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The effects of theophylline on aequorin light transients and force in the isolated dog right ventricular myocardium.

Experiments were carried out to investigate the changes in intracellular Ca2+ transients associated with biphasic contractions that were elicited during interaction of theophylline with isoproterenol in the dog ventricular myocardium. For this purpose, effects of theophylline and isoproterenol on aequorin light transients and isometric contractions were assessed in the isolated canine ventricular trabeculae, superficial cells of which had been microinjected with the Ca2+ sensitive bioluminescent protein aequorin. The positive inotropic effect of theophylline (0.1-0.3 mM) was consistently associated with an increase in the amplitude of aequorin light transients. Theophylline at concentrations of 0.6 mM and higher decreased the amplitude of aequorin light transients, but the force of contraction increased further in association with a prominent prolongation of time to peak force. Theophylline (0.3 mM) enhanced the forskolin-induced increase in aequorin light transients and force. Theophylline (2 mM) inhibited the isoproterenol-induced increase in aequorin light transients associated with early phase of contraction in a reversible manner. A late phase of aequorin light transients was induced in association with late phase of contraction in the presence of both isoproterenol and theophylline. Thus, both the early and late phase of contraction were accompanied by corresponding phases of aequorin light transients. The relation between the amplitude of force and Ca2+ transients was markedly different and the late phase of contraction was associated with much lower aequorin light transients. The late phase of aequorin light transients induced by theophylline at a high concentration (10 mM) was enhanced by isoproterenol. These results indicate that theophylline (0.1-0.3 mM) increases the amplitude of Ca2+ transients through an accumulation of cyclic AMP by inhibition of the cyclic AMP phosphodiesterase activity. In concentrations of 0.6 mM and higher theophylline decreases the amplitude of the early phase aequorin light transients probably by inhibition of release of Ca2+ from the sarcoplasmic reticulum and induces simultaneously the late phase of contraction that may be associated with an increase in responsiveness to Ca2+ of myofibrils.

Aequorin↗

Measurement of muscle contraction with ultrasound imaging.

To investigate the ability of ultrasonography to estimate muscle activity, we measured architectural parameters (pennation angles, fascicle lengths, and muscle thickness) of several human muscles (tibialis anterior, biceps brachii, brachialis, transversus abdominis, obliquus internus abdominis, and obliquus externus abdominis) during isometric contractions of from 0 to 100% maximal voluntary contraction (MVC). Concurrently, electromyographic (EMG) activity was measured with surface (tibialis anterior only) or fine-wire electrodes. Most architectural parameters changed markedly with contractions up to 30% MVC but changed little at higher levels of contraction. Thus, ultrasound imaging can be used to detect low levels of muscle activity but cannot discriminate between moderate and strong contractions. Ultrasound measures could reliably detect changes in EMG of as little as 4% MVC (biceps muscle thickness), 5% MVC (brachialis muscle thickness), or 9% MVC (tibialis anterior pennation angle). They were generally less sensitive to changes in abdominal muscle activity, but it was possible to reliably detect contractions of 12% MVC in transversus abdominis (muscle length) and 22% MVC in obliquus internus (muscle thickness). Obliquus externus abdominis thickness did not change consistently with muscle contraction, so ultrasound measures of thickness cannot be used to detect activity of this muscle. Ultrasound imaging can thus provide a noninvasive method of detecting isometric muscle contractions of certain individual muscles.

Adult↗

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

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

Adult↗

Role of limb movement in the modulation of motor unit discharge rate during fatiguing contractions.

Motor unit firing rates of the triceps brachii muscle have been shown to decline during sustained isometric contractions, but not if the fatiguing contraction incorporates arm movements. The purpose of this study was to determine the impact of the actual physical displacement of the limb on the maintenance of motor unit discharge rate during dynamic muscle fatigue. An isometric force pulse paradigm was used to recreate the motor unit activity patterns that occur during a dynamic contraction. With this paradigm, the variable force output that would occur during a dynamic contraction remained intact, but the movement of the limb was eliminated. Motor unit firing rates declined in the isometric force pulse protocol. Thus, factors related to the actual movement of the limb appear to enable the maintenance of motor unit discharge rates during fatigue.

Adult↗

Dynamics of crossbridge-mediated activation in the heart.

