Dynamic equilibration of airway smooth muscle contraction during physiological loading.

Airway smooth muscle contraction is the central event in acute airway narrowing in asthma. Most studies of isolated muscle have focused on statically equilibrated contractile states that arise from isometric or isotonic contractions. It has recently been established, however, that muscle length is determined by a dynamically equilibrated state of the muscle in which small tidal stretches associated with the ongoing action of breathing act to perturb the binding of myosin to actin. To further investigate this phenomenon, we describe in this report an experimental method for subjecting isolated muscle to a dynamic microenvironment designed to closely approximate that experienced in vivo. Unlike previous methods that used either time-varying length control, force control, or time-invariant auxotonic loads, this method uses transpulmonary pressure as the controlled variable, with both muscle force and muscle length free to adjust as they would in vivo. The method was implemented by using a servo-controlled lever arm to load activated airway smooth muscle strips with transpulmonary pressure fluctuations of increasing amplitude, simulating the action of breathing. The results are not consistent with classical ideas of airway narrowing, which rest on the assumption of a statically equilibrated contractile state; they are consistent, however, with the theory of perturbed equilibria of myosin binding. This experimental method will allow for quantitative experimental evaluation of factors that were previously outside of experimental control, including sensitivity of muscle length to changes of tidal volume, changes of lung volume, shape of the load characteristic, loss of parenchymal support and inflammatory thickening of airway wall compartments.     

Inhibition of the p38 MAP kinase pathway destabilizes smooth muscle length during physiological loading

We tested the hypothesis that mechanical plasticity of airway smooth muscle may be mediated in part by the p38 mitogen-activated protein (MAP) kinase pathway. Bovine tracheal smooth muscle (TSM) strips were mounted in a muscle bath and set to their optimal length, where the active force was maximal (F(o)). Each strip was then contracted isotonically (at 0.32 F(o)) with ACh (maintained at 10(-4) M) and allowed to shorten for 180 min, by which time shortening was completed and the static equilibrium length was established. To simulate the action of breathing, we then superimposed on this steady distending force a sinusoidal force fluctuation with zero mean, at a frequency of 0.2 Hz, and measured incremental changes in muscle length. We found that TSM strips incubated in 10 microM SB-203580-HCl, an inhibitor of the p38 MAP kinase pathway, demonstrated a greater degree of fluctuation-driven lengthening than did control strips, and upon removal of the force fluctuations they remained at a greater length. We also found that the force fluctuations themselves activated the p38 MAP kinase pathway. These findings are consistent with the hypothesis that inhibition of the p38 MAP kinase pathway destabilizes muscle length during physiological loading.     

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.     

Active force inhibition and stretch-induced force enhancement in frog muscle treated with BDM.

There is evidence that the stretch-induced residual force enhancement observed in skeletal muscles is associated with 1) cross-bridge dynamics and 2) an increase in passive force. The purpose of this study was to characterize the total and passive force enhancement and to evaluate whether these phenomena may be associated with a slow detachment of cross bridges. Single fibers from frog lumbrical muscles were placed at a length 20% longer than the plateau of the force-length relationship, and active and passive stretches (amplitudes of 5 and 10% of fiber length and at a speed of 40% fiber length/s) were performed. Experiments were conducted in Ringer solution and with the addition of 2, 5, and 10 mM of 2,3-butanedione monoxime (BDM), a cross-bridge inhibitor. The steady-state active and passive isometric forces after stretch of an activated fiber were higher than the corresponding forces measured after isometric contractions or passive stretches. BDM decreased the absolute isometric force and increased the total force enhancement in all conditions investigated. These results suggest that total force enhancement is directly associated with cross-bridge kinetics. Addition of 2 mM BDM did not change the passive force enhancement after 5 and 10% stretches. Addition of 5 and 10 mM did not change (5% stretches) or increased (10% stretches) the passive force enhancement. Increasing stretch amplitudes and increasing concentrations of BDM caused relaxation after stretch to be slower, and because passive force enhancement is increased at the greatest stretch amplitudes and the highest BDM concentrations, it appears that passive force enhancement may be related to slow-detaching cross bridges.     

