Effects of activation frequency and force on low-frequency fatigue in human skeletal muscle.

No comparison of the amount of low-frequency fatigue (LFF) produced by different activation frequencies exists, although frequencies ranging from 10 to 100 Hz have been used to induce LFF. The quadriceps femoris of 11 healthy subjects were tested in 5 separate sessions. In each session, the force-generating ability of the muscle was tested before and after fatigue and at 2, approximately 13, and approximately 38 min of recovery. Brief (6-pulse), constant-frequency trains of 9.1, 14.3, 33.3, and 100 Hz and a 6-pulse, variable-frequency train with a mean frequency of 14.3 Hz were delivered at 1 train/s to induce fatigue. Immediately postfatigue, there was a significant effect of fatiguing protocol frequency. Muscles exhibited greater LFF after stimulation with the 9.1-, 14.3-, and variable-frequency trains. These three trains also produced the greatest mean force-time integrals during the fatigue test. At 2, approximately 13, and approximately 38 min of recovery, however, the LFF produced was independent of the fatiguing protocol frequency. The findings are consistent with theories suggesting two independent mechanisms behind LFF and may help identify the optimal activation pattern when functional electrical stimulation is used.     

Effects of activation pattern on nonisometric human skeletal muscle performance.

During volitional muscle activation, motor units often fire with varying discharge patterns that include brief, high-frequency bursts of activity. These variations in the activation rate allow the central nervous system to precisely control the forces produced by the muscle. The present study explores how varying the instantaneous frequency of stimulation pulses within a train affects nonisometric muscle performance. The peak excursion produced in response to each stimulation train was considered as the primary measure of muscle performance. The results showed that at each frequency tested between 10 and 50 Hz, variable-frequency trains that took advantage of the catchlike property of skeletal muscle produced greater excursions than constant-frequency trains. In addition, variable-frequency trains that could achieve targeted trajectories with fewer pulses than constant-frequency trains were identified. These findings suggest that similar to voluntary muscle activation patterns, varying the instantaneous frequency within a train of pulses can be used to improve muscle performance during functional electrical stimulation.     

Acoustic myography for investigating human skeletal muscle fatigue.

Sounds produced during voluntary isometric contractions of the quadriceps muscle were studied by acoustic myography (AMG) in five healthy adults. With the subject seated, isometric force, surface electromyography (EMG), and AMG were recorded over rectus femoris, and the EMG and AMG signals were integrated (IEMG and IAMG). Contractions lasting 5 s each were performed at 10, 25, 50, 60, 75, and 100% of maximum voluntary contraction (MVC) force. Fatigue was then induced by repeated voluntary contractions (10 s on, 10 s off) at 75% MVC until only 40% MVC could be sustained. After 15 min of rest, the different force levels were again tested in relation to the fresh MVC. Both before and after fatiguing activity the relationships between force and IEMG [r = 0.99 +/- 0.01 (SD), n = 10] and force and IAMG (r = 0.98 +/- 0.02) were linear. After activity, however, the slopes of the regression lines for force and IEMG increased (P less than 0.01) but those for force and IAMG remained the same (P greater than 0.05). The present results clarify the relationship between AMG and isometric force in fatigued muscle without the problem of fatigue-induced tremor, which hampered previous studies of prolonged activity. This study contributes to the validation of AMG and shows that it is a potentially useful method for noninvasive assessment of force production and fatigue. Further studies to establish the origin of AMG activity are required before AMG can be accepted for use in neuromuscular physiology or rehabilitation.     

Dihydropyridine effects on skeletal muscle fatigue.

