Development Of Peripheral Fatigue Research Articles

Estimation of critical torque using intermittent isometric maximal voluntary contractions of the quadriceps in humans

To determine whether the asymptote of the torque-duration relationship (critical torque) could be estimated from the torque measured at the end of a series of maximal voluntary contractions (MVCs) of the quadriceps, eight healthy men performed eight laboratory tests. Following familiarization, subjects performed two tests in which they were required to perform 60 isometric MVCs over a period of 5 min (3 s contraction, 2 s rest), and five tests involving intermittent isometric contractions at approximately 35-60% MVC, each performed to task failure. Critical torque was determined using linear regression of the torque impulse and contraction time during the submaximal tests, and the end-test torque during the MVCs was calculated from the mean of the last six contractions of the test. During the MVCs voluntary torque declined from 263.9 +/- 44.6 to 77.8 +/- 17.8 N x m. The end-test torque was not different from the critical torque (77.9 +/- 15.9 N x m; 95% paired-sample confidence interval, -6.5 to 6.2 N x m). The root mean squared error of the estimation of critical torque from the end-test torque was 7.1 N x m. Twitch interpolation showed that voluntary activation declined from 90.9 +/- 6.5% to 66.9 +/- 13.1% (P < 0.001), and the potentiated doublet response declined from 97.7 +/- 23.0 to 46.9 +/- 6.7 N.m (P < 0.001) during the MVCs, indicating the development of both central and peripheral fatigue. These data indicate that fatigue during 5 min of intermittent isometric MVCs of the quadriceps leads to an end-test torque that closely approximates the critical torque.

Opioid‐mediated muscle afferents inhibit central motor drive and limit peripheral muscle fatigue development in humans

We investigated the role of somatosensory feedback from locomotor muscles on central motor drive (CMD) and the development of peripheral fatigue during high-intensity endurance exercise. In a double-blind, placebo-controlled design, eight cyclists randomly performed three 5 km time trials: control, interspinous ligament injection of saline (5K(Plac), L3-L4) or intrathecal fentanyl (5K(Fent), L3-L4) to impair cortical projection of opioid-mediated muscle afferents. Peripheral quadriceps fatigue was assessed via changes in force output pre- versus postexercise in response to supramaximal magnetic femoral nerve stimulation (DeltaQ(tw)). The CMD during the time trials was estimated via quadriceps electromyogram (iEMG). Fentanyl had no effect on quadriceps strength. Impairment of neural feedback from the locomotor muscles increased iEMG during the first 2.5 km of 5K(Fent) versus 5K(Plac) by 12 +/- 3% (P < 0.05); during the second 2.5 km, iEMG was similar between trials. Power output was also 6 +/- 2% higher during the first and 11 +/- 2% lower during the second 2.5 km of 5K(Fent) versus 5K(Plac) (both P < 0.05). Capillary blood lactate was higher (16.3 +/- 0.5 versus 12.6 +/- 1.0%) and arterial haemoglobin O(2) saturation was lower (89 +/- 1 versus 94 +/- 1%) during 5K(Fent) versus 5K(Plac). Exercise-induced DeltaQ(tw) was greater following 5K(Fent) versus 5K(Plac) (-46 +/- 2 versus -33 +/- 2%, P < 0.001). Our results emphasize the critical role of somatosensory feedback from working muscles on the centrally mediated determination of CMD. Attenuated afferent feedback from exercising locomotor muscles results in an overshoot in CMD and power output normally chosen by the athlete, thereby causing a greater rate of accumulation of muscle metabolites and excessive development of peripheral muscle fatigue.

Reply from Markus Amann and Jerome A. Dempsey

Reply from Markus Amann and Jerome A. Dempsey

Is peripheral locomotor muscle fatigue during endurance exercise a variable carefully regulated by a negative feedback system?

Is peripheral locomotor muscle fatigue during endurance exercise a variable carefully regulated by a negative feedback system?

