In vivo and in vitro correlation of trachealis muscle contraction in dogs.

Maximal trachealis muscle shortening in vivo was compared with that in vitro in seven anesthetized dogs. In addition, the effect of graded elastic loads on the muscle was evaluated in vitro. In vivo trachealis muscle shortening, as measured using sonomicrometry, revealed maximal active shortening to be 28.8 +/- 11.7% (SD) of initial length. Trachealis muscle preparations from the same animals were studied in vitro to evaluate isometric force generation, isotonic shortening, and the effect of applying linear elastic loads to the trachealis muscle during contraction from optimal length. Maximal isotonic shortening was 66.8 +/- 8.4% of optimal length in vitro. Increasing elastic loads decreased active shortening and velocity of shortening in vitro in a hyperbolic manner. The elastic load required to decrease in vitro shortening to the extent of the shortening observed in vivo was similar to the estimated load provided by the tracheal cartilage. We conclude that decreased active shortening in vivo is primarily due to the elastic afterload provided by cartilage.     

Effect of theophylline on the velocity of diaphragmatic muscle shortening

The present study examined the effect of theophylline on the shortening velocity of submaximally activated diaphragmatic muscle (i.e., muscles were activated by the use of a level of stimulation, 50 Hz, within the range of phrenic neural firing frequencies achieved during breathing, whereas maximum activation is achieved at 300 Hz). Experiments were performed in vitro on strips of diaphragmatic muscle obtained from 21 Syrian hamsters. Muscle shortening velocity was assessed during isotonic contractions against a range of afterloads, and Hill's characteristic equation was used to calculate velocity at zero load. In addition, unloaded shortening velocity was also measured by the slack test, i.e., from the time required for muscles to take up slack after a sudden reduction in muscle length. Theophylline (160 mg/l) increased the velocity of muscle shortening against a wide range of external loads (0-14 N/cm2) and increased the extrapolated unloaded velocity of shortening from 6.4 +/- 0.9 to 7.9 +/- 1.1 (SE) lengths/s (P less than 0.01). Theophylline reduced the time required to take up slack for any given step change in muscle length, increasing the unloaded velocity of shortening assessed by the slack test from 7.6 +/- 0.9 to 9.3 +/- 1.1 lengths/s (P less than 0.002). The effect of theophylline on diaphragmatic shortening velocity was evident at concentrations as low as 40 mg/l and increased progressively as theophylline concentrations were increased to 320 mg/l. Theophylline increased the shortening velocity of fatigued as well as fresh muscles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanical properties of human bronchial smooth muscle in vitro.

The in vitro mechanical properties of smooth muscle strips from 10 human main stem bronchi obtained immediately after pneumonectomy were evaluated. Maximal active isometric and isotonic responses were obtained at varying lengths by use of electrical field stimulation (EFS). At the length (Lmax) producing maximal force (Pmax), resting tension was very high (60.0 +/- 8.8% Pmax). Maximal fractional muscle shortening was 25.0 +/- 9.0% at a length of 75% Lmax, whereas less shortening occurred at Lmax (12.2 +/- 2.7%). The addition of increasing elastic loads produced an exponential decrease in the shortening and velocity of shortening but increased tension generation of muscle strips stimulated by EFS. Morphometric analysis revealed that muscle accounted for 8.7 +/- 1.5% of the total cross-sectional tissue area. Evaluation of two human tracheal smooth muscle preparations revealed mechanics similar to the bronchial preparations. Passive tension at Lmax was 10-fold greater and maximal active shortening was threefold less than that previously demonstrated for porcine trachealis by us of the same apparatus. We attribute the limited shortening of human bronchial and tracheal smooth muscle to the larger load presumably provided by a connective tissue parallel elastic component within the evaluated tissues, which must be overcome for shortening to occur. We suggest that a decrease in airway wall elastance could increase smooth muscle shortening, leading to excessive responses to contractile agonists, as seen in airway hyperresponsiveness.     

