Electro-mechanical failures and lactate production during fatigue

The electrical and mechanical failures observed during sustained and intermittent electrically triggered (30 Hz) contractions of human flexor carpi ulnaris were compared with the blood lactate concentration. The changes recorded during contractions sustained for 60 s were compared with those observed during a series of sixty 1 s contractions separated by 1 s intervals, and also with the changes during the first 30 min of recovery. No significant (P less than 0.05) difference in force reduction or maximal venous lactate concentration was observed in either fatigue test, although electrical failure differed significantly (P less than 0.05). The recovery of electrical failure was poorly correlated with the reduction in lactate concentration following both sustained (r = -0.70) and intermittent contractions (r = 0.72). In contrast, the recovery in tetanic tension, rate of tension development and time to half relaxation correlated closely with the reduction in venous lactate concentration (r = -0.95, -0.93 and 0.96 respectively). It is suggested that, of the peripheral processes which appear to play a dominant role in peripheral fatigue, lactate production controls mechanical failure directly.     

Supraspinal fatigue does not explain the sex difference in muscle fatigue of maximal contractions.

Young women are less fatigable than young men for maximal and submaximal contractions, but the contribution of supraspinal fatigue to the sex difference is not known. This study used cortical stimulation to compare the magnitude of supraspinal fatigue during sustained isometric maximal voluntary contractions (MVCs) performed with the elbow flexor muscles of young men and women. Eight women (25.6 +/- 3.6 yr, mean +/- SD) and 9 men (25.4 +/- 3.8 yr) performed six sustained MVCs (22-s duration each, separated by 10 s). Before the fatiguing contractions, the men were stronger than the women (75.9 +/- 9.2 vs. 42.7 +/- 8.0 N.m; P < 0.05) in control MVCs. Voluntary activation measured with cortical stimulation before fatigue was similar for the men and women during the final control MVC (95.7 +/- 3.0 vs. 93.3 +/- 3.6%; P > 0.05) and at the start of the fatiguing task (P > 0.05). By the end of the six sustained fatiguing MVCs, the men exhibited greater absolute and relative reductions in torque (65 +/- 3% of initial MVC) than the women (52 +/- 9%; P < 0.05). The increments in torque (superimposed twitch) generated by motor cortex stimulation during each 22-s maximal effort increased with fatigue (P < 0.05). Superimposed twitches were similar for men and women throughout the fatiguing task (5.5 +/- 4.1 vs. 7.3 +/- 4.7%; P > 0.05), as well as in the last sustained contraction (7.8 +/- 5.9 vs. 10.5 +/- 5.5%) and in brief recovery MVCs. Voluntary activation determined using an estimated control twitch was similar for the men and women at the start of the sustained maximal contractions (91.4 +/- 7.4 vs. 90.4 +/- 6.8%, n = 13) and end of the sixth contraction (77.2 +/- 13.3% vs. 73.1 +/- 19.6%, n = 10). The increase in the area of the motor-evoked potential and duration of the silent period did not differ for men and women during the fatiguing task. However, estimated resting twitch amplitude and the peak rates of muscle relaxation showed greater relative reductions at the end of the fatiguing task for the men than the women. These results indicate that the sex difference in fatigue of the elbow flexor muscles is not explained by a difference in supraspinal fatigue in men and women but is largely due to a sex difference of mechanisms located within the elbow flexor muscles.     

Men are more fatigable than strength-matched women when performing intermittent submaximal contractions.