Perturbed equilibria of myosin binding in airway smooth muscle: bond-length distributions, mechanics, and ATP metabolism

We carried out a detailed mathematical analysis of the effects of length fluctuations on the dynamically evolving cross-bridge distributions, simulating those that occur in airway smooth muscle during breathing. We used the latch regulation scheme of Hai and Murphy (Am. J. Physiol. Cell Physiol. 255:C86-C94, 1988) integrated with Huxley's sliding filament theory of muscle contraction. This analysis showed that imposed length fluctuations decrease the mean number of attached bridges, depress muscle force and stiffness, and increase force-length hysteresis. At frequencies >0.1 Hz, the bond-length distribution of slowly cycling latch bridges changed little over the stretch cycle and contributed almost elastically to muscle force, but the rapidly cycling cross-bridge distribution changed substantially and dominated the hysteresis. By contrast, at frequencies <0.033 Hz this behavior was reversed: the rapid cycling cross-bridge distribution changed little, effectively functioning as a constant force generator, while the latch bridge bond distribution changed substantially and dominated the stiffness and hysteresis. The analysis showed the dissociation of force/length hysteresis and cross-bridge cycling rates when strain amplitude exceeds 3%; that is, there is only a weak coupling between net external mechanical work and the ATP consumption required for cycling cross-bridges during the oscillatory steady state. Although these results are specific to airway smooth muscle, the approach generalizes to other smooth muscles subjected to cyclic length fluctuations.     

Effect of length oscillations on airway smooth muscle reactivity and cross-bridge cycling

Excessive airway narrowing due to airway smooth muscle (ASM) hyperconstriction is a major symptom in many respiratory diseases. In vitro imposition of length oscillations similar to those produced by tidal breathing on contracted ASM have shown to reduce muscle active forces, which is usually attributed to unconfirmed disruption of actomyosin cross-bridges. This research focuses on an in vitro investigation of the effect of mechanical oscillations on ASM reactivity and actomyosin cross-bridges. A computerized organ bath system was used to test maximally precontracted bovine ASM subjected to length oscillations at frequencies in the range of 10-100 Hz superimposed on tidal breathing oscillation. Using an immunofluorescence technique, two specific antibodies against the phospho-serine19 myosin light chain and the α-smooth muscle actin were used to analyze the colocalization between these two filaments. Data were processed using the plug-in "colocalization threshold" of ImageJ 1.43m software. The results demonstrate that both tidal and superimposed length oscillations reduce the active force in contracted ASM for a relatively long term and that the latter enhances the force reduction of the former. This reduction was also found to be frequency and time dependent. Additionally colocalization analysis indicates that length oscillations cause the detachment of the actomyosin connections and that this condition is sustained even after the cessation of the length oscillations.     

Effects of length oscillation on the subsequent force development in swine tracheal smooth muscle.

It has been shown that deep inspiration (DI) taken before application of bronchoconstricting stimuli causes a reduction in the subsequent bronchoconstriction; a fast DI has a greater inhibitory effect than a slow DI. We hypothesize that periodic length changes imposed on a relaxed airway smooth muscle (ASM) would attenuate subsequent bronchoconstriction by disrupting the organization of the contractile apparatus, and this could be an important mechanism for the observed bronchoprotective effect of DI and tidal breathing. Length oscillations of different amplitude, frequency, and duration were applied to a relaxed muscle. The effects of such perturbations on force development were then assessed. Results show that oscillations reduce the subsequent force generation and that the magnitude of force reduction is proportional to amplitude and duration of the length oscillation. After the oscillation, isometric force recovered to the preoscillation level in a series of isometric contractions, and the rate of recovery was facilitated by frequent stimulation. The in vitro behavior of ASM found in this study could account for the observed temporary reduction in bronchoconstriction subsequent to a DI.     

