Cat Soleus Research Articles

Uniaxial prestress and waveguide effects on estimates of the complex shear modulus using magnetic resonance elastography in a transverse isotropic muscle phantom and excised muscle

Tensile prestress is inherent to the functional role of some biological tissues currently being studied using elastography, such as skeletal and cardiac muscle, arterial walls, and the cornea. Therefore, the impact of prestress coupled with waveguide effects due to small dimensions in one or more directions needs to be better understood. An experimental configuration is designed, fabricated and experimentally tested using magnetic resonance elastography (MRE). Cylindrically-shaped isotropic and transversely isotropic phantoms, as well as the excised cat soleus muscle are statically stretched along their main axis to specific prestrain levels while simultaneously conducting MRE measurements that enable synchronous motion-encoding in all three dimensions (polarization directions). In the case of the excised cat soleus, diffusion tensor imaging is also performed to enable a co-registered mapping of fiber structure. Guided by analytical models and numerical finite element simulations, experimental measurements are post-processed to obtain an estimate of the complex (viscoelastic) shear modulus as a function of prestress level and frequency of vibratory motion.

Elastography using torsional wave motion in transverse isotropic material

An experimental configuration for driving and measuring torsional wave motion is designed, fabricated and experimentally tested using magnetic resonance elastography (MRE) in both a ultra-high field preclinical MRI system and in a cryogen-free low-field tabletop MRI system. Cylindrically-shaped isotropic and transversely isotropic phantoms, as well as the excised cat soleus muscle are statically stretched along their main axis to specific prestrain levels while simultaneously conducting MRE measurements with torsional waves. In the case of the excised cat soleus, diffusion tensor imaging is also performed to enable a co-registered mapping of fiber structure. The potential advantage of torsional wave excitation to drive shear wave motion over a large volume with uniform amplitude, and hence SNR, is tested by comparison to excitation of shear waves using other methods.

Passive force enhancement is not abolished by shortening of single fibres.

Passive force enhancement is defined as the increase in steady-state passive force following active muscle stretching compared to the corresponding passive force following passive muscle stretching. This mechanical property has been discovered just two decades ago (Herzog & Leonard, 2002), and has been associated with contributing to the residual force enhancement property, stability of sarcomeres, and preventing over-stretching during eccentric contractions. The molecular mechanisms underlying passive force enhancement development and abolishment remain unknown. An incidental observation on cat soleus muscle led to the speculation that passive force enhancement could be abolished instantaneously when the actively stretched muscle was deactivated and then passively shortened to its pre-stretched length (Herzog et al., 2003). We tested this hypothesis systematically using single skinned fibres from rabbit psoas. However, initial results led to the rejection of this hypothesis. Rather, we found that passive force enhancement increased following a shortening-stretch cycle of fibres to their pre-stretched length (2.4 µm), and back. Furthermore, we observed that the passive force enhancement increased by 70-106% when the shortening and subsequent stretch to the original length (3.6 µm) increased in duration (200 ms, 6 s, and 14 s). When reversing the order of the shortening-stretch experiments from slowest to fastest, the general result was the same as that of the primary experiment. These findings indicated that passive force enhancement increases during a shortening-stretch cycle, and that this increase is time-dependent. We propose that this increase in passive force enhancement may be caused by titin; specifically, with a refolding of titin's immunoglobulin domains that were unfolded during the active fibre stretching that produced the residual and passive force enhancement. Using fluorescent antibody labeling of selected titin segments, we will be testing this hypothesis in the near future.

