Low-frequency Fatigue Research Articles

An Investigation into the Mechanism of Action of Almitrine on Isolated Rat Diaphragm Muscle Fatigue

Background: Previous studies have shown that almitrine bismesylate, a respiratory stimulant which acts on the mitochondrial electron transport chain, enhances recovery of rat diaphragm muscle from fatigue. Objectives: Our aim is to investigate if the enhanced recovery is due to an anti-oxidant property of almitrine, since the electron transport chain is a major site of intracellular free radical production. Methods: A low-frequency fatigue protocol was used (30 Hz; 250 ms; delivered once every 2 s for 5 min), and the effects of almitrine before and after fatigue onset were compared to those of the anti-oxidant compound N-acetylcysteine (NAC). Results: Almitrine (6 and 10 µg/ml) given before fatigue gave better recovery rates than postfatigue application. In contrast, NAC (100 µM) application before fatigue onset was not as effective as NAC given immediately after the cessation of the fatigue protocol. However, almitrine (6 µg/ml) completely reversed the reduction in baseline twitch tension brought about by a free-radical-producing mixture of FeCl₃ + ADP (1 mM + 2.5 mM, respectively). Conclusion: The results of this study confirm that almitrine enhances recovery from fatigue and, in contrast to NAC prefatigue application, is more effective. Also, almitrine was shown to have an anti-oxidant effect, but it does not act like a typical anti-oxidant.

The effects of training on fatigue and twitch potentiationin human skeletal muscle

Twitch postactivation potentiation (PAP) in skeletal muscle is a well recognized and accepted phenomenon. However, the mechanisms responsible for potentiation are not understood in detail, and the possible role of potentiation in normal human movement has remained unclear. It is known that potentiation is increased in fatigued compared to rested muscle. We hypothesized that if fatigue and potentiation were directly linked, a training program should increase PAP and reduce fatigue in parallel. Six subjects underwent a muscle stimulation protocol in which twitch contractions were elicited in the knee extensor muscles before and after a 10-s maximal voluntary contraction (MVC) to detect the degree of PAP. This was done before and after subjects underwent a protocol designated to induce low-frequency fatigue (knee extensions at 180 · s −1, organized in three repetitions of 60-s bouts, separated by 3 min). This whole protocol was done before and after a 4-week period of isokinetic training, consisting of two sets (5-min interval) of 10 single MVCs (10-s intervals), at 90° · s −1. In non-fatigued muscles, PAP was greater after training (51.2 ± 4.8%) than before training (44.4 ± 2.4%). In fatigued muscles, PAP was similar before and after training (59.9 ± 2.8% and 60.2 ± 2.6%, respectively). Low-frequency fatigue was observed before training, as twitch force decreased to 66.8 ± 3.1% of the pre-fatigue value. After the training period, low-frequency fatigue was attenuated, as force decreased only to 81.8 ± 2.6% of the pre-fatigue value. Therefore, it appears that training decreases low-frequency fatigue and increases PAP. Therefore, the hypothesis that potentiation is partially linked to fatigue in voluntary contracting human skeletal muscles was confirmed.

A decrease in soleus muscle force generation in rats after downhill running.

The purpose of the present study was to investigate the immediate and 48-hr post-exercise effects of eccentric contraction-biased exercise on the contractile properties of the soleus muscle in situ. Adult male Wistar rats were categorised into sedentary control rats (n = 10), rats studied immediately (n = 10), and rats studied 48 hours after the exercise (n = 10). The exercise protocol consisted of a 90-min intermittent downhill running (-16 degrees, 16 m/min) on a motor-driven treadmill. The contractile properties of the soleus muscle were recorded following i.p. chloral hydrate anaesthesia. Isometric twitch force (Pt), time-to-peak tension (TPT), half-relaxation time (1/2 RT), and tetanic force at stimulation frequencies of 40, 80, and 100 Hz were recorded. A low-frequency muscle fatigue protocol (stimulation at 4 Hz for 5 min) was applied to test for fatigability. The main findings indicated that Pt generation dropped both immediately and 48 hr after the exercise, while tetanic force was partially restored after 48 hr. Exercise-induced E-C coupling failure and contractile machinery disorganisation due to muscle injury are put forward as the main force reduction causes.