Both intracellular calcium and strongly bound crossbridges contribute to thin filament activation in the heart, but the magnitude and the duration of the effects due to crossbridges are not well characterized. In this study, crossbridge attachment was altered in tetanized ferret papillary muscles and changes in the rate constant for the recovery of force (k (TR)) and unloaded shortening velocity (V (U)) were measured to track thin filament activation. k (TR) decreased as the time the muscles spent at low levels of crossbridge attachment (shortening deactivation) increased (0.02 s=17.9+/-2.3 s(-1), 0.32 s=3.3+/-0.4 s(-1); half-time=0.052 s; P<0.05). Furthermore, the deactivation was reversible and k (TR) recovered when muscles were allowed to regenerate force isometrically during the same tetanus. V (U) also decreased when the preceding load was lower (isometric load, V (U)=1.93+/-0.26 muscle lengths/s (ML/s); zero load, V (U)=0.93+/-0.14 ML/s, P<0.05) and as the length of time the muscle spent unloaded increased (>60% decline after 0.3 s). In addition, V (U) recovered when the muscle was allowed to regenerate force isometrically. These results indicate that crossbridge attachment increases thin filament activation as reflected in measurements of V (U) and k (TR). This 'extra' activation by crossbridges appears to be a dynamic process that decays during unloaded shortening and redevelops during isometric contraction.

Animals↗

Human group I excitatory projections from ankle dorsiflexors to quadriceps muscle.

A short latency projection of group I afferent fibers from ankle dorsiflexors to knee extensor muscles has been categorized as species specific to humans. However, the effects of the pathway have only been inferred from conditioning homonymous reflexes in relaxed muscle. This study focused directly on the responses evoked in the electromyogram of the heteronymous muscles when active, in two experiments. In the first, preferential activation of group I afferents of ankle dorsiflexors, by electrical stimulation of the common peroneal nerve, excited both vastus medialis (mean latency, 26.3 ms) and rectus femoris (mean latency, 33.5 ms). No excitation or inhibition in either muscle was associated with stimulation of the tibial nerve. The second experiment compared vastus medialis responses with common peroneal nerve stimulation during three different movement conditions in which the muscle was equally contracted: rhythmic isotonic (pedalling); episodic isotonic; isometric contraction. Responses were identified in all three active states, with no significant differences in amplitude or latency. No responses were seen in the relaxed muscle.

Adult↗

Energetics of the time-varying elastance model, a visco-elastic model, matches Mommaerts' unifying concept of the Fenn effect of muscle.

It is generally believed that the Fenn effect contradicts all visco-elastic models of muscle, including the new elastic body and the time-varying elastance models. Although it is clear that the new elastic body model can be discarded, the Fenn effect does not preclude the time-varying elastance model. Although no visco-elastic models can simulate the extra energy utilization for work above the level of the energy utilized for the maximal isometric contraction, the extra energy observed by Fenn is not generally observed, even in skeletal muscles. However, work-related extra energy utilization, above the isometric energy utilization at equivalent force (Mommaerts' unifying concept of the Fenn effect), is generally observed in both skeletal and cardiac muscles. This unifying concept of the Fenn effect in cardiac muscle can be simulated by a simple time-varying elastance model. This study demonstrates the essential difference in energetics between the new elastic body model and the time-varying elastance model.

Elasticity↗

Stump length as related to atrophy and strength of the thigh muscles in trans-tibial amputees.

Stump length and the thigh muscles strength of the amputated limb are among the major factors influencing outcome of prosthetic rehabilitation of trans-tibial amputees. In the present study the authors evaluated and compared the strength of quadriceps and hamstrings muscles of both limbs in trans-tibial amputees, as measured by means of an electrical dynamometer. The obtained results showed that the thigh muscles of the sound limbs are significantly stronger than those of the amputated limbs (p < 0.01). The results obtained for amputees with shorter stumps were compared with those with longer stumps. In the group of amputees (n = 9) with a stump shorter than 15.1 cm, values of peak torque (in isokinetic contraction) and maximal average torque (in isometric contraction) were significantly (p < 0.5) weaker when compared to those (n = 9) with a stump longer than 15.1 cm. The results obtained for amputees with a higher rate of thigh muscle atrophy were compared to those with lesser atrophy. In the group of amputees where muscle atrophy was accompanied by decrease in thigh girth of over 5.9 cm, muscles strength did not significantly decrease (p < 0.5) as compared to amputees where thigh girth decrease was less than 5.9 cm. It is concluded that atrophy of the thigh muscles of trans-tibial amputees is accompanied with a significant decrease in strength. In amputees with a short stump, the short lever action provided by the stump interferes with the ability of the thigh muscles to control the prosthesis efficiently during daily activities such as standing and walking.