Passive force enhancement is not abolished by shortening of single rabbit psoas fibres

Passive force enhancement is defined as the increase in steady-state passive force following deactivation of an actively stretched muscle compared to the corresponding passive force following passive stretching of the muscle. Passive force enhancement has been associated with contributing to the residual force enhancement property, providing stability to sarcomeres, and preventing sarcomeres from over-stretching during eccentric muscle action. Despite its functional importance, the molecular mechanisms underlying passive force enhancement remain unknown. Specifically, it remains unknown how passive force enhancement develops and how it is abolished. Incidental observations on cat soleus muscles led to the speculation that passive force enhancement is abolished when the actively stretched muscle is deactivated and then passively shortened to its pre-stretched length. Here, we tested this hypothesis using skinned fibres from rabbit psoas and rejected it. Rather, we found that passive force enhancement increased following shortening of the fibres to their pre-stretched length (2.4 µm), and furthermore, that the passive force enhancement increased by 70–106% when the shortening and subsequent stretch to the original length (3.6 µm) increased in duration (200 ms, 6 s, and 14 s). These results indicate that passive force enhancement increases during a shortening–stretch cycle, and that this increase is time-dependent. We propose that this increase in passive force enhancement is caused by titin; specifically, with a refolding of titin’s immunoglobulin domains that were unfolded during the active fibre stretching that produced the residual and passive force enhancement. Molecular level experiments are required to test this proposal.

Residual force enhancement is attenuated for quick stretch conditions

It is generally accepted that the magnitude of residual force enhancement is not affected by stretching velocity. However, we recently found that when the stretching velocity was too large, the magnitude of residual force enhancement was attenuated or vanished in cat soleus muscle in situ. Therefore, the purpose of this study was to extend the knowledge by conducting very quick stretches in skinned rabbit psoas and soleus muscle fibers. Skinned psoas (N = 17) or soleus (N = 13) muscle fibers were activated isometrically at an average sarcomere length of 2.7 μm, and then, actively stretched to an average sarcomere length of 3.0 μm in 0.5 or 500 ms, followed by an isometric contraction at that length. In addition, a purely isometric reference contraction was conducted at an average sarcomere length of 3.0 μm to calculate the magnitude of residual force enhancement for both stretch velocities. The magnitude of residual force enhancement was significantly different between 0.5 ms stretch (101.5 ± 5.6% for psoas, and 101.5 ± 2.3% for soleus) and 500 ms stretch (106.2 ± 5.9% for psoas, and 106.8 ± 5.1% for soleus) while the magnitude of residual force enhancement was not significantly different between muscles. In line with our previous finding, the magnitude of residual force enhancement can vary when the stretch velocity is very large. This finding can contribute to clarify the key mechanism for inducing residual force enhancement and to explain contradicting results obtained in previous studies.

A mass-flowing muscle model with shape restrictive soft tissues: correlation with sonoelastography.

Skeletal muscles are always embedded in sheets of connective tissues, which influences muscle biomechanics by shaping the fascicle geometry and encapsulating muscular mass flow. However, existing Hill-type muscle models typically take surrounding tissues into account as a nonlinear spring, without consideration of the muscle geometry and inertia. In this paper, a new muscle model is proposed to simultaneously account for soft tissue constraints on the muscle's shape together with mass flow during stretch. To accomplish this, a mass-variable cable element of the muscle-tendon unit, with parameterization of its geometrical influence on the force-producing capability, is newly formulated based on an arbitrary Lagrangian-Eulerian description. Also, sliding joints are presented to further constrain possible mass flow of the elements via epimuscular soft tissue connections between adjacent muscle bellies. Available experimental data from cat soleus and rat gastrocnemius medialis muscles validates the proposed method. For further verification, a planar model of the triceps surae is developed by integration of this modeling framework, and subject-specific simulations of the passive ankle dynamometry tests are performed and correlated with sonoelastographic evaluations of two male participants. The results confirm that the flow of the muscle mass can alternate its force-generating behaviors, and the established model provides an accurate prediction of muscle behavior under transverse loading. The proposed muscle element could be integrated with larger musculoskeletal models to better investigate biomechanical functions of muscles during locomotion, such as heel impact or vibration responses of the spine, when dynamic effects are substantial.

Does stretching velocity affect residual force enhancement?