AN ALTERNATIVE TECHNIQUE TO EXAMINE THE FORCE-FREQUENCY RELATIONSHIP IN HUMAN SKELETAL MUSCLE

We devised a method to assess the force-frequency relationship in human skeletal muscle that can be administered in 3s, is well tolerated by subjects (n = 10) and is sensitive to low frequency fatigue. The method consists of a single 3s train of shocks delivered directly to the femoral nerve. The frequency of the train increases rapidly and exponentially over 3s from 5 to 100 Hz. The force response of the knee extensors to this increasing frequency train (IFT) was compared to that of a standard series of constant frequency trains (CFT), where is trains of shocks are delivered at single frequencies, ranging from 5 to 100Hz. Both force-frequency curves were examined in two conditions known to alter contractile properties. First, we changed the knee angle to alter muscle length and, in separate experiments, induced muscular fatigue by having subjects perform repeated isometric contractions until the target force was unattainable. Because the frequency required to produce 50% of peak force (50%) was not different between stimulation protocols, we conclude that there was no leftward shift in the curve when the knee extensors were shortened. In contrast, we observed a rightward shift in the curve after fatigue with both protocols; the f50% increased by 48% (p < 0.01) with CFT and 58% (p < 0.001) with an IFT. Low frequency fatigue, as assessed by the ratio of forces produced at 20 and 50Hz stimulation (20:50 ratio), was marked during recovery. The CFT produced an irregular pattern of low frequency fatigue recovery, but the IFT 20:50 ratio, which was most depressed immediately following fatigue, increased smoothly and by 300s was not different from control. These experiments show that the IFT stimulation protocol reveals the same alterations in muscle performance as the traditional CFT. Moreover, the IFT requires only 3s to administer and was judged more tolerable by 70% of our subjects. This suggests that the technique may be an effective alternative for determining the force-frequency relationship in human muscle for clinical and experimental purposes. Supported by NSERC

Sarcoplasmic reticulum function and muscle contractile character following fatiguing exercise in humans.

1. This study examined the alterations in calcium release, calcium uptake and calcium ATPase activity of skeletal muscle sarcoplasmic reticulum in response to a bout of intense dynamic knee extensor exercise, and the relationship between these changes and alterations in muscle contractile characteristics in the human quadriceps. 2. In biopsy samples taken from the vastus lateralis, sarcoplasmic reticulum calcium release and calcium uptake were significantly depressed (P < 0.01 and 0.05, respectively) immediately following the exercise with no alteration in the sarcoplasmic reticulum Ca2+-ATPase activity. 3. A 33 % reduction in the maximum voluntary isometric torque was found following the exercise, with reduced torques from electrically evoked isometric contractions at low frequencies of stimulation (10 and 20 Hz) but not at higher frequencies (50 and 100 Hz). 4. The depressed calcium release was correlated (P < 0.05) with a decreased ratio of torques generated at 20:50 Hz, indicating an involvement in low frequency fatigue; however, no correlations between the muscle relaxation times or rates of change of torque and calcium uptake were observed.

The effects of dietary creatine supplements on the contractile properties of rat soleus and extensor digitorum longus muscles.

