Viscous properties of human muscle during contraction.

The purpose of this study was to determine viscous properties of human muscle during plantarflexion efforts. Experiments were performed on 17 subjects with an ankle ergometer allowing sinusoidal oscillations during isometric contractions and isokinetic movements. Sinusoidal oscillations led to the expression of (i) Bode diagrams of the musculo-articular system allowing the determination of a damping coefficient (Bbode); and (ii) a viscous coefficient (Bsin) using an adaptation of Hill's equation to sinusoidal oscillations. Isokinetic movements led to torque-velocity relationships. They showed a fall in torque associated to an increase in angular velocity what was quantified by calculating a damping coefficient (Biso). Both experiments gave consistent results indicating that Bbode was the lowest viscous parameter. This difference is discussed in terms of (i) "analog" viscosity originating from muscle cross-bridges; and (ii) real mechanical damping of passive structures.     

New insights into the behavior of muscle during active lengthening.

A muscle fiber was modeled as a series-connected string of sarcomeres, using an A. V. Hill type model for each sarcomere and allowing for some random variation in the properties of the sarcomeres. Applying stretches to this model led to the prediction that lengthening of active muscle on or beyond the plateau of the length tension curve will take place very nonuniformly, essentially by rapid, uncontrolled elongation of individual sarcomeres, one at a time, in order from the weakest toward the strongest. Such a "popped" sarcomere, at least in a single fiber, will be stretched to a length where there is no overlap between thick and thin filaments, and the tension is borne by passive components. This prediction allows modeling of many results that have previously been inexplicable, notably the permanent extra tension after stretch on the descending limb of the length tension curve, and the continued rise of tension during a continued stretch.     

Modulation of passive force in single skeletal muscle fibres

In this study, we investigated the effects of activation and stretch on the passive force-sarcomere length relationship in skeletal muscle. Single fibres from the lumbrical muscle of frogs were placed at varying sarcomere lengths on the descending limb of the force-sarcomere length relationship, and tetanic contractions, active stretches and passive stretches (amplitudes of ca 10% of fibre length at a speed of 40% fibre length/s) were performed. The passive forces following stretch of an activated fibre were higher than the forces measured after isometric contractions or after stretches of a passive fibre at the corresponding sarcomere length. This effect was more pronounced at increased sarcomere lengths, and the passive force-sarcomere length relationship following active stretch was shifted upwards on the force axis compared with the corresponding relationship obtained following isometric contractions or passive stretches. These results provide strong evidence for an increase in passive force that is mediated by a length-dependent combination of stretch and activation, while activation or stretch alone does not produce this effect. Based on these results and recently published findings of the effects of Ca2+ on titin stiffness, we propose that the observed increase in passive force is caused by the molecular spring titin.     

Force enhancement above the initial isometric force on the descending limb of the force-length relationship

Edman et al. (J. General Physiol. 80 (1982) 769) observed in single fibres of frog that the steady-state forces following active fibre stretch were greater than the purely isometric force obtained at the length from which the stretch was initiated. Operating on the descending limb of the force-length relationship, such a result can only be explained within the framework of the sarcomere length non-uniformity theory, if some fibre segments shortened during the fibre stretch. However, such a result was not found, leaving Edman's observation unexplained. Force enhancement above the initial isometric force has not been investigated systematically in whole muscle, and therefore it is not known whether this property is also part of whole muscle mechanics. The purpose of this study was to test if the steady-state forces following active stretch of cat semitendinosus were greater than the corresponding purely isometric forces at the muscle length from which the stretch was started. Cat semitendinosus was stretched by various amounts on the descending limb of the force-length relationship, and the steady-state forces following these stretches were compared to the corresponding isometric forces at the initial and final muscle lengths. In 109 of 131 tests, the steady-state forces following stretching were greater than the isometric forces at the initial muscle lengths. Force enhancement increased with increasing amounts of stretching, and force enhancement above the initial isometric force was more likely to occur following stretches of great compared to small amplitude. Passive forces following active muscle stretching were often significantly greater than the passive forces at the same muscle length following an isometric contraction or a passive stretching of the muscle. This observation was made consistently at the longest muscle lengths tested. It appears, therefore, that there is a passive force that accounts for part of the force enhancement above the isometric force at the initial muscle length, and that provides increased passive force when a muscle is actively, rather than passively, stretched at long muscle lengths. We conclude that cat semitendinosus demonstrates steady-state force enhancement above the corresponding purely isometric force at the initial muscle length on the descending limb of the force-length relationship for many contractile conditions, and that a unique, and so far undetected, passive, parallel element contributes to this force enhancement, particularly at long muscle lengths where muscle is assumed to be most vulnerable to injuries associated with sarcomere length instability.     