It is thought that the magnitude of residual force enhancement (RFE) is not affected by stretch velocity. However, the range of stretch velocities studied in previous investigations has been limited to slow and moderate velocities. High velocities of muscle stretching are associated with a loss of force and incomplete cross-bridge attachment to actin, thus creating a unique set of eccentric conditions referred to as slippage. The purpose of this study was to extend the relationship between stretch velocity and RFE to high velocities. We hypothesized that slippage at high velocities might affect RFE. We stretched cat soleus muscles for 4 mm to the plateau of the force-length relationship at speeds of 2, 4, 8, 16, 32, 64 mm/s to induce RFE, and slippage for the fastest condition. For each RFE test, a corresponding isometric reference test was conducted. Residual force enhancement was quantified as the relative increase in isometric steady state force between the experimental stretch and the isometric reference tests. Residual force enhancement was similar for all stretch speeds, as expected, with the exception of the fastest speed (64 mm/s), which was associated with slippage and no significant RFE. These results suggest that if stretch speeds are too fast, and are associated with slippage, RFE is abolished. We conclude from these findings that proper cross-bridge engagement is required during eccentric muscle action to produce RFE.

Analysis of Proprioceptive Sensory Innervation of the Mouse Soleus: A Whole-Mount Muscle Approach.

Muscle proprioceptive afferents provide feedback critical for successful execution of motor tasks via specialized mechanoreceptors housed within skeletal muscles: muscle spindles, supplied by group Ia and group II afferents, and Golgi tendon organs, supplied by group Ib afferents. The morphology of these proprioceptors and their associated afferents has been studied extensively in the cat soleus, and to a lesser degree, in the rat; however, quantitative analyses of proprioceptive innervation in the mouse soleus are comparatively limited. The present study employed genetically-encoded fluorescent reporting systems to label and analyze muscle spindles, Golgi tendon organs, and the proprioceptive sensory neuron subpopulations supplying them within the intact mouse soleus muscle using high magnification confocal microscopy. Total proprioceptive receptors numbered 11.3 ± 0.4 and 5.2 ± 0.2 for muscle spindles and Golgi tendon organs, respectively, and these receptor counts varied independently (n = 27 muscles). Analogous to findings in the rat, muscle spindles analyzed were most frequently supplied by two proprioceptive afferents, and in the majority of instances, both were classified as primary endings using established morphological criteria. Secondary endings were most frequently observed when spindle associated afferents totaled three or more. The mean diameter of primary and secondary afferent axons differed significantly, but the distributions overlap more than previously observed in cat and rat studies.

An action potential-driven model of soleus muscle activation dynamics for locomotor-like movements

Objective. The goal of this study was to develop a physiologically plausible, computationally robust model for muscle activation dynamics (A(t)) under physiologically relevant excitation and movement. Approach. The interaction of excitation and movement on A(t) was investigated comparing the force production between a cat soleus muscle and its Hill-type model. For capturing A(t) under excitation and movement variation, a modular modeling framework was proposed comprising of three compartments: (1) spikes-to-[Ca2+]; (2) [Ca2+]-to-A; and (3) A-to-force transformation. The individual signal transformations were modeled based on physiological factors so that the parameter values could be separately determined for individual modules directly based on experimental data. Main results. The strong dependency of A(t) on excitation frequency and muscle length was found during both isometric and dynamically-moving contractions. The identified dependencies of A(t) under the static and dynamic conditions could be incorporated in the modular modeling framework by modulating the model parameters as a function of movement input. The new modeling approach was also applicable to cat soleus muscles producing waveforms independent of those used to set the model parameters. Significance. This study provides a modeling framework for spike-driven muscle responses during movement, that is suitable not only for insights into molecular mechanisms underlying muscle behaviors but also for large scale simulations.

Emulated muscle spindle and spiking afferents validates VLSI neuromorphic hardware as a testbed for sensorimotor function and disease.

