Twitch Amplitude Research Articles

The ForceLAB simulator: Application to the comparison of current models of cardiomyocyte contraction

Mathematical models are useful tools in the study of physiological phenomena. However, due to differences in assumptions and formulations, discrepancy in simulations may occur. Among the models for cardiomyocyte contraction based on Huxley's cross-bridge cycling, those proposed by Negroni and Lascano (NL) and Rice et al. (RWH) are the most frequently used. This study was aimed at developing a computational tool, ForceLAB, which allows implementing different contraction models and modifying several functional parameters. As an application, electrically-stimulated twitches triggered by an equal Ca2+ input and steady-state force x pCa relationship (pCa = -log of the molar free Ca2+ concentration) simulated with the NL and RWH models were compared. The equilibrium Ca2+-troponin C (TnC) dissociation constant (Kd) was modified by changing either the association (kon) or the dissociation (koff) rate constant. With the NL model, raising Kd by either maneuver decreased monotonically twitch amplitude and duration, as expected. With the RWH model, in contrast, the same Kd variation caused increase or decrease of peak force depending on which rate constant was modified. Additionally, force x pCa curves simulated using Ca2+ binding constants estimated in cardiomyocytes bearing wild-type and mutated TnC were compared to curves previously determined in permeabilized fibers. Mutations increased kon and koff, and decreased Kd. Both models produced curves fairly comparable to the experimental ones, although sensitivity to Ca2+ was greater, especially with RWH model. The NL model reproduced slightly better the qualitative changes associated with the mutations. It is expected that this tool can be useful for teaching and investigation.

Acute effect of tendon vibration applied during isometric contraction at two knee angles on maximal knee extension force production

The aim of the current study was to investigate the effect of a single session of prolonged tendon vibration combined with low submaximal isometric contraction on maximal motor performance. Thirty-two young sedentary adults were assigned into two groups that differed based on the knee angle tested: 90° or 150° (180° = full knee extension). Participants performed two fatigue-inducing exercise protocols: one with three 10 min submaximal (10% of maximal voluntary contraction) knee extensor contractions and patellar tendon vibration (80 Hz) another with submaximal knee extensor contractions only. Before and after each fatigue protocol, maximal voluntary isometric contractions (MVC), voluntary activation level (assessed by the twitch interpolation technique), peak-to-peak amplitude of maximum compound action potentials of vastus medialis and vastus lateralis (assessed by electromyography with the use of electrical nerve stimulation), peak twitch amplitude and peak doublet force were measured. The knee extensor fatigue was significantly (P<0.05) greater in the 90° knee angle group (-20.6% MVC force, P<0.05) than the 150° knee angle group (-8.3% MVC force, P = 0.062). Both peripheral and central alterations could explain the reduction in MVC force at 90° knee angle. However, tendon vibration added to isometric contraction did not exacerbate the reduction in MVC force. These results clearly demonstrate that acute infrapatellar tendon vibration using a commercial apparatus operating at optimal conditions (i.e. contracted and stretched muscle) does not appear to induce knee extensor neuromuscular fatigue in young sedentary subjects.

Six weeks of localized heat therapy does not affect muscle mass, strength and contractile properties in healthy active humans.

Animal and human studies have shown that repeated heating may induce skeletal muscle adaptations, increasing muscle strength. The aim of this study is to investigate the effect of 6weeks of localized heating on skeletal muscle strength, volume and contractile properties in healthy humans. Fifteen active participants (8 males/7 females, 35 ± 6 years, 70 ± 14kg, 173 ± 7cm, average training of 87min per week) were subjected to 6weeks of single-leg heat therapy. Heat pads were applied for 8h/day, 5days/week, on one randomly selected calf of each participant, while the contralateral leg acted as control. The heat pads increased muscle temperature by 4.6 ± 1.2°C (p < 0.001). Every 2weeks, participants were tested for morphological (MRI), architectural (ultrasound), contractile (electrically evoked twitch), and force (isometric and isokinetic) adaptations. Repeated localized heating did not affect the cross-sectional area (p = 0.873) or pennation angle (p = 0.345) of the gastrocnemius muscles; did not change the evoked peak twitch amplitude (p = 0.574) or rate of torque development (p = 0.770) of the plantar flexors; and did not change maximal voluntary isometric (p = 0.214) or isokinetic (p = 0.973) plantar flexor torque. Whereas previous studies have observed improved skeletal muscle function following whole-body and localized heating in active and immobilized humans, respectively, the current data suggested that localized heating may not be a potent stimulus for muscle adaptations in active humans.