Activities of Daily Living↗

Neuromuscular variables affecting the magnitude of force loss after eccentric exercise.

The aim of this study was to examine neuromuscular variables contributing to differences in force loss after participants were exposed to the same relative bout of eccentric exercise. Thirty-six males performed 50 maximal eccentric contractions of the elbow flexors and were stratified into high responders (n = 10) and low responders (n = 10) based on force loss 36 h after exercise. Maximal voluntary isometric contractions (MVCs) and electromyography (EMG) were measured at baseline and 36 h after exercise. During eccentric exercise, mean peak torque, mean end-range torque from the final 25% of each trial and total angular impulse were computed over 25 contractions in each of two bouts. The slope of the change in these values for each 25 eccentric contractions was calculated for each participant using linear regression. At baseline, MVC was not different between groups (low responders: 97.0 +/- 9.6 N x m; high responders: 82.7 +/- 6.4 N x m; P = 0.08). High responders demonstrated a 68% (range 62-78%) reduction in MVC and low responders a 39% (29-48%) reduction after exercise. Peak torque, end-range torque and total angular impulse were 13%, 40% and 33% higher, respectively, in the low than in the high responders (peak torque: P = 0.0002; end-range torque: P < 0.0001; total angular impulse: P < 0.001). The rate of decline in peak torque slope was greater in high than in low responders (P = 0.044). In conclusion, lower peak torque, end-range torque and total angular impulse during eccentric contractions and a greater peak torque slope may identify high responders to eccentric exercise.

Adult↗

Ultrastructure of skeletal muscle fibers studied by a plunge quick freezing method: myofilament lengths.

We have set up a system to rapidly freeze muscle fibers during contraction to investigate by electron microscopy the ultrastructure of active muscles. Glycerinated fiber bundles of rabbit psoas muscles were frozen in conditions of rigor, relaxation, isometric contraction, and active shortening. Freezing was carried out by plunging the bundles into liquid ethane. The frozen bundles were then freeze-substituted, plastic-embedded, and sectioned for electron microscopic observation. X-ray diffraction patterns of the embedded bundles and optical diffraction patterns of the micrographs resemble the x-ray diffraction patterns of unfixed muscles, showing the ability of the method to preserve the muscle ultrastructure. In the optical diffraction patterns layer lines up to 1/5.9 nm-1 were observed. Using this method we have investigated the myofilament lengths and concluded that there are no major changes in length in either the actin or the myosin filaments under any of the conditions explored.

Actin Cytoskeleton↗

RyR isoforms and fibre type-specific expression of proteins controlling intracellular calcium concentration in skeletal muscles.

Muscle fibres which shorten with high maximum shortening velocity also exhibit fast kinetics of contraction, i.e. short values of time to peak tension and time to half relaxation. This short review aims to discuss the molecular basis of such correlation, to reach, based on the available literature, an answer to the question whether there is a correlation in expression of proteins determining shortening velocity, myosin isoforms in the first place, and proteins controlling cytosolic calcium concentration and its variations at rest or during contraction. Although the isoforms of RyR, the sarcoplasmic calcium release channels, do not show a tightly coordinated expression with myosin isoforms, other proteins involved in controlling intracellular calcium do. This is likely sufficient to guarantee the correlation between maximum shortening velocity and speed of isometric contraction.

Animals↗

Functional neurochemical evidence for the presence of presynaptic nicotinic acetylcholine receptors at the terminal region of myenteric motoneurons: a study with epibatidine.

