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ROK-induced cross-link formation stiffens passive muscle: reversible strain-induced stress softening in rabbit detrusor.

Passive mechanical properties of strips of rabbit detrusor smooth muscle were examined and found by cyclic loading in a calcium-free solution to display viscoelastic softening and strain-induced stress softening (strain softening). Strain softening, or the Mullins effect, is a loss of stiffness attributed to the breakage of cross-links, and appeared irreversible in detrusor even after the return of spontaneous rhythmic tone during 120 min of incubation in a calcium-containing solution. However, 3 min of KCl or carbachol (CCh)-induced contraction permitted rapid regeneration of the passive stiffness lost to strain softening, and 3 microM of the RhoA kinase (ROK) inhibitor Y-27632 prevented this regeneration. The degree of ROK-induced passive stiffness was inversely dependent on muscle length over a length range where peak CCh-induced force was length independent. Thus rabbit detrusor displayed variable passive stiffness both strain- and activation-history dependent. In conclusion, activation of ROK by KCl or CCh increased passive stiffness softened by muscle strain and thereby attributed to cross-links that remained stable during tissue incubation in a calcium-free solution. Degradation of this signaling system could potentially contribute to urinary incontinence.

Amides↗

Effects of jump training on passive mechanical stress and stiffness in rabbit skeletal muscle: role of collagen.

AIMS: This study evaluated the effect of a 15-week jump training period on mechanical parameters and collagen concentration of different muscle types in rabbits, at 50, 90 and 140 days of age. METHODS: Trained (T) animals were made to jump over obstacles in order to get food and water. The height of the obstacle was increased according to the animal's age. Control (C) animals were sedentary. Mechanical parameters (force, stress, stiffness) and collagen concentration were measured in Extensor Digitorum Longus (EDL), Rectus Femoris (RF), Semimembranosus Proprius (SMP) and Psoas Major (PSOAS). RESULTS: Both EDL and RF collagen concentrations and passive mechanical parameters increased between 50 and 140 days of age (P<0.001), whereas SMP and PSOAS collagen concentrations decreased (P<0.001). Soluble collagen concentration decreased similarly with age in all muscles and groups. Exercise training at 140 days induced a significant increase in force (EDL 20.4% and RF 15.3%, 0.01<P<0.05), stress (EDL 26.8% and RF 22.6%, P<0.001), and stiffness (EDL 13.2% and RF 16%, 0.001<P<0.05) with a greater collagen concentration (EDL 16.1% and RF 19.1%, 0.001<P<0.05). Finally, stiffness and stress are well correlated with collagen concentration in EDL and RF muscles at 140 days (0.74<r<0.84, P<0.05). CONCLUSION: These results suggest that jump training can increase muscle capabilities of strength and stiffness in fast-twitch mixed muscles with pennate architecture (EDL, RF). This increase is essentially mediated by a rise in cross-linked collagen fraction, coupled with a relative decrease in soluble collagen. The collagen covalent cross-links improve resistance and stability in force transmission processes during stretching.

Aging↗

Influence of muscle cooling on the viscoelastic response of the human ankle to sinusoidal displacements.

The changes in passive mechanical muscle properties due to cooling of the calf in healthy human volunteers were investigated. The technique, using sinusoidal driving of the foot, permitted the separation of muscle stiffness response into its elastic and viscous components. Cooling the calf with ice for 30 minutes increases the rate of change of elastic stiffness with frequency, and it increases the frictional stiffness over a frequency range of 3 to 12Hz. Such cooling would produce an estimated 3% to 10% increase in total stiffness, on average, in a spastic person. This increase in stiffness would counteract reductions in total stiffness achieved during the application of cryotherapy to relieve spasticity. However, one could expect that for a clinically significant reduction of spasticity, the increase in passive stiffness of the muscle generated by cooling would be largely overshadowed by the decrease in reflex reactivity.

Adult↗

Separation of active and passive components of short-range stiffness of muscle.

The short-range stiffness of smoothly but submaximally contracting isometric soleus muscles of anesthetised cats was measured by applying small fast stretches. The ratio of isometric tension to stiffness was plotted against tension over a wide range of muscle lengths and stimulus rates. The results fitted a straight line well, as predicted from crossbridge theory, showing the stiffness to be a function of tension only, independent of the combination of length and stimulus rate used to generate the tension. The major deviation from this line was attributed to incomplete fusion at low frequencies of stimulation. Values believed to be tendon compliance and crossbridge tension per unit of stiffness were found from the graph, and the tendon compliance correlated with the maximum muscle tension. Shortening the tendon by attaching nearer to the muscle changed the results in a manner consistent with the theory, provided that appropriate precautions were taken against slippage.

