusion, BOLD signal, pH and force–time integral were obtained from mouse legs for each exercise. All reached a steady state after the second exercise, justifying the pointwise summation of the last 10 exercises to compensate for the limited ³¹P signal. In this way, a high temporal resolution of 2.5 s was achieved to provide a time constant for phosphocreatine (PCr) recovery (τ_PCr). The higher signal‐to‐noise ratio improved the precision of τ_PCr measurement [coefficient of variation (CV) = 16.5% vs CV = 49.2% for a single exercise at a resolution of 30 s]. Inter‐animal summation confirmed that τ_PCr was stable at steady state, but shorter (89.3 ± 8.6 s) than after the first exercise (148 s, p < 0.05). This novel experimental approach provides an assessment of muscle vascular response simultaneously to energetic function in vivo. Its pertinence was illustrated by observing the establishment of a metabolic steady state. This comprehensive tool offers new perspectives for the study of muscle pathology in mice models. Copyright © 2010 John Wiley & Sons, Ltd.     

Combined spiroergometry and 31P–MRS of human calf muscle during high‐intensity exercise

Simultaneous measurements of pulmonary oxygen consumption (VO₂), carbon dioxide exhalation (VCO₂) and phosphorus magnetic resonance spectroscopy (³¹P–MRS) are valuable in physiological studies to evaluate muscle metabolism during specific loads. Therefore, the aim of this study was to adapt a commercially available spirometric device to enable measurements of VO₂ and VCO₂ whilst simultaneously performing ³¹P–MRS at 3 T. Volunteers performed intense plantar flexion of their right calf muscle inside the MR scanner against a pneumatic MR‐compatible pedal ergometer. The use of a non‐magnetic pneumotachograph and extension of the sampling line from 3 m to 5 m to place the spirometric device outside the MR scanner room did not affect adversely the measurements of VO₂ and VCO₂. Response and delay times increased, on average, by at most 0.05 s and 0.79 s, respectively. Overall, we were able to demonstrate a feasible ventilation response (VO₂ = 1.05 ± 0.31 L/min; VCO₂ = 1.11 ± 0.33 L/min) during the exercise of a single calf muscle, as well as a good correlation between local energy metabolism and muscular acidification (τ_{PCr fast} and pH; R² = 0.73, p < 0.005) and global respiration (τ_{PCr fast} and VO₂; R² = 0.55, p = 0.01). This provides improved insights into aerobic and anaerobic energy supply during strong muscular performances.     

Effect of endurance training on muscle microvascular filtration capacity and vascular bed morphometry in the elderly

Aim: Exercise training is a strong stimulus for vascular remodelling and could restore age‐induced vascular alterations. The purpose of the study was to test the hypothesis that an increase in vascular bed filtration capacity would corroborate microvascular adaptation with training. Methods: We quantified (1) microvascularization from vastus lateralis muscle biopsy to measure the capillary to fibre interface (LC/PF) and (2) the microvascular filtration capacity (K_f) in lower limbs through a venous congestion plethysmography procedure. Twelve healthy older subjects (74 ± 4 years) were submitted to a 14‐week training programme during which lower‐limbs were trained for endurance exercise. Results: The training programme induced a significant increase in the aerobic exercise capacity of lower limbs (+11%Vo _2peak; P < 0.05; +28% Citrate Synthase Activity; P < 0.01). K_f was largely increased (4.3 ± 0.9 10^?3 mL min^?1 mmHg^?1 100 mL^?1 post‐training vs. 2.4 ± 0.8 pre‐training, mean ± SD; P < 0.05) and microvascularization developed as shown by the rise in LC/PF (0.29 ± 0.06 post‐ vs. 0.23 ± 0.06 pre‐training; P < 0.05). Furthermore, K_f and LC/PF were correlated (r = 0.65, P < 0.05). Conclusion: These results demonstrated the microvascular adaptation to endurance training in the elderly. The increase in K_f with endurance training was probably related to a greater surface of exchange with an increased microvessel/fibre interface area. We conclude that measurement of the microvascular filtration rate reflects the change in the muscle exchange area and is influenced by exercise training.     