Respiratory System Determinants of Peripheral Fatigue and Endurance Performance

We briefly summarize recent evidence pertaining to how mechanisms primarily under the control of the respiratory system-namely, arterial oxyhemoglobin desaturation, respiratory muscle work and fatigue, and cyclical fluctuations in intrathoracic pressure-may contribute to exercise limitation. Respiratory influences on cardiac output and on sympathetic vasoconstrictor activity and blood flow distribution are shown to be important determinants of performance. We also address how a compromised O2 transport exacerbates the rate of development of peripheral muscle fatigue and, in turn, precipitates central fatigue and exercise limitation.

Locomotor muscle fatigue modifies central motor drive in healthy humans and imposes a limitation to exercise performance

We asked whether the central effects of fatiguing locomotor muscle fatigue exert an inhibitory influence on central motor drive to regulate the total degree of peripheral fatigue development. Eight cyclists performed constant-workload prefatigue trials (a) to exhaustion (83% of peak power output (W(peak)), 10 +/- 1 min; PFT(83%)), and (b) for an identical duration but at 67% W(peak) (PFT(67%)). Exercise-induced peripheral quadriceps fatigue was assessed via changes in potentiated quadriceps twitch force (DeltaQ(tw,pot)) from pre- to post-exercise in response to supra-maximal femoral nerve stimulation (DeltaQ(tw,pot)). On different days, each subject randomly performed three 5 km time trials (TTs). First, subjects repeated PFT(83%) and the TT was started 4 min later with a known level of pre-existing locomotor muscle fatigue (DeltaQ(tw,pot) -36%) (PFT(83%)-TT). Second, subjects repeated PFT(67%) and the TT was started 4 min later with a known level of pre-existing locomotor muscle fatigue (DeltaQ(tw,pot) -20%) (PFT(67%)-TT). Finally, a control TT was performed without any pre-existing level of fatigue. Central neural drive during the three TTs was estimated via quadriceps EMG. Increases in pre-existing locomotor muscle fatigue from control TT to PFT(83%)-TT resulted in significant dose-dependent changes in central motor drive (-23%), power output (-14%), and performance time (+6%) during the TTs. However, the magnitude of locomotor muscle fatigue following various TTs was not different (DeltaQ(tw,pot) of -35 to -37%, P = 0.35). We suggest that feedback from fatiguing muscle plays an important role in the determination of central motor drive and force output, so that the development of peripheral muscle fatigue is confined to a certain level.

Arterial oxygenation, central motor output and exercise performance in humans

The studies of Amann et al. (2006, 2007) conclude that feedback from fatiguing skeletal muscle during exercise at different reduces central motor output to the working muscles “in order to reinvent excessive development of peripheral muscle fatigue beyond a critical threshold or sensory tolerance limit” (Amann et al. 2006, p. 950). We suggest that their findings can be better explained by hypoxia-induced changes in central motor output acting in an anticipatory manner.

Convective oxygen transport and fatigue

During exercise, fatigue is defined as a reversible reduction in force- or power-generating capacity and can be elicited by "central" and/or "peripheral" mechanisms. During skeletal muscle contractions, both aspects of fatigue may develop independent of alterations in convective O(2) delivery; however, reductions in O(2) supply exacerbate and increases attenuate the rate of accumulation. In this regard, peripheral fatigue development is mediated via the O(2)-dependent rate of accumulation of metabolic by-products (e.g., inorganic phosphate) and their interference with excitation-contraction coupling within the myocyte. In contrast, the development of O(2)-dependent central fatigue is elicited 1) by interference with the development of central command and/or 2) via inhibitory feedback on central motor drive secondary to the peripheral effects of low convective O(2) transport. Changes in convective O(2) delivery in the healthy human can result from modifications in arterial O(2) content, blood flow, or a combination of both, and they can be induced via heavy exercise even at sea level; these changes are exacerbated during acute and chronic exposure to altitude. This review focuses on the effects of changes in convective O(2) delivery on the development of central and peripheral fatigue.

