Force dynamic response of tibialis anterior-ankle joint unit in humans.

The aim of this study was to estimate the dynamic response of a human muscle joint unit by means of the analysis of the torque signal recorded during electrical stimulation of the tibialis anterior (TA). Ten subjects (age: 23-50 years, 7 males, 3 females) volunteered for the study. The leg was fixed in an ergometer designed for isometric contraction of the ankle dorsiflexors and the detection of the generated torque. The amplitude of a 30 Hz stimulation train administered at the TA motor point was varied sinusoidally, thus changing the number of the recruited motor units, and hence the tension at the tendon, in the same fashion. A sequence of 14 frequencies (0.4, 0.6, 0.8, 1.0, 1.2, 1.4, 1.6, 1.8, 2.0, 2.5, 3.0, 4.0, 5.0, and 6.0 Hz) was administered. RESULTS: (a) at the 14 frequencies the sinusoidal responses presented distortions always below 2%; (b) from the Bode plots reporting the average gain attenuation and phase shift at each of the 14 input frequencies, it was possible to model the force dynamic response as the one of a critically damped II order system with two real coincident poles (at 2.04 Hz) and a pure time delay (15.6 ms). The possibility to obtain, by means of the system input-output transfer function, data regarding the in vivo mechanics of the muscle-joint unit may represent a novel tool to investigate the functional features of different muscle groups. It may be useful for designing functional electrical stimulation programs as well as training and rehabilitation procedures.     

Muscular sound and force relationship during isometric contraction in man

The contracting muscle generates a low frequency sound detectable at the belly surface, ranging from 11 to 40 Hz. To study the relationship between the muscular sound and the intensity of the contraction a sound myogram (SMG) was recorded by a contact sensor from the biceps brachii of seven young healthy males performing 4-s isometric contractions from 10% to 100% of the maximal voluntary contraction (MVC), in 10% steps. Simultaneously, the electromyogram (EMG) was recorded as an index of muscle activity. SMG and EMG were integrated by conventional methods (iSMG and iEMG). The relationship between iSMG and iEMG vs MVC% is described by parabolic functions up to 80% and 100% MVC respectively. Beyond 80% MVC the iSMG decreases, being about half of its maximal value at 100% MVC. Our results indicate that the motor unit recruitment and firing rate affect the iSMG and iEMG in the same way up to 80% MVC. From 80% to 100% MVC the high motor units' discharge rate and the muscular stiffness together limit the pressure waves generated by the dimensional changes of the active fibres. The muscular sound seems to reflect the intramuscular visco-elastic characteristics and the motor unit activation pattern of a contracting muscle.     

Plasma norepinephrine and heart rate dynamics during recovery from submaximal exercise in man

The time course of heart rate (HR) and venous blood norepinephrine concentration [NE], as an expression of the sympathetic nervous activity (SNA), was studied in six sedentary young men during recovery from three periods of cycle ergometer exercise at 21% +/- 2.8%, 43% +/- 2.1% and 65% +/- 2.3% of VO2max respectively (mean +/- SE). The HR decreased mono-exponentially with tau values of 13.6 +/- 1.6 s, 32.7 +/- 5.6 s and 55.8 +/- 8.1 s respectively in the three periods of exercise. At the low exercise level no change in [NE] was found. At medium and high exercise intensity: (a) [NE] increased significantly at the 5th min of exercise (delta [NE] = 207.7 +/- 22.5 pg.ml-1 and 521.3 +/- 58.3 pg.ml-1 respectively); (b) after a time lag of 1 min [NE] decreased exponentially (tau = 87 s and 101 s respectively); (c) in the 1st min HR decreased about 35 beats.min-1; (d) from the 2nd to 5th min of recovery HR and [NE] were linearly related (100 pg.ml-1 delta [NE] congruent to 5 beats.min-1). In the 1st min of recovery, independent of the exercise intensity, the adjustment of HR appears to have been due mainly to the prompt restoration of vagal tone. The further decrease in HR toward the resting value could then be attributed to the return of SNA to the pre-exercise level.     

Overexpression of sialidase NEU3 increases the cellular radioresistance potential of U87MG glioblastoma cells

The plasma membrane-associated sialidase NEU3 is known to play important roles in different physiological and pathophysiological processes such as proliferation, cellular differentiation and tumorigenesis. Up-regulation of NEU3 has been associated to several tumors and recently it was demonstrated that its down-modulation in glioblastoma cells promotes cell invasiveness. To date, no information concerning the possible role played by NEU3 in relation to tumor radioresistance is available. Here we show that overexpression of NEU3 in glioblastoma U87MG cells activates PI3K/Akt signaling pathway resulting in an increased radioresistance capacity and in an improved efficiency of double strand DNA-repair mechanisms after irradiation. Our results demonstrate for the first time that NEU3 contributes to the radioresistance features of U87MG cells, bringing to evidence a novel rand peculiar role of the enzyme in cancer biology.     

