Active Force-length Relationship Research Articles

Endomysium determines active and passive force production in muscle fibers

Connective tissues can be recognized as an important structural support element in muscles. Recent studies have also highlighted its importance in active force generation and transmission between muscles, particularly through the epimysium. In the present study, we aimed to investigate the impact of the endomysium, the connective tissue surrounding muscle fibers, on both passive and active force production. Pairs of skeletal muscle fibers were extracted from the extensor digitorum longus muscles of rats and, after chemical skinning, their passive and active force–length relationships were measured under two conditions: (i) with the endomysium between muscle fibers intact, and (ii) after its dissection. We found that the dissection of the endomysium caused force to significantly decrease in both active (by 22.2 % when normalized to the maximum isometric force; p < 0.001) and passive conditions (by 25.9 % when normalized to the maximum isometric force; p = 0.034). These findings indicate that the absence of endomysium compromises muscle fiber’s not only passive but also active force production. This effect may be attributed to increased heterogeneity in sarcomere lengths, enhanced lattice spacing between myofilaments, or a diminished role of trans-sarcolemmal proteins due to dissecting the endomysium. Future investigations into the underlying mechanisms and their implications for various extracellular matrix-related diseases are warranted.

Skeletal muscle contractile properties in a novel murine model for limb girdle muscular dystrophy 2i.

Limb-girdle muscular dystrophy (LGMD) 2i results from mutations in fukutin-related protein and aberrant α-dystroglycan glycosylation. Although this significantly compromises muscle function and ambulation, the comprehensive characteristics of contractile dysfunction are unknown. Therefore, we quantified the in situ contractile properties of the medial gastrocnemius in young adult P448L mice, an affected muscle of a novel model of LGMD2i. Normalized maximal twitch force, tetanic force, and power were significantly smaller in P448L mice, compared with sex-matched, wild-type mice. These differences were consistent with the replacement of contractile fibers by passive tissue. The shape of the active force-length relationships were similar in both groups, regardless of sex, consistent with an intact sarcomeric structure in P448L mice. Passive force-length curves normalized to maximal isometric force were steeper in P448L mice, and passive elements contribute disproportionately more to total contractile force in P448L mice. Sex differences were mostly noted in the force-velocity curves, as normalized values for maximal and optimal velocities were significantly slower in P448L males, compared with wild-type, but not in P448L females. This suggests that the dystrophic phenotype, which may include possible changes in cross-bridge kinetics and fiber-type proportions, progresses more quickly in P448L males. These results together indicate that active force and power generation are compromised in both sexes of P448L mice, while passive forces increase. More importantly, the results identified several functional markers of disease pathophysiology that could aid in developing and assessment of novel therapeutics for LGMD2i and possibly other dystroglycanopathies as well. NEW & NOTEWORTHY Comprehensive assessments of muscle contractile function have, until now, never been performed in an animal model for any dystroglycanopathy. This study suggests that skeletal muscle contractile properties are significantly compromised in a recently developed model for limb-girdle muscular dystrophy 2i, the P448L mouse. It further identifies novel pathological markers of muscle function that are suitable for developing therapeutics and for better understanding of disease pathogenesis.

Biomechanical simulation of thorax deformation using finite element approach.

BackgroundThe biomechanical simulation of the human respiratory system is expected to be a useful tool for the diagnosis and treatment of respiratory diseases. Because the deformation of the thorax significantly influences airflow in the lungs, we focused on simulating the thorax deformation by introducing contraction of the intercostal muscles and diaphragm, which are the main muscles responsible for the thorax deformation during breathing.MethodsWe constructed a finite element model of the thorax, including the rib cage, intercostal muscles, and diaphragm. To reproduce the muscle contractions, we introduced the Hill-type transversely isotropic hyperelastic continuum skeletal muscle model, which allows the intercostal muscles and diaphragm to contract along the direction of the fibres with clinically measurable muscle activation and active force–length relationship. The anatomical fibre orientations of the intercostal muscles and diaphragm were introduced.ResultsThorax deformation consists of movements of the ribs and diaphragm. By activating muscles, we were able to reproduce the pump-handle and bucket-handle motions for the ribs and the clinically observed motion for the diaphragm. In order to confirm the effectiveness of this approach, we simulated the thorax deformation during normal quiet breathing and compared the results with four-dimensional computed tomography (4D-CT) images for verification.ConclusionsThorax deformation can be simulated by modelling the respiratory muscles according to continuum mechanics and by introducing muscle contractions. The reproduction of representative motions of the ribs and diaphragm and the comparison of the thorax deformations during normal quiet breathing with 4D-CT images demonstrated the effectiveness of the proposed approach. This work may provide a platform for establishing a computational mechanics model of the human respiratory system.

Optimization of Active Muscle Force-Length Models Using Least Squares Curve Fitting.

The objective of this paper is to propose an asymmetric Gaussian function as an alternative to the existing active force-length models, and to optimize this model along with several other existing models by using the least squares curve fitting method. The minimal set of coefficients is identified for each of these models to facilitate the least squares curve fitting. Sarcomere simulated data and one set of rabbits extensor digitorum II experimental data are used to illustrate optimal curve fitting of the selected force-length functions. The results shows that all the curves fit reasonably well with the simulated and experimental data, while the Gordon-Huxley-Julian model and asymmetric Gaussian function are better than other functions in terms of statistical test scores root mean squared error and R-squared. However, the differences in RMSE scores are insignificant (0.3-6%) for simulated data and (0.2-5%) for experimental data. The proposed asymmetric Gaussian model and the method of parametrization of this and the other force-length models mentioned above can be used in the studies on active force-length relationships of skeletal muscles that generate forces to cause movements of human and animal bodies.