The purpose of this study was to compare the time to task failure for a series of intermittent submaximal contractions performed with the elbow flexor muscles by men and women who were matched for strength (n = 20, 18-34 yr). The fatigue task comprised isometric contractions at 50% of maximal voluntary contraction (MVC) torque (6-s contraction, 4-s rest). The MVC torque was similar for the men and women [64.8 +/- 9.2 (SD) vs. 62.2 +/- 7.9 N.m; P > 0.05]. However, the time to task failure was longer for the women (1,408 +/- 1,133 vs. 513 +/- 194 s; P < 0.05), despite the similar torque levels. The mean arterial pressure, heart rate, and rating of perceived exertion started and ended at similar values for the men and women, but the rate of increase was less for the women. The rate of increase in the average of the rectified electromyogram (AEMG; % peak MVC) for the elbow flexor muscles was less for the women: the AEMG was greater for the men compared with the women at task failure (72 +/- 28 vs. 50 +/- 21%; P < 0.05), despite similar AEMG values at the start of the fatiguing contraction (32 +/- 9 vs. 36 +/- 13%). These results indicate that for intermittent contractions performed with the elbow flexor muscles 1) the sex difference in time to task failure was not explained by the absolute strength of the men and women, but involved another mechanism that is present during perfused conditions, and 2) men required a more rapid increase in descending drive to maintain a similar torque.     

The effect of age and gender on the relative fatigability of the human adductor pollicis muscle

The purpose of this study was to examine the relative influence of such factors as age, gender, and absolute force on the fatiguability of the human adductor pollicis muscle. 12 young males (YM, 25.3 +/- 2.1 y), 12 young females (YF. 23.5 +/- 2.1 y), 12 older males (OM, 71.7 +/- 5.6 y) and 12 older females (OF, 69.5 +/- 4.6 y) participated. Three minutes of intermittent (5 s contraction, 2 s rest) maximal voluntary contractions (MVC) were used to fatigue the adductor pollicis muscle; the ulnar nerve was also stimulated in each 2 s rest period to evoke a maximal twitch. Males were stronger than females in both voluntary and evoked force (PT) in the young age group (MVC: YM, 10.0 +/- 2.7 kg vs. YF, 6.6 +/- 1.1 kg, P < 0.05) (PT: YM, 0.99 +/- 0.21 kg vs. YF, 0.71 +/- 0.12 kg, P < 0.05). In the older adults, however, males were stronger only in the evoked twitch (OM, 0.73 +/- 0.24 kg vs. OF, 0.48 +/- 0.07 kg, P < 0.05). There was no significant effect of gender or absolute muscle force on relative fatigability; the only variable found to significantly affect fatigability was age. Older adults were significantly less fatigable than young adults as indicated by the voluntary fatigue index (FI) (percentage of force reduction from baseline; FI-young, 40.2 +/- 12.6% vs. FI-old, 25.2 +/- 12.3%). This age effect, however, was more prominent in males than females (FI-YM, 44.7 +/- 10.5% vs. FI-OM, 24.2 +/- 10.7%, P < 0.01; FI-YF, 37.8 +/- 14.1% vs. FI-OF, 26.3 +/- 14.5%, P = 0.13). In conclusion, age was found to be the strongest single predictor of fatigability during short duration, intermittent exercise in human adductor pollicis muscle.     

Distinct profiles of neuromuscular fatigue during muscle contractions below and above the critical torque in humans

Whether the transition in fatigue processes between "low-intensity" and "high-intensity" contractions occurs gradually, as the torque requirements are increased, or whether this transition occurs more suddenly at some identifiable "threshold", is not known. We hypothesized that the critical torque (CT; the asymptote of the torque-duration relationship) would demarcate distinct profiles of central and peripheral fatigue during intermittent isometric quadriceps contractions (3-s contraction, 2-s rest). Nine healthy men performed seven experimental trials to task failure or for up to 60 min, with maximal voluntary contractions (MVCs) performed at the end of each minute. The first five trials were performed to determine CT [~35-55% MVC, denoted severe 1 (S1) to severe 5 (S5) in ascending order], while the remaining two trials were performed 10 and 20% below the CT (denoted CT-10% and CT-20%). Dynamometer torque and the electromyogram of the right vastus lateralis were sampled continuously. Peripheral and central fatigue was determined from the fall in potentiated doublet torque and voluntary activation, respectively. Above CT, contractions progressed to task failure in ~3-18 min, at which point the MVC did not differ from the target torque (S1 target, 88.7 ± 4.3 N·m vs. MVC, 89.3 ± 8.8 N·m, P = 0.94). The potentiated doublet fell significantly in all trials, and voluntary activation was reduced in trials S1-S3, but not trials S4 and S5. Below CT, contractions could be sustained for 60 min on 17 of 18 occasions. Both central and peripheral fatigue developed, but there was a substantial reserve in MVC torque at the end of the task. The rate of global and peripheral fatigue development was four to five times greater during S1 than during CT-10% (change in MVC/change in time S1 vs. CT-10%: -7.2 ± 1.4 vs. -1.5 ± 0.4 N·m·min(-1)). These results demonstrate that CT represents a critical threshold for neuromuscular fatigue development.     

