A surgical technique for individual control of the muscles of the rabbit lower hindlimb.

Little is known regarding the precise muscle, bone and joint actions resulting from individual and simultaneous muscle activation(s) of the lower limb. An in situ experimental approach is described herein to control the muscles of the rabbit lower hindlimb, including the medial and lateral gastrocnemius, soleus, plantaris and tibialis anterior. The muscles were stimulated using nerve-cuff electrodes placed around the innervating nerves of each muscle. Animals were fixed in a stereotactic frame with the ankle angle set at 90 deg. To demonstrate the efficacy of the experimental technique, isometric plantarflexion torque was measured at the 90 deg ankle joint angle at a stimulation frequency of 100, 60 and 30 Hz. Individual muscle torque and the torque produced during simultaneous activation of all plantarflexor muscles are presented for four animals. These results demonstrate that the experimental approach was reliable, with insignificant variation in torque between repeated contractions. The experimental approach described herein provides the potential for measuring a diverse array of muscle properties, which is important to improve our understanding of musculoskeletal biomechanics.

A methodological approach for collecting simultaneous measures of muscle, aponeurosis, and tendon behaviour during dynamic contractions.

Skeletal muscles and the tendons that attach them to bone are structurally complex and deform non-uniformly during contraction. While these tissue deformations dictate force production during movement, our understanding of this behaviour is limited due to challenges in obtaining complete measures of the constituent structures. To address these challenges, we present an approach for simultaneously measuring muscle, fascicle, aponeurosis, and tendon behaviour using sonomicrometry. To evaluate this methodology, we conducted isometric and dynamic contractions in in situ rabbit medial gastrocnemius. We found comparable patterns of strain in the muscle belly, fascicle, aponeurosis, and tendon during the isometric trials to those published in the literature. For the dynamic contractions, we found that our measures using this method were consistent across all animals and aligned well with our theoretical understanding of muscle-tendon unit behaviour. Thus, this method provides a means to fully capture the complex behaviour of muscle-tendon units across contraction types.

The energy of muscle contraction. IV. Greater mass of larger muscles decreases contraction efficiency.

While skeletal muscle mass has been shown to decrease mass-specific mechanical work per cycle, it is not yet known how muscle mass alters contraction efficiency. In this study, we examined the effect of muscle mass on mass-specific metabolic cost and efficiency during cyclic contractions in simulated muscles of different sizes. We additionally explored how tendon and its stiffness alters the effects of muscle mass on mass-specific work, mass-specific metabolic cost and efficiency across different muscle sizes. To examine contraction efficiency, we estimated the metabolic cost of the cycles using established cost models. We found that for motor contractions in which the muscle was primarily active during shortening, greater muscle mass resulted in lower contraction efficiency, primarily due to lower mass-specific mechanical work per cycle. The addition of a tendon in series with the mass-enhanced muscle model improved the mass-specific work and efficiency per cycle with greater mass for motor contractions, particularly with a shorter excitation duty cycle, despite higher predicted metabolic cost. The results of this study indicate that muscle mass is an important determinant of whole muscle contraction efficiency.

EMG Signals Can Reveal Information Sharing between Consecutive Pedal Cycles.

PURPOSE: Producing a steady cadence and power while cycling results in fairly consistent average pedal forces for every revolution, although small fluctuations about an average force do occur. This force can be generated by several combinations of muscles, each with slight fluctuations in excitation for every pedal cycle. Fluctuations such as these are commonly thought of as random variation about average values. However, research into fluctuations of stride length and stride time during walking shows information can be contained in the order of fluctuations. This order, or structure, is thought to reveal underlying motor control strategies. Previously, we found persistent structure in the fluctuations of EMG signals during cycling using entropic half-life analysis. These EMG signals contained fluctuations across multiple timescales, such as those within a burst of excitation, between the burst and quiescent period of a cycle, and across multiple cycles. It was not clear which sources of variation contributed to the persistent structure in the EMG. METHODS: In this study, we manipulated variation at different timescales in EMG intensity signals to identify the sources of structure observed during cycling. Nine participants cycled at a constant power and cadence for 30 min while EMG was collected from six muscles of the leg. RESULTS: We found persistent structure across multiple pedal cycles of average EMG intensities, as well as average pedal forces and durations. In addition, we found the entropic half-life did not quantify fluctuations within a burst of EMG intensity; instead, it detected unstructured variation between the burst and quiescent period within a cycle. CONCLUSIONS: The persistent structure in average EMG intensities suggests that fluctuations in muscle excitation are regulated from cycle to cycle.