Animals↗

Myotubes differentiate optimally on substrates with tissue-like stiffness: pathological implications for soft or stiff microenvironments.

Contractile myocytes provide a test of the hypothesis that cells sense their mechanical as well as molecular microenvironment, altering expression, organization, and/or morphology accordingly. Here, myoblasts were cultured on collagen strips attached to glass or polymer gels of varied elasticity. Subsequent fusion into myotubes occurs independent of substrate flexibility. However, myosin/actin striations emerge later only on gels with stiffness typical of normal muscle (passive Young's modulus, E approximately 12 kPa). On glass and much softer or stiffer gels, including gels emulating stiff dystrophic muscle, cells do not striate. In addition, myotubes grown on top of a compliant bottom layer of glass-attached myotubes (but not softer fibroblasts) will striate, whereas the bottom cells will only assemble stress fibers and vinculin-rich adhesions. Unlike sarcomere formation, adhesion strength increases monotonically versus substrate stiffness with strongest adhesion on glass. These findings have major implications for in vivo introduction of stem cells into diseased or damaged striated muscle of altered mechanical composition.

Acrylic Resins↗

Effect of passive stretching and jogging on the series elastic muscle stiffness and range of motion of the ankle joint.

OBJECTIVE: To determine the effect of stretching and jogging on the series elastic muscle stiffness of the plantar flexors and on the range of dorsiflexion at the ankle joint. METHODS: 24 healthy subjects participated in this study. Each subject undertook all of the following protocols, in random order: (1) stretching protocol: five 30 s static stretches with 30 s rest between stretches; (2) aerobic jogging protocol: subjects ran on a treadmill for 10 min at 60% of their maximum age predicted heart rate; (3) combined protocol: subjects ran first and then stretched. A damped oscillation technique was used to measure the series elastic stiffness of the plantar flexors. Dorsiflexion of the ankle was assessed with a weights and pulley system that moved the ankle joint from a neutral position into dorsiflexion passively. Electromyography was used to monitor the activity of the plantar and dorsiflexors during these procedures. The statistical analysis of these data involved an analysis of covariance. RESULTS: For decreasing series elastic muscle stiffness running was more effective than stretching (P < 0.05). In contrast, the results for range of motion showed that the combination protocol and the stretching only protocol were more effective than the running only protocol (P < 0.05) for increasing dorsiflexion range of motion at the ankle. CONCLUSIONS: Both jogging and static stretching exercises appear to be beneficial to individuals participating in sporting activities.

Ankle Injuries↗

Passive characteristics of conditioned skeletal muscle for ventricular assistance.

Systems to drive a ventricular assist device (VAD) with power from skeletal muscle have been proposed and are under development. During VAD filling, these systems must counter passive muscle force to control the precontraction length and optimize power output. To determine how muscle conditioning with electrical stimulation alters basic biomechanical characteristics and influences available power, goat latissimus dorsi were evaluated in vivo after an 8 week training protocol with an implanted myostimulator. Conditioned muscles displayed increased passive stiffness. After conditioning, the slope of the exponential passive force-length relation, at a passive force of 10 N, significantly increased from 5.1 to 7.6 N/cm (p = 0.003). Similarly, for a passive force of 10 N, the length relative to the zero developed force length decreased from 5.5 to 4.2 cm (p < 0.014). The linear relationship between slope (dF/dL) and force (F) also demonstrated a significant intercept shift. The latter relationship is independent of absolute length. Consistent with other studies, conditioning also resulted in fatigue resistance, fiber type transformation, and reductions in maximum developed force and shortening velocity. In the context of available power for cardiac assist, the results demonstrate that the influence of passive characteristics is accentuated after conditioning and has a substantial effect on available power.

Animals↗

The spontaneously hypertensive rat as a model of the transition from compensated left ventricular hypertrophy to failure.