Smooth muscle length adaptation and actin filament length: a network model of the cytoskeletal dysregulation

Length adaptation of the airway smooth muscle cell is attributable to cytoskeletal remodeling. It has been proposed that dysregulated actin filaments may become longer in asthma, and that such elongation would prevent a parallel-to-series transition of contractile units, thus precluding the well-known beneficial effects of deep inspirations and tidal breathing. To test the potential effect that actin filament elongation could have in overall muscle mechanics, we present an extremely simple model. The cytoskeleton is represented as a 2-D network of links (contractile filaments) connecting nodes (adhesion plaques). Such a network evolves in discrete time steps by forming and dissolving links in a stochastic fashion. Links are formed by idealized contractile units whose properties are either those from normal or elongated actin filaments. Oscillations were then imposed on the network to evaluate both the effects of breathing and length adaptation. In response to length oscillation, a network with longer actin filaments showed smaller decreases of force, smaller increases in compliance, and higher shortening velocities. Taken together, these changes correspond to a network that is refractory to the effects of breathing and therefore approximates an asthmatic scenario. Thus, an extremely simple model seems to capture some relatively complex mechanics of airway smooth muscle, supporting the idea that dysregulation of actin filament length may contribute to excessive airway narrowing.     

Force enhancement and relaxation rates after stretch of activated muscle fibres

The residual force enhancement following muscle stretch might be associated with an increase in the proportion of attached cross-bridges, as supported by stiffness measurements. In this case, it could be caused by an increase in the attachment or a decrease in the detachment rate of cross-bridges, or a combination of the two. The purpose of this study was to investigate if the stretch-induced force enhancement is related to cross-bridge attachment/detachment kinetics. Single muscle fibres dissected from the lumbrical muscle of frog were place at a length approximately 20% longer than the plateau of the force-length relationship; they were maximally activated, and after full isometric force was reached, ramp stretches were imposed with amplitudes of 5 and 10% fibre length, at a speed of 40% fibre length s(-1). Experiments were performed in Ringer's solution, and with the addition of 2, 5 and 10 nM of 2,3-butanedione monoxime (BDM), a drug that places cross-bridges in a pre-power-stroke, state, inhibiting force production. The total force following stretch was higher than the corresponding force measured after isometric contraction at the corresponding length. This residual force enhancement was accompanied by an increase relaxation time. BDM, which decreases force production during isometric contractions, considerably increased the relative levels of force enhancement. BDM also increased relaxation times after stretch, beyond the levels observed during reference contractions in Ringer's solution, and beyond isometric control tests at the corresponding BDM concentrations. Together, these results support the idea that force enhancement is caused, at least in part, by a decrease in cross-bridge detachment rates, as manifested by the increased relaxation times following fibre stretch.     

Effects of tracheal airway occlusion on hyoid muscle length and upper airway volume

Complex relationships exist among electromyograms (EMGs) of the upper airway muscles, respective changes in muscle length, and upper airway volume. To test the effects of preventing lung inflation on these relationships, recordings were made of EMGs and length changes of the geniohyoid (GH) and sternohyoid (SH) muscles as well as of tidal changes in upper airway volume in eight anesthetized cats. During resting breathing, tracheal airway occlusion tended to increase the inspiratory lengthening of GH and SH. In response to progressive hypercapnia, the GH eventually shortened during inspiration in all animals; the extent of muscle shortening was minimally augmented by airway occlusion despite substantial increases in EMGs. SH lengthened during inspiration in six of eight animals under hypercapnic conditions, and in these cats lengthening was greater during airway occlusion even though EMGs increased. Despite the above effects on SH and GH length, upper airway tidal volume was increased significantly by tracheal occlusion under hypercapnic conditions. These data suggest that the thoracic and upper airway muscle reflex effects of preventing lung inflation during inspiration act antagonistically on hyoid muscle length, but, because of the mechanical arrangement of the hyoid muscles relative to the airway and thorax, they act agonistically to augment tidal changes in upper airway volume. The augmentation of upper airway tidal volume may occur in part as a result of the effects of thoracic movements being passively transmitted through the hyoid muscles.     