Daily creatine supplements (0.258 g kg(-1) ) were administered to adult male Wistar rats (n = 7) in the drinking water. Age matched rats (n = 6) acted as controls. After 5-6 days, contractile properties were examined in soleus and extensor digitorum longus (EDL) muscle strips in vitro at 30 degrees C. In soleus muscles, creatine supplements decreased the half-relaxation time of the isometric twitch from 53.6 +/- 4.3 ms in control muscles to 48.4 +/- 5.5 ms but had no effect on twitch or tetanic tension or on twitch contraction time. In EDL muscles twitch tension, tetanic tension, twitch contraction and half-relaxation times were all unaffected by creatine supplements. Creatine supplements increased the fatigue resistance of the soleus muscles but had no effect on that of the EDL muscles. After a 5 min low-frequency fatigue test, tension (expressed as a percentage of initial tension) was 56 +/- 3 % in control soleus muscles, whereas that in the creatine-supplemented muscles was 78 +/- 6 % (P < 0.01). In the EDL muscles, the corresponding values were 40 +/- 2 % and 41 +/- 9 %, respectively. The force potentiation which occurred in the EDL muscles during the initial 20-30 s of the fatigue test was 170 +/- 10 % of initial tension in the control muscles 24 s after the initial stimulus train but was reduced (P < 0.01) to 130 +/- 20 % in the creatine-supplemented muscles. In conclusion, soleus muscle endurance was increased by creatine supplements. EDL endurance was unaffected but force potentiation during repetitive stimulation was decreased. Experimental Physiology (2001) 86.2, 185-190.

Functional significance of Ca 2+ in long-lasting fatigue of skeletal muscle

Repeated activation of skeletal muscle causes fatigue, which involves a reduced ability to produce force and slowed contraction regarding both the speed of shortening and relaxation. One important component in skeletal muscle fatigue is a reduced sarcoplasmic reticulum (SR) Ca2+ release. In the present review we will describe different types of fatigue-induced inhibition of SR Ca2+ release. We will focus on a type of long-lasting failure of SR Ca2+ release which is called low-frequency fatigue, because this type of fatigue may be involved in the muscle dysfunction and chronic pain experienced by computer workers. Paradoxically it appears that the Ca2+ released from the SR, which is required for contraction, may actually be responsible for the failure of SR Ca2+ release during low-frequency fatigue. We will also discuss the relationship between gross morphological changes in muscle fibres and long-lasting failure of SR Ca2+ release. Finally, a model linking muscle cell dysfunction and muscle pain is proposed.

Fatigue after submaximal intensive stretch-shortening cycle exercise.

The aim of the present study was to examine some sites of neuromuscular fatigue after submaximal intensity stretch-shortening cycle exercise. Twelve male subjects performed consecutive sledge jumps at 60% of maximal height until exhaustion (mean duration 443.7 s +/- 304.9 s, mean +/- SD). During the exercise, the blood lactate increased from 1.8 +/- 0.6 mmol x L(-1) (before exercise) to 6.1 +/- 1.7 mmol x L(-1) (P < 0.001) and serum creatine-kinase from 248 +/- 142 IU x L(-1) to 584 +/- 344 IU x L(-1) (P < 0.001). Electrical stimulation of the vastus lateralis and quadriceps femoris muscles to induce isometric knee extension resulted in decreased peak torque during single and double twitch after workout (from 22.1 +/- 6.3 Nm to 17.3 +/- 8.0 Nm, P < 0.05, and from 96.6 +/- 15.4 Nm to 76.2 x 19.8 Nm, P < 0.001, respectively), whereas there were no significant changes in contraction and relaxation times. Torque during 20-Hz stimulation decreased significantly (from 23.7 +/- 9.2 to 16.1 +/- 7.8 Nm, P < 0.01) but not at 100-Hz stimulation. During maximal voluntary isometric knee extensions, the rate of torque development was significantly (P < 0.01) more impaired than maximal torque (from 1619 +/- 390 Nm x s(-1) to 1,004 +/- 360 Nm x s(-1) and from 185 +/- 30.7 Nm to 151 +/- 32.3 Nm, respectively, both P < 0.001). At the same time, the muscle activation level increased by 15.8 +/- 24.1% (P < 0.05). The mean EMG amplitude of vastus lateralis during MVC increased by 34.9 +/- 39.2% (P > 0.05). It was concluded that after submaximal stretch-shortening exercise, the low-frequency fatigue occurred, very likely caused by lower Ca2+ release per single action potential.