Studies of hemodynamics and intrinsic left ventricular myocardial function are carried out to investigate the transition from stable hypertrophy to cardiac decompensation in the aging (18-24 months) spontaneously hypertensive rat (SHR). Echocardiographic data in awake animals demonstrate increased end-diastolic and end-systolic volumes and depressed ejection fractions in left ventricles from SHR with failure (SHR-F) as compared to age matched hypertensive (SHR-NF) and non-hypertensive control animals (WKY). Cardiac catheterization data in anesthetized animals demonstrate depression of both systolic pressure and +dP/dt, and elevated end-diastolic pressure in the SHR-F relative to the two control groups. Since loading conditions and altered demand states may contribute to altered ventricular function, studies of isolated perfused hearts were carried out which demonstrate impaired systolic stress development in the SHR-F group under conditions in which loading conditions are controlled; in addition, it is observed that increasing perfusion pressure by 30 mm Hg has little effect on function. Depression of systolic function and increases in passive stiffness of isolated muscle preparations from the SHR-F indicate impairment of systolic and diastolic function at the tissue level. While all of the preparations studied have potential shortcomings, an integration of findings from these complementary approaches supports the conclusion that heart failure develops in the aging SHR. Furthermore, these data suggest that impaired function is due to changes in the intrinsic properties of the myocardium and that the connective tissue response may play an important role. These studies, in conjunction with the findings of others who have studied the aging SHR, provide support for the use of the aging SHR as a model of the transition from compensated hypertrophy to failure.

Animals↗

The effects of trunk stiffness on postural control during unstable seated balance.

This paper focused on the relationship between trunk stiffness and postural control during unstable seated balancing. We hypothesized that an increase in trunk stiffness would degrade postural control, and further hypothesized that signal dependent noise (SDN), resulting in increased muscle force variability, was responsible for this impairment. Ten subjects balanced on an unstable seat during four randomized conditions: normal balancing (control condition), trunk muscle co-activation (active stiffness), arm muscle co-activation (attention control), and belt (passive stiffness). Center of pressure (CoP) and EMG data were collected during three 20 s trials. Postural control was quantified by CoP velocity (total path divided by sample time in seconds). Trunk muscle co-activation resulted in significantly higher CoP velocity than the control (P < 0.001) and arm co-activation (P < 0.001) conditions. EMG data confirmed that the trunk co-activation condition had significantly higher muscle activity than the control (P = 0.001) and arm co-activation (P = 0.001) conditions. The belt condition, which increases passive trunk stiffness, showed no degraded postural control, but interestingly produced slightly lower levels of trunk muscle activity than the control condition (P < 0.001). Increased active trunk stiffness from muscle co-activation degraded postural control. Since the arm co-activation condition showed no impairment, attention demands cannot explain this result. Furthermore, since passive trunk stiffness from wearing a belt did not affect performance, it is believed that SDN from increased trunk muscle recruitment, and not an altered postural control strategy from increased joint stiffness, was responsible for the impairment.

Adult↗

Correlation between impairment and motor performance during reaching tasks in subjects with spastic hemiparesis.

OBJECTIVE: The main purposes of this study were to examine, in subjects with chronic hemiparesis following a stroke: (i) the correlations between tests of muscle tone, stiffness, spasticity, paresis and co-contraction, and (ii) the correlations of these tests and measurements of impairment to upper extremity motor performance. DESIGN: Prospective, cross-sectional, correlation matrix using sample of convenience. SUBJECTS: Thirteen subjects with chronic hemiparesis secondary to a cerebrovascular accident (stroke) were tested. METHODS: Subjects were assessed using the Fugl-Meyer Upper Extremity Motor Assessment, modified Ashworth scale, deep tendon reflexes, and muscle characteristics that included quantification of muscle stiffness, paresis and co-contraction during a voluntary reaching task and during passive movements. Surface electromyographic and myotonometric muscle stiffness data were obtained during movement trials. RESULTS: Biceps and triceps brachii muscle paresis and excess biceps brachii co-contraction during voluntary reaching had the highest correlations to decreased motor performance. Muscle tone measurements did not have significant correlations to upper extremity performance. CONCLUSION: Paresis of elbow flexors and extensors and excess co-contraction of the biceps brachii during voluntary reaching appear to be most predictive of upper extremity motor performance. Results are discussed in relation to the specific challenges these findings pose for spastic paresis clinical management.

Aged↗

Passive properties of human skeletal muscle during stretch maneuvers. A review.