Is the healthy respiratory system (always) built for exercise?

Is the healthy respiratory system (always) built for exercise?

The rate of fatigue accumulation as a sensed variable

The rate of fatigue accumulation as a sensed variable

Arterial Oxygen Content Influences Exercise Performance via Effects on Limb Fatigue

PURPOSE: It is well known that arterial oxygen content (CaO2) is positively correlated with whole body exercise performance. We previously demonstrated, by comparing the effects of ΔCaO2 at equal exercise work rates and durations, that CaO2 is negatively correlated with peripheral locomotor muscle fatigue. Accordingly, we investigated the role of locomotor muscle fatigue as a determinant of the effects of ΔCaO2, on exercise performance. METHODS: On separate days, 8 healthy, trained males performed four 5 km cycling time trials (TT) [inspired O2 fraction (FIO2) / CaO2 (ml O2·dl blood−1): 0.15/17.6 (TTHYPO); 0.21/20.9 (TTNORM); 0.28/22.6 (TTISO); 1.0/24.4 (TTHYPER)], as well as 3 constant work-load trials (314 ±13 W; FIO2 / CaO2: 0.15/18.2, 0.21/21.3, 1.0/24.5) to the limit of exhaustion. Quadriceps muscle fatigue was assessed via evoking quadriceps twitch force (Qtw) through magnetic stimulation of the femoral nerve (1–100 Hz) pre- and 2.5-min post-exercise. We determined that this method for peripheral locomotor muscle fatigue assessment was highly reproducible within and between days (coefficient of variation <6%) and highly sensitive to small variations in exercise duration at the same work rate. RESULTS: With each increment in CaO2 from hypoxia to hyperoxia, time trial performance (time required to completion and mean power output) was increased significantly (e.g. 483 s / 270 W with TTHYPO vs. 438 s / 349 W with TTHYPER, p <0.05). Despite these wide differences in time trial performance with varying CaO2, the amount of exercise-induced quadriceps fatigue (% ΔQtw) was nearly identical (ΔQtw pre- to post-exercise = −27 to −29%, p = 0.4). During the constant work-load trials, varying CaO2 resulted in a wide range in time to exhaustion (4.5 ±0.4 min in FIO2 0.15 to 19.4 ±3.9 min in FIO2 1.0; p <0.01), however, similar levels of peripheral locomotor muscle fatigue (ΔQtw −26 to −27%, p = 0.8) were observed following exhaustive exercise. CONCLUSIONS: These findings indicate that a certain critical level of peripheral locomotor muscle fatigue is an important regulated variable during exercise which determines the level of motor output and therefore exercise performance, i.e. power output and time to task completion. Thus, we propose that variations in CaO2 and O2 transport to muscle affect time trial performance secondary to the rate of quadriceps fatigue development, which in turn may feed back to higher motor areas of the central nervous system to modulate or titrate motor output so as to prevent “excessive” development of peripheral locomotor muscle fatigue beyond a critical threshold.

Determining central activation failure and peripheral fatigue in the course of sustained maximal voluntary contractions: a model-based approach

In the study of fatigue, several methods have been used to calculate the development of central activation failure (CAF) and peripheral fatigue (PF) in the course of a sustained maximal voluntary contraction (MVC). This paper presents a model that enables simultaneous determination of CAF and PF during sustained MVC by using only force registration and superimposed electrical stimulation. In the model, we explicitly use the assumption, which is virtually always made implicitly in earlier studies, that a constant relative fraction of maximal possible force is activated by the electrical stimulation. That fraction can be determined at the start and at the end of a sustained MVC. The model shows that in the course of a sustained MVC, CAF can be calculated by merely using 1) this fraction, 2) the amplitudes of the superimposed force responses to stimulation, and 3) the course of voluntary force. After CAF quantification, the development of PF during MVC becomes available as well. The present study first examines the model assumption with data of sustained MVCs of variable durations on six healthy subjects. Subsequently, it shows CAF values in a group of 27 healthy subjects determined with both the model and a method of linear interpolation for PF estimation. Model-based CAF values were significantly higher during, but not at the start and at the end of, a 2-min sustained MVC. Next to a well-justified CAF determination, the model has the advantage of simultaneously quantifying PF, which was not possible with the previous methods.