Failure of neuromuscular propagation during human maximal voluntary contraction

The mechanism for fatigue of the adductor pollicis was studied in normal subjects during maximal voluntary contractions (MVC) sustained for 90-100 s, by comparing the force and electrical response of this muscle to voluntary motor drive with that obtainable with artificial stimulation of the ulnar nerve. The adequacy of nerve stimulation was checked by recording simultaneously the electrical response of a nonfatiguing muscle, the abductor of the small finger. The decrease in force and in the natural electrical activity with fatigue was accompanied by a parallel decrease in the amplitude of synchronous muscle action potentials (M waves) evoked by artificial stimulation of the ulnar nerve at different frequencies. The decline in M-wave amplitude in the adductor pollicis was not due to a submaximal nerve stimulation, since the amplitudes recorded simultaneously from the nonfatiguing abductor digiti minimi remained unchanged. The force and the electrical responses from the adductor pollicis recovered in parallel with a half time of approximately 1 min. These results suggest that the loss of force of the adductor pollicis with fatigue and its subsequent recovery are largely determined by the extent of neuromuscular propagation failure. The slow recovery of the M-wave amplitude during repetitive stimulation suggests that it may be related to some aspect of muscle metabolism.     

Electromyography and fatigue during prolonged, low-level static contractions

Findings from five separate studies of EMG changes and muscle fatigue during prolonged low-level static contractions are summarized, and the possible mechanisms behind the changes are briefly discussed. Sustained static contractions (10%, 7% and 5% MVC) of up to 1 h duration were performed by finger flexors, elbow flexors and extensors, and knee extensors. In one experiment, intermittent static arm pulling (triceps) (10 s contraction and 5 s rest, average work load 14% and 10% MVC) was performed for 7 h. The endurance time for the sustained contractions was around one hour for 10% MVC, and it was shown--all in all--that the concept of "indefinite" endurance times at contractions below 15-20% MVC cannot be maintained. After 5% MVC sustained contractions for one hour a 12% reduction in MVC was seen, and significant increases in EMG amplitude and decreases in the mean spectral frequency of the EMG-power spectrum were found. Marked differences were also seen in the EMG changes in the elbow flexors and extensors, and transcutaneous electrical stimulation of the knee extensors showed that low frequency fatigue was present after the contraction. With intermittent contractions similar changes in the EMG parameters were seen after 2-3 h of contractions at 14% MVC. On average, during contractions of 10% MVC no EMG changes were detected. Increased extracellular potassium concentration in the contracting muscles is suggested as a possible explanation of these findings.     

The frequency of alternate muscle activity is associated with the attenuation in muscle fatigue.

Alternate muscle activity between synergist muscles has been demonstrated during low-level sustained contractions [< or =5% of maximal voluntary contraction (MVC) force]. To determine the functional significance of the alternate muscle activity, the association between the frequency of alternate muscle activity during a low-level sustained knee extension and the reduction in knee extension MVC force was studied. Forty-one healthy subjects performed a sustained knee extension at 2.5% MVC force for 1 h. Before and after the sustained knee extension, MVC force was measured. The surface electromyogram was recorded from the rectus femoris (RF), vastus lateralis (VL), and vastus medialis (VM) muscles. The frequency of alternate muscle activity for RF-VL, RF-VM, and VL-VM pairs was determined during the sustained contraction. The frequency of alternate muscle activity ranged from 4 to 11 times/h for RF-VL (7.0 +/- 2.0 times/h) and RF-VM (7.0 +/- 1.9 times/h) pairs, but it was only 0 to 2 times/h for the VL-VM pair (0.5 +/- 0.7 times/h). MVC force after the sustained contraction decreased by 14% (P < 0.01) from 573.6 +/- 145.2 N to 483.3 +/- 130.5 N. The amount of reduction in MVC force was negatively correlated with the frequency of alternate muscle activity for the RF-VL and RF-VM pairs (P < 0.001 and r = 0.65 for both) but not for the VL-VM pair. The results demonstrate that subjects with more frequent alternate muscle activity experience less muscle fatigue. We conclude that the alternate muscle activity between synergist muscles attenuates muscle fatigue.     