Effect of stimulation timing on testing voluntary muscle force generation

BackgroundThe interpolated twitch technique (ITT) is a ubiquitous test for assessing the level of voluntary muscle force generation, in which muscle twitches are evoked via percutaneous electrical stimulation. Traditionally, the stimulation timing during the ITT is not computer-controlled and usually delivered from 5 to 10 s after the maximal voluntary contraction (MVC) of the potentiated muscle. MethodsIn this work, we evaluated the sizes of the evoked twitches in the lower limb with different controlled stimulation time delays with respect to the MVC of the ankle plantar flexors. Fifteen healthy participants were included. We recorded the un-potentiated muscle twitch amplitudes at rest in response to doublet supramaximal stimulation of the tibial nerve, superimposed twitches (SITs) at three different delays from the beginning of the MVC force plateau (0.1, 0.75, and 1.5 s), and resting twitches in the potentiated muscle at four different delays once the MVC was finished (0.1, 2.5, 5.0, and 10.0 s). ResultsThe magnitude of the SITs did not vary among the delays tested but varied among the potentiated resting twitch (PRT) amplitudes, with 2.5 s being largest and 0.1 s being the smallest. Remarkably, the resting twitch amplitudes reduced during the session despite the long rest periods between MVCs (5 min). ConclusionWe conclude that proper control of the stimulation timing is mandatory to increase the sensitivity of the ITT, and a 2.5 s delay from the end of the MVC is recommended for the PRT. Controlling the development of fatigue, which can be intrinsic to testing with repeated MVCs, is also essential. We recommend reducing the number of MVC repetitions and increasing the rest periods between them.

Oxygen availability affects exercise capacity, but not neuromuscular fatigue characteristics of knee extensors, during exhaustive intermittent cycling.

To compare the effects of different hypoxia severities on exercise capacity, cardio-respiratory, tissue oxygenation and neuromuscular fatigue characteristics in response to exhaustive intermittent cycling. Eleven well-trained cyclists, repeated supra-maximal cycling efforts of 15s (30% of anaerobic power reserve, 609 ± 23W), interspersed with 45s of passive rest until task failure. The exercise was performed on separate days in normoxia (SL; simulated altitude/end-exercise arterial oxygen saturation = 0m/~ 96%), moderate (MH; 2200m/~ 90%) and severe (SH; 4200m/~ 79%) hypoxia in a cross-over design. Neuromuscular tests, including brief (5s) and sustained (30s) maximal isometric voluntary contractions of the knee extensors, were performed at baseline and exhaustion. Exercise capacity decreased with hypoxia severity (23 ± 9, 16 ± 6 and 9 ± 3 cycle efforts in SL, MH and SH, respectively; P < 0.001; η2 = 0.72). Both cerebral (P < 0.001; η2 = 0.86) and muscle (P < 0.01; η2 = 0.54) oxygenation decreased throughout the exercise, independent of condition (P ≥ 0.45; η2 ≥ 0.14). Compared to SL, muscle oxygenation was globally lower in MH and SH (P = 0.011; η2 = 0.36). Cardiovascular solicitation neared maximal values at exhaustion in all conditions. Peak twitch amplitude with single and paired electrical stimuli (P < 0.001; η2 ≥ 0.87), maximal torque (P < 0.001; η2 ≥ 0.48) and voluntary activation measured using transcranial magnetic stimulation (P ≤ 0.034; η2 ≥ 0.31) during brief and sustained MVCs were all reduced at exhaustion, independent of condition (P ≥ 0.196; η2 ≥ 0.15). Despite reduced exercise capacity with increasing severity of hypoxia during exhaustive intermittent cycling, neuromuscular fatigue characteristics were not different at task failure and cardiovascular solicitation neared maximum values.

Greater fatigue resistance of dorsiflexor muscles in people with prediabetes than type 2 diabetes

Although exercise can prevent progression to T2D among people with prediabetes, little is known about fatigue during exercise in people with prediabetes compared to T2D. The purpose of the study was to compare the magnitude and mechanisms of fatigability of the ankle dorsiflexor muscles between people with prediabetes and T2D. Ten people with prediabetes (6 females, 51.7 ± 6.9 years) and fourteen with T2D (6 females, 52.6 ± 6.2 years) who were matched for age, body mass index and physical activity performed an intermittent (6 s contraction: 4 s relaxation) fatiguing task at 75% maximal voluntary contraction (MVC) with the dorsiflexors. Electrical stimulation was used to assess contractile properties of the dorsiflexor muscles before and after the fatiguing task. People with prediabetes had a longer time-to-task failure, i.e. greater fatigue resistance (7.9 ± 5.1 vs. 4.9 ± 2.5 min, P = 0.04), and slower rate of decline of the (potentiated) twitch amplitude (6.5 ± 3.1 vs. 16.5 ± 11.7%·min−1, P = 0.03) than people with T2D. Shorter time-to-task failure (i.e. greater fatigability) was associated with greater baseline MVC torque (r2 = 0.21, P = 0.02) and faster rate of decline of twitch amplitude (r2 = 0.39, P = 0.04). The ankle dorsiflexor muscles of males and females with prediabetes were more fatigue resistant than people with T2D, and fatigability was associated with contractile mechanisms.