Additivity of adrenaline and contractions on hormone‐sensitive lipase,but not on glycogen phosphorylase,in rat muscle

Aim: Hormone‐sensitive lipase (HSL) has been proposed to regulate triacylglycerol (TG) breakdown in skeletal muscle. In muscles with different fibre type compositions the influence on HSL of two major stimuli causing TG mobilization was studied. Methods: Incubated soleus and extensor digitorum longus (EDL) muscles from 70 g rats were stimulated by adrenaline (5.5 μm , 6 min) or contractions (200 ms tetani, 1 Hz, 1 min) in maximally effective doses or by both adrenaline and contractions. Results: Hormone‐sensitive lipase activity was increased significantly by adrenaline as well as contractions, and the highest activity (P < 0.05) was seen with combined stimulation [Soleus: 0.40 ± 0.03 (SE) m‐unit mg protein^?1 (basal), 0.65 ± 0.02 (adrenaline), 0.65 ± 0.03 (contractions), 0.78 ± 0.03 (adrenaline and contractions); EDL: 0.18 ± 0.01, 0.30 ± 0.02, 0.26 ± 0.02, 0.32 ± 0.01]. Glycogen phosphorylase activity was always increased more by adrenaline compared with contractions [Soleus: 60 ± 4 (a/a + b)% vs. 46 ± 3 (P < 0.05); EDL: 60 ± 5 vs. 39 ± 6 (P < 0.05)]. After combined stimulation glycogen phosphorylase activity in soleus [59 ± 3 (a/a + b)%] was identical to and in EDL [45 ± 4 (a/a + b)%] smaller (P < 0.05) than the activity after adrenaline only. Conclusions: In slow‐twitch oxidative as well as in fast‐twitch glycolytic muscle HSL is activated by both adrenaline and contractions. These stimuli are partially additive indicating at least partly different mechanisms of action. Contractions may impair the enhancing effect of adrenaline on glycogen phosphorylase activity in muscle.     

Changes in phosphocreatine concentration of skeletal muscle during high-intensity intermittent exercise in children and adults

Purpose

The aim of the present study was to test the hypotheses that a greater oxidative capacity in children results in a lower phosphocreatine (PCr) depletion, a faster PCr resynthesis and a lower muscle acidification during high-intensity intermittent exercise compared to adults.

Methods

Sixteen children (9.4 ± 0.5 years) and 16 adults (26.1 ± 0.3 years) completed a protocol consisting of a dynamic plantar flexion (10 bouts of 30-s exercise at 25 % of one repetition maximum separated by 20-s recovery), followed by 10 min of passive recovery. Changes of PCr, ATP, inorganic phosphate, and phosphomonoesters were measured by means of ³¹Phosphorous-magnetic resonance spectroscopy during and post-exercise.

Results

Average PCr (percentage of [PCr] at initial rest (%[PCr]_i)) at the end of the exercise (adults 17 ± 12 %[PCr]_i, children 38 ± 17 %[PCr]_i, P < 0.01) and recovery periods (adults 37 ± 14 %[PCr]_i, children 57 ± 17 %[PCr]_i, P < 0.01) was significantly lower in adults compared to children, induced by a stronger PCr decrease during the first exercise interval (adults ?73 ± 10 %[PCr]_i, children ?55 ± 15 %[PCr]_i, P < 0.01). End-exercise pH was significantly higher in children compared to adults (children 6.90 + 0.20, ?0.14; adults 6.67 + 0.23, ?0.15, P < 0.05).

Conclusions

From our results we suggest relatively higher rates of oxidative ATP formation in children’s muscle for covering the ATP demand of high-intensity intermittent exercise compared to adults, enabling children to begin each exercise interval with significantly higher PCr concentrations and leading to an overall lower muscle acidification.     

Skeletal muscle buffering capacity is higher in the superficial vastus than in the soleus of spontaneously running rats

Skeletal muscle buffering capacity (βm_titr) was determined in soleus (type I) and superficial vastus (type II) muscles of 16 Long–Evans rats with differing levels of spontaneous activity and in 11 sedentary control rats. βm_titr was 24% higher (P<0.001) in superficial vastus muscle than in soleus muscle (268±50 vs. 216±30 μmol H⁺ g muscle dry wt^-1 pH unit^-1) (mean±SD). There was no relationship between βm_titr and mean weekly running distance amongst spontaneously running rats, nor was βm_titr any greater in these rats than in a group of sedentary control rats. Protein to wet wt ratio was 31% higher (P<0.0001) in the superficial vastus muscle when compared with soleus muscle (22.04±3.74 vs. 16.77±3.00 mg protein, 100 mg wet wt muscle^-1), but there was no relationship between protein to wet wt ratio and running distance. Initial muscle homogenate pH (pH_i) was lower in superficial vastus muscle compared with soleus muscle (6.36±0.25 vs. 6.63±0.16). Running rats had a significantly lower pH_i in both soleus and superficial vastus than sedentary controls. There was an exponential relationship between weekly running distance and pH_i in both the superficial vastus muscle (r=-0.86, P<0.001) and the soleus muscle (r=-0.73, P<0.01). Citrate synthase activity correlated with weekly running distance in superficial vastus muscle (r=0.66, P<0.01) but not in soleus muscle. The results confirm a higher βm_titr in the type II superficial vastus muscle when compared with the predominantly type I soleus muscle. We suggest that this may be partly the result of a higher protein concentration in type II muscle. Future studies measuring βm_titr in mixed muscle (e.g. human vastus lateralis) should report fibre type composition.