Evidence of Significant Central Fatigue in Patients with Cancer-Related Fatigue during Repetitive Elbow Flexions till Perceived Exhaustion

Objective

To investigate whether fatigue induced by an intermittent motor task in patients with cancer-related fatigue (CRF) is more central or peripheral.

Methods

Ten patients with CRF who were off chemo and radiation therapies and 14 age-matched healthy controls were enrolled. Participants completed a Brief Fatigue Inventory (BFI) and performed a fatigue task consisting of intermittent elbow-flexion contractions at submaximal (40% maximal voluntary contraction) intensity till self-perceived exhaustion. Twitch force was elicited by an electrical stimulation applied to the biceps brachii muscle. The relative degree of peripheral (muscle) vs. central contribution to fatigue induced by the intermittent motor task (IMT) was assessed using twitch force ratio (TF_ratio) defined as post IMT twitch force to pre IMT twitch force. The total number of trials (intermittent contractions) and total duration of all trials performed by each subject were also quantified.

Results

BFI scores were higher (p<0.001) in CRF than controls, indicating greater feeling of fatigue in CRF patients than controls. A significantly smaller number of trials and shorter total duration of the trials (p<0.05) were observed in CRF than control participants. The TF_ratio (0.81±0.05) in CRF was higher (p<0.05) compared with that of controls (0.62±0.05), suggesting CRF patients experienced a significantly lower degree of muscle (peripheral) fatigue at the time of perceived exhaustion.

Conclusion

Consistent with prior findings for fatigue under submaximal sustained contraction, our results indicate that motor fatigue in CRF is more of central than peripheral origin during IMT. Significant central fatigue in CRF patients limits their ability to prolong motor performance.     

Effect of low frequency fatigue on human muscle strength and fatigability during subsequent stimulated activity

Fatiguing contractions of the adductor pollicis muscle were produced by intermittent supramaximal stimulation of the ulnar nerve in a set frequency pattern, in six normal subjects. At the end of an initial fatiguing contraction series, low frequency fatigue (LFF) had been induced and persisted at 15 min of recovery. Stimulated fatiguing activity was then repeated in an identical fashion to the initial series. At high frequencies, declines in force were similar for both series. At low frequencies, declines in force were greater during the second series despite similar changes in compound muscle action potential amplitude. This confirmation that LFF persists during subsequent stimulated activity, and reduces low but not high frequency fatigue resistance, suggests that the impaired endurance of fatigued muscle during voluntary activity primarily results from peripheral changes at low frequency. These findings also have implications for therapeutic electrical stimulation of muscle.     

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.     

Rate of fatigue during repeated submaximal contractions of human quadriceps muscle.

Our purpose was to determine the effect of eight different combinations of contraction intensity, duration, and rest on the rate of fatigue in vastus lateralis muscle. A single combination consisted of contractions at 30 or 70% maximal voluntary contraction (MVC), held for 3 or 7 s with 3- or 7-s rest intervals. Contractions were repeated until the subject could not hold the force for the requisite duration. At regular intervals during each experiment, a brief MVC, a single twitch, and the response to eight stimulation pulses at 50 Hz were elicited. The rate of fatigue was the rate of decline of MVC calculated from regression analysis. Mean rate of fatigue (n = 8) ranged from 0.3 to 25% MVC/min and was closely related (r = 0.98) to the product of the relative force and the duty cycle. Force from 50 Hz stimulation fell linearly and in parallel with MVC. Twitch force was first potentiated and then fell twice as fast as 50 Hz stimulation and MVC (p less than 0.05). Differentiated twitch contraction and relaxation rates were higher at potentiation and lower at the limit of endurance, compared with control values (p less than 0.05). The maximal electromyogram decreased 25% and the submaximal EMG increased to maximal by the end of the protocol, indicating that the entire motor unit pool had been recruited. The close relation between rate of fatigue and the force x time product probably reflects the off-setting interaction of contraction amplitude, duration, and rest interval. This occurs despite the changes in twitch characteristics and the apparent recruitment of fast fatiguing motor units.     