Force and surface mechanomyogram frequency responses in cat gastrocnemius

Muscle surface displacement is a mechanical event taking place simultaneously with the tension generation at the tendon. The two phenomena can be studied by the surface mechanomyogram signal (MMG) (produced by a laser distance sensor) and the force signal (from a load cell). The aim of this paper was to provide data on the reliability of the laser detected MMG in muscle mechanics research. To this purpose it was verified if the laser detected MMG was suitable to estimate a frequency response in the cat medial gastrocnemius and its frequency response was compared with the one retrieved by the force signal at the tendon level. The force and MMG from the exposed medial gastrocnemius of four cats were analysed. The frequency response was investigated by sinusoidally changing the number of orderly recruited motor units, in different trials, in the 0.4-6 Hz range. It resulted that it was possible to model the force and MMG frequency response by a critically damped second-order system with two real double poles and a pure time delay. On the average, the poles were at 1.83 Hz (with 22.6 ms delay) and at 2.75 Hz (with 38 ms delay) for force and MMG, respectively. It can be concluded that MMG appears to be a reliable tool to investigate the muscle frequency response during stimulated isometric contraction. Even though not statistically significant. the differences in the second-order system parameters suggest that different components of the muscle mechanical model may specifically affect the force or MMG.     

Force and surface mechanomyogram relationship in cat gastrocnemius.

The aim of this study was to compare the force (F) and the muscle transverse diameter changes during electrical stimulation of the motor nerve. In four cats the exposed motor nerves of the medial gastrocnemius were stimulated as follows: (a) eight separate trials at fixed firing rates (FR) from 5 to 50 Hz (9 s duration, supramaximal amplitude); (b) 5 to 50 Hz linear sweep in 2.5, 5, 7.5 and 10 s (supramaximal amplitude, separate trials); (c) four separate trials at 40 Hz, the motor units (MUs) being orderly recruited in 2.5, 5, 7.5 and 10 s. The muscle surface displacement was detected by a laser distance sensor pointed at the muscle surface. The resulting electrical signal was termed surface mechanomyogram (MMG). In stimulation patterns (a) and (b) the average F and MMG increased with FR. With respect to their values at 50 Hz the amplitude of the unfused signal oscillations at 5 Hz was much larger in MMG than in force. The signal rising phase was always earlier in MMG than in F. In (c) trials, F increased less in the first than in the second half of the recruiting time. MMG had an opposite behaviour. The results indicate that the force and the lateral displacement are not linearly related. The different behaviour of F and MMG, from low to high level of the MUs' pool activation, suggests that the force generation and the muscle dimensional change processes are influenced by different components of the muscle mechanical model.     

Investigation of motor unit recruitment during stimulated contractions of tibialis anterior muscle

This work investigated motor unit (MU) recruitment during transcutaneous electrical stimulation (TES) of the tibialis anterior (TA) muscle, using experimental and simulated data. Surface electromyogram (EMG) and torque were measured during electrically-elicited contractions at different current intensities, on eight healthy subjects.EMG detected during stimulation (M-wave) was simulated selecting the elicited MUs on the basis of: (a) the simulated current density distribution in the territory of each MU and (b) the excitation threshold characteristic of the MU. Exerted force was simulated by adding the contribution of each of the elicited MUs. The effects of different fat layer thickness (between 2 and 8 mm), different distributions of excitation thresholds (random excitation threshold, higher threshold for larger MUs or smaller MUs), and different MU distributions within the muscle (random distribution, larger MU deeper in the muscle, smaller MU deeper) on EMG variables and torque were tested.Increase of the current intensity led to a first rapid increase of experimental M-wave amplitude, followed by a plateau. Further increases of the stimulation current determined an increase of the exerted force, without relevant changes of the M-wave. Similar results were obtained in simulations.Rate of change of conduction velocity (CV) and leading coefficient of the second order polynomial interpolating the force vs. stimulation level curve were estimated as a function of increasing current amplitudes. Experimental data showed an increase of estimated CV with increasing levels of the stimulation current (for all subjects) and a positive leading coefficient of force vs. stimulation current curve (for five of eight subjects). Simulations matched the experimental results only when larger MUs were preferably located deeper in the TA muscle (in line with a histochemical study). Marginal effect of MU excitation thresholds was observed, suggesting that MUs closer to the stimulation electrode are recruited first during TES regardless of their excitability.     