Changes in height of jump, maximal voluntary contraction force and low‐frequency fatigue after 100 intermittent or continuous jumps with maximal intensity

Healthy untrained males (age 25.4 +/- 1.7 years, n=12) gave their informed consent to take part in all experiments within the study. After 100 intermittent (every 20 s) drop jumps from the height of 0. 4 m, jumps with counter-movement to 90 degrees angle in the knee and immediate maximal rebound (eccentric-concentric exercise; E-C) and 100 continuous jumps (five bouts of 20 jumps with counter-movement to 90 degrees angle in the knee with 10 s between bouts) (maximal exercise; M) with maximal intensity, the height of vertical jump decreased in a similar way, and this decrease did not depend on the performance mode of jumps. After E-C and M jumping exercises, there was a significant (P < 0.001) decrease in maximal voluntary contraction force, as well in the force generated by electrical stimulation at all stimulation frequencies, and these values were not restored to the initial level even after 24 h. After the E-C exercise, however, the muscle contraction force generated at different stimulation frequencies and, especially, at low-stimulation frequencies (1-20 Hz) decreased to a significantly (P < 0.05-0.001) greater extent than after M exercise. Twenty minutes after the end of M exercise, there was still a greater increase in low-frequency fatigue (LFF) and it was no different from the LFF registered 20 min after the end of E-C exercise. Twenty-four hours after the M exercise, however, LFF was smaller than its respective value after E-C exercise. There was no significant relationship between the values of LFF after E-C and M exercises. This may indicate that there are differences in the origin of the LFF after the E-C and M exercises.

Fatigue effects in the cat gastrocnemius during frequency-modulated efferent stimulation

Effects of low- and high-frequency fatigue were studied on muscle dynamics in isometric conditions of the cat gastrocnemius. Fatiguing sessions consisted of 25–28 repetitions of the standard tests that included an 18-s interval of continuous frequency-modulated stimulation preceded and followed by single stimuli evoking twitch contractions. The rate of the continuous part was changed in accordance with a symmetrical double-trapezoidal signal, including three successive phases of constant rate at 10, 40 and 10 s −1; between these phases, each lasting for 4 s, the rate changed linearly within a 2-s interval. The following modes of muscle activation were applied: (i) stimulation of single filaments constituting approximately one-fifth to one-seventh of the total cross-section of the L 7 and S 1 ventral roots; (ii) the distributed stimulation of five similar filaments; and (iii) direct stimulation of muscle through bipolar wire electrodes. A relative drop in tension, the fatigue index, expressed as the ratio at the end of a fatigue session over its value at the beginning of the test, was used to quantify fatigue effects. The fatigue indices during low-rate stimulation were 0.56±0.03 (mean±S.D.) at the first phase and 0.64±0.02 at the third phase, while during high-rate stimulation this parameter was only 0.32±0.02. The high-rate stimulation noticeably increased the mean tension during low-rate stimulation; the ratio between the reactions at the third and the first phases could be as much as two to three times greater than that at the beginning of the fatigue session. It was demonstrated that the potentiation was connected with after-effects of the rate–tension hysteresis. The hysteresis decreased with fatigue, the fatigue index for the rate–tension loop areas ranging from 0.39 to 0.52 (0.45±0.05, mean±S.D.). The fatigue processes developed more quickly and intensively in the previously fatigued muscles: the obtained fatigue indices were 0.73±0.05 and 0.70±0.10 at the first and third phases, and 0.62±0.06 (mean±S.D.) at the second phase of stimulation, respectively. In the cases of distributed and direct stimulation applied to muscles in a fresh state, fatigue dynamics did not differ significantly from those observed during single-filament stimulation. In experiments with distributed stimulation applied to previously fatigued muscles, a powerful depression of the high-rate components was registered in several cases, which seemed to be connected with depressive effects at the level of nerve–muscle synaptic transmission. The effects of low- and high-frequency fatigue were studied in isometric conditions of muscle contraction. In addition to the well-known differentiation between low- and high-frequency fatigue effects, the complex pattern of efferent stimulation used allowed us to identify additional fatigue-related changes in the rate–tension hysteresis. This hysteresis seems to be one of the possible mechanisms directed to compensate for low-frequency fatigue in the muscle contraction.