Muscle blood flow during isometric activity and its relation to muscle fatigue

The effect of isometric exercise on blood flow, blood pressure, intramuscular pressure as well as lactate and potassium efflux from exercising muscle was examined. The contractions performed were continuous or intermittent (5 s on, 5 s off) and varied between 5% and 50% maximal voluntary contraction (MVC). A knee-extensor and a hand-grip protocol were used. Evidence is presented that blood flow through the muscle is sufficient during low-level sustained contractions (less than 10% MVC). Despite this muscle fatigue occurs during prolonged contractions. One mechanism for this fatigue may be the disturbance of the potassium homeostasis. Such changes may also play a role in the development of fatigue during intermittent isometric contractions and even more so in the recovery from such exercise. In addition the role of impaired transport of substances within the muscle, due to long-lasting daily oedema formation, is discussed in relation to fatigue in highly repetitive, monotonous jobs.     

Non-uniform electromyographic activity during fatigue and recovery of the vastus medialis and lateralis muscles

The aim of the study was to investigate EMG signal features during fatigue and recovery at three locations of the vastus medialis and lateralis muscles. Surface EMG signals were detected from 10 healthy male subjects with six 8-electrode arrays located at 10%, 20%, and 30% of the distance from the medial (for vastus medialis) and lateral (vastus lateralis) border of the patella to the anterior superior spine of the pelvic. Subjects performed contractions at 40% and 80% of the maximal force (MVC) until failure to maintain the target force, followed by 20 2-s contractions at the same force levels every minute for 20 min (recovery). Average rectified value, mean power spectral frequency, and muscle fiber conduction velocity were estimated from the EMG signals in 10 epochs from the beginning of the contraction to task failure (time to task failure, mean ± SD, 70.7 ± 25.8 s for 40% MVC; 27.4 ± 16.8 s for 80% MVC) and from the 20 2 s time intervals during recovery. During the fatiguing contraction, the trend over time of EMG average rectified value depended on location for both muscles (P < 0.05). After 20-min recovery, mean frequency and conduction velocity of both muscles were larger than in the beginning of the fatigue task (P < 0.05) (supernormal values). Moreover, the trend over time of mean frequency during recovery was affected by location and conduction velocity values depended on location for both muscles (P < 0.05). The results indicate spatial dependency of EMG variables during fatigue and recovery and thus the necessity of EMG spatial sampling for global muscle assessment.     

Modification of a three-compartment muscle fatigue model to predict peak torque decline during intermittent tasks

This study aimed to test whether adding a rest recovery parameter, r, to the analytical three-compartment controller (3CC) fatigue model (Xia and Frey Law, 2008) will improve fatigue estimates during intermittent contractions. The 3CC muscle fatigue model uses differential equations to predict the flow of muscle between three muscle states: Resting (M_R), Active (M_A), and Fatigued (M_F). This model uses a feedback controller to match the active state to target loads and two joint-specific parameters: F, fatigue rate controlling flow from active to fatigued compartments) and R, the recovery rate controlling flow from the fatigued to the resting compartments. This model does well to predict intensity-endurance time curves for sustained isometric tasks. However, previous studies find when rest intervals are present that the model over predicts fatigue. Intermittent rest periods would allow for the occurrence of subsequent reactive vasodilation and post-contraction hyperemia. We hypothesize a modified 3CC-r fatigue model will improve predictions of force decay during intermittent contractions with the addition of a rest recovery parameter, r, to augment recovery during rest intervals, representing muscle re-perfusion. A meta-analysis compiling intermittent fatigue data from 63 publications reporting decline in peak torque (% torque decline) were used for comparison. The original model over-predicted fatigue development from 19 to 29% torque decline; the addition of a rest multiplier significantly improved fatigue estimates to 6–10% torque decline. We conclude the addition of a rest multiplier to the three-compartment controller fatigue model provides a physiologically consistent modification for tasks involving rest intervals, resulting in improved estimates of muscle fatigue.     