Changes of the force-frequency relationship in human tibialis anterior at fatigue.

This work estimates the influence of the single twitch (ST) parameters changes on specific regions of the force-frequency relationship (FFR) in fatigued human tibialis anterior (TA). In 20 subjects (age 20-40) the TA underwent three stimulation phases: (a) five STs at 1 Hz followed by 5 s stimulation with increasing rate (1-50 Hz, to obtain FFR); (b) fatiguing stimulation (35 Hz for 40 s); (c) same as in "a". By the average STs (mean of the five responses) of a and c phases, the peak twitch (Pt) was calculated. Moreover, after ST normalization to Pt, the maximum contraction rate (MCR) and the maximum relaxation rate (MRR) were computed. By the FFR, normalized to the 50 Hz force, we first defined the threshold frequency (TF) when the force oscillation presented the same value in (a) and (c), and then the areas below the FFR in the 1 Hz-TF and in the TF-50 Hz ranges. RESULTS: In unfatigued and fatigued muscle Pt, and MRR changed from 6.12 +/- 3.08 to 3.27 +/- 1.16 N and from 0.87 +/- 0.13 to 0.65 +/- 0.09% Pt/ms, respectively. MCR did not change significantly. The 1 Hz-TF area ratio (c/a) was > 1 for muscles having fatigued Pt > 60% of its basal value. The TF-50 Hz area ratio (c/a) was mostly below 1. CONCLUSIONS: At fatigue, MRR reduction, leading to a better fusion of muscle mechanical output, is able to compensate, in the 1 Hz-TF frequency range, up to 40% Pt loss; beyond TF, the changes of FFR are related to the degree of force loss indicated by the fatigued Pt.     

Surface mechanomyogram reflects the changes in the mechanical properties of muscle at fatigue

The contractile properties of muscle are usually investigated by analysing the force signal recorded during electrically elicited contractions. The electrically stimulated muscle shows surface oscillations that can be detected by an accelerometer; the acceleration signal is termed the surface mechanomyogram (MMG). In the study described here we compared, in the human tibialis anterior muscle, changes in the MMG and force signal characteristics before, and immediately after fatigue, as well as during 6 min of recovery, when changes in the contractile properties of muscle occur. Fatigue was induced by sustained electrical stimulation. The final aim was to evaluate the reliability of the MMG as a tool to follow the changes in the mechanical properties of muscle caused by fatigue. Because of fatigue, the parameters of the force peak, the peak rate of force production and the peak of the acceleration of force production (d2F/dt2) decreased, while the contraction time and the half-relaxation time (1/2-RT) increased. The MMG peak-to-peak (p-p) also decreased. The attenuation rate of the force oscillation amplitude and MMG p-p at increasing stimulation frequency was greater after fatigue. With the exception of 1/2-RT, all of the force and MMG parameters were restored within 2 min of recovery. A high correlation was found between MMG and d2F/dt2 in un-fatigued muscle and during recovery. In conclusion, the MMG reflects specific aspects of muscle mechanics and can be used to follow the changes in the contractile properties of muscle caused by localised muscle fatigue.     

Kinetics of heart rate and catecholamines during exercise in humans The effect of heart denervation

To elucidate the role of factors other than the nervous system in heart rate (f _c) control during exercise, the kinetics off _c and plasma catecholamine concentrations were studied in ten heart transplant recipients during and after 10-min cycle ergometer exercise at 50 W. Thef _c did not increase at the beginning of the exercise for about 60 s. Then in the eight subjects who completed the exercise it increased following an exponential kinetic with a mean time constant of 210 (SEM 22) s. The two other subjects were exhausted after 5 and 8 min of exercise during whichf _c increased linearly. At the cessation of the exercise,f _c remained unchanged for about 50 s and then decreased exponentially with a time constant which was unchanged from that at the beginning of exercise. In the group of eight subjects plasma noradrenaline concentration ([NA]) increased after 30 s to a mean value above resting of 547 (SEM 124) pg · ml^–1, showing a tendency to a plateau, while adrenaline concentration ([A]) did not increase significantly. In the two subjects who became exhausted an almost linear increase in [NA] occurred up to about 1,300 pg · ml^–1 coupled with a significant increase in [A]. During recovery an immediate decrease in [NA] was observed towards resting values. The values of thef _c increase above resting levels determined at the time of blood collection were linearly related with [NA] increments both at the beginning and end of exercise with a similar slope, i.e. about 2.5 beats · min^–1 per 100 pg · ml^–1 of [NA] change. These findings would seem to suggest that in the absence of heart innervation the increase inf _c depends on plasma [NA].