Attenuation of rat diaphragm low-frequency fatigue by vanadate in vitro

Sodium vanadate inhibits protein tyrosine phosphatases, including in skeletal muscle. Vanadate increases contractile force of airway, vascular and gastrointestinal smooth muscle. The present study tested the hypothesis that vanadate augments skeletal muscle contractility. Rat diaphragm muscle strips ( n=26 from 12 animals) were studied in vitro at 37°C. Muscles contracted isometrically while stimulated supramaximally with one of two protocols: 30 min of continuous 0.1 Hz stimulation, or 5 min of intermittent 20 Hz stimulation (duty cycle 0.33). Vanadate (500 μM)-treated muscle strips were compared with untreated muscle. Vanadate did not affect force or isometric twitch kinetics of otherwise quiescent muscle. During prolonged 0.1 Hz stimulation, force of control muscles declined by 17±4% over 30 min, whereas muscles incubated with vanadate maintained force virtually unchanged. Force over time was significantly greater with than without vanadate ( P=0.03), with values being significantly different during the last 10 min of the 30 min stimulation period. In the absence of vanadate force declined at a rate of ∼0.6% per min, whereas with vanadate the rate of force decline was less than 0.1% per min ( P<0.02). During intermittent 20 Hz stimulation, the degree of force decline was not affected by vanadate at any time over a course of 5 min. Isometric contractile kinetics were not altered by vanadate during either 0.1 or 20 Hz stimulation. These data suggest that vanadate ameliorates low- but not higher-frequency fatigue in diaphragm, suggesting a role for protein tyrosine phosphorylation in the regulation of muscle fatigue resistance.

High intracellular [Ca2+] alters sarcoplasmic reticulum function in skinned skeletal muscle fibres of the rat.

1. The effect on sarcoplasmic reticulum (SR) function of exposure to high intracellular [Ca2+] was studied in mechanically skinned fibres from the extensor digitorum longus muscle of the rat, using caffeine to assay the SR Ca2+ content. 2. A 15 s exposure to 50 microM Ca2+ irreversibly reduced the ability of the SR to load/retain Ca2+ and completely abolished depolarization-induced Ca2+ release, whereas a 90 s exposure to 10 microM Ca2+ had no detectable effect on either function. The reduction in net SR Ca2+ uptake: (a) was near-maximal with treatment at 50 microM Ca2+, (b) was unrelated to voltage-sensor function, and (c) persisted unchanged for > 20 min. The reduction was primarily due to a threefold increase in leakage of Ca2+ out of the SR. This increased leakage was not substantially blocked by the presence of 10 mM Mg2+ or 2 microM Ruthenium Red. 3. The adverse effect on SR function of exposure to high [Ca2+] could also be observed by the reduction in the ability of the SR to maintain a low [Ca2+] within the skinned fibre in the face of elevated [Ca2+] in the bathing solution. When bathed in a solution with approximately 1.5 microM Ca2+ (0.75 mM CaEGTA-EGTA), skinned fibres produced only low force responses for many minutes, but after high [Ca2+] treatment (15 s exposure to 50 microM Ca2+) they showed large, steady or oscillatory force responses. 4. These findings indicate that, in addition to uncoupling the Ca2+ release channels from the voltage sensors, exposure of skinned fibres to high [Ca2+] causes a persistent increase in resting Ca2+ efflux from the SR. Such efflux in an intact fibre would alter the distribution of Ca2+ between the SR, the cytoplasm and the extracellular solution. These results may be relevant to the basis of low-frequency fatigue and possibly other conditions in muscle.

Variable‐frequency trains offset low‐frequency fatigue in human skeletal muscle

Variable-frequency trains that exploit the catchlike property of skeletal muscle can augment force production in fatigued skeletal muscle. The present study is the first to examine the effect of such trains during recovery. The quadriceps femoris muscles of 12 healthy individuals were fatigued using six-pulse, 14.3-Hz trains delivered at a rate of 1/s for 3 min. The force-generating ability of the muscle was tested with several constant-frequency trains (8.3–100 Hz) and a variable-frequency train before and after fatigue and at 2, ∼13, and ∼38 min of recovery. The variable-frequency train produced significant augmentation of force versus the best constant-frequency train (12.5 Hz) in acute fatigue and during recovery. The fatiguing protocol also induced low-frequency fatigue (LFF); the time courses of the degree of LFF and the amount of variable-frequency train force augmentation were inversely related (r = 0.629; F = 38.024; P ≤ 0.001), suggesting a common mechanism between the two phenomena. These results suggest that clinical use of variable-frequency trains (e.g., functional electrical stimulation) will enable the muscle to generate more force during acute fatigue and offset, at least partially, the long-term effects of LFF. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 874–882, 1999

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.