Simultaneous potentiation and fatigue in quadriceps after a 60-second maximal voluntary isometric contraction

Potential mechanisms of fatigue (metabolic factors) and potentiation (phosphate incorporation by myosin phosphorylatable light chains) were investigated during recovery from a 60-s maximal voluntary isometric contraction (MVC) in the quadriceps muscle of 12 subjects. On separate days before and for 2 h after the 60-s MVC, either a 1-s MVC or electrically stimulated contractions were used as indexes to test muscle performance. Torque at the end of the 60-s MVC was 57% of the initial level, whereas torques from a 1-s MVC and 50-Hz stimulation were most depressed in the immediate recovery period. At this time, muscle biopsy analyses revealed significant decreases in ATP and phosphocreatine and a 19-fold increase in muscle lactate. Conversely, isometric twitch torque and torque from a 10-Hz stimulus were the least depressed of six contractile indexes and demonstrated potentiation of 25 and 34%, respectively, by 4 min of recovery (P less than 0.05). At this time, muscle lactate concentration was still 16 times greater than at rest. An increased phosphate content of the myosin phosphorylatable light chains (P less than 0.05) was also evident both immediately and 4 min after the 60-s MVC. We conclude that the 60-s MVC produced marked force decreases likely due to metabolic displacement, while the limited decline in the twitch and 10-Hz torques and their significant potentiation suggested that myosin phosphorylation may provide a mechanism to enhance contractile force under conditions of submaximal activation during fatigue.     

Evidence of long term muscle fatigue following prolonged intermittent contractions based on mechano- and electromyograms.

The focus of the present study is the long term element of muscle fatigue provoked by prolonged intermittent contractions at submaximal force levels and analysed by force, surface electromyography (EMG) and mechanomyogram (MMG). It was hypothesized that fatigue related changes in mechanical performance of the biceps muscle are more strongly reflected in low than in high force test contractions, more prominent in the MMG than in the EMG signal and less pronounced following contractions controlled by visual compared to proprioceptive feedback. Further, it was investigated if fatigue induced by 30 min intermittent contractions at 30% as well as 10% of maximal voluntary contraction (MVC) lasted more than 30 min recovery. In six male subjects the EMG and MMG were recorded from the biceps brachii muscle during three sessions with fatiguing exercise at 10% with visual feedback and at 30% MVC with visual and proprioceptive feedback. EMG, MMG, and force were evaluated during isometric test contractions at 5% and 80% MVC before prolonged contraction and after 10 and 30 min of recovery. MVC decreased significantly after the fatiguing exercise in all three sessions and was still decreased even after 30 min of recovery. In the time domain significant increases after the fatiguing exercise were found only in the 5% MVC tests and most pronounced for the MMG. No consistent changes were found for neither EMG nor MMG in the frequency domain and feedback mode did not modify the results. It is concluded that long term fatigue after intermittent contractions at low force levels can be detected even after 30 min of recovery in a low force test contraction. Since the response was most pronounced in the MMG this may be a valuable variable for detection of impairments in the excitation-contraction coupling.     

Adverse effects of myasthenia gravis on rat phrenic diaphragm contractile performance.

