Although skeletal muscle perfusion is fundamental to proper muscle function, in vivo measurements are typically limited to those of limb or arterial blood flow, rather than flow within the muscle bed itself. We present a noninvasive functional MRI (fMRI) technique for measuring perfusion-related signal intensity (SI) changes in human skeletal muscle during and after contractions and demonstrate its application to the question of occlusion during a range of contraction intensities. Eight healthy men (aged 20-31 yr) performed a series of isometric ankle dorsiflexor contractions from 10 to 100% maximal voluntary contraction. Axial gradient-echo echo-planar images (repetition time = 500 ms, echo time = 18.6 ms) were acquired continuously before, during, and following each 10-s contraction, with 4.5-min rest between contractions. Average SI in the dorsiflexor muscles was calculated for all 240 images in each contraction series. Postcontraction hyperemia for each force level was determined as peak change in SI after contraction, which was then scaled to that obtained following a 5-min cuff occlusion of the thigh (i.e., maximal hyperemia). A subset of subjects (n = 4) performed parallel studies using venous occlusion plethysmography to measure limb blood flow. Hyperemia measured by fMRI and plethysmography demonstrated good agreement. Postcontraction hyperemia measured by fMRI scaled with contraction intensity up to approximately 60% maximal voluntary contraction. fMRI provides a noninvasive means of quantifying perfusion-related changes during and following skeletal muscle contractions in humans. Temporal changes in perfusion can be observed, as can the heterogeneity of perfusion across the muscle bed.

The aim of this study was to determine how ATP synthesis and contractility in vivo are altered by ischaemia in working human skeletal muscle. The hypotheses were: (1) glycolytic flux would be higher during ischaemic (ISC) compared to free-flow (FF) muscle contractions, in compensation for reduced oxidative ATP synthesis, and (2) ischaemic muscle fatigue would be related to the accumulation of inhibitory metabolic by-products rather than to the phosphorylation potential ([ATP]/[ADP][P i ]) of the muscle. Twelve healthy adults (6 men, 6 women) performed six intermittent maximal isometric contractions of the ankle dorsiflexors (12 s contract, 12 s relax), once with intact blood flow and once with local ischaemia by thigh cuff inflation to 220 Torr. Intracellular phosphorous metabolites and pH were measured non-invasively with magnetic resonance spectroscopy, and rates of ATP synthesis through oxidative phosphorylation, anaerobic glycolysis, and the creatine kinase reaction were determined. The force-time integral declined more during ISC (66 ± 3% initial) than FF (75 ± 2% initial, P = 0.002), indicating greater fatigue in ISC.[ATP] was preserved in both protocols, indicating matching of ATP production and use under both conditions. Glycolytic flux (mM s −1 ) was similar during FF and ISC (P = 0.16). Total ATP synthesis rate was lower during ISC, despite adjustment for the greater muscle fatigue in this condition (P < 0.001). Fatigue was linearly associated with diprotonated inorganic phosphate (FF r = 0.94 ± 0.01, ISC r = 0.92 ± 0.02), but not phosphorylation potential. These data provide novel evidence that ATP supply and demand in vivo are balanced in human skeletal muscle during ischaemic work, not through higher glycolytic flux, but rather through increased metabolic economy and decreased rates of ATP consumption as fatigue ensues.

These data indicate that age-related differences in fatigue are observed even during intermittent MVC with a high duty cycle, and that these differences are independent of central and peripheral activation. Further, it seems that sex-based differences in both fatigue and central activation failure were abolished with this duty cycle. Overall, these results suggest that age- and sex-based differences in fatigue arise from distinct mechanisms.

It has been suggested that a transient limitation in blood flow during intermittent muscular contractions can contribute to muscle fatigue, and that this limitation is greater as contraction intensity increases. We investigated skeletal muscle blood flow and fatigue in 13 healthy, untrained men (21-27 years) during 16 min of intermittent (4 s contract, 6 s relax) isometric dorsiflexor contractions. Contractions began at 10% of pre-exercise maximal voluntary contraction (MVC) force and increased by 10% every 2 min. Hyperemia (i.e., post-contraction blood flow, measured by venous occlusion plethysmography) and MVC were measured at the end of each stage. Muscle volume measures were obtained using magnetic resonance imaging. After 10 min of exercise, submaximal force and post-contraction hyperemia plateaued. MVC fell from 8 min of exercise onwards (p=0.004), and this onset of fatigue preceded the plateau in submaximal force and hyperemia. Despite a large range in dorsiflexor muscle size (66.3-176.4 cm(3)) and strength (112.5-421.8 N), neither muscle size nor strength were related to fatigue. The temporal dissociation between changes in blood flow and the onset of fatigue (fall of MVC) suggest that limited blood flow was not a factor in the impaired force production observed during intermittent isometric dorsiflexor contractions in healthy young men. Additionally, post-contraction hyperemia increased linearly with increasing contraction intensity, reflecting a match between blood flow and force production throughout the protocol that was independent of fatigue.