Despite limited scientific knowledge, stretching of human skeletal muscle to improve flexibility is a widespread practice among athletes. This article reviews recent findings regarding passive properties of the hamstring muscle group during stretch based on a model that was developed which could synchronously and continuously measure passive hamstring resistance and electromyographic activity, while the velocity and angle of stretch was controlled. Resistance to stretch was defined as passive torque (Nm) offered by the hamstring muscle group during passive knee extension using an isokinetic dynamometer with a modified thigh pad. To simulate a clinical static stretch, the knee was passively extended to a pre-determined final position (0.0875 rad/s, dynamic phase) where it remained stationary for 90 s (static phase). Alternatively, the knee was extended to the point of discomfort (stretch tolerance). From the torque-angle curve of the dynamic phase of the static stretch, and in the stretch tolerance protocol, passive energy and stiffness were calculated. Torque decline in the static phase was considered to represent viscoelastic stress relaxation. Using the model, studies were conducted which demonstrated that a single static stretch resulted in a 30% viscoelastic stress relaxation. With repeated stretches muscle stiffness declined, but returned to baseline values within 1 h. Long-term stretching (3 weeks) increased joint range of motion as a result of a change in stretch tolerance rather than in the passive properties. Strength training resulted in increased muscle stiffness, which was unaffected by daily stretching. The effectiveness of different stretching techniques was attributed to a change in stretch tolerance rather than passive properties. Inflexible and older subjects have increased muscle stiffness, but a lower stretch tolerance compared to subjects with normal flexibility and younger subjects, respectively. Although far from all questions regarding the passive properties of humans skeletal muscle have been answered in these studies, the measurement technique permitted some initial important examinations of vicoelastic behavior of human skeletal muscle.

Age Factors↗

Paradoxical muscle movement in human standing.

In human standing, gravity causes forward toppling about the ankle joint which is prevented by activity in the soleus and gastrocnemius muscles. It has long been assumed that when people sway forwards the calf muscles are stretched and conversely that they shorten with backward sway. Consequently, for many years, two explanations for standing stabilization have flourished. First, tonic muscle activity itself may generate adequate intrinsic ankle stiffness. Second, if intrinsic ankle stiffness is inadequate, the resistance to stretch of the calf muscles may be augmented by stretch reflexes or by central control. These explanations require that the passive tissue (Achilles' tendon, foot) transmitting the calf muscle tension is stiff. However, our recent measurements have indicated that this passive tissue is not stiff during standing. Accordingly, we predicted a counterintuitive mode of control where the muscles and body must, on average, move in opposite directions (paradoxical movements). Here we use dynamic ultrasound imaging in vivo with novel automated tracking of muscle length to test our hypothesis. We show that soleus and gastrocnemius do indeed move paradoxically, shortening when the body sways forward and lengthening when the body returns. This confirms that intrinsic ankle stiffness is too low to stabilize human standing. Moreover, it shows that the increase in active tension is associated with muscle shortening. This pattern cannot be produced by muscle stretch reflexes and can only arise from the anticipatory neural control of muscle length that is necessary for balance.

Achilles Tendon↗

Unstimulated force during hypoxia of rat cardiac muscle: stiffness and calcium dependence.

The stiffness of rat cardiac trabeculae was measured in vitro to distinguish between an increase in unstimulated force (Fu) caused by rapid cycling of cross bridges or caused by rigor bridges during hypoxia. The force was measured with a strain gauge, the sarcomere length was determined by laser diffraction techniques, and muscle length was controlled by means of a motor. Stiffness was analyzed by using small (less than 1% of muscle length) sinusoidal length perturbations of 1 and 100 Hz. The stiffness at 100 Hz increased linearly with force during tetani at a varied [Sr2+] (0.25-10 mM) in the Krebs-Henseleit (K-H) buffer, but remained virtually unchanged at 1 Hz. In contrast, the stiffness of both the passive muscle and the muscle exposed to either CN- or to PO2 less than 1.5 mmHg up to development of maximal Fu (Fumax) was similar at 1- and 100-Hz perturbations. Less profound hypoxia (PO2 6-10 mmHg) resulted in spontaneous sarcomere activity during the rise in Fu, and an increase in the ratio of stiffness at 100 Hz to stiffness at 1 Hz was detected. When oxidative phosphorylation was inhibited by CN- (2 mM) while the muscle was stimulated in the absence of both Ca2+ and Na+ (choline+substituted), the addition of Na+ at the time at which Fu had reached 30-40% of Fumax did not affect the rate of rise of Fu. These results show that the development of Fu during more complete anoxia in rat trabeculae is completely due to the formation of rigor links and that Ca2(+)-dependent cross-bridge activation can contribute to the rise in Fu during less severe hypoxia.

Animals↗

Osmotic compression and stiffness changes in relaxed skinned cardiac myocytes in PVP-40 and dextran T-500.

Sarcomere lengths, cell widths, indices of stiffness, and striation pattern uniformity were determined from radially compressed isolated adult cardiac myocytes from the rat. Single cells were bathed in a series of relaxing solutions containing 0-15% concentrations of nonpenetrating long chain polymers PVP-40 and dextran T-500. There were no significant changes observed in average sarcomere lengths or in striation pattern uniformity at any concentration. But cell widths decreased and stiffness increased in both polymers in a concentration-osmotic pressure-dependent relationship. Changes in cell width and stiffness were repeatable in either polymer, but only after an initial compression with a 10 or 15% concentration solution. The observed reduction in cell width after initial compression correlates well with known myofilament lattice spacing compression in rat cardiac muscle and is qualitatively similar to compressions seen in skeletal muscle preparations. But the cardiac myofilament lattice may not be as compressible as the skeletal lattice. Like skeletal muscle, stiffness exhibits a two-phase relationship where most of the increase occurs at solution osmotic pressures greater than 20 Torr. Finally, the inherently greater passive stiffness-length relationship of cardiac muscle is maintained at higher osmotic pressures such that the passive elastic modulus is strongly length dependent.