The Energy of Muscle Contraction. III. Kinetic Energy During Cyclic Contractions.

During muscle contraction, chemical energy is converted to mechanical energy when ATP is hydrolysed during cross-bridge cycling. This mechanical energy is then distributed and stored in the tissue as the muscle deforms or is used to perform external work. We previously showed how energy is distributed through contracting muscle during fixed-end contractions; however, it is not clear how the distribution of tissue energy is altered by the kinetic energy of muscle mass during dynamic contractions. In this study we conducted simulations of a 3D continuum muscle model that accounts for tissue mass, as well as force-velocity effects, in which the muscle underwent sinusoidal work-loop contractions coupled with bursts of excitation. We found that increasing muscle size, and therefore mass, increased the kinetic energy per unit volume of the muscle. In addition to greater relative kinetic energy per cycle, relatively more energy was also stored in the aponeurosis, and less was stored in the base material, which represented the intra and extracellular tissue components apart from the myofibrils. These energy changes in larger muscles due to greater mass were associated lower mass-specific mechanical work output per cycle, and this reduction in mass-specific work was greatest for smaller initial pennation angles. When we compared the effects of mass on the model tissue behaviour to that of in situ muscle with added mass during comparable work-loop trials, we found that greater mass led to lower maximum and higher minimum acceleration in the longitudinal (x) direction near the middle of the muscle compared to at the non-fixed end, which indicates that greater mass contributes to tissue non-uniformity in whole muscle. These comparable results for the simulated and in situ muscle also show that this modelling framework behaves in ways that are consistent with experimental muscle. Overall, the results of this study highlight that muscle mass is an important determinant of whole muscle behaviour.

The Contributions of Extracellular Matrix and Sarcomere Properties to Passive Muscle Stiffness in Cerebral Palsy.

Cerebral palsy results from an upper motor neuron lesion and significantly affects skeletal muscle stiffness. The increased stiffness that occurs is partly a result of changes in the microstructural components of muscle. In particular, alterations in extracellular matrix, sarcomere length, fibre diameter, and fat content have been reported; however, experimental studies have shown wide variability in the degree of alteration. Many studies have reported changes in the extracellular matrix, while others have reported no differences. A consistent finding is increased sarcomere length in cerebral palsy affected muscle. Often many components are altered simultaneously, making it difficult to determine the individual effects on muscle stiffness. In this study, we use a three dimensional modelling approach to isolate individual effects of microstructural alterations typically occurring due to cerebral palsy on whole muscle behaviour; in particular, the effects of extracellular matrix volume fraction, stiffness, and sarcomere length. Causation between the changes to the microstructure and the overall muscle response is difficult to determine experimentally, since components of muscle cannot be manipulated individually; however, utilising a modelling approach allows greater control over each factor. We find that extracellular matrix volume fraction has the largest effect on whole muscle stiffness and mitigates effects from sarcomere length.

The Energy of Muscle Contraction. II. Transverse Compression and Work.