Greater fatigability and motor unit discharge variability in human type 2 diabetes.

This study determined the discharge characteristics of motor units from two lower limb muscles before and after fatiguing exercise in people with type 2 diabetes (T2D) with no symptoms of polyneuropathy and activity‐matched controls. Seventeen people with T2D (65.0 ± 5.6 years; 8 women) and 17 controls (63.6 ± 4.5 years; 8 women) performed: (a) intermittent, isometric contractions at 50% maximal voluntary isometric contraction (MVIC) sustained to failure with the ankle dorsiflexors, and (b) a dynamic fatiguing task (30% MVIC load) for 6 min with the knee extensors. Before and after the fatiguing tasks, motor unit characteristics (including coefficient of variation (CV) of interspike intervals (ISI)) were quantified from high‐density electromyography and muscle contractile properties were assessed via electrical stimulation. Fatigability was ~50% greater for people with T2D than controls for the dorsiflexors (time‐to‐failure: 7.3 ± 4.1 vs. 14.3 ± 9.1 min, p = .010) and knee extensors (power reduction: 56.7 ± 11.9 vs. 31.5 ± 25.5%, p < .001). The CV of ISI was greater for the T2D than control group for the tibialis anterior (23.1 ± 11.0 vs. 21.3 ± 10.7%, p < .001) and vastus lateralis (27.8 ± 20.2 vs. 24.5 ± 16.1%, p = .011), but these differences did not change after the fatiguing exercises. People with T2D had greater reductions in the electrically evoked twitch amplitude of the dorsiflexors (8.5 ± 5.1 vs. 4.0 ± 3.4%·min‐1, p = .013) and knee extensors (49.1 ± 10.0 vs. 31.8 ± 15.9%, p = .004) than controls. Although motor unit activity was more variable in people with T2D than controls, the greater fatigability of the T2D group for lower limb muscles was due to mechanisms involving disruption of contractile function of the exercising muscles rather than motor unit behavior.

Deficits In Performance Fatigability And Contractile Function Of The Plantar Flexor Muscles In Achilles Tendinopathy

Achilles tendinopathy (AT) is an overuse condition resulting in pain and stiffness of the Achilles tendon. While experts agree that strength and endurance deficits persist in AT, this claim lacks empirical evidence. PURPOSE: To determine whether individuals with AT present with deficits in strength and fatigability compared to healthy controls (CON) during a single-leg heel raise (SLHR) performed to task failure. METHODS: 6 people with AT (3 male, 26.8±8.9 yrs) and 6 controls (CON, 3 male, 21.9±1.8 yrs) performed maximal voluntary isometric contraction (MVIC) of the plantar flexor muscles before and immediately after SLHR repetitions performed to task failure (test of fatigability). Electrical stimulation of the tibial nerve was used to evoke twitch contractions of the plantar flexor muscles before and after the fatigability test at rest and during MVICs to determine contractile properties and voluntary activation, respectively. RESULTS: At baseline, the AT and CON groups exhibited similar plantar flexor strength (MVIC), voluntary activation and resting twitch amplitude. However, the AT group performed fewer SLHR repetitions than CON (33 vs 59, p=0.009). At task failure of the SLHR task, the reduction in plantar flexor MVIC (17.3% AT vs 23.7% CON, p=0.32) and voluntary activation (5.8% AT vs 7.5% CON, p=0.78) was similar for the two groups. However, persons with AT demonstrated larger reductions in resting twitch amplitude (34.4 Nm to 31.5 Nm, 8.4% reduction, p=0.047), while CON demonstrated no change (p=0.23). CONCLUSION: The plantar flexor muscles of persons with AT were more fatigable for a SLHR task compared with strength-matched controls. Deficits in contractile function rather than the ability to centrally drive the muscle appear to be responsible for deficits in endurance in people with AT. *This work was supported by a Promotion of Doctoral Studies Level I Scholarship from the Foundation for Physical Therapy and by Marquette University’s Exercise and Rehabilitation Sciences Graduate Program.

Chemical and Pharmacological Screening of Rhinella icterica (Spix 1824) Toad Parotoid Secretion in Avian Preparations.