The aim of this study was to verify the presence of presynaptic nicotinic acetylcholine receptors (nAChRs) at the terminals of myenteric motoneurons using a potent and highly selective nicotinic agonist, epibatidine. We examined contraction, and release of [3H]ACh on a guinea-pig longitudinal muscle strip preparation. First, we compared the ability of epibatidine and nicotine to induce isometric contraction and found epibatidine (EC50 = 23.1 nM) to be 300-fold more potent than nicotine (EC50 = 7.09 microM). The release and contraction induced by 30 nM epibatidine were inhibited by the nicotinic antagonist mecamylamine (3 microM) and the Na(+)-channel blocker TTX (1 microM), indicating that the effects are mediated via nAChRs and are fully dependent on the propagation of action potentials. Atropine (0.1 microM) significantly increased the [3H]ACh release but could not block contraction suggesting that a substantial part of the response develops via a noncholinergic mechanism. Epibatidine at a higher concentration (300 nM) induced contraction, which was only partly (45%) inhibited by TTX (1 microM). The TTX-resistant contraction, however, was completely blocked by mecamylamine (3 microM). Our data provide functional neurochemical evidence for the existence of presynaptic nAChRs at myenteric motoneuron terminals and suggest that these receptors can be activated only/by a higher concentration of agonists.

Acetylcholine↗

Role of the sodium-calcium exchange mechanism and the effect of magnesium on sodium-free and high-potassium contractures in pregnant human myometrium.

OBJECTIVE: Periodic uterine relaxation in labor relieves the fetus from hypoxia related to sustained contractions. A reduction in intracellular calcium is essential for relaxation. Therefore we aimed to clarify the extrusion mechanisms of intracellular calcium ions in pregnant human myometrium. STUDY DESIGN: Isometric contraction of small muscle bundles obtained from human myometrium at term was recorded. High-potassium and sodium-free solutions could induce stable contractures that revealed initial phasic contractions followed by tonic contractions. The effects of external calcium, external magnesium, nifedipine, and calcium adenosine triphosphatase inhibitors on both contractures were then examined. RESULTS: Because maximum tonic contraction was induced by 48 mmol/L potassium, this concentration was used. Both contractures depended on external calcium concentrations. Nifedipine, 10(-7) mol/L inhibited both initial phasic contractions and the tonic phase of the high-potassium contracture; however, it could not suppress the tonic phase of the sodium-free contracture. Calcium adenosine triphosphatase inhibitors, cyclopiazonic acid and lauryl sulfate, potentiated the tensions of tonic phases in both contractures; the effect of lauryl sulfate was stronger than that of cyclopiazonic acid. When external magnesium was gradually increased (from 0 to 9.6 mmol/L), both phasic contractions and the tonic phase of the high-potassium contracture transiently increased, followed by a reduction of tension, whereas the tonic phase of the sodium-free contracture was markedly inhibited by magnesium in a dose-dependent manner. CONCLUSION: The presence of the sodium-calcium exchange mechanism and the specific inhibitory effect of magnesium were indicated in human myometrium during pregnancy. These mechanisms might prevent the long tonic contractions, to protect the fetus from hypoxia during pregnancy and parturition.

Calcium-Transporting ATPases↗

Neurokinin receptors mediating substance P-induced contraction in adult rabbit airways.

Airway contractile responses to substance P (SP) were examined in isolated adult rabbit bronchial (BSM) and tracheal smooth muscle (TSM) segments. The tissues were placed in organ baths containing modified Krebs-Ringer solution, and isometric contractions to SP were monitored in the presence of phosphoramidon, an inhibitor of neutral endopeptidase (NEP). Under these conditions, BSM segments were significantly more reactive and more sensitive to SP than TSM segments. Removal of SPs cholinergic component with atropine (ATP) eliminated these regional differences in reactivity without affecting sensitivity. In considering the basis for these observations, it has been suggested that SP activates up to three different neurokinin (NK) subset receptors. Accordingly, we examined the regional airway contractile responses to Senktide, a selective NK-3 receptor agonist, and Septide, a selective NK-1 receptor agonist. In the presence of ATR, Senktide was inactive in both BSM and TSM, whereas Septide produced significantly greater contractions in BSM than in TSM. Subsequent desensitization of NK-1 receptors with Septide virtually eliminated the regional differences in airway sensitivity to SP. These findings indicate that 1) endogenous NEP activity can mask significant regional airway differences in SP-mediated contraction; and 2) these latter differences are the result of cholinergic, NK-1, and NK-2 receptor influences.

Animals↗

[Mechanomyography - results in a normal population and in patients with thyroid dysfunction (author's transl)].