Neutrophil accumulation following passive stretches contributes to adaptations that reduce contraction-induced skeletal muscle injury in mice.

Skeletal muscles can be injured by their own contractions, especially when the muscle is stretched during a lengthening contraction. Exposing a muscle to a conditioning protocol of stretches without activation (passive stretches) before lengthening contractions reduces contraction-induced injury. Although passive stretching does not damage muscle fibers, neutrophils are elevated in the muscle after passive stretches. Our purpose was to investigate the relationship between neutrophil accumulation following passive stretches and the protection from subsequent contraction-induced injury provided by the passive stretches. Our hypothesis was that passive stretch conditioning would not provide protection from subsequent lengthening contraction-induced injury under circumstances when the increase in muscle neutrophils in response to the conditioning was prevented. Extensor digitorum longus muscles of mice were conditioned with passive stretches 14 days before exposure to a protocol of damaging lengthening contractions. Mice were either untreated or treated with an antibody (RB6-8C5) that reduced the level of circulating neutrophils by over 95% before administration of passive stretches. Neutrophil levels recovered in treated mice by the time lengthening contractions were performed. Lengthening contractions were also administered to muscles with no prior exposure to passive stretches. Maximum isometric force, number of damaged fibers, and muscle neutrophil concentration were measured 3 days after lengthening contractions. Compared with nonconditioned control muscles, the severity of contraction-induced injury was not reduced by prior passive stretch conditioning when mice were treated with RB6-8C5 before conditioning. We conclude that neutrophils contribute to adaptations that protect muscles from injury.     

Rises in whole muscle passive tension of mammalian muscle after eccentric contractions at different lengths.

This is a report of experiments carried out on the medial gastrocnemius muscle of the anesthetized cat, investigating the effects of eccentric contractions carried out at different muscle lengths on the passive and active length-tension relationships. In one series of experiments, the motor supply to the muscle was divided into three approximately equal parts; in the other, whole muscles were used. Fifty eccentric contractions were carried out over different regions of the active length-tension curve for each partial or whole muscle. Active and passive length-tension curves were measured before and after the eccentric contractions. When eccentric contractions were carried out at longer lengths, there was a larger shift of the optimum length for active tension in the direction of longer muscle lengths and a larger fall in peak isometric tension. Passive tension was higher immediately after the eccentric contractions, and if the muscle was left undisturbed for 40 min, it increased further to higher values, particularly after contractions at longer lengths. A series of 20 passive stretches of the same speed and amplitude and covering the same length range as the active stretches, reduced the passive tension which redeveloped over a subsequent 40-min period. It is hypothesized that there are two factors influencing the level of passive tension in a muscle after a series of eccentric contractions. One is injury contractures in damaged muscle fibers tending to raise passive tension; the other is the presence of disrupted sarcomeres in series with still-functioning sarcomeres tending to reduce it.     

Residual force enhancement after lengthening is present during submaximal plantar flexion and dorsiflexion actions in humans.

Stretch of an activated muscle causes a transient increase in force during the stretch and a sustained, residual force enhancement (RFE) after the stretch. The purpose of this study was to determine whether RFE is present in human muscles under physiologically relevant conditions (i.e., when stretches were applied within the working range of large postural leg muscles and under submaximal voluntary activation). Submaximal voluntary plantar flexion (PF(v)) and dorsiflexion (DF(v)) activation was maintained by providing direct visual feedback of the EMG from soleus or tibialis anterior, respectively. RFE was also examined during electrical stimulation of the plantar flexion muscles (PF(s)). Constant-velocity stretches (15 degrees /s) were applied through a range of motion of 15 degrees using a custom-built ankle torque motor. The muscles remained active throughout the stretch and for at least 10 s after the stretch. In all three activation conditions, the stable joint torque measured 9-10 s after the stretch was greater than the isometric joint torque at the final joint angle. When expressed as a percentage of the isometric torque, RFE values were 7, 13, and 12% for PF(v), PF(s), DF(v), respectively. These findings indicate that RFE is a characteristic of human skeletal muscle and can be observed during submaximal (25%) voluntary activation when stretches are applied on the ascending limb of the force-length curve. Although the underlying mechanisms are unclear, it appears that sarcomere popping and passive force enhancement are insufficient to explain the presence of RFE in these experiments.     

Muscle inflammatory cells after passive stretches, isometric contractions, and lengthening contractions.