Isotonic relaxation of control and sensitized airway smooth muscle

Smooth muscle relaxation has most often been studied in isometric mode. However, this only tells us about the stiffness properties of the bronchial wall and thus only about wall capacitative properties. It tells us little about airflow. To study the latter, which of course is the meaningful parameter in regulation of ventilation and in asthma, we studied isotonic shortening of bronchial smooth muscle (BSM) strips. Failure of BSM to relax could be another important factor in maintaining high airway resistance. To analyze relaxation curves, we developed an index of isotonic relaxation, t1/2(P, lCE), which is the half-time for relaxation that is independent of muscle load (P) and of initial contractile element length (lCE). This index was measured in curves of relaxation initiated at 2 s (normally cycling crossbridges) and at 10 s (latch-bridges). At 10 s no difference was seen for adjusted t1/2(P, lCE) between curves obtained from control and sensitized BSM, (8.38 +/- 0.92 s vs. 7.78 +/- 0.93 s, respectively). At 2 s the half-time was almost doubled in the sensitized BSM (6.98 +/- 0.01 s (control) vs. 12.74 +/- 2.5 s (sensitized)). Thus, changes in isotonic relaxation are only seen during early contraction. Using zero load clamps, we monitored the time course of velocity during relaxation and noted that it varied according to 3 phases. The first phase (phase i) immediately followed cessation of electrical field stimulation (EFS) at 10 s and showed almost the same velocity as during the latter 1/3 of shortening; the second phase (phase ii) was linear in shape and is associated with zero load velocity, we speculate it could stem from elastic recoil of the cells' internal resistor; and the third phase (phase iii) was convex downwards. The zero load velocities in phase iii showed a surprising spontaneous increase suggesting reactivation of the muscle. Measurements of intracellular calcium (Fura-2 study) and of phosphorylation of the 20 kDa myosin light chain showed simultaneous increments, indicating phase iii represented an active process. Studies are under way to determine what changes occur in these 3 phases in a sensitized muscle. And of course, in the context of this conference, just what role the plastic properties of the muscle play in relaxation requires serious consideration.     

The measurement of force/velocity relationships of fresh and fatigued human adductor pollicis muscle

The purpose of the study was to obtain force/velocity relationships for electrically stimulated (80 Hz) human adductor pollicis muscle (n = 6) and to quantify the effects of fatigue. There are two major problems of studying human muscle in situ; the first is the contribution of the series elastic component, and the second is a loss of force consequent upon the extent of loaded shortening. These problems were tackled in two ways. Records obtained from isokinetic releases from maximal isometric tetani showed a late linear phase of force decline, and this was extrapolated back to the time of release to obtain measures of instantaneous force. This method gave usable data up to velocities of shortening equivalent to approximately one-third of maximal velocity. An alternative procedure (short activation, SA) allowed the muscle to begin shortening when isometric force reached a value that could be sustained during shortening (essentially an isotonic protocol). At low velocities both protocols gave very similar data (r2 = 0.96), but for high velocities only the SA procedure could be used. Results obtained using the SA protocol in fresh muscle were compared to those for muscle that had been fatigued by 25 s of ischaemic isometric contractions, induced by electrical stimulation at the ulnar nerve. Fatigue resulted in a decrease of isometric force [to 69 (3)%], an increase in half-relaxation time [to 431 (10)%], and decreases in maximal shortening velocity [to 77 (8)%] and power [to 42 (5)%]. These are the first data for human skeletal muscle to show convincingly that during acute fatigue, power is reduced as a consequence of both the loss of force and slowing of the contractile speed.     

Effects of elastic loading on porcine trachealis muscle mechanics

To shorten in vivo, airway smooth muscle must overcome an elastic load provided by cartilage and lung parenchyma. We examined the effects of linear elastic loads (0.2-80 g/cm) on the active changes in porcine trachealis muscle length and tension in response to electrical field stimulation in vitro. Increasing elastic loads produced an exponential decrease in the shortening and velocity of shortening while causing an increase in tension generation of muscle strips stimulated by electrical field stimulation. Shortening was decreased by 50% at a load of 8 g/cm. At small elastic loads (less than or equal to 1 g/cm) contractile responses approximated isotonic responses (shortening approximately 60% of starting length), whereas at large loads (20 g/cm) responses approximated isometric responses with minimal shortening (20%). We conclude that elastic loading significantly alters the mechanical properties of airway smooth muscle in vitro, effects that are likely relevant to the loads against which the smooth muscle must contract in vivo.     