Assessment of abdominal muscle contractility, strength, and fatigue.

We evaluated abdominal muscle contractility and fatigue by measuring twitch gastric pressure (Pgat) after percutaneous supramaximal electrical stimulation of the abdominal wall before and after sit-ups to task failure. Mouth pressures during maximal voluntary expulsive maneuvers (PEmax) at TLC and FRC with superimposed twitches, and maximum voluntary ventilation (MVV) were also assessed. Mean fresh Pgat was 36.1 +/- 3.0 cm H2O with a coefficient of variation that ranged between 3.0 to 4.8%. Pgat decreased by 25% (p < 0.001) and 37% (p < 0.001) at 1 and 30 min after sit-ups. During maximal voluntary contraction twitch occlusion never occurred. PEmax at TLC and FRC decreased by 15% (p < 0.001) and 11% (p < 0.017) at 1 min, and 8% (p < 0.036) and 9% (p < 0.030) at 30 min after sit-ups, respectively. Despite the abdominal muscle fatigue, MVV values at 1 and 30 min after sit-ups were not significantly different from the value obtained before the sit-ups. We conclude that (1) Pgat is a useful objective indicator of abdominal muscle contractility and fatigue; (2) during maximal voluntary expulsive maneuvers the abdominal muscles are never fully activated; (3) sit-ups lead to substantial low-frequency fatigue but little high-frequency fatigue of the abdominal muscles, which has little effect on maximal breathing capacity.

M-wave changes after high- and low-frequency electrically induced fatigue in different muscles.

The mechanisms of fatigue-induced changes in evoked compound muscle action potential (M-waves) are not well documented. In rats, isolated fast-glycolytic (tibialis anterior, or TA) and slow-oxidative muscles (soleus, or SOL) were stimulated repetitively at a low (10-Hz) or high (80-Hz) rate. Decreased amplitude and prolonged duration of M-waves were only significant after high-frequency fatigue in TA and SOL muscles; that is, in the conditions in which an influx of calcium was measured. On the other hand, maximal force failure and maximal lactic acid increase in the bath medium occurred in TA muscle after high- and low-frequency fatigue trials. Postfatigue increase in potassium concentration occurred in all circumstances. Thus, M-wave alterations depend mainly on the stimulation paradigm and not on the muscle type, and cannot be used as a marker of changes in intracellular potassium or lactate ions. This amplifies understanding of the significance of M-wave changes in human exercise protocols.

Vacuole formation in fatigued single muscle fibres from frog and mouse.

Force recovery from fatigue in skeletal muscle may be very slow. Gross morphological changes with vacuole formation in muscle cells during the recovery period have been reported and it has been suggested that this is the cause of the delayed force recovery. To study this we have used confocal microscopy of isolated, living muscle fibres from Xenopus and mouse to visualise transverse tubules (t-tubules) and mitochondria and to relate possible fatigue-induced morphological changes in these to force depression. T-tubules were stained with either RH414 or sulforhodamine B and mitochondrial staining was with either rhodamine 123 or DiOC6(3). Fatigue was produced by repeated, short tetanic contractions. Xenopus fibres displayed a marked vacuolation which started to develop about 2 min after fatiguing stimulation, reached a maximum after about 30 min, and then receded in about 2 h. Vacuoles were never seen during fatiguing stimulation. The vacuoles developed from localised swellings of t-tubules and were mostly located in rows of mitochondria. Mitochondrial staining, however, showed no obvious alterations of mitochondrial structure. There was no clear correlation between the presence of vacuoles and force depression; for instance, some fibres showed massive vacuole formation at a time when force had recovered almost fully. Vacuole formation was not reduced by cyclosporin A, which inhibits opening of the non-specific pore in the mitochondrial inner membrane. In mouse fibres there was no vacuole formation or obvious changes in mitochondrial structure after fatigue, but still these fibres showed a marked force depression at low stimulation frequencies ('low-frequency fatigue'). Vacuoles could be produced in mouse fibres by glycerol treatment and these vacuoles were not associated with any force decline. In conclusion, vacuoles originating from the t-tubular system develop after fatigue in Xenopus but not in mouse fibres. These vacuoles are not the cause of the delayed force recovery after fatigue.