Actin Cytoskeleton↗

Muscle and tendon stiffness in patients with upper motor neuron lesion following a stroke.

The objective of this study was to investigate muscle and tendon stiffness in the triceps surae muscles in patients who had previously had a stroke. The participants were 12 men showing slight to moderate degrees of muscle tonus in the affected leg. All patients showed minimal or no overt clinical motor symptoms, and all walked without mechanical aid. Muscle strengths in isometric and isokinetic activities were measured, as was passive resistance during plantarflexion in each leg. Walking speed was also measured. Evaluations of physical performance and muscle tone were made. Muscle and tendon stiffness was calculated from measurements whilst passively stretching during electrical stimulation, separately for each leg. Muscle strength was significantly higher in the non-affected than in the affected leg. Muscle stiffness was significantly higher in the affected leg than in the non-affected leg. Tendon stiffness was significantly higher in the non-affected than in the affected leg. The higher muscle stiffness in the affected leg might enhance the possibility for storing elastic energy during preactivation. Lower tendon stiffness in the affected leg might reduce the development of fatigue in movements at low velocities.

Adult↗

Magnetic resonance elastography of skeletal muscle.

While the contractile properties of skeletal muscle have been studied extensively, relatively little is known about the elastic properties of muscle in vivo. Magnetic resonance elastography (MRE) is a phase contrast-based method for observing shear waves propagating in a material to determine its stiffness. In this work, MRE is applied to skeletal muscle under load to quantify the change in stiffness with loading. A mathematical model of muscle is developed that predicts a linear relationship between shear stiffness and muscle load. The MRE technique was applied to bovine muscle specimens (N = 10) and human biceps brachii in vivo (N = 5). Muscle stiffness increased linearly for both passive tension (14.5 +/- 1.77 kPa/kg) and active tension, in which the increase in stiffness was dependent upon muscle size, as predicted by the model. A means of noninvasively assessing the viscoelastic pro-perties of skeletal muscle in vivo may provide a useful method for studying muscle biomechanics in health and disease.

Animals↗

Relationship between muscle force and stiffness in the whole mammalian muscle: a simulation study.

Several types of analyses in biomechanics require estimates of both muscle force and stiffness. Simulations were performed using the two-state cross-bridge Bond Distribution-Moment muscle model of Zahalak (1981), together with other parameters for passive elasticity and tendon compliance, to estimate instantaneous stiffness and to compare these estimates with the wide range of values reported in the literature. While the relatively simple cross-bridge theory appears to approximate the stiffness of skinned muscle fibers, the stiffness of a complete muscle-tendon unit become complex and non-linear due to relative changes in muscle-tendon length and interaction with activation and length dependent passive elastic components. It would appear that the variability in muscle stiffness values reported in the literature can be explained with the D-M approach.

Biomechanical Phenomena↗

Changes in arterial wall properties during development and maintenance of renal hypertension.

Segments of carotid and tail arteries were used to determine the effects of two-kidney Goldblatt hypertension on mechanical properties and chemical contents. Arteries were obtained after 4 and 12 wk of hypertension. Systolic pressures averaged 129 mmHg in control animals and 150 mmHg in hypertensive ones. Pressure-diameter data were recorded under conditions of active (145 mM K+) and passive (0 Ca2+ and 2 mM EGTA) smooth muscle. Small increases in passive stiffness were found after 4 and 12 wk in the carotid arteries of hypertensive animals, but no significant change occurred in the tail arteries. Small but significant decreases in total connective tissue content of these arteries were found after 12 wk of hypertension. Maximum values of active stress response were significantly larger in carotid arteries from hypertensive animals at both 4 and 12 wk of hypertension. No significant differences were found for the tail arteries. The K+ content of the carotid but not the tail artery was larger for the hypertensive animals. When corrected for differences in relative cell content most of the differences in active force development were eliminated. The differences in passive mechanics can not be explained on the basis of the changes in connective tissue content. The active smooth muscle responses and content changes suggest that they are directly related to the moderate elevation of arterial pressure.

Animals↗