In this study we examined how the strain energies within a muscle are related to changes in longitudinal force when the muscle is exposed to an external transverse load. We implemented a three-dimensional (3D) finite element model of contracting muscle using the principle of minimum total energy and allowing the redistribution of energy through different strain energy-densities. This allowed us to determine the importance of the strain energy-densities to the transverse forces developed by the muscle. We ran a series of in silica experiments on muscle blocks varying in initial pennation angle, muscle length, and external transverse load. As muscle contracts it maintains a near constant volume. As such, any changes in muscle length are balanced by deformations in the transverse directions such as muscle thickness or muscle width. Muscle develops transverse forces as it expands. In many situations external forces act to counteract these transverse forces and the muscle responds to external transverse loads while both passive and active. The muscle blocks used in our simulations decreased in thickness and pennation angle when passively compressed and pushed back on the load when they were activated. Activation of the compressed muscle blocks led either to an increase or decrease in muscle thickness depending on whether the initial pennation angle was less than or greater than 15°, respectively. Furthermore, the strain energy increased and redistributed across the different strain-energy potentials during contraction. The volumetric strain energy-density varied with muscle length and pennation angle and was reduced with greater transverse load for most initial muscle lengths and pennation angles. External transverse load reduced the longitudinal muscle force for initial pennation angles of ß0 = 0°. Whereas for pennate muscle (ß0 > 0°) longitudinal force changed (increase or decrease) depending on the muscle length, pennation angle and the direction of the external load relative to the muscle fibres. For muscle blocks with initial pennation angles ß0 ≤ 20° the reduction in longitudinal muscle force coincided with a reduction in volumetric strain energy-density.

The Energy of Muscle Contraction. I. Tissue Force and Deformation During Fixed-End Contractions.

During contraction the energy of muscle tissue increases due to energy from the hydrolysis of ATP. This energy is distributed across the tissue as strain-energy potentials in the contractile elements, strain-energy potential from the 3D deformation of the base-material tissue (containing cellular and extracellular matrix effects), energy related to changes in the muscle's nearly incompressible volume and external work done at the muscle surface. Thus, energy is redistributed through the muscle's tissue as it contracts, with only a component of this energy being used to do mechanical work and develop forces in the muscle's longitudinal direction. Understanding how the strain-energy potentials are redistributed through the muscle tissue will help enlighten why the mechanical performance of whole muscle in its longitudinal direction does not match the performance that would be expected from the contractile elements alone. Here we demonstrate these physical effects using a 3D muscle model based on the finite element method. The tissue deformations within contracting muscle are large, and so the mechanics of contraction were explained using the principles of continuum mechanics for large deformations. We present simulations of a contracting medial gastrocnemius muscle, showing tissue deformations that mirror observations from magnetic resonance imaging. This paper tracks the redistribution of strain-energy potentials through the muscle tissue during fixed-end contractions, and shows how fibre shortening, pennation angle, transverse bulging and anisotropy in the stress and strain of the muscle tissue are all related to the interaction between the material properties of the muscle and the action of the contractile elements.

Management of Acute Pain From Non-Low Back, Musculoskeletal Injuries : A Systematic Review and Network Meta-analysis of Randomized Trials.

BACKGROUND: Patients and clinicians can choose from several treatment options to address acute pain from non-low back, musculoskeletal injuries. PURPOSE: To assess the comparative effectiveness of outpatient treatments for acute pain from non-low back, musculoskeletal injuries by performing a network meta-analysis of randomized clinical trials (RCTs). DATA SOURCES: MEDLINE, EMBASE, CINAHL, PEDro (Physiotherapy Evidence Database), and Cochrane Central Register of Controlled Trials to 2 January 2020. STUDY SELECTION: Pairs of reviewers independently identified interventional RCTs that enrolled patients presenting with pain of up to 4 weeks' duration from non-low back, musculoskeletal injuries. DATA EXTRACTION: Pairs of reviewers independently extracted data. Certainty of evidence was evaluated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. DATA SYNTHESIS: The 207 eligible studies included 32 959 participants and evaluated 45 therapies. Ninety-nine trials (48%) enrolled populations with diverse musculoskeletal injuries, 59 (29%) included patients with sprains, 13 (6%) with whiplash, and 11 (5%) with muscle strains; the remaining trials included various injuries ranging from nonsurgical fractures to contusions. Topical nonsteroidal anti-inflammatory agents (NSAIDs) proved to have the greatest net benefit, followed by oral NSAIDs and acetaminophen with or without diclofenac. Effects of these agents on pain were modest (around 1 cm on a 10-cm visual analogue scale, approximating the minimal important difference). Regarding opioids, compared with placebo, acetaminophen plus an opioid improved intermediate pain (1 to 7 days) but not immediate pain (≤2 hours), tramadol was ineffective, and opioids increased the risk for gastrointestinal and neurologic harms (all moderate-certainty evidence). LIMITATIONS: Only English-language studies were included. The number of head-to-head comparisons was limited. CONCLUSION: Topical NSAIDs, followed by oral NSAIDs and acetaminophen with or without diclofenac, showed the most convincing and attractive benefit-harm ratio for patients with acute pain from non-low back, musculoskeletal injuries. No opioid achieved benefit greater than that of NSAIDs, and opioids caused the most harms. PRIMARY FUNDING SOURCE: National Safety Council. (PROSPERO: CRD42018094412).