In vivo force-velocity relation of human muscle: a modelling from sinusoidal oscillation behaviour

Isokinetic tests performed on human muscle in vivo during plantar flexion contractions lead to torque–angular velocity relationships usually fitted by Hill's equation expressed in angular terms. However, such tests can lead to discrepant results since they require maximal voluntary contractions performed in dynamic conditions. In the present study, another way to approach mechanical behaviour of a musculo-articular structure was used, i.e. sinusoidal oscillations during sub-maximal contractions. This led to the expression of (i) Bode diagrams allowing the determination of a damping coefficient (B_bode); and (ii) a viscous parameter (B_sin) using an adaptation of Hill's equation to sinusoidal oscillations. Then torque–angular velocity relationships were predicted from a model based on the interrelation between B_bode and B_sin and on the determination of optimal conditions of contraction. This offers the possibility of characterizing muscle dynamic properties by avoiding the use of isokinetic maximal contractions.     

Sarcomere length dependence of the force-velocity relation in single frog muscle fibers.

The force-velocity relation of single frog fibers was measured at sarcomere lengths of 2.15, 2.65, and 3.15 microns. Sarcomere length was obtained on-line with a system that measures the distance between two markers attached to the surface of the fiber, approximately 800 microns apart. Maximal shortening velocity, determined by extrapolating the Hill equation, was similar at the three sarcomere lengths: 6.5, 6.0, and 5.7 microns/s at sarcomere lengths of 2.15, 2.65, and 3.15 microns, respectively. For loads not close to zero the shortening velocity decreased with increasing sarcomere length. This was the case when force was expressed as a percentage of the maximal force at optimal fiber length or as a percentage of the sarcomere-isometric force at the respective sarcomere lengths. The force-velocity relation was discontinuous around zero velocity: load clamps above the level that kept sarcomeres isometric resulted in stretch that was much slower than when the load was decreased below isometric by a similar amount. We fitted the force-velocity relation for slow shortening (less than 600 nm/s) and for slow stretch (less than 200 nm/s) with linear regression lines. At a sarcomere length of 2.15 microns the slopes of these lines was 8.6 times higher for shortening than for stretch. At 2.65 and 3.15 microns the values were 21.8 and 14.1, respectively. At a sarcomere length of 2.15 microm, the velocity of stretch abruptly increased at loads that were 160-170% of the sarcomere isometric load, i.e., the muscle yielded. However, at a sarcomere length of 2.65 and 3.15 microm yield was absent at such loads. Even the highest loads tested (260%) resulted in only slow stretch.(ABSTRACT TRUNCATED AT 250 WORDS)     

Genetic ablation of acetylcholinesterase alters muscle function in mice

Although acetylcholinesterase (AChE) knockout mice survive, they have abnormal neuromuscular function. We analysed further the effects of the mutation on hind limb muscle contractile properties. Tibialis anterior muscle from AChE KO mice is unable to maintain tension during a short period of repetitive nerve stimulation (tetanic fade) and has an increased twitch tension in response to a single nerve electric stimulation. In response to direct muscle stimulation, we found that maximal velocity of shortening of soleus muscle is increased and maximum tetanic force is decreased in AchE KO mice versus control animals. As the contractile properties of the soleus muscle were altered by AChE ablation, our results suggest cellular and molecular changes in AChE ablated muscle containing both fast and slow muscle fibres.     