Heat shock does not attenuate low-frequency fatigue

Whole-body hyperthermia or heat shock confers protection to myocardial contractility against reperfusion-induced injury. The purpose of this study was to determine whether heat shock could provide similar protection to skeletal muscle contractility against low-frequency fatigue. Male Sprague-Dawley rats (6 rats/group) were heat shocked at 41.5°C for 15 min either 24 h or 4 days prior to fatiguing stimulation to compare the contractile responses of the plantaris muscle with those of a nonheated group. Both 24 h and 4 days after heat shock, the 72-kDa heat shock protein (HSP72) was elevated above control levels. There were no differences between the heat-shocked and non-heat-shocked animals in measures of contractility prior to fatiguing contractions or in resistance to fatigue. Heat-shock preconditioning did not lead to improved postfatigue force recovery above control responses and, in fact, delayed the recovery of force. This study does not support the use of heat-shock therapy to improve skeletal muscle contractile performance under fatiguing conditions.Key words: heat shock proteins, rat, skeletal muscle, contractile properties, HSP72.

Heat shock does not attenuate low-frequency fatigue.

Whole-body hyperthermia or heat shock confers protection to myocardial contractility against reperfusion-induced injury. The purpose of this study was to determine whether heat shock could provide similar protection to skeletal muscle contractility against low-frequency fatigue. Male Sprague-Dawley rats (6 rats/group) were heat shocked at 41.5 degrees C for 15 min either 24 h or 4 days prior to fatiguing stimulation to compare the contractile responses of the plantaris muscle with those of a nonheated group. Both 24 h and 4 days after heat shock, the 72-kDa heat shock protein (HSP72) was elevated above control levels. There were no differences between the heat-shocked and non-heat-shocked animals in measures of contractility prior to fatiguing contractions or in resistance to fatigue. Heat-shock preconditioning did not lead to improved postfatigue force recovery above control responses and, in fact, delayed the recovery of force. This study does not support the use of heat-shock therapy to improve skeletal muscle contractile performance under fatiguing conditions.

Mechanisms of fatigue-induced activation of group IV muscle afferents: the roles played by lactic acid and inflammatory mediators

We already showed that group IV muscle afferents are activated during electrically-induced fatigue. The purpose of this study is to identify the mechanisms of stimulation of these muscle afferents by electrically-induced fatigue at a high (100 Hz; high frequency fatigue, HFF) or a low rate (10 Hz; low frequency fatigue, LFF) of stimulation. In 23 paralyzed and anaesthetized rabbits, group IV afferent activity from the tibialis anterior muscle was recorded before and after 3-min HFF or 5-min LFF runs eliciting the same force failure. Plasma lactic acid concentration (LA) was also measured in leg venous blood. We tested the effects of dichloroacetate (DCA), which reduces lactic acid production, and of acetylsalicylic acid (ASA), a blocker of cyclooxygenase, on fatigue-induced activation of group IV muscle afferents after HFF and LFF trials. Pretreatment by ASA or DCA did not modify HFF-induced activation of muscle afferents. On the other hand, LFF-induced response was markedly depressed by each pharmacological agent (−44% after ASA and −75% after DCA). We verified that DCA markedly lowered LA production after LFF. The present results show that the activation of group IV muscle afferents by LFF or HFF results from different mechanisms and also demonstrate the major role played by lactic acid production and, to a lesser extent, the release of inflammatory mediators in LFF-induced activation of group IV muscle afferents.