Added mass in rat plantaris muscle causes a reduction in mechanical work.

Most of what we know about whole muscle behaviour comes from experiments on single fibres or small muscles that are scaled up in size without considering the effects of the additional muscle mass. Previous modelling studies have shown that tissue inertia acts to slow the rate of force development and maximum velocity of muscle during shortening contractions and decreases the work and power per cycle during cyclic contractions; however, these results have not yet been confirmed by experiments on living tissue. Therefore, in this study we conducted in situ work-loop experiments on rat plantaris muscle to determine the effects of increasing the mass of muscle on mechanical work during cyclic contractions. We additionally simulated these experimental contractions using a mass-enhanced Hill-type model to validate our previous modelling work. We found that greater added mass resulted in lower mechanical work per cycle relative to the unloaded trials in which no mass was added to the muscle (P=0.041 for both 85 and 123% increases in muscle mass). We additionally found that greater strain resulted in lower work per cycle relative to unloaded trials at the same strain to control for length change and velocity effects on the work output, possibly due to greater accelerations of the muscle mass at higher strains. These results confirm that tissue mass reduces muscle mechanical work at larger muscle sizes, and that this effect is likely amplified for lower activations.

Size, History-Dependent, Activation and Three-Dimensional Effects on the Work and Power Produced During Cyclic Muscle Contractions.

Muscles undergo cycles of length change and force development during locomotion, and these contribute to their work and power production to drive body motion. Muscle fibers are typically considered to be linear actuators whose stress depends on their length, velocity, and activation state, and whose properties can be scaled up to explain the function of whole muscles. However, experimental and modeling studies have shown that a muscle's stress additionally depends on inactive and passive tissues within the muscle, the muscle's size, and its previous contraction history. These effects have not been tested under common sets of contraction conditions, especially the cyclic contractions that are typical of locomotion. Here we evaluate the relative effects of size, history-dependent, activation and three-dimensional effects on the work and power produced during cyclic contractions of muscle models. Simulations of muscle contraction were optimized to generate high power outputs: this resulted in the muscle models being largely active during shortening, and inactive during lengthening. As such, the history-dependent effects were dominated by force depression during simulated active shortening rather than force enhancement during active stretch. Internal work must be done to deform the muscle tissue, and to accelerate the internal muscle mass, resulting in reduced power and work that can be done on an external load. The effect of the muscle mass affects the scaling of muscle properties, with the inertial costs of contraction being relatively greater at larger sizes and lower activation levels.

A modelling approach for exploring muscle dynamics during cyclic contractions.

Hill-type muscle models are widely used within the field of biomechanics to predict and understand muscle behaviour, and are often essential where muscle forces cannot be directly measured. However, these models have limited accuracy, particularly during cyclic contractions at the submaximal levels of activation that typically occur during locomotion. To address this issue, recent studies have incorporated effects into Hill-type models that are oftentimes neglected, such as size-dependent, history-dependent, and activation-dependent effects. However, the contribution of these effects on muscle performance has yet to be evaluated under common contractile conditions that reflect the range of activations, strains, and strain rates that occur in vivo. The purpose of this study was to develop a modelling framework to evaluate modifications to Hill-type muscle models when they contract in cyclic loops that are typical of locomotor muscle function. Here we present a modelling framework composed of a damped harmonic oscillator in series with a Hill-type muscle actuator that consists of a contractile element and parallel elastic element. The intrinsic force-length and force-velocity properties are described using Bézier curves where we present a system to relate physiological parameters to the control points for these curves. The muscle-oscillator system can be geometrically scaled while preserving dynamic and kinematic similarity to investigate the muscle size effects while controlling for the dynamics of the harmonic oscillator. The model is driven by time-varying muscle activations that cause the muscle to cyclically contract and drive the dynamics of the harmonic oscillator. Thus, this framework provides a platform to test current and future Hill-type model formulations and explore factors affecting muscle performance in muscles of different sizes under a range of cyclic contractile conditions.