1. The purpose of this investigation was to determine if alterations in extracellular calcium (Ca2+) influx by the dihydropyridine derivatives Bay K 8644 and nifedipine affected skeletal muscle fatigue. 2. Tetanic contractions (80 Hz, 100 msec) of frog sartorius muscles were evoked every sec for 3 min. Muscles were fatigued in normal Ringer's solution (NR), in NR containing 1 microM nifedipine of 10 microM Bay K 8644 or in low Ca2+ Ringer's. 3. In each case, the experimental conditions increased the rate and magnitude of fatigue. Rate constants of fatigue obtained during Bay K 8644, nifedipine and low Ca2+ conditions (-.0122 +/- .0016, -.0397 +/- 0022 and 0.0169 +/- .0064 sec-1, respectively) were significantly greater than NR (-.0104 +/- .0006 sec-1, p less than .05). In addition, tetanic forces developed at the end of the stimulation period under the experimental conditions (3.90 +/- 0.81, 1.21 +/- 1.40 and 2.04 +/- 1.10% of initial) were significantly less than NR (7.18 +/- 1.27%, p less than .05). 4. Caffeine contracture forces (10 mM) evoked immediately after stimulation were not significantly different between conditions. 5. These results suggest that alterations in sarcolemmal Ca2+ exchange has some influence on the fatigue process.     

Effects of fatigue and training on sarcoplasmic reticulum Ca(2+) regulation in human skeletal muscle.

Little is known about fatigue and training effects on sarcoplasmic reticulum (SR) function in human muscle, and we therefore investigated this in eight untrained controls (UT), eight endurance-trained (ET), and eight resistance-trained athletes (RT). Muscle biopsies (vastus lateralis) taken at rest and after 50 maximal quadriceps contractions (180 degrees/s, 0.5 Hz) were analyzed for fiber composition, metabolites and maximal SR Ca(2+) release, Ca(2+) uptake, and Ca(2+)-ATPase activity. Fatigue reduced (P < 0.05) Ca(2+) release (42.1 +/- 3.8%, 43.4 +/- 3.9%, 31.3 +/- 6.1%), Ca(2+) uptake (43.0 +/- 5.2%, 34.1 +/- 4.6%, 28.4 +/- 2.8%), and Ca(2+)-ATPase activity (38.6 +/- 4.2%, 48.5 +/- 5.7%, 29.6 +/- 5.0%), in UT, RT, and ET, respectively. These decreases were correlated with fatigability and with type II fiber proportion (P < 0.05). Resting SR measures were correlated with type II proportion (r > or = 0.51, P < 0.05). ET had lower resting Ca(2+) release, Ca(2+) uptake, and Ca(2+)-ATPase (P < 0.05) than UT and RT (P < 0.05), probably because of their lower type II proportion; only minor effects were found in RT. Thus SR function is markedly depressed with fatigue in controls and in athletes, is dependent on fiber type, and appears to be minimally affected by chronic training status.     

Effects of 7 wk of endurance training on human skeletal muscle metabolism during submaximal exercise.

This is the first study to examine the effects of endurance training on the activation state of glycogen phosphorylase (Phos) and pyruvate dehydrogenase (PDH) in human skeletal muscle during exercise. We hypothesized that 7 wk of endurance training (Tr) would result in a posttransformationally regulated decrease in flux through Phos and an attenuated activation of PDH during exercise due to alterations in key allosteric modulators of these important enzymes. Eight healthy men (22 +/- 1 yr) cycled to exhaustion at the same absolute workload (206 +/- 5 W; approximately 80% of initial maximal oxygen uptake) before and after Tr. Muscle biopsies (vastus lateralis) were obtained at rest and after 5 and 15 min of exercise. Fifteen minutes of exercise post-Tr resulted in an attenuated activation of PDH (pre-Tr: 3.75 +/- 0.48 vs. post-Tr: 2.65 +/- 0.38 mmol.min(-1).kg wet wt(-1)), possibly due in part to lower pyruvate content (pre-Tr: 0.94 +/- 0.14 vs. post-Tr: 0.46 +/- 0.03 mmol/kg dry wt). The decreased pyruvate availability during exercise post-Tr may be due to a decreased muscle glycogenolytic rate (pre-Tr: 13.22 +/- 1.01 vs. post-Tr: 7.36 +/- 1.26 mmol.min(-1).kg dry wt(-1)). Decreased glycogenolysis was likely mediated, in part, by posttransformational regulation of Phos, as evidenced by smaller net increases in calculated muscle free ADP (pre-Tr: 111 +/- 16 vs. post-Tr: 84 +/- 10 micromol/kg dry wt) and P(i) (pre-Tr: 57.1 +/- 7.9 vs. post-Tr: 28.6 +/- 5.6 mmol/kg dry wt). We have demonstrated for the first time that several signals act to coordinately regulate Phos and PDH, and thus carbohydrate metabolism, in human skeletal muscle after 7 wk of endurance training.     