Myasthenia gravis has variable effects on the respiratory system, ranging from no abnormalities to life-threatening respiratory failure. Studies characterized diaphragm muscle contractile performance in rat autoimmune myasthenia gravis. Rats received monoclonal antibody that recognizes acetylcholine receptor determinants (or inactive antibody); 3 days later, phrenic nerve and diaphragm were studied in vitro. Myasthenic rats segregated into two groups, those with normal vs. impaired limb muscle function when tested in intact animals ("mild" and "severe" myasthenic). Baseline diaphragm twitch force was reduced for both severe (P < 0.01) and mild (P < 0.05) myasthenic compared with control animals (twitch force: normal 1,352 +/- 140, mild myasthenic 672 +/- 99, severe myasthenic 687 +/- 74 g/cm2). However, only severe myasthenic diaphragm had impaired diaphragm endurance, based on significantly (P < 0.05) accelerated rate of peak force decline during the initial period of stimulation (0.02 + 0.02, 0.03 +/- 0.01, and 0.09 +/- 0.01%/pulse for normal, mild myasthenic, and severe myasthenic, respectively, during continuous stimulation) and intratrain fatigue (up to 30.5 +/- 7.4% intratrain force drop in severe myasthenic vs. none in normal and mild myasthenic, P < 0.01). Furthermore, compared with continuous stimulation, intermittent stimulation had a protective effect on force of severe myasthenic diaphragm (force after 2,000 pulses was 31.4 +/- 2.0% of initial during intermittent stimulation vs. 13.0 +/- 2.1% of initial during continuous stimulation, P < 0.01) but not on normal diaphragm. These data indicate that baseline force and fatigue may be affected to different extents by varying severity of myasthenia gravis and furthermore provide a mechanism by which alterations in breathing pattern may worsen respiratory muscle function in neuromuscular diseases.     

Effect of lactate infusion on M-wave characteristics and force in the rat plantaris muscle during repeated stimulation in situ.

It is unclear whether accumulation of lactate in skeletal muscle during exercise contributes to muscle fatigue. The purpose of the present study was to examine the effect of lactate infusion on muscle fatigue during prolonged indirect stimulation in situ. For this purpose, the plantaris muscle was electrically stimulated (50 Hz, for 200 ms, every 2.7 s, 5 V) in situ through the sciatic nerve to perform concentric contractions for 60 min while either saline or lactate was infused intravenously (8 rats/group). Lactate infusion (lactate concentration approximately 12 mM) attenuated the reduction in submaximal dynamic force (-49 vs. -68% in rats infused with saline; P < 0.05). Maximum dynamic and isometric forces at the end of the period of stimulation were also higher (P < 0.05) in rats infused with lactate (3.8 +/- 0.3 and 4.4 +/- 0.3 N) compared with saline (3.1 +/- 0.2 and 3.6 +/- 0.2 N). The beneficial effect of lactate infusion on muscle force during prolonged stimulation was associated with a better maintenance of M-wave characteristics compared with control. In contrast, lactate infusion was not associated with any reduction in muscle glycogen utilization or with any reduction of fatigue at the neuromuscular junction (as assessed through maximal direct muscle stimulation: 200 Hz, 200 ms, 150 V).     

A comparison of central aspects of fatigue in submaximal and maximal voluntary contractions.

Magnetic and electrical stimulation at different levels of the neuraxis show that supraspinal and spinal factors limit force production in maximal isometric efforts ("central fatigue"). In sustained maximal contractions, motoneurons become less responsive to synaptic input and descending drive becomes suboptimal. Exercise-induced activity in group III and IV muscle afferents acts supraspinally to limit motor cortical output but does not alter motor cortical responses to transcranial magnetic stimulation. "Central" and "peripheral" fatigue develop more slowly during submaximal exercise. In sustained submaximal contractions, central fatigue occurs in brief maximal efforts even with a weak ongoing contraction (<15% maximum). The presence of central fatigue when much of the available motor pathway is not engaged suggests that afferent inputs contribute to reduce voluntary activation. Small-diameter muscle afferents are likely to be activated by local activity even in sustained weak contractions. During such contractions, it is difficult to measure central fatigue, which is best demonstrated in maximal efforts. To show central fatigue in submaximal contractions, changes in motor unit firing and force output need to be characterized simultaneously. Increasing central drive recruits new motor units, but the way this occurs is likely to depend on properties of the motoneurons and the inputs they receive in the task. It is unclear whether such factors impair force production for a set level of descending drive and thus represent central fatigue. The best indication that central fatigue is important during submaximal tasks is the disproportionate increase in subjects' perceived effort when maintaining a low target force.