The biological activity of Rhinella icterica parotoid secretion (RIPS) and some of its chromatographic fractions (RI18, RI19, RI23, and RI24) was evaluated in the current study. Mass spectrometry of these fractions indicated the presence of sarmentogenin, argentinogenin, (5β,12β)-12,14-dihydroxy-11-oxobufa-3,20,22-trienolide, marinobufagin, bufogenin B, 11α,19-dihydroxy-telocinobufagin, bufotalin, monohydroxylbufotalin, 19-oxo-cinobufagin, 3α,12β,25,26-tetrahydroxy-7-oxo-5β-cholestane-26-O-sulfate, and cinobufagin-3-hemisuberate that were identified as alkaloid and steroid compounds, in addition to marinoic acid and N-methyl-5-hydroxy-tryptamine. In chick brain slices, all fractions caused a slight decrease in cell viability, as also seen with the highest concentration of RIPS tested. In chick biventer cervicis neuromuscular preparations, RIPS and all four fractions significantly inhibited junctional acetylcholinesterase (AChE) activity. In this preparation, only fraction RI23 completely mimicked the pharmacological profile of RIPS, which included a transient facilitation in the amplitude of muscle twitches followed by progressive and complete neuromuscular blockade. Mass spectrometric analysis showed that RI23 consisted predominantly of bufogenins, a class of steroidal compounds known for their cardiotonic activity mediated by a digoxin- or ouabain-like action and the blockade of voltage-dependent L-type calcium channels. These findings indicate that the pharmacological activities of RI23 (and RIPS) are probably mediated by: (1) inhibition of AChE activity that increases the junctional content of Ach; (2) inhibition of neuronal Na+/K+-ATPase, leading to facilitation followed by neuromuscular blockade; and (3) blockade of voltage-dependent Ca2+ channels, leading to stabilization of the motor endplate membrane.

Astaxanthin Improves Tetanic Force Without Altering Skeletal Muscle Excitation-Contraction Coupling in Mice

Astaxanthin (AX) is a powerful natural anti-oxidant that protects against the risk of oxidative damage from free radicals and reactive oxygen species. Up to date, there are no studies concerning how and if AX feeding affects the excitation-contraction coupling (ECC) mechanism in skeletal muscle. 8 young adult C57Bl6 mice were divided into two groups: 1) control and 2) AX supplemented for 4 weeks (AstaReal1010, 0.05% w/w added in standard rodent chow). Following the feeding the AX group gained significantly less weight on average (0.16±0.33g vs 1.22±0.31g). When examining the in vitro force of the extensor digitorum longus (EDL) muscle the amplitude of single twitches (5 V, 100 ms) was not altered, but the amplitude of tetani (200 Hz, 200 ms) was significantly increased in the AX group. We also measured the activity-dependent mitochondrial Ca2+ uptake in rhod-2 [SzP1] loaded flexor digitorum brevis (FDB) fibers at rest and during tetanic stimulation. The average (±SE) time course of mitochondrial normalized fluorescence was significantly decreased in the AX group at rest (0.28±0.01 vs 0.12±0.01), after the 1st tetanus (0.3±0.01 vs 0.13±0.01) and after the 5th tetanus (0.39±0.08 vs 0.14±0.02) (p<0.05), respectively. Lastly, we studied the voltage activation of calcium transients in single FDB fibers under whole cell voltage clamp. The voltage dependence of calcium release (fitted with the Boltzmann function) was not statistically different between the two groups (V1/2: -12.4±2.3 mV, k=6.7±0.5 for Ctrl, n=12 vs. V1/2: -14.9±2.7 mV, k=8.1±0.8 for AX, n=17). We conclude that AX supplementation increases the in vitro force of the EDL muscles without affecting the ECC mechanism in skeletal muscle. AX feeding seem to exert a protecting effect on the mitochondria as the Ca2+ uptake was significantly less in the AX group.

Greater Lower Limb Fatigability in People with Prediabetes than Controls.