Breathing pattern of anesthetized humans during pancuronium-induced partial paralysis

We investigated the breathing patterns of 17 subjects anesthetized with enflurane before and after partial muscle paralysis produced by pancuronium bromide. In the face of significant muscle weakness produced by pancuronium, breathing patterns are characterized by decreases in both tidal volume and respiratory frequency. The decreased tidal volume corresponded to the decrease in occlusion pressure, indicating that the decreased tidal volume results solely from a decreased contractile force of the respiratory muscles. The decreased respiratory frequency was due to prolongation of both inspiratory and expiratory time without changing the ratio of the inspiratory time to the total breath time. Withdrawal of phasic vagal influence by airway occlusion before partial muscle paralysis revealed that an active Breuer-Hering inflation reflex was operative in only 8 of all 17 subjects. Since the contribution of the Breuer-Hering inflation reflex alone does not seem to account for the consistent decrease in respiratory frequency, some other mechanisms modulating respiratory frequency might be involved in the characteristic breathing patterns during partial muscle paralysis under enflurane anesthesia.     

Adaptive response of pulmonary arterial smooth muscle to length change.

Hypervasoconstriction is associated with pulmonary hypertension and dysfunction of the pulmonary arterial smooth muscle (PASM) is implicated. However, relatively little is known about the mechanical properties of PASM. Recent advances in our understanding of plastic adaptation in smooth muscle may shed light on the disease mechanism. In this study, we determined whether PASM is capable of adapting to length changes (especially shortening) and regain its contractile force. We examined the time course of length adaptation in PASM in response to step changes in length and to length oscillations mimicking the periodic stretches due to pulsatile arterial pressure. Rings from sheep pulmonary artery were mounted on myograph and stimulated using electrical field stimulation (12-16 s, 20 V, 60 Hz). The length-force relationship was determined at L(ref) to 0.6 L(ref), where L(ref) was a reference length close to the in situ length of PASM. The response to length oscillations was determined at L(ref), after the muscle was subjected to length oscillation of various amplitudes for 200 s at 1.5 Hz. Release (or stretch) of resting PASM from L(ref) to 0.6 (and vice versa) was followed by a significant force recovery (73 and 63%, respectively), characteristic of length adaptation. All recoveries of force followed a monoexponential time course. Length oscillations with amplitudes ranging from 5 to 20% L(ref) caused no significant change in force generation in subsequent contractions. It is concluded that, like many smooth muscles, PASM possesses substantial capability to adapt to changes in length. Under pathological conditions, this could contribute to hypervasoconstriction in pulmonary hypertension.     

Force output during and following active stretches of rat plantar flexor muscles: effect of velocity of ankle rotation

During the development of force deficits by repeated stretches, velocity-sensitive changes in the extra force produced during and after subsequent stretching has not been studied. In the present study, repeated dorsiflexion of the foot of rats with maximally contracting plantar flexor muscles was performed at two angular velocities [0.87 (slow muscle stretch) and 10.47rads(-1) (fast muscle stretch)] to examine the active force of the muscles during and following dorsiflexion. Dorsiflexion was performed 30 times with a rest period of 3min between the stretches to minimize muscle fatigue. The ability of rat plantar flexor muscles to produce additional force during the stretch was not velocity sensitive. In contrast, repeated dorsiflexion with fast muscle stretches, but not with slow muscle stretches, resulted in an increase in the force decay with time following the stretches (i.e. increased stress relaxation), as indicated by a change in the time constant of force decay during stress relaxation. Apparently, the stress-relaxation of rat plantar flexor muscles is sensitive to angular velocity of ankle movements; repeated fast, but not slow dorsiflexion, alters the stress relaxation process of active skeletal muscles exposed to stretches which create a force deficit. The change in time constant of force decay during stress relaxation in response to a series of repeated stretches might provide information on the sarcomere length distribution in skeletal muscles.     