The neural basis of catalepsy in the stick insect cuniculina impigra

The femur-tibia control system which is responsible for catalepsy is studied in the open-loop configuration (input: stimulation of the femoral chordotonal organ; output: spike-frequency of FETi and SETi as well as the force produced by the extensor tibiae muscle). Comparison of motor neuron activities and muscle force reveals the input-output relationships of the extensor tibiae muscle. This muscle behaves like a low-pass filter with a small time constant for rising inputs and a large time constant for falling inputs. It forms the decisive low-pass filter for force production of the complete system. For freely moving tibia, the elastic properties of the muscles combined with the inert mass of the tibia contribute to the low-pass filter properties. The muscle does not contribute to the high-pass filter properties of the complete system. During repetitive stimulation FETi habituates quickly.Supported by DFG Ba 578     

In vivo loads on airway smooth muscle: the role of noncontractile airway structures.

The degree of airway smooth muscle contraction and shortening that occurs in vivo is modified by many factors, including those that influence the degree of muscle activation, the resting muscle length, and the loads against which the muscle contracts. Canine trachealis muscle will shorten up to 70% of starting length from optimal length in vitro but will only shorten by around 30% in vivo. This limitation of shortening may be a result of the muscle shortening against an elastic load such as could be applied by tracheal cartilage. Limitation of airway smooth muscle shortening in smaller airways may be the result of contraction against an elastic load, such as could be applied by lung parenchymal recoil. Measurement of the elastic loads applied by the tracheal cartilage to the trachealis muscle and by lung parenchymal recoil to smooth muscle of smaller airways were performed in canine preparations. In both experiments the calculated elastic loads applied by the cartilage and the parenchymal recoil explained in part the limitation of maximal active shortening and airway narrowing observed. We conclude that the elastic loads provided by surrounding structures are important in determining the degree of airway smooth muscle shortening and the resultant airway narrowing.     

Bronchial smooth muscle mechanics of a canine model of allergic airway hyperresponsiveness.

Although we have reported that tracheal smooth muscle from sensitized dogs shows altered mechanical properties, we did not know, because of technical difficulties with the preparation, whether similar changes occur in the properties of sensitized central bronchial smooth muscle (BSM), the site at which the acute asthmatic response is believed to develop. We have now succeeded in developing a cartilage-free BSM preparation that retains optimal mechanical properties. Such strips were obtained from mongrel dogs that had been sensitized to ragweed pollen. Controls were littermates injected with adjuvant alone. Length-tension relationships were obtained for both control and sensitized BSM strips (CBSM and SBSM, respectively). The maximal active stresses were the same (P greater than 0.05) when normalized to muscle fraction in total tissue cross-sectional area [6.2 +/- 0.6 x 10(4) and 5.9 +/- 0.6 x 10(4) (SE) for SBSM and CBSM, respectively]. This suggests that optimal tension is an insensitive indicator of bronchial hyperresponsiveness and that isotonic studies might be more revealing. The maximal shortening velocity (Vo) for SBSM at 2 s [0.35 +/- 0.017 (SE) lo/s, where lo signifies optimal muscle length], in the course of a 10-s contraction, was significantly greater (P less than 0.05) than Vo measured for CBSM (0.27 +/- 0.015 lo/s). However, Vo did not differ at the 8-s point of contraction. The sensitized group demonstrated a statistically significantly greater maximal shortening capacity (0.67 +/- 0.04 lo) than the control group (0.51 +/- 0.04 lo). At 2 s of contraction, 80% of maximal SBSM shortening had been completed and was significantly greater than for CBSM.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dynamic performance of a load-moving skeletal muscle

The dynamic response of the tibialis anterior muscle of the cat was determined while it was subjected to sinusoidally varying orderly stimulation of motor units and to different isotonic loads in the range of 14-85% of the maximal isometric force. The dynamic response consisted of three major components: the displacement gain, the displacement attenuation, and a pure time delay. The displacement gain was dependent on the passive load applied to the muscle and the active force generated during contraction, which could be determined from the length-tension relationships and the corresponding shortening velocity. In general, the load displacement decreased as the load mass increased from 25 to 85% of the maximal isometric force. For loads less than 25% of the maximal isometric force, slight decrease in displacement was consistently observed. The displacement attenuation was dependent on the contraction frequency but uniform for all the load masses applied to the muscle. A pure time delay of 5 ms was present and accounted for various physiological processes such as conduction time in nerve and muscle, neuromuscular junction transmission, and excitation-contraction coupling. A quantitative equation was developed to describe the muscle's dynamic response under isotonic conditions and for a wide range of loads for use in various applications.     