A1 receptor activation decreases fatigue in mammalian slow-twitch skeletal muscle in vitro.

To test the hypothesis that adenosine improves skeletal muscle cell function, we exposed curarized mouse soleus and extensor digitorum longus (EDL) to a range of concentrations of adenosine (10(-9) M to 10(-5) M). Muscles contracted in Krebs-Henseleit bicarbonate buffer (27 degrees C, 95% O2 and 5% CO2) for 500 ms at 50 Hz once every 90 s. Soleus fatigued significantly less with adenosine present at concentrations of 10(-8) M and higher than with the Krebs-Henseleit vehicle control. Adenosine significantly improved force generation or delayed fatigue of EDL only with the initial adenosine challenge. To investigate the receptor population involved, we exposed soleus to agonists specific for A1 receptors (N6-cyclopentyladenosine, CPA), or A2 receptors (CGS 21680 hydrochloride, CGS), or A3 receptors (N6-benzyl-5'-N-ethylcarboxamidoadenosine, BNECA). CPA (A1) significantly decreased fatigue compared with the Krebs-Henseleit vehicle control at concentrations of 10(-9) M and higher. Muscles exposed to the A2 and A3 agonists did not differ from a Krebs-Henseleit plus methanol control. Phenylephrine (10(-6) M), an alpha-adrenergic agonist that increases the concentration of inositol triphosphate (IP3), significantly improved developed force in soleus. Neither a permeable cAMP analog, 8-bromo-cAMP (10(-5) M), nor a beta, agonist, isoproterenol (10(-6) M), had an effect on force generation in the soleus when compared with a saline control. Thus adenosine slowed fatigue in slow-twitch skeletal muscle through A1 receptors.     

Effects of fatigue and recovery on electromyographic and isometric force- and relaxation-time characteristics of human skeletal muscle

Effects of fatigue produced by a maintained 60% isometric loading on electromyographic and isometric force-time and relaxation-time characteristics of human skeletal muscle were studied in 21 males accustomed to strength training. Fatigue loading resulted in a slight but not significant change in the maximal integrated EMG of a maximal isometric contraction, and a large decrease (20.4 +/- 6.3%, p less than 0.001) in maximal force. Fatigue loading increased (p less than 0.05-0.01) neural activation of the muscles during rapidly produced submaximal isometric forces, but had a considerable adverse effect (p less than 0.001) on the corresponding force-time characteristics. Correlations between the relative changes after fatigue in the IEMG/force ratio at the maximal force level, and in the IEMG/force ratios of the early phases of the force-time curve were not significant, but gradually became significant (p less than 0.01) at higher force levels. The average IEMG of the muscles in the relaxation phase of contraction remained unaltered by fatigue, while a marked deleterious change in the relaxation-time variables (p less than 0.001) occurred concomitantly. During the subsequent 3 min rest period considerable (12.1 +/- 7.0%, p less than 0.001) recovery was noted in the maximal force, with smaller (insignificant or p less than 0.05-0.01) changes in the force-time and relaxation-time variables, while the average IEMG of force production decreased (p less than 0.01-0.001). The present findings suggest that fatigue leading to a worsening in force-time, in maximal force and in the relaxation-time parts of a maximal isometric contraction might take place primarily in the contractile processes.     