We tested the hypotheses that lengthening contractions, isometric contractions, and passive stretches increase muscle inflammatory cells (neutrophils and macrophages) and that prior conditioning with lengthening contractions, isometric contractions, or passive stretches reduces neutrophils and macrophages after subsequent lengthening contractions. Extensor digitorum longus muscles in anesthetized mice were subjected in situ to lengthening contractions, isometric contractions, or passive stretches. Six hours or 3 days after a protocol of contractions or passive stretches, neutrophils and macrophages were quantified in muscle cross sections. Three days after isometric contractions or passive stretches, neutrophils were elevated (P < 0.05) 3.7- and 5.5-fold, respectively, relative to controls. Both macrophages and neutrophils were increased 51.2- and 7.9-fold, respectively, after lengthening contractions. Prior lengthening contractions, isometric contractions, or passive stretches reduced inflammatory cells after lengthening contractions performed 2 wk later. The major finding of this study was that passive stretches and isometric contractions elevated neutrophils without causing overt signs of injury. Because both passive stretches and isometric contractions elevated neutrophils and afforded some protection from contraction-induced muscle injury, neutrophils and/or the related inflammatory events may contribute to the induction of a protective mechanism.     

Effect of the pacing interval and extrasystole on amplitude and damping of diastolic oscillations in the rabbit papillary muscle

Diastolic mechanical oscillations of right ventricular rabbit papillary muscles investigated at 15 degrees C in the perfusion chamber were analysed using a relaxation model with 6 parameters. From this analysis follows that the first diastolic oscillation amplitude plotted against the driving interval ("interval amplitude curve" of the first diastolic oscillation) shows tow maxima thus differing from the shape of the interval strength curve of the preceding driven contraction. It is concluded that the amplitude of diastolic oscillations is less determined by the Ca-amount released from the sarcoplasmic reticulum during the action potential than by the frequency of processes which effect the Ca release and the Ca-sequestration. The damping ratio varies within the range of tested driving intervals (0.36 to 10 s). After an extrasystole damping ratio and period of diastolic oscillation are diminished compared with the values after regularly driven contractions.     

Series elasticity in frog sartorius muscle during release and stretch

When a stretch is applied to an isolated muscle during tetanic stimulation, the force developed is higher than the maximal isometric tension (Po). This force puts the series elastic component (SEC) under tension and in a domain which is not well defined in terms of tension-extension curve. In the present work, an attempt was made to determine the stiffness of the SEC for tensions greater than Po, using the sartorius muscle of the frog. For this purpose, rapid releases and stretches of different amplitudes were given during maximal isometric contractions. Plotting normalized tension (P/Po) against normalized length changes (negative or positive extensions, delta L/Lo.10(2] produced a tension-extension curve. The slopes of the linear part of each relationship on both sides of Po indicated an increase in SEC stiffness when the muscle was rapidly stretched. Furthermore, the transient character of the increase in stiffness was studied by measuring SEC stiffness during rapid releases applied at various time intervals after stretches: the muscle was found to be stiffer as the time interval was shorter. The results are discussed in terms of (i) non-linear behaviour of the passive and active parts of the SEC, (ii) enhancement of storage and release of potential energy.     

Correlation between active and passive isometric force and intramuscular pressure in the isolated rabbit tibialis anterior muscle

The purpose of this study was to quantify the relationship between intramuscular pressure (IMP) and muscle force during isometric muscle contraction of the rabbit tibialis anterior (TA) absent the effect of either bone or fascia. To quantify this relationship, length-tension experiments were performed on the isolated TA of the New Zealand White rabbit (mass=2.5+/-0.5kg, n=12). The knee was fixed in a custom jig, the distal tendon of the TA was attached to a servomotor, and a 360 microm fiber optic pressure transducer was inserted into the TA. The peroneal nerve was stimulated to define optimal length (L(0)). The length-tension curve was created using 40Hz isometric contractions with 2-min rest intervals between each contraction. Measurements began at L(0)-50%L(f) and progressed to L(0)+50%L(f), changing the length-tension in 5% L(f) increments after each contraction. Qualitatively, the length-tension curve for isometric contractions was mimicked by the length-pressure curve for both active and passive conditions. Linear regression was performed individually for each animal for the ascending and descending limb of the length-tension curve and for active and passive conditions. Pressure-force coefficients of determination ranged from 0.138-0.963 for the active ascending limb and 0.343-0.947 for the active descending limb. Passive pressure coefficients of determination ranged from 0.045-0.842 for the ascending limb and 0.672-0.982 for the descending limb. These data indicate that IMP measurement provide a fairly accurate index of relative muscle force, especially at muscle lengths longer than optimal.     