Effect of hypercapnia and PEEP on expiratory muscle EMG and shortening

The present study examined the effects of hypercapnia and positive end-expiratory pressure (PEEP) on the electromyographic (EMG) activity and tidal length changes of the expiratory muscles in 12 anesthetized, spontaneously breathing dogs. The integrated EMG activity of both abdominal (external oblique, internal oblique, rectus abdominis, and transverse abdominis) and thoracic (triangularis sterni, internal intercostal) expiratory muscles increased linearly with increasing PCO2 and PEEP. However, with both hypercapnia and PEEP, the percent increase in abdominal muscle electrical activity exceeded that of thoracic expiratory muscle activity. Both hypercapnia and PEEP increased the tidal shortening of the external oblique and rectus abdominis muscles. Changes in tidal length correlated closely with simultaneous increases in muscle electrical activity. However, during both hypercapnia and PEEP, length changes of the external oblique were significantly greater than those of the rectus abdominis. We conclude that both progressive hypercapnia and PEEP increase the electrical activity of all expiratory muscles and augment their tidal shortening but produce quantitatively different responses in the several expiratory muscles.     

Prolonged muscle vibration increases stretch reflex amplitude, motor unit discharge rate, and force fluctuations in a hand muscle.

The purpose of this study was to compare the influence of prolonged vibration of a hand muscle on the amplitude of the stretch reflex, motor unit discharge rate, and force fluctuations during steady, submaximal contractions. Thirty-two young adults performed 10 isometric contractions at a constant force (5.0 +/- 2.3% of maximal force) with the first dorsal interosseus muscle. Each contraction was held steady for 10 s, and then stretch reflexes were evoked. Subsequently, 20 subjects had vibration applied to the relaxed muscle for 30 min, and 12 subjects received no vibration. The muscle vibration induced a tonic vibration reflex. The intervention (vibration or no vibration) was followed by 2 sets of 10 constant-force contractions with applied stretches (After and Recovery trials). The mean electromyogram amplitude of the short-latency component of the stretch reflex increased by 33% during the After trials (P < 0.01) and by 38% during the Recovery trials (P < 0.01). The standard deviation of force during the steady contractions increased by 21% during the After trials (P < 0.05) and by 28% during the Recovery trials (P < 0.01). The discharge rate of motor units increased from 10.3 +/- 2.7 pulses/s (pps) before vibration to 12.2 +/- 3.1 pps (P < 0.01) during the After trials and to 11.9 +/- 2.6 pps during the Recovery trials (P < 0.01). There was no change in force fluctuations or stretch reflex magnitude for the subjects in the Control group. The results indicate that prolonged vibration increased the short-latency component of the stretch reflex, the discharge rate of motor units, and the fluctuations in force during contractions by a hand muscle. These adjustments were necessary to achieve the target force due to the vibration-induced decrease in the force capacity of the muscle.     

Inspiratory and expiratory muscle function during continuous positive airway pressure in dogs

Continuous positive airway pressure (CPAP) is known to produce activation of the expiratory muscles. Several factors may determine whether this activation can assist inspiration. In this study we asked how and to what extent expiratory muscle contraction can assist inspiration during CPAP. Respiratory muscle response to CPAP was studied in eight supine anesthetized dogs. Lung volume and diaphragmatic initial length were defended by recruitment of the expiratory muscles. At the maximum CPAP of 18 cmH2O, diaphragmatic initial lengths were longer than predicted by the passive relationship by 52 and 46% in the costal and crural diaphragmatic segments, respectively. During tidal breathing after cessation of expiratory muscle activity, a component of passive inspiration occurred before the onset of inspiratory diaphragmatic electromyogram (EMG). At CPAP of 18 cmH2O, passive inspiration represented 24% of the tidal volume (VT) and tidal breathing was within the relaxation characteristic. Diaphragmatic EMG decreased at CPAP of 18 cmH2O; however, VT and tidal shortening were unchanged. We identified passive and active components of inspiration. Passive inspiration was limited by the time between the cessation of expiratory activity and the onset of inspiratory activity. We conclude that increased expiratory activity during CPAP defends diaphragmatic initial length, assists inspiration, and preserves VT. Even though breathing appeared to be an expiratory act, there remained a significant component of active inspiratory diaphragmatic shortening, and the major portion of VT was produced during active inspiration.     

The 1- to 2-Hz oscillations in muscle force are exacerbated by stress, especially in older adults.