Effects of membrane potential on mechanical activation in skeletal muscle

The effect of subthreshold depolarization on mechanical threshold was investigated in tetrodotoxin-poisoned mammalian and amphibian skeletal muscle fibers using a two-microelectrode voltage-clamp technique. Mechanical threshold was determined with a 2-ms test pulse. The immediate effect of depolarization was inhibition of the mechanical system. The consequent increase in the test pulse threshold was linearly related to the size of the depolarization and there was, on the average, a 10% increase in threshold for a 10-mV depolarization in mammalian fibers. The duration of the inhibitory period was also related to the size of the depolarization. Inhibition was interrupted by the onset of activation (seen as a reduction in the test pulse threshold), and in rat soleus fibers this occurred within 100 ms with a 20-mV depolarization, inhibition decayed within 10 ms. The decay of activation after brief conditioning pulses was initially rapid (on the average, the test pulse threshold recovered to 80% of its control value within 1 ms) and then slow (full recovery took 100-500 ms). After long conditioning pulses, activation often decayed into a period of inhibition. When depolarization (of 20 mV or more) was maintained for several seconds, the fibers became inactivated. Rat extensor digitorum longus and sternomastoid fibers were strongly inactivated by depolarization to -40 mV and the test pulse to +40 mV did not cause contraction.     

Local temperature changes and human skeletal muscle metabolism

The aim of this review is to describe the effects induced by local temperature changes on human skeletal muscle metabolism. More specifically, we will consider the influence of temperature on the mechanical properties of muscle contraction, on aerobic metabolism, anaerobic metabolism and on the Lohmann reaction. The text has been voluntarily organized on the basis of a simple bioenergetic model describing the different energy fluxes appearing in the muscle system. This approach should better highlight some of the points that still need to be investigated. Although it was not always possible to restrict the discussion to human muscle, the references report mainly data obtained directly on humans or on isolated human fibres. A short comment on skeletal muscle temperature measurement techniques, on humans, is also included.     

Ammonia and amino acid metabolism in human skeletal muscle during exercise.

This review focuses on the ammonia and amino acid metabolic responses of active human skeletal muscle, with a particular emphasis on steady-state exercise. Ammonia production in skeletal muscle involves the purine nucleotide cycle and the amino acids glutamate, glutamine, and alanine and probably also includes the branched chain amino acids as well as aspartate. Ammonia production is greatest during prolonged, steady state exercise that requires 60-80% VO2max and is associated with glutamine and alanine metabolism. Under these circumstances it is unresolved whether the purine nucleotide cycle (AMP deamination) is active; if so, it must be cycling with no IMP accumulation. It is proposed that under these circumstances the ammonia is produced from slow twitch fibers by the deamination of the branched chain amino acids. The ammonia response can be suppressed by increasing the carbohydrate availability and this may be mediated by altering the availability of the branched chain amino acids. The fate of the ammonia released into the circulation is unresolved, but there is indirect evidence that a considerable portion may be excreted by the lung in expired air.     

Effect of old age on human skeletal muscle force-velocity and fatigue properties

It is generally accepted that the muscles of aged individuals contract with less force, have slower relaxation rates, and demonstrate a downward shift in their force-velocity relationship. The factors mediating age-related differences in skeletal muscle fatigue are less clear. The present study was designed to test the hypothesis that age-related shifts in the force-velocity relationship impact the fatigue response in a velocity-dependent manner. Three fatigue protocols, consisting of intermittent, maximum voluntary knee extension contractions performed for 4 min, were performed by 11 young (23.5 ± 0.9 yr, mean ± SE) and 10 older (68.9 ± 4.3) women. The older group fatigued less during isometric contractions than the young group (to 71.1 ± 3.7% initial torque and 59.8 ± 2.5%, respectively; P = 0.02), while the opposite was true during contractions performed at a relatively high angular velocity of 270°·s(-1) (old: 28.0 ± 3.9% initial power, young: 52.1 ± 6.9%; P < 0.01). Fatigue was not different (P = 0.74) between groups during contractions at an intermediate velocity, which was selected for each participant based on their force-velocity relationship. There was a significant association between force-velocity properties and fatigue induced by the intermediate-velocity fatigue protocol in the older (r = 0.72; P = 0.02) and young (r = 0.63; P = 0.04) groups. These results indicate that contractile velocity has a profound impact on age-related skeletal muscle fatigue resistance and suggest that changes in the force-velocity relationship partially mediate this effect.     

The cross-bridge cycle and skeletal muscle fatigue.