The effects of muscle stretching and shortening on isometric forces on the descending limb of the force-length relationship

The purpose of this study was to examine the effects of stretching and shortening on the isometric forces at different lengths on the descending limb of the force-length relationship. Cat soleus (N = 10) was stretched and shortened by various amounts on the descending limb of the force-length relationship, and the steady-state forces following these dynamic contractions were compared to the isometric forces at the corresponding muscle lengths. We found a shift of the force-length relationship to greater force values following muscle stretching, and to smaller force values following muscle shortening. Shifts in both directions critically depended on the magnitude of stretching/shortening and the final muscle length. We confirm recent findings that the steady-state isometric force following some stretch conditions clearly exceeded the maximal isometric forces at optimum muscle length, and that force enhancement was associated with an increase in the passive force, i.e., a passive force enhancement. When the passive force enhancement was subtracted from the total force enhancement, forces following stretch were always equal to or smaller than the isometric force at optimum muscle length. Together, these findings led to the conclusions: (a). that force enhancement is composed of an "active and a "passive" component; (b). that the "passive" component of force enhancement allows for forces greater than the maximal isometric forces at the muscle's optimum length; and (c). that force enhancement and force depression are critically affected by muscle length and stretch/shortening amplitude.     

Effect of passive stretch on intracellular nitric oxide and superoxide activities in single skeletal muscle fibres: influence of ageing

Skeletal muscle is repeatedly exposed to passive stretches due to the activation of antagonist muscles and to external forces. Stretch has multiple effects on muscle mass and function, but the initiating mechanisms and intracellular signals that modulate those processes are not well understood. Mechanical stretch applied to some cell types induces production of reactive oxygen species (ROS) and nitric oxide that modulate various cellular signalling pathways. The aim of this study was to assess whether intracellular activities of ROS and nitric oxide were modulated by passive stretches applied to single mature muscle fibres isolated from young and old mice. We developed a novel approach to apply passive stretch to single mature fibres from the flexor digitorum brevis muscle in culture and to monitor the activities of ROS and nitric oxide in situ by fluorescence microscopy. Passive stretch applied to single skeletal muscle fibres from young mice induced an increase in dihydroethidium oxidation (reflecting intracellular superoxide) with no increase in intracellular DAF-FM oxidation (reflecting nitric oxide activity) or CM-DCFH oxidation. In contrast, in fibres isolated from muscles of old mice passive stretch was found to induce an increase in intracellular nitric oxide activities with no change in DHE oxidation.     

Intravenous papain-induced cartilage softening decreases preload of tracheal smooth muscle

To study the interaction between tracheal cartilage and the trachealis muscle we measured trachealis muscle contraction in response to electrical field stimulation and methacholine in excised tracheal segments from control and papain-treated rabbits. Papain treatment softened the tracheal cartilage and altered the passive pressure volume curve of the tracheal segments at transmural pressures below 5 cmH2O. The transmural pressure required for maximal active changes in volume (isobaric contraction) with electrical field stimulation was increased in papain-treated animals. We conclude that tracheal cartilage provides a preload which stretches the trachealis muscle toward optimal length and that papain, by altering the elastic mechanical properties of cartilage, decreases this preload.     

Lengthening contractions are not required to induce protection from contraction-induced muscle injury

We tested the hypothesis that lengthening contractions and subsequent muscle fiber degeneration and/or regeneration are required to induce exercise-associated protection from lengthening contraction-induced muscle injury. Extensor digitorum longus muscles in anesthetized mice were exposed in situ to repeated lengthening contractions, isometric contractions, or passive stretches. Three days after lengthening contractions, maximum isometric force production was decreased by 55%, and muscle cross sections contained a significant percentage (18%) of injured fibers. Neither isometric contractions nor passive stretches induced a deficit in maximum isometric force or a significant number of injured fibers at 3 days. Two weeks after an initial bout of lengthening contractions, a second identical bout produced a force deficit (19%) and a percentage of injured fibers (5%) that was smaller than those for the initial bout. Isometric contractions and passive stretches also provided protection from lengthening contraction-induced injury 2 wk later (force deficits = 35 and 36%, percentage of injured fibers = 12 and 10%, respectively), although the protection was less than that provided by lengthening contractions. These data indicate that lengthening contractions and fiber degeneration and/or regeneration are not required to induce protection from lengthening contraction-induced injury.     

Reflex stiffness of man''s anti-gravity muscles during kneebends while carrying extra weights

The effective lumped stiffness and damping ratio of the human leg system was determined from measurements of parallel and antiparallel-mode oscillations while standing on a linear spring. Knee flexion angle was held fixed in each trial, and varied systematically from 0° to 75°. At each knee angle, subjects carried weights up to twice body weight on their shoulders to determine the effect of increasing muscle force. For small knee flexion angles (θ ≤ 30°), reflex stiffness was independent of muscle force, but rose slightly with muscle force for large flexions. The damping ratio was calculated to be 0.34, showing the underdamped character often reported for skeletomotor feflex mechanisms. Leg stiffness measured in this way is consistent with measurements taken during human running.     

