Danielle M. Wigmore

In vivo ATP production during free-flow and ischaemic muscle contractions in humans

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][Pi]) 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.

Contrasting influences of age and sex on muscle fatigue

PURPOSE Greater resistance to muscle fatigue has been observed in women versus men and in older versus young individuals. As suggested mechanisms for these differences include task intensity and duty cycle, the purpose of this study was to evaluate fatigue in healthy young and older men and women during maximum-effort isometric contractions with a 70% duty cycle (7 s of contraction, 3 s of rest). We hypothesized that no differences in fatigue would be observed across age or sex, in contrast to studies incorporating lower duty cycles. METHODS The protocol was carried out on ankle dorsiflexors of older (73 +/- 1 yr) and younger (25 +/- 1 yr) men and women. Volitional and stimulated force, compound muscle action potential, and muscle contractile responses were collected before, during, and immediately after the fatigue protocol. These measurements allowed for assessment of fatigue as well as central and peripheral activation. RESULTS At baseline, older subjects had longer force half-relaxation times and less twitch potentiation than younger subjects, consistent with a slower muscle phenotype. During contractions, younger subjects fatigued more than older subjects did, with no differences between men and women. Central activation decreased similarly in all groups with fatigue. There were no fatigue-related differences in peripheral excitation or contractile properties attributable to age or sex. CONCLUSIONS 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.

Contraction frequency modulates muscle fatigue and the rate of myoglobin desaturation during incremental contractions in humans

The metabolic cost of force production, and therefore the demand for oxygen, increases with intensity and frequency of contraction. This study investigated the interaction between fatigue and oxygenation, as reflected by deoxymyoglobin (dMb), during slow and rapid rhythmic isometric contractions having the same duty cycles and relative force-time integrals (FTIs). We used 1H magnetic resonance spectroscopy and measures of dorsiflexor muscle force to compare dMb and fatigue (fall of maximal voluntary force, MVC) in 11 healthy adults (29 +/- 7 y) during 16 min of slow (4 s contraction, 6 s relaxation) and rapid (1.2 s, 1.8 s) incremental (10%-80% MVC) contractions. We tested the hypotheses that (i) the rate of Mb desaturation would be faster in rapid than in slow contractions and (ii) fatigue, Mb desaturation, and the fall in FTI would be greater, and PO2 (oxygen tension) lower, at the end of rapid contractions than at the end of slow contractions. Although dMb increased more quickly during rapid contractions (p = 0.05), it reached a plateau at a similar level in both protocols (approximately 42% max, p = 0.49), likely due to an inability to further increase force production and thus metabolic demand. Despite the similar dMb at the end of both protocols, fatigue was greater in rapid (56.6% +/- 2.7% baseline) than in slow (69.5% +/- 4.0%, p = 0.01) contractions. These results indicate that human skeletal muscle fatigue during incremental isometric contractions is in part a function of contraction frequency, possibly due to metabolic inhibition of the contractile process.