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.

Intramuscular drug transport under mechanical loading: Resonance between tissue function and uptake

Dynamic architecture and motion in mechanically active target tissues can influence the pharmacokinetics of locally delivered agents. Drug transport in skeletal muscle under controlled mechanical loads was investigated. Static (0–20%) and cyclic (± 2.5% amplitude, 0–20% mean, 1–3 Hz) strains and electrically paced isometric contractions (0.1–3 Hz, 0% strain) were applied to rat soleus incubated in 1 mM 20 kDa FITC–dextran. Dextran penetration, tissue porosity, and active force–length relationship over 0–20% strain correlated ( r = 0.9–1.0), and all increased 1.5-fold from baseline at 0% to a maximum at 10% (Lo), demonstrating biologic significance of Lo and impact of fiber size and distribution on function and pharmacokinetics. Overall penetration decreased but relative enhancement of penetration at Lo increased with dextran size (4–150 kDa). Penetration increased linearly (0.084 mm/Hz) with cyclic stretch, demonstrating dispersion. Penetration increased with contraction rate by 1.5-fold from baseline to a maximum at 0.5 Hz, revealing architectural modulation of dispersion. Impact of architecture and dispersion on intramuscular transport was computationally modeled. Mechanical architecture and function underlie intramuscular pharmacokinetics and act in concert to effect resonance between optimal physiologic performance and drug uptake. Therapeutic management of characteristic function in tissue targets may enable a physiologic mechanism for controlled drug transport.

Altered contractile properties of the gastrocnemius muscle poststroke

Spasticity, contracture and muscle weakness often occur together poststroke and cause considerable motor impairments to stroke survivors. The underlying changes in contractile properties of muscle fascicles are still not clear. The purpose of this study was to investigate the contractile property changes of the medial gastrocnemius muscle fascicles poststroke. Ten stroke survivors and ten healthy subjects participated in the study. The medial gastrocnemius fascicular length was measured at various combinations of ankle and knee positions using ultrasonography, with the muscle activated selectively using electrical stimulation. The stimulation intensity was kept constant across different ankle and knee positions to establish the active force-length relationship of the muscle fascicles. It was found that stroke survivors showed a shift of the force-length curve with a significantly shorter optimal fascicle length (33.2 +/- 3.2 mm) compared with that of healthy controls (47.4 +/- 2.7 mm) with P < 0.001. Furthermore, the width span of the fascicular force-length curve of stroke survivors was significantly narrower with steeper slopes than that of controls (P <or= 0.001), suggesting reduced number of sarcomeres along the fascicles and/or reduced sarcomere length poststroke. Regression analysis showed that the medial gastrocnemius fascicular length of stroke survivors varied significantly less with ankle and knee flexions (P <or= 0.001) than that of controls, suggesting shorter and stiffer muscle fascicles poststroke, which might be attributed to muscle architectural adaptation. This study showed that there are considerable changes in the contractile properties of muscle fascicles poststroke, which may contribute directly to the joint-level changes of decreased range of motion, increased stiffness, muscle weakness, and impaired motor functions in stroke survivors.

Dantrolene, like fatigue, has a length‐dependent effect on submaximal force–length relationships of rat gastrocnemius muscle

Fatigue is length-dependent; relative active force depression is greater when measured at short lengths than at long lengths. Several unsatisfactory mechanisms have been proposed to explain this length dependence of fatigue, including: damaged myofilaments, stretch of 'in-series' structures, impaired t-tubule conduction and reduced intensity of activation. Dantrolene targets the ryanodine receptors, inhibiting stimulation-induced release of Ca2+. The purpose of this study was to determine if the force depression caused by dantrolene treatment also has a length dependence. Submaximal (single-pulse, double-pulse and 50 Hz stimulation) active force-length relationships were obtained from the medial gastrocnemius muscle of anaesthetized rats, before and after intravenous injection with dantrolene dissolved in propylene glycol. Dantrolene treatment was sufficient to reduce twitch amplitude by 25%. Similar to the consequences of repetitive stimulation, dantrolene treatment caused the same decrease in absolute active force across a broad range of test lengths, for twitch, double-pulse and 50 Hz contractions. Considering that active force is smaller at short lengths than at long lengths, this similar absolute force decrease represents a greater relative decrease at short lengths. Clearly, there is a length-dependent impact of attenuated Ca2+ release by dantrolene on relative active force. This study demonstrates that there is a length dependence of force depression associated with decreased Ca2+ release due to dantrolene treatment; therefore, if fatigue is due to decreased Ca2+ release, then additional length-dependent mechanisms are not required to explain the reported length dependence of force depression.

Bronchial Hyporesponsiveness

<ul><li>1Normal bronchial hyporesponsiveness may be more important to explain than asthmatic hyperresponsiveness, which is predictable from the active force-length relationship of bronchial smooth muscle.</li><li>2In vitro isometric force measurements on bronchial smooth muscle may have little relevance to asthma.</li><li>3Whether these conclusions are correct depends on whether bronchoconstriction is quasi-isotonic. We need the answer to this question.</li><li>4Whatever the answer, in vivo responses to inhalational challenges depend on the change in length of bronchial smooth muscle cells. Therefore, investigation should focus on the factors which determine change in length rather than change in force.</li></ul>