The study purpose was to compare perceived fatigability and performance fatigability after high-velocity contractions with knee extensor muscles between people with prediabetes, people with type 2 diabetes (T2D), and controls without diabetes matched for age, body mass index, and physical activity. Twenty people with prediabetes (11 men, 9 women: 63.1 ± 6.0 yr, 26.9 ± 4.2 kg·m, 8030 ± 3110 steps per day), 39 with T2D (23 men, 16 women: 61.2 ± 8.5 yr, 29.4 ± 6.4 kg·m, 8440 ± 4220 steps per day), and 27 controls (13 men, 14 women: 58.1 ± 9.4 yr, 27.3 ± 4.3 kg·m, 8400 ± 3000 steps per day) completed the Fatigue Impact Scale as a measure of perceived fatigability and a fatigue protocol including 120 maximal-effort, high-velocity concentric contractions (MVCC; 1 contraction/3 s) with the knee extensors using a submaximal load (30% maximum) to quantify performance fatigability. Electrical stimulation was used to assess voluntary activation and contractile function of the knee extensor muscles before and after the fatigue protocol. Fatigue Impact Scale scores were not different between people with prediabetes, people with T2D, and controls (12.5 ± 15.1, 18.3 ± 22.7, and 12.6 ± 18.6, respectively; P = 0.517). However, people with prediabetes had greater reductions in MVCC power during the fatigue protocol than did controls (31.8% ± 22.6% vs 22.1% ± 21.1%, P < 0.001), and both groups had lesser reductions than the T2D group (44.8% ± 21.9%, P < 0.001). Similarly, the prediabetes group had larger reductions in electrically evoked twitch amplitude than the control group (32.5% ± 24.9% vs 21.3% ± 33.0%, P < 0.001), but lesser reductions than those with T2D (44.0% ± 23.4%, P < 0.001). For all three groups, a greater decline in MVCC power was associated with larger reductions of twitch amplitude (r = 0.350, P < 0.001). People with prediabetes have greater performance fatigability of the knee extensors due to contractile mechanisms compared with controls, although less performance fatigability than that of people with T2D.

Central fatigue is greater than peripheral fatigue in people with joint hypermobility syndrome

PurposePeople with Joint Hypermobility Syndrome (JHS) suffer with fatigue. The purpose of this project was to investigate the contribution of central and peripheral fatigue. MethodsElectrical stimulation of the musculocutaneous nerve to biceps brachii, and transcranial magnetic stimulation over the motor cortex supplying biceps brachii were used. Peripheral and central fatigue were assessed during a control, fatiguing and recovery phase protocol. ResultsJHS participants perceived greater fatigue during the protocol compared to a control group and did not recover. Central and peripheral fatigue did not occur in the control group. However, the JHS group showed central fatigue. MEP amplitude increased in the JHS group during the fatiguing protocol (p < 0.01) before recovering. Superimposed twitch amplitude increased in the JHS group during the fatiguing protocol and stayed elevated during the recovery phase (p < 0.04). Time to peak (TTP) amplitude of the torque generated by the TMS was longer in the JHS group (p < 0.05). RMS during MVCs decreased during the fatiguing protocol reaching significance during the recovery phase (p < 0.01). ConclusionJHS participants suffered central but not peripheral fatigue. A modified strength programme to target this is discussed.

Changes in Fatigue Are the Same for Trained Men and Women after Resistance Exercise.

To measure changes in fatigue and knee-extensor torque in the 48 h after trained men and women completed a full-body resistance exercise session. Eight trained women (mean ± SD: age, 25.6 ± 5.9 yr; height, 1.68 ± 0.06 m; mass, 71.0 ± 8.6 kg) and eight trained men (age, 25.5 ± 6.2 yr; height, 1.79 ± 0.05 m; mass, 86.4 ± 9.8 kg) performed a full-body resistance exercise session based on real-world athletic practice. Measurements were performed before and after the exercise session, as well as 1, 24, and 48 h after the session. Fatigue and pain were measured with standardized self-report measures. Maximal isometric contractions with the knee extensors and superimposed femoral nerve stimulation were performed to examine maximal torque, rate of torque development, voluntary activation, and muscle contractility. Two sets of 10 isokinetic contractions (60°·s) with the knee extensors were performed during the protocol with use of near-infrared spectroscopy to assess muscle oxygenation. EMG were recorded from two quadriceps muscles during all isometric and isokinetic contractions. Fatigue was increased from baseline for both sexes until 48 h after training (P < 0.001). Maximal torque and evoked twitch amplitudes were similarly reduced after exercise for men and women (P < 0.001). Voluntary activation and EMG amplitudes were unchanged after the training session. Muscle oxygenation was 13.3% ± 17.4% (P = 0.005) greater for women during the isokinetic repetitions, and the values were unchanged after the training session. This is the first study to show similar changes in the fatigue reported by trained men and women in the 48 h after a training session involving full-body resistance exercises. Sex differences in muscle oxygenation during exercise do not influence the reductions in muscle force, activation, or contractility after the training session.