The lack of multi-scale empirical measurements (e.g., recording simultaneously from neurons, muscles, whole body, etc.) complicates understanding of sensorimotor function in humans. This is particularly true for the understanding of development during childhood, which requires evaluation of measurements over many years. We have developed a synthetic platform for emulating multi-scale activity of the vertebrate sensorimotor system. Our design benefits from Very Large Scale Integrated-circuit (VLSI) technology to provide considerable scalability and high-speed, as much as 365× faster than real-time. An essential component of our design is the proprioceptive sensor, or muscle spindle. Here we demonstrate an accurate and extremely fast emulation of a muscle spindle and its spiking afferents, which are computationally expensive but fundamental for reflex functions. We implemented a well-known rate-based model of the spindle (Mileusnic et al., 2006) and a simplified spiking sensory neuron model using the Izhikevich approximation to the Hodgkin–Huxley model. The resulting behavior of our afferent sensory system is qualitatively compatible with classic cat soleus recording (Crowe and Matthews, 1964b; Matthews, 1964, 1972). Our results suggest that this simplified structure of the spindle and afferent neuron is sufficient to produce physiologically-realistic behavior. The VLSI technology allows us to accelerate this behavior beyond 365× real-time. Our goal is to use this testbed for predicting years of disease progression with only a few days of emulation. This is the first hardware emulation of the spindle afferent system, and it may have application not only for emulation of human health and disease, but also for the construction of compliant neuromorphic robotic systems.

Force enhancement in lengthening contractions of cat soleus muscle in situ: transient and steady-state aspects

Force enhancement (FE) associated with lengthening is a well-accepted phenomenon of active skeletal muscle, but the underlying mechanism(s) remain unknown. Similar to force depression (FD) following active shortening, the mechanism of FE may be attributed, at least in part, to cross-bridge kinetics. To examine this relationship, a post hoc analysis was performed on the transient force relaxation phase of previous in-situ FE experiments in soleus muscle-tendon units of anesthetized cats. For each muscle (n = 8), nine eccentric lengthenings (3 amplitudes, 3 velocities) were performed while tetanically stimulated (3T at 30 Hz, 3× α motorneuron, 35 ± 1°C). To determine transient aspects of FE, the period immediately following stretching was fit with an exponential decay function (R2 > 0.95). Statistical analyses revealed that total steady-state FE (FESS) increased with stretching amplitude and applied mechanical work. A positive relationship was observed between the active FESS and rate of force decay (k), indicating that a kinetic mechanism may explain active FE. However, for all muscles and stretch conditions, there was no correlation between the total amount of FESS and rate of decay. Therefore, FE cannot be explained solely by an active FE mechanism involving the interaction of actin and myosin. Rather, these findings suggest a combination of underlying mechanisms, including a kinetic mechanism for active FE, contributions of a passive elastic element, and possibly an activatable passive component operating outside of actin–myosin cross-bridging. Moreover, this transient analysis identifies that FE is not simply the opposite of FD, and its underlying mechanism(s) cannot simply be the opposite in nature.

ELECTRO-MECHANICAL DELAY IN HILL-TYPE MUSCLE MODELS

In this study, we investigated to which extent Hill-type muscle models can explain the electro-mechanical delay (EMD). The EMD is a phenomenon that has been well examined in muscle experiments. The EMD is the time lag between a change in muscle stimulation and the subsequent measurable change in muscle force. A variety of processes as, e.g., signal conduction and interaction of contractile and elastic muscle structures contribute to the EMD. The relative contributions of the particular processes have not been fully unveiled so far. Thereto, we simulated isometric muscle contractions using two Hill-type muscle models. Their parameters were extracted from experiments on the cat soleus muscle. In agreement with literature data, predicted EMD values depend on muscle-tendon complex (MTC) length and increase when reducing MTC lengths. The highest EMD values (28 and 27 ms) occur at the lowest MTC length examined (78% of optimal length). Above optimal MTC length, we find EMD saturation (2 ms) in one model. In the other model, the EMD slightly re-increases up to 9 ms at the highest length examined (113% of optimal length). The EMD values predicted by the two models were then compared to EMD values found in the same experiments from which the muscle parameters were extracted. At optimal MTC length, the EMD values, mapping ion release and visco-elastic interactions, predicted by both models (3.5 and 5.5 ms) just partly account for the measured value (15.8 ms). The biggest share (about 9 ms) of the remaining 11 ms can be attributed to signal conduction along the nerve and on the muscle surface. Further potential sources of delayed force generation are discussed.