The functional correlates of fatigue observed in both animals and humans during exercise include a decline in peak force (P0), maximal velocity, and peak power. Establishing the extent to which these deleterious functional changes result from direct effects on the myofilaments is facilitated through understanding the molecular mechanisms of the cross-bridge cycle. With actin-myosin binding, the cross-bridge transitions from a weakly bound low-force state to a strongly bound high-force state. Low pH reduces the number of high-force cross bridges in fast fibers, and the force per cross bridge in both fast and slow fibers. The former is thought to involve a direct inhibition of the forward rate constant for transition to the strong cross-bridge state. In contrast, inorganic phosphate (Pi) is thought to reduce P0 by accelerating the reversal of this step. Both H+ and Pi decrease myofibrillar Ca2+ sensitivity. This effect is particularly important as the amplitude of the Ca2+ transient falls with fatigue. The inhibitory effects of low pH and high Pi on P0 are reduced as temperature increases from 10 to 30 degrees C. However, the H+-induced depression of peak power in the slow fiber type, and Pi inhibition of myofibrillar Ca2+ sensitivity in slow and fast fibers, are greater at high compared with low temperature. Thus the depressive effects of H+ and Pi at in vivo temperatures cannot easily be predicted from data collected below 25 degrees C. In vitro, reactive oxygen species reduce myofibrillar Ca2+ sensitivity; however, the importance of this mechanism during in vivo exercise is unknown.     

Effects of caffeine on mouse skeletal muscle power output during recovery from fatigue.

The effects of 10 mM (high) and 70 microM (physiologically relevant) caffeine on force, work output, and power output of isolated mouse extensor digitorum longus (EDL) and soleus muscles were investigated in vitro during recovery from fatigue at 35 degrees C. To monitor muscle performance during recovery from fatigue, we regularly subjected the muscle to a series of cyclical work loops. Force, work, and power output during shortening were significantly higher after treatment with 10 mM caffeine, probably as a result of increased Ca2+ release from the sarcoplasmic reticulum. However, the work required to relengthen the muscle also increased in the presence of 10 mM caffeine. This was due to a slowing of relaxation and an increase in muscle stiffness. The combination of increased work output during shortening and increased work input during lengthening had different effects on the two muscles. Net power output of mouse soleus muscle decreased as a result of 10 mM caffeine exposure, whereas net power output of the EDL muscle showed a transient, significant increase. Treatment with 70 microM caffeine had no significant effect on force, work, or power output of EDL or soleus muscles, suggesting that the plasma concentrations found when caffeine is used to enhance performance in human athletes might not directly affect the contractile performance of fatigued skeletal muscle.     

Sex differences in human skeletal muscle fatigue are eliminated under ischemic conditions.

Several studies have suggested that women may be more resistant to muscle fatigue than men (Fulco CS, Rock PB, Muza SA, Lammi E, Cymerman A, Butterfield G, Moore, LG, Braun B, and Lewis SF. Acta Physiol Scand 167: 233-239, 1999) possibly because of differences in muscle oxidative metabolism. We evaluated muscle fatigue produced by intermittent, maximal volitional isometric contractions of the dorsiflexor muscles of healthy young (21-34 yr) men (n = 8) and women (n = 8) under two conditions: free-flow (FF) circulation and ischemia. Measures of voluntary and stimulated (10- and 50-Hz) force, central activation ratio (CAR), and compound muscle action potential (CMAP) were collected in each session. The ischemic protocol induced greater fatigue than the FF protocol, in both sexes, and was associated with greater reductions in CAR, CMAP, stimulated force, and the ratio of 10- to 50-Hz force compared with the FF condition. Women fatigued less than men in FF but not during ischemia, and this difference was roughly paralleled by a difference in CAR. No sex effects on the CMAP, tetanic force, and measures of excitation-contraction coupling function were found in the FF condition, suggesting that the primary mechanism behind the difference in fatigue was a relatively greater impairment of central activation in men. The observation that ischemia eliminated the sex differences in fatigue is consistent with a number of studies (Kent-Braun JA, Ng AV, Doyle JW, and Towse TF. J Appl Physiol 93: 1813-1823, 2002) relating fatigue to muscle metabolism and might be the result of sex-based differences in metabolic pathway utilization during muscle contraction.     

Effects of hyperoxia on skeletal muscle carbohydrate metabolism during transient and steady-state exercise.