Assessment of Performance Fatiguability During Resistance Exercise Anchored to Ratings of Perceived Exertion

PURPOSE: According to the critical threshold hypothesis, fatiguing single-leg exercise at intensities above the critical force should result in performance fatiguability that is unvarying. The purpose of the present study was to examine the fatigue-related decreases in maximal voluntary isometric contractions (MVIC) as an indirect measure of performance fatiguability at intensities anchored by ratings of perceived exertion (RPE). METHODS: Ten recreationally-active men (22.9 ± 2.0 yr) performed 3 randomly ordered, sustained submaximal isometric leg extension muscle actions anchored to RPE values of 2, 5, and 8 (OMNI-RES 10-point scale) until the RPE value could no longer be maintained or a maximal time-limit of 5-min was reached. The percent decline in MVIC was defined as the difference between pretest and posttest values. A 1×3 repeated measures ANOVA was used to examine mean differences in MVIC percent decline values at RPE=2, 5, and 8. RESULTS: The mean (±SD) actual time-limits for the sustained muscle actions anchored to RPE=2, RPE=5, and RPE=8 were 300.0 ± 0.0 s, 202.0 ± 95.5 s, and RPE 8 = 72.7 ± 27.6 s, respectively. The pretest to posttest decreases in MVIC values for RPE=2, 5, and 8 were 61.9 ± 14.3 to 42.8 ± 11.4, 62.4 ± 14.3 to 47.9 ± 12.8 and 63.0 ± 12.6 to 54.0 ± 14.7 kg, respectively. There was a significant (p=0.023) difference in MVIC percent decline, and the pairwise comparisons indicated that the percent decline in MVIC was significantly (p<0.001) greater for RPE=2 (30.4 ± 11.6 %) than RPE=8 (15.1 ± 13.6%), but there were no differences (p>0.05) for RPE=5 (22.0 ± 14.0%) versus RPE= 2 or 8. CONCLUSIONS: In general, the similar MVIC percent decline values at RPE=5 and 8, as well as the greater percent decline at RPE=2, supported the critical threshold hypothesis. Furthermore, performance fatiguability as assessed from MVIC measurements followed the expected pattern of responses as those previously described for involuntary potentiated twitch amplitude. These findings also suggested that RPE=2 was below critical intensity, but RPE=5 and RPE=8 were not.

Children Exhibit a More Comparable Neuromuscular Fatigue Profile to Endurance Athletes Than Untrained Adults.

The present study compared neuromuscular fatigue profiles between children, untrained adults and adult endurance athletes during repeated maximal muscle contractions. Eighteen prepubertal boys, 19 untrained men and 13 endurance male athletes performed 5-s maximal voluntary isometric knee extensor contractions (MVICs) interspersed with 5-s recovery until MVIC reached 60% of its initial value. Single and doublet magnetic stimulations were delivered to the femoral nerve to quantify the time course of potentiated twitch amplitude (Ttw,pot), high-frequency torque (T100 Hz) and the low-to-high frequency torque ratio (T10 Hz/T100 Hz), i.e., indicators of peripheral fatigue. M-wave-normalized EMG amplitudes (EMG/M) and the maximal voluntary activation level (VA) were calculated to quantify central fatigue. Adults (15.9 ± 3.9 repetitions) performed fewer MVICs than children (40.4 ± 19.7) and endurance athletes (51.7 ± 19.6), however, no difference was observed between children and athletes (P = 0.13). Ttw,pot (∼52%, P < 0.001), T100 Hz (∼39%, P < 0.001) and T10 Hz/T100 Hz (∼23%, P < 0.001) decreased only in adults. Similar decrements in vastus medialis and vastus lateralis EMG/M were observed in children and endurance athletes (range: 40–50%), and these were greater than in adults (∼15%). Whilst VA decreased more in children (-38.4 ± 22.5%, P < 0.001) than endurance athletes (-20.3 ± 10.1%, P < 0.001), it did not change in adults. Thus, children fatigued more slowly than adults and as much as endurance athletes. They developed less peripheral and more central fatigue than adults and, although central fatigue appeared somewhat higher in children than endurance athletes, both children and endurance athletes experienced greater decrements than adults. Therefore, children exhibit a more comparable neuromuscular fatigue profile to endurance athletes than adults.

Exercise-induced hyperemia is associated with knee extensor fatigability in adults with type 2 diabetes.