A phenomenological muscle model to assess history dependent effects in human movement

Most musculoskeletal models used to analyze human movement utilize Hill-type muscle models that account for state dependent intrinsic muscle properties (e.g., force–length–velocity relationships), but rarely do these models include history dependent effects (e.g., force depression or enhancement). While the relationship between muscle shortening and force depression can be well characterized by muscle mechanical work, the relationship between muscle stretch and force enhancement is more complex. Further, it is not well known how these properties influence dynamic movements. Therefore, the goal of this study was to develop a modified Hill-type muscle model that incorporated stretch-induced force enhancement into a previously described model that included shortening-induced force depression. The modified muscle model was based on experimental data from isolated cat soleus muscles. Simulations of in situ muscle experiments were used to validate the model and simulations of a simple human movement task (counter-movement jumping) were used to examine the interactions of the history dependent effects. The phenomenological model of stretch-induced force enhancement was dependent on both the magnitude of stretch and relative length of the muscle fiber. Simulations of the in situ muscle experiments showed that the model could accurately reproduce force enhancement and force depression, as well as the complex additive relationship between these effects. Simulations of counter-movement jumping showed that a similar jump pattern could be achieved with and without history dependent effects and that a relatively minor change in muscle activation could mitigate the impact of these effects.

Motoneuron afterhyperpolarisation duration in amyotrophic lateral sclerosis

Motor unit (MU) potentials were registered from 20 ALS patients and 13 age-matched control individuals during isometric constant force contractions of brachial biceps (BB). The registered signals were decomposed into single MU potential trains. The estimates of duration of the afterhyperpolarisation (AHP) in MNs, derived from the interspike interval variability, was compared between ALS patients (124 MNs) and control subjects (111 MNs) and no significant differences were encountered. However, the relationship between TI and age for patients appeared to be qualitatively different from that of the control group. The dependence of patients' AHPs on relative force deficit (RFD), which quantified muscle involvement, was more specific. For RFDs below 30%, the AHP estimate was significantly lower than control values and then increased thereafter with increasing RFDs. Moreover, firing rates of patients with the smallest RFDs were significantly higher while firing rates of patients with the greatest RFDs were significantly lower than control values. The AHP shortening in the early stages of muscle impairment is consistent with the decrease in firing threshold of ‘fast' MNs found in spinal cord slices from neonatal SOD1 mice. The later elongation of the AHP may be caused by the higher vulnerability of ‘fast' MNs to degeneration and by the influence of reinnervation. Our results are comparable to what has been observed in acute experiments in animal models, providing a bridge between animal and clinical research that may be relevant for identification of mechanism(s) underlying neurodegeneration in ALS.

Does residual force enhancement increase with increasing stretch magnitudes?

It is generally accepted that force enhancement in skeletal muscles increases with increasing stretch magnitudes. However, this property has not been tested across supra-physiological stretch magnitudes and different muscle lengths, thus it is not known whether this is a generic property of skeletal muscle, or merely a property that holds for small stretch magnitudes within the physiological range. Six cat soleus muscles were actively stretched with magnitudes varying from 3 to 24mm at three different parts of the force–length relationship to test the hypothesis that force enhancement increases with increasing stretch magnitude, independent of muscle length. Residual force enhancement increased consistently with stretch amplitudes on the descending limb of the force–length relationship up to a threshold value, after which it reached a plateau. Force enhancement did not increase with stretch amplitude on the ascending limb of the force–length relationship. Passive force enhancement was observed for all test conditions, and paralleled the behavior of the residual force enhancement. Force enhancement increased with stretch magnitude when stretching occurred at lengths where there was natural passive force within the muscle. These results suggest that force enhancement does not increase unconditionally with increasing stretch magnitude, as is generally accepted, and that increasing force enhancement with stretch appears to be tightly linked to that part of the force–length relationship where there is naturally occurring passive force.