Muscle shortening velocity depends on tissue inertia and level of activation during submaximal contractions.

In order to perform external work, muscles must do additional internal work to deform their tissue, and in particular, to overcome the inertia due to their internal mass. However, the contribution of the internal mass within a muscle to the mechanical output of that muscle has only rarely been studied. Here, we use a dynamic, multi-element Hill-type muscle model to examine the effects of the inertial mass within muscle on its contractile performance. We find that the maximum strain-rate of muscle is slower for lower activations and larger muscle sizes. As muscle size increases, the ability of the muscle to overcome its inertial load will decrease, as muscle tension is proportional to cross-sectional area and inertial load is proportional to mass. Thus, muscles that are larger in size will have a higher inertial cost to contraction. Similarly, when muscle size and inertial load are held constant, decreasing muscle activation will increase inertial cost to contraction by reducing muscle tension. These results show that inertial loads within muscle contribute to a slowing of muscle contractile velocities (strain-rates), particularly at the submaximal activations that are typical during animal locomotion.

Association between shortened leukocyte telomere length and cardiometabolic outcomes: systematic review and meta-analysis.

BACKGROUND: Telomeres are repetitive, gene-poor regions that cap the ends of DNA and help maintain chromosomal integrity. Their shortening is caused by inflammation and oxidative stress within the cellular environment and ultimately leads to cellular senescence. Shortened leukocyte telomere length is hypothesized to be a novel biomarker for age and age-related diseases, yet reports on its association with cardiometabolic outcomes in the literature are conflicting. METHODS AND RESULTS: MEDLINE (1966 to present) and EMBASE (1980 to present) were last searched on September 9, 2013. Reference lists of retrieved citations were hand searched for relevant studies. No restrictions were placed on sample size, language, or publication type or date. Fifteen cohort and 12 case-control studies reporting the association between leukocyte telomere length and stroke, myocardial infarction, and type 2 diabetes mellitus were independently selected for inclusion by 2 reviewers. Data extraction and risk of bias assessment were completed independently by 2 reviewers using predefined criteria. Studies were pooled using the generic inverse variance method and both fixed and random effects models. A 1-SD decrease in leukocyte telomere length was significantly associated with stroke (odds ratio, 1.21; 95% confidence interval, 1.06-1.37; I(2)=61%), myocardial infarction (odds ratio, 1.24; 95% confidence interval, 1.04-1.47; I(2)=68%), and type 2 diabetes mellitus (odds ratio, 1.37; 95% confidence interval, 1.10-1.72; I(2)=91%). Stratification by measurement technique, study design, study size, and ethnicity explained heterogeneity in certain cardiometabolic outcomes. CONCLUSIONS: Shortened leukocyte telomere length demonstrates a significant association with stroke, myocardial infarction, and type 2 diabetes mellitus. Larger, well-designed studies are needed to confirm these findings and explore sources of heterogeneity.

Relative risk of cervical cancer in indigenous women in Australia, Canada, New Zealand, and the United States: a systematic review and meta-analysis.

We performed a systematic review and meta-analysis of cervical cancer risk in indigenous women in Australia, Canada, New Zealand, and the United States, in order to identify whether risks of cervical dysplasia, cervical cancer, and cervical cancer-related mortality are higher in indigenous relative to non-indigenous populations. We identified 35 studies published in 1969-2008. In our findings, indigenous populations did not have an elevated risk of cervical dysplasia or carcinoma in situ relative to non-indigenous populations, but had elevated risks of invasive cervical cancer (pooled RR=1.72) and cervical cancer-related mortality (pooled RR=3.45). There was a log-linear relationship between relative risk and disease stage. In conclusion, the indigenous women have a markedly higher risk of cervical cancer morbidity and mortality than non-indigenous women, but no increased risk of early-stage disease, suggesting that structural, social, or individual barriers to screening, rather than baseline risk factors, are influencing poor health outcomes.