Cation permeability induced by spermine and polybrene in rat liver mitochondria

The effect of the polybasic substances Polybrene and spermine on the passive and active transport of monovalent cations in mitochondria was studied. These agents were found to stimulate the low amplitude swelling of mitochondria. Volume oscillations were induced by addition of substrate in the presence of spermine. In conditions where weak oscillations were obtained without these substances, oscillations were stimulated and their frequencies increased in the presence of Polybrene and spermine. Their effects were maximal with 100–300 moles spermine per litre and 3–5 mg Polybrene per litre. These results are discussed in relation to an interaction of the agents studied with membrane negative charges which may be important regulators of ion transport.     

The role of intersegmental dynamics during rapid limb oscillations

The interactive dynamic effects of muscular, inertial and gravitational moments on rapid, multi-segmented limb oscillations were studied. Using three-segment, rigid-body equations of motion, hip, knee and ankle intersegmental dynamics were calculated for the steady-state cycles of the paw-shake response in adult spinal cats. Hindlimb trajectories were filmed to obtain segmental kinematics, and myopotentials of flexors and extensors at each of the three joints were recorded synchronously with the ciné film. The segmental oscillations that emerged during the paw-shake response were a consequence of an interplay between active and passive musculotendinous forces, inertial forces, and gravity. During steady-state oscillations, the amplitudes of joint excursions, peak angular velocities, and peak angular accelerations increased monotonically and significantly in magnitude from the proximal joint (hip) to the most distal joint (ankle). In contrast to these kinematic relationships, the maximal values of net moments at the hip and knee were equal in magnitude, but of significantly lower magnitude than the large net moment at the ankle joint. At both the ankle and the knee, the flexor and extensor muscle moments were equal, but at the hip the magnitude of the peak flexor muscle moment was significantly greater than the extensor muscle moment. Muscle moments at the hip not only acted to counterbalance accelerations of the more distal segments, but also acted to maintain the postural orientation of the hindlimb. Large muscle moments at the knee functioned to counterbalance the large inertial moments generated by the large angular accelerations of the paw. At the ankle, the muscle moments dominated the generation of the paw accelerations. At the ankle and the knee, muscle moments controlled limb dynamics by slowing and reversing joint motions, and the active muscle forces contributing to ankle and knee moments were derived from lengthening of active musculotendinous units. In contrast to the more distal joints, the active muscles crossing the hip predominantly shortened as a result of the interplay among inertial forces and gravitational moments. The muscle function and kinetic data explain key features of the complex interactions that occur between central control mechanisms and multi-segmented, oscillating limb segments during the paw-shake response.     

Upper limb H reflexes and somatosensory evoked potentials modulated by movement.

In the human lower limb, the magnitudes of both Hoffmann (H) reflexes and primary somatosensory evoked potentials (SEPs) from scalp electrodes, are reduced by active and/or passive movement. We surmised that similar effects occur for the upper limb and specifically hypothesised that amplitudes of median nerve induced flexor carpii radialis H reflexes and cortical SEPs are reduced with passive movement about the wrist or elbow. The results showed (P<0. 05) that either movement significantly attenuated mean magnitudes of SEPs elicited from stimulation at elbow or wrist and that reflex magnitudes attenuated with wrist movement. Thus, the upper limb shows similar movement-induced modulation to the lower limb. These attenuations of fast conducting sensory paths consequent to movement per se, may be a basic level of motor control, initiated from muscle mechanoreceptor discharge. Upon this basic level, more complex modulations then may be laid as appropriate for the particular characteristics of active motor tasks.     

A study of the relationship between muscle length, tension-time area and stiffness in cat areflexic soleus

The relationship between muscle length and both tension-time area and stiffness were studied in the isolated cat soleus muscle during tetanic isometric contraction at different stimulus rates. The results show that: The area subtending the tension curve remains constant in a range of 8-10 mm of muscle length, for stimulation frequencies between 15 and 66 Hz. The muscle stiffness, measured using different amplitude stretches, remains constant over changes in muscle length of 10 mm. The stiffness is higher for smaller stretches than for larger ones. The data therefore show an approximately constant tension-time area and no significant changes in stiffness for variations in muscle length that exceed the physiological length variations during quiet standing. These results are discussed in the context of postural mechanisms.