THE EFFECTS OF PARALLEL AND SERIES ELASTIC COMPONENTS ON THE ACTIVE CAT SOLEUS FORCE-LENGTH RELATIONSHIP

Typically, active muscle force is calculated by subtracting measured passive force from measured total force for corresponding whole muscle lengths (standard method). From a mechanical point of view, this requires a parallel elastic component (PEC) that is arranged in parallel to both the series elastic component (SEC) and the contractile component (CC). From a morphological point of view, however, the PEC should be rather in parallel to the CC, and both in series to the SEC (model [CC]). In this study, we investigated the differences in active muscle force estimated with these two different approaches and their impact on the interpretation of experiments. We measured passive forces without stimulation and total forces during supramaximal stimulation of six cat soleus muscles in end-held isometric contractions from lengths near active insufficiency to lengths close to inducing stretch damage. The active forces estimated with model [CC] reach about 10% higher maximum isometric forces and reveal about 10% longer optimal lengths of the CC compared to the standard method. Model choice affects the interpretation of the physiological working range and residual force enhancement. The active force-length relationships of the contractile component determined with model [CC] agree better with the theoretical sarcomere force-length relationship.

Distinct muscle fascicle length changes in feline medial gastrocnemius and soleus muscles during slope walking

On the basis of differences in physiology, e.g., histochemical properties and spindle density, and the structural design of the cat soleus (SO) and medial gastrocnemius (MG) muscles, we hypothesized that 1) fascicle length changes during overground walking would be both muscle and slope dependent, which would have implications for the muscles' force output as well as sensory function, and that 2) muscle-tendon unit (MTU) and fascicle length changes would be different, in which case MTU length could not be used as an indicator of muscle spindle strain. To test these hypotheses, we quantified muscle fascicle length changes and compared them with length changes of the whole MTU in the SO and MG during overground walking at various slopes (0, +/- 25, +/- 50, +75, and +100%). The SO and MG were surgically instrumented with sonomicrometry crystals and fine-wire electromyogram electrodes to measure changes in muscle fascicle length and muscle activity, respectively. MTU lengths were calculated using recorded ankle and knee joint angles and a geometric model of the hindlimb. The resultant joint moments were calculated using inverse dynamics analysis to infer muscle loading. It was found that although MTU length and velocity profiles of the SO and MG appeared similar, length changes and velocities of muscle fascicles were substantially different between the two muscles. Fascicle length changes of both SO and MG were significantly affected by slope intensity acting eccentrically in downslope walking (-25 to -50%) and concentrically in upslope walking (+25 to +100%). The differences in MTU and fascicle behaviors in both the SO and MG muscles during slope walking were explained by the three distinct features of these muscles: 1) the number of joints spanned, 2) the pennation angle, and 3) the in-series elastic component. It was further suggested that the potential role of length feedback from muscle spindles is both task and muscle dependent.

The Influence of Shortening History on Dynamic Muscle Function

Previous investigators have reported that shortening history (e.g. velocity and distance of shortening) influenced the isometric force produced subsequent to muscle shortening. Few investigators, however, have reported the influence of shortening history on dynamic muscle function. PURPOSE: The purpose of this investigation was to compare the effect of shortening history on dynamic muscle function and isometric force following muscle shortening. METHODS: Cat soleus muscle (n=4) was isolated and subjected to a series of constant velocity and constant load contractions. During both of these protocols shortening started from three initial muscle lengths and terminated at a constant final muscle length, resulting in three shortening distances (50%, 75% and 100%). Furthermore, subsequent to end of the constant velocity shortening, stimulation remained on for one second allowing the muscle to perform a final isometric contraction. The muscular force produced during the constant velocity conditions, and the shortening velocity produced during the constant load conditions were recorded and analyzed at a consistent predetermined muscle length. Repeated measures analysis was used to determine if shortening history altered isometric force following shortening, force during constant velocity conditions and velocity during constant load conditions. RESULTS: These results indicated that shortening distance altered isometric force and dynamic muscle function unequally. More specifically, shortening distance influenced isometric force following shortening by only 4.6±2.7%. On the other hand, shortening distance altered force produced during constant velocity contractions and shortening velocity during constant load contractions by up to 30.3±9.3% and 63.3±9.7% respectively. In addition, power produced at specific velocities decreased with greater shortening distances resulting in an overall downward shift in the power velocity curve. CONCLUSION: Shortening history alters dynamic muscle function to a much greater extent than isometric force. This dynamic force and velocity depression are important when considering functional electrical stimulation, motor behavior models and sport performance.