Isometric contraction of the adductor pollicis by stimulating the ulnar nerve was determined in 20 normal adult subjects. We measured mechanical latency, electro-mechanical latency, contraction time, time to half relaxation and isometric twitch force. Besides that we registered the compound muscle action potential and the nerve conduction velocity. The median nerve was used to elicit the nerve action potential and to determine conduction velocity and relative refractory period. In 6 pat. with hypothyroidism and in 7 pat. with hyperthyroidism the above mentioned parameters were measured. There was a significant change concerning contractile properties, i.e. muscular contraction became slower in hypothyroidism and faster in hyperthyroidism as compared to values obtained in the control group. The isometric twitch force was reduced in both conditions. To assure the close relationship between thyroid hormone (L-thyroxin) and muscle contraction a group of patients who have undergone thyroidectomy was investigated in the same way. Muscle and nerve parameters were determined during a levothyroxin-therapy and in a period without any treatment. The same phenomenon was observed, i.e. reduction of twitch velocity in the hypothyroid state. The twitch force was not reduced in this group. The close relationship between thyroid hormone and contractile properties allows a discrimination between hypo-and hyperthyroid state and a control of thyroxin substitution.

Electric Stimulation↗

Effects of dehydration and rehydration on EMG changes during fatiguing contractions.

PURPOSE: This study measured the effects of sauna-induced dehydration (Dhy) and the effectiveness of rapid rehydration on muscle performance and EMG frequency spectrum changes associated with fatigue during isometric contractions. METHODS: Knee extensor muscle strength during isometric maximal voluntary contraction (MVC) and endurance time at 25% and 70% of MVC (ET25 and ET70, respectively) were measured three times in 11 healthy male subjects, under euhydration conditions (Eu), after Dhy, and after rehydration following Dhy (Rhy). RESULTS: Dhy led to a decrease in body weight by 2.95 +/- 0.05%. No significant effect of the hydration status was shown on MVC values. A 23% decrease in ET25 was recorded during Dhy (P < 0.01), whereas ET70 only tended to decrease (-13%, P = 0.06). ET25 was higher during Rhy than Dhy (8%, P < 0.05) but remained lower than during Eu (-17%, P < 0.05). The EMG root mean square (RMS) increased earlier during Dhy than Eu. Opposite changes were shown for the mean power frequency (MPF) of EMG, and Dhy resulted in an accelerated fall in MPF. However, because ET25 decreased with dehydration, RMS and MPF changes were similar during Eu and Dhy when reported to normalized contraction time, exhaustion was thus associated with similar values of RMS and MPF for all conditions. RMS and MPF changes during Rhy showed an intermediate pattern between Eu and Dhy. CONCLUSIONS: Dhy induced an increase in muscle fatigue, associated with early changes in EMG spectral parameters. It is not clear whether these alterations could be attributed to biochemical modifications, and the role of increased perception of effort when subjects were dehydrated should be clarified.

Adult↗

The effect of pectoralis muscle training in tetraplegic subjects.

We have previously shown that subjects with traumatic tetraplegia use the clavicular portion of the pectoralis major to expire actively. To determine if we could improve the expiratory function of these subjects, we studied six patients in whom the pectoralis major was trained by repetitive, strenuous, isometric contractions for 6 wk. Six patients receiving conventional respiratory rehabilitation served as control subjects. Training of the pectoralis major produced marked increases in the maximal isometric muscle strength (mean +/- SE: 54.6 +/- 5.8%; p less than 0.005) and in expiratory reserve volume (46.6 +/- 9.9%; p less than 0.005). Functional residual capacity did not change, such that residual volume decreased by 14.1 +/- 2.9% (p less than 0.005). In contrast, the control patients did not develop any significant alterations. We conclude that unlike conventional rehabilitation, training the pectoralis major for strength improves expiratory function in tetraplegic subjects. Therefore, training of this muscle should increase the effectiveness of coughing and might reduce the prevalence of bronchopulmonary infections in such subjects.

Adult↗

Relationships of the surface electromyogram to the force, length, velocity, and contraction rate of the cineplastic human biceps.

A series of experiments was performed to measure the relationships between the integrated surface EMG and the mechanical state of the cineplastic biceps muscle of one subject. The muscle was studied during static and dynamic isometric contractions at different muscle lengths and during constant velocity isotonic contractions at different loads. The cineplastic biceps results are compared with results obtained from the intact biceps.

Arm↗