This study compared the effects of inspiring either a hyperoxic (60% O(2)) or normoxic gas (21% O(2)) while cycling at 70% peak O(2) uptake on 1) the ATP derived from substrate phosphorylation during the initial minute of exercise, as estimated from phosphocreatine degradation and lactate accumulation, and 2) the reliance on carbohydrate utilization and oxidation during steady-state cycling, as estimated from net muscle glycogen use and the activity of pyruvate dehydrogenase (PDH) in the active form (PDH(a)), respectively. We hypothesized that 60% O(2) would decrease substrate phosphorylation at the onset of exercise and that it would not affect steady-state exercise PDH activity, and therefore muscle carbohydrate oxidation would be unaltered. Ten active male subjects cycled for 15 min on two occasions while inspiring 21% or 60% O(2), balance N(2). Blood was obtained throughout and skeletal muscle biopsies were sampled at rest and 1 and 15 min of exercise in each trial. The ATP derived from substrate-level phosphorylation during the initial minute of exercise was unaffected by hyperoxia (21%: 52.2 +/- 11.1; 60%: 54.0 +/- 9.5 mmol ATP/kg dry wt). Net glycogen breakdown during 15 min of cycling was reduced during the 60% O(2) trial vs. 21% O(2) (192.7 +/- 25.3 vs. 138.6 +/- 16.8 mmol glycosyl units/kg dry wt). Hyperoxia had no effect on PDH(a), because it was similar to the 21% O(2) trial at rest and during exercise (21%: 2.20 +/- 0.26; 60%: 2.25 +/- 0.30 mmol.kg wet wt(-1).min(-1)). Blood lactate was lower (6.4 +/- 1.0 vs. 8.9 +/- 1.0 mM) at 15 min of exercise and net muscle lactate accumulation was reduced from 1 to 15 min of exercise in the 60% O(2) trial compared with 21% (8.6 +/- 5.1 vs. 27.3 +/- 5.8 mmol/kg dry wt). We concluded that O(2) availability did not limit oxidative phosphorylation in the initial minute of the normoxic trial, because substrate phosphorylation was unaffected by hyperoxia. Muscle glycogenolysis was reduced by hyperoxia during steady-state exercise, but carbohydrate oxidation (PDH(a)) was unaffected. This closer match between pyruvate production and oxidation during hyperoxia resulted in decreased muscle and blood lactate accumulation. The mechanism responsible for the decreased muscle glycogenolysis during hyperoxia in the present study is not clear.     

Anaerobic metabolism in human skeletal muscle during short-term, intense activity.

The ability of human skeletal muscle to provide anaerobically derived ATP during short-term, intense activity is examined. The paper emphasizes the information obtained from direct measurements of substrates, intermediates, and products of the pathways in muscle that provide anaerobically derived ATP. The capacity of muscle to provide ATP via anaerobic pathways is approximately 370 mmol/kg dry muscle (dm) during dynamic exercise lasting approximately 3 min. Anaerobic glycolysis provided approximately 80%, phosphocreatine (PCr) degradation approximately 16%, and depletion of the ATP store approximately 4% of the total ATP provided. When the blood flow to the working muscles is reduced or occluded, the anaerobic capacity decreases to approximately 300 mmol/kg dm. This reduction is due to a lower glycolytic capacity associated with an inability to remove lactate from the muscles. Directly measured maximal rates of anaerobically derived ATP provision from PCr degradation and glycolysis during intense muscular activity are each approximately 9-10 mmol.kg-1 dm.s-1. Evidence suggests that both of these pathways are activated instantaneously at the onset of maximal activity. Spring training does little to the capacity or rates of the pathways, although a 10-20% increase in glycolytic ATP provision has been reported. The only study comparing direct and indirect estimates of the anaerobic capacity in humans suggests that O2 deficit measured at the mouth accurately predicts the anaerobic capacity of a single muscle group and that O2 debt does not. There are many unresolved issues regarding the capacity of the PCr and glycogenolytic--glycolytic systems to provide ATP during short-term intense muscular activity in humans.(ABSTRACT TRUNCATED AT 250 WORDS)