Spatial and temporal heterogeneity of superficial muscle strain during in situ fixed-end contractions

Numerical models of contracting muscle offer a powerful tool to study local mechanical load. For validation of these models, the spatial and temporal distribution of strain was quantified in fixed-end contracting rat tibialis anterior muscle in situ at optimal muscle length (L(o)) and at 120 degrees plantar flexion as well as at 125 and 33Hz stimulation frequency. We studied the hypothesis that after termination of stimulation in situ muscle segments near the motor endplates elongate while segments away from the endplates shorten. We show that both spatial and temporal inhomogeneities in muscle deformation occurred during contraction. Muscle plateau shortening strain equalled 4.1%. Maximal plateau shortening of a muscle segment was much larger (9.6%) and occurred distally (at 0.26 of the scaled length of the muscle). Manipulating torque levels by decreasing the stimulation frequency at the same muscle length induced a decrease in torque ( approximately 20%) with a smaller effect on the level and no effect on the pattern of muscle deformation. During relaxation, distal segments actively shortened at the expense of proximal muscle segments, which elongated. The segments undergoing lengthening were nearer to motor endplates than segments undergoing shortening.In conclusion, the present study provides experimental data on magnitude of contraction-induced deformation needed for validation of numerical models. Local muscle deformation is heterogeneous both temporally and spatially and may be related to proximity to the motor endplates.     

The effect of shortening history on isometric and dynamic muscle function

Despite numerous reports on isometric force depression, few reports have quantified force depression during active muscle shortening (dynamic force depression). The purpose of this investigation was to determine the influence of shortening history on isometric force following active shortening, force during isokinetic shortening, and velocity during isotonic shortening. The soleus muscles of four cats were subjected to a series of isokinetic contractions at three shortening velocities and isotonic contractions under three loads. Muscle excursions initiated from three different muscle lengths but terminated at a constant length. Isometric force produced subsequent to active shortening, and force or shortening velocity produced at a specific muscle length during shortening, were compared across all three conditions. Results indicated that shortening history altered isometric force by up to 5%, force during isokinetic shortening up to 30% and shortening velocity during isotonic contractions by up to 63%. Furthermore, there was a load by excursion interaction during isotonic contractions such that excursion had the most influence on shortening velocity when the loads were the greatest. There was not a velocity by excursion interaction during isokinetic contractions. Isokinetic and isotonic power–velocity relationships displayed a downward shift in power as excursions increased. Thus, to discuss force depression based on differences in isometric force subsequent to active shortening may underestimate its importance during dynamic contractions. The presence of dynamic force depression should be realized in sport performance, motor control modeling and when controlling paralyzed limbs through artificial stimulation.     

A rheological motor model for vertebrate skeletal muscle in due consideration of non-linearity

A rheological motor model that satisfies the major mechanical properties of the skeletal muscle is proposed. The model consists of two Maxwell elements and a Voigt element connected in parallel with each other and has a force generator in it. The model well explains the mechanical behavior in quick and slow recovery phases in the isometric contraction of the muscle and achieves a sufficient isotonic shortening speed. The energy liberation of the motor in isotonic contraction is calculated and a mechanism of control is proposed, which operates so as to decrease the dissipated energy by altering the weights of the elastic and viscous constants in Maxwell elements. And thereby it becomes possible for the motor to possess non-linearity in energy liberation and load-velocity relation alike in muscle. The model would be a base model to be utilized for analyzing the kinetics of human macrosystems and/or for modeling the human neuromuscular system of motion control.     