Although force fluctuations during a steady contraction are often heightened in old adults compared with young adults and are enhanced in young adults during the stress response, the mechanisms underlying the augmentation are uncertain. The purpose of the study was to compare the effect of a stressor on the plasma concentrations of selected stress hormones and on the force fluctuations experienced by young and old adults during the performance of a precision grip. Thirty-six men and women (19-86 yr) participated in a protocol that comprised anticipatory (30 min), stressor (15 min), and recovery periods (25 min). The stressor was a series of noxious electrical stimuli applied to the dorsal surface of the left hand. Subjects sustained a pinch-grip force with the right hand at 2% of the maximal voluntary contraction force. The fluctuations in pinch-grip force, the interference electromyogram (EMG) of six muscles, and the spectra for the force and EMG were quantified across the 70-min protocol. The stressor increased the force fluctuations, largely due to an enhancement of the power at 1-2 Hz in the force spectrum (r(2) = 0.46). The effect was greatest for the old adults compared with young and middle-aged adults. The plasma concentrations of the stress hormones (adrenocorticotropin, epinephrine, and norepinephrine) were elevated to similar levels for all three age groups, and the changes were not associated with modulation of the force fluctuations. Furthermore, the heightened EMG activity exhibited by the old adults during all periods was not related to the changes in the force fluctuations or the 1- to 2-Hz force oscillations. The absence of a change in the mean pinch-grip force during the protocol and the lack of an association between elevation of the plasma concentrations for the stress hormones and modulation of the force fluctuations suggest that the enhanced force fluctuations caused by the stressor was due to an increase in the low-frequency output of the spinal motor neurons.     

Geniohyoid muscle function in awake canines.

The geniohyoid (Genio) upper airway muscle shows phasic, inspiratory electrical activity in awake humans but no activity and lengthening in anesthetized cats. There is no information about the mechanical action of the Genio, including length and shortening, in any awake, nonanesthetized mammal during respiration (or swallowing). Therefore, we studied four canines, mean weight 28.8 kg, 1.5 days after Genio implantation with sonomicrometry transducers and bipolar electromyogram (EMG) electrodes. Awake recordings of breathing pattern, muscle length and shortening, and EMG activity were made with the animal in the right lateral decubitus position during quiet resting, CO2-stimulated breathing, inspiratory-resisted breathing (80 cmH2O. l-1. s), and airway occlusion. Genio length and activity were also measured during swallowing, when it shortened, showing a 9.31% change from resting length, and its EMG activity increased 6.44 V. During resting breathing, there was no phasic Genio EMG activity at all, and Genio showed virtually no movement during inspiration. During CO2-stimulated breathing, Genio showed minimal lengthening of only 0.07% change from resting length, whereas phasic EMG activity was still absent. During inspiratory-resisted breathing and airway occlusion, Genio showed phasic EMG activity but still lengthened. We conclude that the Genio in awake, nonanesthetized canines shows active contraction and EMG activity only during swallowing. During quiet or stimulated breathing, Genio is electrically inactive with passive lengthening. Even against resistance, Genio is electrically active but still lengthens during inspiration.     

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.     

Severity of contraction-induced injury is affected by velocity only during stretches of large strain.

Our purpose was to investigate the effect of velocity of stretch on contraction-induced injury to whole skeletal muscles. Single stretches provide an effective method for studying factors that initiate contraction-induced injury. We tested the null hypothesis that the severity of injury is not dependent on the velocity of the stretch. From the plateau of maximum isometric contractions, extensor digitorum longus muscles of mice were administered single stretches in situ of 30--50% strain relative to muscle fiber length (L(f)) at rates of 1--16 L(f)/s. The magnitude of injury was represented by the isometric force deficit 1--10 min after the stretch. Although the null hypothesis was not supported because the force deficit was affected by velocity (r(2) = 0.09), the effect was relatively weak and was not significant except at the largest strain. Velocity had no effect on peak or average force or work input, factors established to have significant relationships with the force deficit. Velocity may play a minor role in contraction-induced injury, but its importance is negligible relative to that of strain.