The aim of this study was to compare fatigability, contractile function, and blood flow to the knee extensor muscles after dynamic exercise in patients with type 2 diabetes mellitus (T2DM) and controls. The hypotheses were that patients with T2DM would demonstrate greater fatigability than controls, and greater fatigability would be associated with a lower exercise-induced increase in blood flow and greater impairments in contractile function. Patients with T2DM ( n = 15; 8 men; 62.4 ± 9.0 yr; 30.4 ± 7.7 kg/m2; 7,144 ± 3,294 steps/day) and 15 healthy control subjects (8 men, 58.4 ± 6.9 yr; 28.4 ± 4.6 kg/m2; 7,893 ± 2,323 steps/day) were matched for age, sex, body mass index, and physical activity. Fatigability was quantified as the reduction in knee extensor power during a 6-min dynamic exercise. Before and after exercise, vascular ultrasonography and electrical stimulation were used to assess skeletal muscle blood flow and contractile properties, respectively. Patients with T2DM had greater fatigability (30.0 ± 20.1% vs. 14.6 ± 19.0%, P < 0.001) and lower exercise-induced hyperemia (177 ± 90% vs. 194 ± 79%, P = 0.04) than controls but similar reductions in the electrically evoked twitch amplitude (37.6 ± 24.8% vs. 31.6 ± 30.1%, P = 0.98). Greater fatigability of the knee extensor muscles was associated with postexercise reductions in twitch amplitude ( r = 0.64, P = 0.001) and lesser exercise-induced hyperemia ( r = -0.56, P = 0.009). Patients with T2DM had greater lower-limb fatigability during dynamic exercise, which was associated with reduced contractile function and lower skeletal muscle blood flow. Thus, treatments focused on enhancing perfusion and reversing impairments in contractile function in patients with T2DM may offset lower-limb fatigability and aid in increasing exercise capacity. NEW & NOTEWORTHY Although prior studies compare patients with type 2 diabetes mellitus (T2DM) with lean controls, our study includes controls matched for age, body mass, and physical activity to more closely assess the effects of T2DM. Patients with T2DM demonstrated no impairment in macrovascular endothelial function, evidenced by similar flow-mediated dilation to controls. However, patients with T2DM had greater fatigability and reduced exercise-induced increase in blood flow (hyperemia) after a lower-limb dynamic fatiguing exercise compared with controls.

Impacts of prolonged chlorpyrifos exposure on locomotion and slow-and fast- twitch skeletal muscles contractility in rats.

Investigate the effect of dietary exposure to chlorpyrifos on locomotion and contraction of soleus andextensor digitorum longus (edl) involved in locomotion. Methods: Rats were fed diets containing 1 or 5 mg kg-1 of chlorpyrifos for six weeks. Locomotion has been assessed weekly using beam walking and beam balance tests. Soleus and edl were removed to study contractile properties, myofibrillar protein content and myosin heavy chain isoforms. Animals treated with 5 mg kg-1 chlorpyrifos had a decrease body weight. An increase by 28% and 24% in latency time assessed by beam walking test and a decrease by 9% and 13% in the beam balance time was reported after 6 weeks of 1 and 5 chlorpyrifos exposure respectively. The contractile properties in soleus showed an increase in twitch amplitude by 25% and 63% in 1 and 5 doses respectively, without modification in the contraction time and half relaxation time. edl treated with 1 mg kg-1 showed a decrease by 35%, 42% and 22% in twitch amplitude, contraction time and half relaxation time respectively. edl treated with 5 mg kg-1 showed an increase of 23% in twitch amplitude without modification of the other parameters. These changes were associated with modification of myofibrillar protein content in all treated groups. Myosin heavy chain isoforms were altered in both skeletal muscles treated with 1 mg kg-1. Exposure to chlorpyrifos can alter the locomotion and produce physiological changes in a dose and muscle type related manner.

In vitro effects of levosimendan on muscle of malignant hyperthermia susceptible and non-susceptible swine

BackgroundThe calcium sensitizer levosimendan is increasingly used to improve hemodynamics in patients with acutely decompensated heart failure. By binding to cardiac troponin C the conformation of the calcium-troponin C complex is stabilized, which leads to acceleration of actin-myosin crossbrigde formation and increased force generating capacity of muscle fibers. Besides indications in cardiac failure, beneficial effects of levosimendan in skeletal muscle disorders are currently evaluated. The aim of this study was to investigate differential effects of levosimendan on skeletal muscle of pigs with and without susceptibility to malignant hyperthermia (MH) in order to identify possible risks of this emerging drug for patients with predisposition to MH.MethodsMuscle bundles of 17 pigs (9 MH susceptible (MHS); 8 MH non-susceptible (MHN)) were excised under general anesthesia and examined in the tissue bath with increasing concentrations of levosimendan (0.065; 0.125; 0.5; 1.0; 10 and 50 μg/ml). Baseline tension and twitch force were monitored continuously. Data are presented as median and interquartile range. Statistical evaluation was performed using D’Agostino & Pearson test for normal distribution and student’s t test and 2-way ANOVA for differences between the groups. P < 0.05 was considered significant.ResultsThere were no differences between the groups concerning length, weight, initial twitch force and pre-drug resting tension of the investigated muscle strips. After an initial decrease in both groups, twitch amplitude was significantly higher in MHN (− 3.0 [− 5.2–0.2] mN) compared to MHS (− 7.5 [− 10.8- -4.5] mN) (p = 0.0034) muscle at an applied levosimendan concentration of 50 μg/ml. A marked increase in resting tension was detected following levosimendan incubation with 50 μg/ml in MHS muscle bundles (3.3 [0.9–6.1] mN) compared to MHN (− 0.7 [− 1.3–0.0] mN) (p < 0.0001).ConclusionsThis in vitro investigation revealed the development of significant contractures in muscle bundles of MHS pigs after incubation with levosimendan. However, the effect appeared only at supra-therapeutic concentrations and further research is needed to determine the impact of levosimendan on MHS individuals in vivo.