Are skeletal muscles independent actuators? Force transmission from soleus muscle in the cat

It is unclear if skeletal muscles act mechanically as independent actuators. The purpose of the present study was to investigate force transmission from soleus (SO) muscle for physiological lengths as well as relative positions in the intact cat hindlimb. We hypothesized that force transmission from SO fibers will be affected by length changes of its two-joint synergists. Ankle plantar flexor moment on excitation of the SO was measured for various knee angles (70-140 degrees ). This involved substantial length changes of gastrocnemius and plantaris muscles. Ankle angle was kept constant (80 degrees -90 degrees ). However, SO ankle moment was not significantly affected by changes in knee angle; neither were half-relaxation time and the maximal rate of relaxation (P > 0.05). Following tenotomy, SO ankle moment decreased substantially (55 +/- 16%) but did not reach zero, indicating force transmission via connective tissues to the Achilles tendon (i.e., epimuscular myofascial force transmission). During contraction SO muscle shortened to a much greater extent than in the intact case (16.0 +/- 0.6 vs. 1.0 +/- 0.1 mm), which resulted in a major position shift relative to its synergists. If the SO was moved back to its position corresponding to the intact condition, SO ankle moment approached zero, and most muscle force was exerted at the distal SO tendon. Our results also suggested that in vivo the lumped intact tissues linking SO to its synergists are slack or are operating on the toe region of the stress-strain curve. Thus, within the experimental conditions of the present study, the intact cat soleus muscle appears to act mechanically as an independent actuator.

Botox produces functional weakness in non-injected muscles adjacent to the target muscle

Botulinum type-A (BTX-A) neurotoxin exerts a paralytic effect on muscles and is used increasingly to treat a variety of muscle spasticity disorders. While its pathogenesis for muscle-induced weakness has been well elucidated, the functional effects of BTX-A administration are incomplete. Specifically, weakness as a function of muscle length and stimulation frequency has only been investigated qualitatively in a few muscles and the possible effect of the toxin on non-target muscles, although considered possible based on laboratory experiments, has not been studied widely and the functional implications remain unknown. Therefore, the purpose of this study was to measure the functional implications of BTX-A on force production and possible weakness of a target muscle and a non-injected neighbouring muscle. The cat soleus was chosen as the target muscle and was injected with 3.2–3.5 U of BTX-A/kg in one hind limb, while the soleus of the other hind limb served as a non-injected control. Force–length properties within and exceeding the functional range of motion were determined at frequencies of stimulation of 10, 30 and 50 Hz. Force–length properties of the adjacent non-injected plantaris were also determined in the experimental and contralateral hind limb. Four weeks following BTX-A injections, peak soleus forces were decreased by 30% (50 Hz), 29% (30 Hz) and 29% (10 Hz) and peak plantaris forces were decreased by 11% (50 Hz), 16% (30 Hz) and 16% (10 Hz), in the experimental compared to the contralateral hind limb. Absolute BTX-associated force loss was significantly different at all frequencies of stimulation and all lengths for the soleus, while in the plantaris there was a significant force loss across long (⩾−4 mm) but not short muscle lengths. Decreases in peak force were independent of the stimulation frequency. We concluded from the results of this study that BTX-A injection in the target muscle caused a measurable effect on force production and that force production was decreased in non-target neighbouring muscles at and near lengths of peak force production. These results are of particular importance in therapeutic procedures where isolated muscles are targeted for treatment. They should also be considered in neurophysiological studies in which BTX-A injections are used to selectively diminish muscle function.