Contraction dynamics and function of the muscle-tendon complex depend on the muscle fibre-tendon length ratio: a simulation study

Experimental studies show different muscle-tendon complex (MTC) functions (e.g. motor or spring) depending on the muscle fibre-tendon length ratio. Comparing different MTC of different animals examined experimentally, the extracted MTC functions are biased by, for example, MTC-specific pennation angle and fibre-type distribution or divergent experimental protocols (e.g. influence of temperature or stimulation on MTC force). Thus, a thorough understanding of variation of these inner muscle fibre-tendon length ratios on MTC function is difficult. In this study, we used a hill-type muscle model to simulate MTC. The model consists of a contractile element (CE) simulating muscle fibres, a serial element (SE) as a model for tendon, and a parallel elastic element (PEE) modelling tissue in parallel to the muscle fibres. The simulation examines the impact of length variations of these components on contraction dynamics and MTC function. Ensuring a constant overall length of the MTC by \(L_\mathrm{MTC} = L_\mathrm{SE} + L_\mathrm{CE}\), the SE rest length was varied over a broad physiological range from 0.1 to 0.9 MTC length. Five different MTC functions were investigated by simulating typical physiological experiments: the stabilising function with isometric contractions, the motor function with contractions against a weight, the capability of acceleration with contractions against a small inertial mass, the braking function by decelerating a mass, and the spring function with stretch-shortening cycles. The ratio of SE and CE mainly determines the MTC function. MTC with comparably short tendon generates high force and maximal shortening velocity and is able to produce maximal work and power. MTC with long tendon is suitable to store and release a maximum amount of energy. Variation of muscle fibre-tendon ratio yielded two peaks for MTC’s force response for short and long SE lengths. Further, maximum work storage capacity of the SE is at long \(\mathrm{rel}L_\mathrm{SE,0}\). Impact of fibre-tendon length ratio on MTC functions will be discussed. Considering a constant set of MTC parameters, quantitative changes in MTC performance (work, stiffness, force, energy storage, dissipation) depending on varying muscle fibre-tendon length ratio were provided, which enables classification and grading of different MTC designs.     

The mechanics of mouse skeletal muscle when shortening during relaxation

The dynamic properties of relaxing skeletal muscle have not been well characterised but are important for understanding muscle function during terrestrial locomotion, during which a considerable fraction of muscle work output can be produced during relaxation. The purpose of this study was to characterise the force-velocity properties of mouse skeletal muscle during relaxation. Experiments were performed in vitro (21 degrees C) using bundles of fibres from mouse soleus and EDL muscles. Isovelocity shortening was applied to muscles during relaxation following short tetanic contractions. Using data from different contractions with different shortening velocities, curves relating force output to shortening velocity were constructed at intervals during relaxation. The velocity component included contributions from shortening of both series elastic component (SEC) and contractile component (CC) because force output was not constant. Early in relaxation force-velocity relationships were linear but became progressively more curved as relaxation progressed. Force-velocity curves late in relaxation had the same curvature as those for the CC in fully activated muscles but V(max) was reduced to approximately 50% of the value in fully activated muscles. These results were the same for slow- and fast-twitch muscles and for relaxation following maximal tetani and brief, sub-maximal tetani. The measured series elastic compliance was used to partition shortening velocity between SEC and CC. The curvature of the CC force-velocity relationship was constant during relaxation. The SEC accounted for most of the shortening and work output during relaxation and its power output during relaxation exceeded the maximum CC power output. It is proposed that unloading the CC, without any change in its overall length, accelerated cross-bridge detachment when shortening was applied during relaxation.     

Optimal distance from the implement to the axis of rotation in hammer and discus throws.

It is a well-known fact that a dramatic improvement in the range of any projective throw can be achieved by increasing the release velocity. In this paper a simple model of a competitor with an implement (hammer or discus) in the turns is considered. The thrower is regarded as a rigid body, and the implement as a point mass. The transverse velocity component of the implement at the release moment is maximized. For finding the optimal distance of the implement from the axis of rotation optimal control theory is applied. According to the proposed model, the optimal hammer throwing technique requires constant and maximal distance of the implement from the axis of rotation, followed by the rapid shortening of the distance immediately prior to the release. In the discus throw, however, this shortening is useless.