Stroke increases ischemia-related decreases in motor unit discharge rates.

Following stroke, hyperexcitable sensory pathways, such as the group III/IV afferents that are sensitive to ischemia, may inhibit paretic motor neurons during exercise. We quantified the effects of whole leg ischemia on paretic vastus lateralis motor unit firing rates during submaximal isometric contractions. Ten chronic stroke survivors (>1 yr poststroke) and 10 controls participated. During conditions of whole leg occlusion, the discharge timings of motor units were identified from decomposition of high-density surface electromyography signals during repeated submaximal knee extensor contractions. Quadriceps resting twitch responses and near-infrared spectroscopy measurements of oxygen saturation as an indirect measure of blood flow were made. There was a greater decrease in paretic motor unit discharge rates during the occlusion compared with the controls (average decrease for stroke and controls, 12.3 ± 10.0% and 0.1 ± 12.4%, respectively; P < 0.001). The motor unit recruitment thresholds did not change with the occlusion (stroke: without occlusion, 11.68 ± 5.83%MVC vs. with occlusion, 11.11 ± 5.26%MVC; control: 11.87 ± 5.63 vs. 11.28 ± 5.29%MVC). Resting twitch amplitudes declined similarly for both groups in response to whole leg occlusion (stroke: 29.16 ± 6.88 vs. 25.75 ± 6.78 Nm; control: 38.80 ± 13.23 vs 30.14 ± 9.64 Nm). Controls had a greater exponential decline (lower time constant) in oxygen saturation compared with the stroke group (stroke time constant, 22.90 ± 10.26 min vs. control time constant, 5.46 ± 4.09 min; P < 0.001). Ischemia of the muscle resulted in greater neural inhibition of paretic motor units compared with controls and may contribute to deficient muscle activation poststroke. NEW & NOTEWORTHY Hyperexcitable inhibitory sensory pathways sensitive to ischemia may play a role in deficient motor unit activation post stroke. Using high-density surface electromyography recordings to detect motor unit firing instances, we show that ischemia of the exercising muscle results in greater inhibition of paretic motor unit firing rates compared with controls. These findings are impactful to neurophysiologists and clinicians because they implicate a novel mechanism of force-generating impairment poststroke that likely exacerbates baseline weakness.

The role of PLC-IP3 cascade on 4-aminopyridine (4-AP) contracture in electrically-driven rat atrial and diaphragmatic strips: new evidence by neomycin and heparin

Induction of cardiac contractures by 4-AP in Ca2+-free medium implied the involvement of SR and PLC-IP3 cascade. Thus, the role of PLC-IP3 cascade against contractile actions of 4-AP in electrically-driven rat atrial and diaphragmatic strips were studied both in the presence, and absence of Ca2+ using neomycin, a PLC inhibitor, and heparin, an IP3-R antagonist. 4-AP was applied cumulatively in logarithmically increasing concentrations in the range of 1-16µg/ml, and the preparations were treated with neomycin (400µM) or heparin (400µg/ml) for 3min prior to 4-AP injection. Post-rest potentiation in atrial strips was obtained by interruption of stimulation for 30min. 4-AP caused biphasic alteration in twitch amplitudes, as initially increased up to 16mM and then depressed due to contracture development, which were not affected significantly by neomycin and heparin. Both atrial and denervated diaphragmatic strips challenged to 4-AP in the presence and absence of Ca2+ developed dose dependent contractures which were significantly antagonized both by neomycin and heparin (p&lt;0.05). Post-rest first contractions in controls were found to be reduced by 2min exposure to 4mM 4-AP and augmented by 3min exposure to heparin alone. 4-AP responses in the presence of neomycin and heparin were significantly higher than with those only treated with 4-AP alone and lesser than controls. Because of the fact that 4-AP inducing contracture in Ca2+-free medium, Ca2+ causing contracture should be of SR in origin. Depending on these results, it was concluded that activation of PLC-IP3 cascade by 4-AP is involved in the mediation of contracture and contractile actions of this molecule.