Central and peripheral contributions to fatigue in relation to level of activation during repeated maximal voluntary isometric plantar flexions

This study aimed to investigate central and peripheral contributions to fatigue during repeated maximal voluntary isometric plantar flexions (MVCs). Changes in joint torque, level of activation (LOA), resting twitch amplitude (RT), electromyographic signals (EMG), and presynaptic inhibition of Ia afferents were investigated during 9 bouts of 10 MVCs. MVCs lasted for 2 s and were separated by 1 s. The interval between bouts was 10 s. Electrical stimulation was applied to the tibial nerve; at rest to evoke RTs, M waves, and two (1.5-s interval) H reflexes; with the soleus EMG at 30% of that during MVC to evoke M waves and two H reflexes; and during MVCs to measure LOA. Over the nine bouts, LOA decreased by 12.6% and RT by 16.2%. EMG root mean square during MVCs remained unchanged for the soleus and tibialis anterior muscles, but it decreased for medial gastrocnemius. Peripheral fatigue (decrease in RT) was positively correlated to LOA, whereas central fatigue (decrease in LOA) was not. Depression of both H reflexes suggests that presynaptic inhibition after the first bout was partly induced by homosynaptic postactivation depression of the Ia terminal. The H-reflex-to-M-wave ratio increased with fatigue in both passive and active states, with no change in the ratio of the second H reflex to the first, thereby indicating a decrease of presynaptic inhibition during fatigue. The results indicate that both central and peripheral mechanisms contributed to the fatigue observed during repeated MVCs and that the development of peripheral fatigue was influenced by the level of voluntary activation and initial plantar flexor torque.

Amlodipine versus atenolol in essential hypertension

The efficacy and safety of amlodipine (2.5–10 mg) once daily was compared with atenolol (50–100 mg) once daily in patients with mild-to-moderate essential hypertension in a randomized, doubleblind, parallel, placebo-controlled study. A total of 125 patients were randomly allocated at the end of a 4-week run-in placebo period to 8 weeks of double-blind treatment with amlodipine (n = 41), atenolol (n = 43), or placebo (n = 41). The placebo group had small mean changes in supine and standing blood pressure compared with baseline. The mean blood pressure changes from baseline 24 hours postdose in the amlodipine group (mean daily dose 8.8 mg) were −12.8/−10.1 mm Hg for supine blood pressure and −11.5/−9.8 mm Hg for standing blood pressure (p < 0.001 compared with placebo), and for the atenolol group (mean daily dose 83.7 mg) the changes were −11.3/−11.7 mm Hg for supine blood pressure and −13.3/−12.3 mm Hg for standing blood pressure (p < 0.001 compared with placebo). There were no statistically significant blood pressure differences between active treatments. The responder rates for amlodipine, atenolol, and placebo were 61.1, 64.9, and 11.1%, respectively. The blood pressure values taken over the 24-hour period at final visit revealed that amlodipine and atenolol maintained the supine blood pressure ≤ 140/90 mm Hg throughout the period of observation; the corresponding time-effect curve for the placebo group was clearly in the hypertensive range. Heart rate was significantly lowered by atenolol only. Both amlodipine and atenolol were well tolerated. Only 1 patient was withdrawn due to adverse effects (development of peripheral edema, arthralgia and fatigue) related to amlodipine. This study demonstrates that once-daily therapy with amlodipine or atenolol was well tolerated in patients with mild-to-moderate essential hypertension and provided control of blood pressure throughout the 24-hour dosing interval.