Active Lengthening Research Articles

Muscle force loss and soreness subsequent to maximal eccentric contractions depend on the amount of fascicle strain invivo.

Defining the origins of muscle injury has important rehabilitation and exercise applications. However, current knowledge of muscle damage mechanics in human remains unclear invivo. This study aimed to determine the relationships between muscle-tendon unit mechanics during maximal eccentric contractions and the extent of subsequent functional impairments induced by muscle damage. The length of the muscle-tendon unit, fascicles and tendinous tissues was continuously measured on the gastrocnemius medialis using ultrasonography, in time with torque, during 10 sets of 30 maximal eccentric contractions of plantar flexors at 45°s(-1) , in seventeen participants. Muscle-tendon unit, fascicles and tendinous tissues were stretched up to 4.44±0.33cm, 2.31±0.64cm and 1.92±0.61cm respectively. Fascicle stretch length, lengthening amplitude and negative fascicle work beyond slack length were significantly correlated with the force decrease 48h post-exercise (r=0.51, 0.47 and 0.68, respectively; P<0.05). This study demonstrates that the strain applied to human muscle fibres during eccentric contractions strongly influences the magnitude of muscle damage invivo. Achilles tendon compliance decreases the amount of strain, while architectural gear ratio may moderately contribute to attenuating muscle fascicle lengthening and hence muscle damage. Further studies are necessary to explore the impact of various types of task to fully understand the contribution of muscle-tendon interactions during active lengthening to muscle damage.

Effect of Active Shortening and Stretching on Lattice Spacing and Cross-Bridge Binding in Skinned Muscle Fibres

When a tetanized skeletal muscle is actively shortened or stretched the resulting steady-state force is different from the purely isometric force at the corresponding length. Active shortening reduces steady-state force (termed force depression-FD), while active lengthening increases steady-state force (termed force enhancement-FE). According to the cross-bridge theory, FD and FE can occur if myofilament lattice spacing was modified after active shortening and stretching leading to a change in the proportion of attached cross-bridges, or if the kinetics of cross-bridges were modified leading to a change in the proportion of attached cross-bridges and/or the average force per cross-bridge. Here, we determined the effect of active shortening and stretching on the myofilament lattice spacing and the proximity of the myosin heads to the thin filaments using small angle X-ray diffraction.Lattice spacing (d1,0) was calculated from the spacing between the 1,0 and 1,1 equatorial reflections. The ratio of the intensities of the 1,1 and 1,0 equatorial reflections (I1,1:I1,0) was used as an estimate of the degree of association of myosin heads with the thin filaments.d1,0 increased (38.9±0.1 versus 38.1±0.2nm, p 0.05) between the FE state and its reference state, and I1,1:I1,0 was increased (2.5±0.2 versus 1.3±0.1, p<0.05) in the FE state. These results suggest that the proportion of attached cross-bridges might be increased after active stretch and that this increase is not due to a decrease in lattice spacing but rather a change in cross-bridge kinetics.

Neural control of lengthening contractions.

A number of studies over the last few decades have established that the control strategy employed by the nervous system during lengthening (eccentric) differs from those used during shortening (concentric) and isometric contractions. The purpose of this review is to summarize current knowledge on the neural control of lengthening contractions. After a brief discussion of methodological issues that can confound the comparison between lengthening and shortening actions, the review provides evidence that untrained individuals are usually unable to fully activate their muscles during a maximal lengthening contraction and that motor unit activity during submaximal lengthening actions differs from that during shortening actions. Contrary to common knowledge, however, more recent studies have found that the recruitment order of motor units is similar during submaximal shortening and lengthening contractions, but that discharge rate is systematically lower during lengthening actions. Subsequently, the review examines the mechanisms responsible for the specific control of maximal and submaximal lengthening contractions as reported by recent studies on the modulation of cortical and spinal excitability. As similar modulation has been observed regardless of contraction intensity, it appears that spinal and corticospinal excitability are reduced during lengthening compared with shortening and isometric contractions. Nonetheless, the modulation observed during lengthening contractions is mainly attributable to inhibition at the spinal level.

A new experimental model for force enhancement: steady-state and transient observations of the Drosophila jump muscle.

The increase in steady-state force after active lengthening in skeletal muscle, termed force enhancement (FE), has been observed for nearly one century. Although demonstrated experimentally at various structural levels, the underlying mechanism(s) remain unknown. We recently showed that the Drosophila jump muscle is an ideal model for investigating mechanisms behind muscle physiological properties, because its mechanical characteristics, tested thus far, duplicate those of fast mammalian skeletal muscles, and Drosophila has the advantage that it can be more easily genetically modified. To determine if Drosophila would be appropriate to investigate FE, we performed classic FE experiments on this muscle. Steady-state FE (FESS), following active lengthening, increased by 3, 7, and 12% of maximum isometric force, with increasing stretch amplitudes of 5, 10, and 20% of optimal fiber length (FLOPT), yet was similar for stretches across increasing stretch velocities of 4, 20, and 200% FLOPT/s. These FESS characteristics of the Drosophila jump muscle closely mimic those observed previously. Jump muscles also displayed typical transient FE characteristics. The transient force relaxation following active stretch was fit with a double exponential, yielding two phases of force relaxation: a fast initial relaxation of force, followed by a slower recovery toward steady state. Our analyses identified a negative correlation between the slow relaxation rate and FESS, indicating that there is likely an active component contributing to FE, in addition to a passive component. Herein, we have established the Drosophila jump muscle as a new and genetically powerful experimental model to investigate the underlying mechanism(s) of FE.

Increased spinal reflex excitability is associated with enhanced central activation during voluntary lengthening contractions in human spinal cord injury.

This study of chronic incomplete spinal cord injury (SCI) subjects investigated patterns of central motor drive (i.e., central activation) of the plantar flexors using interpolated twitches, and modulation of soleus H-reflexes during lengthening, isometric, and shortening muscle actions. In a recent study of the knee extensors, SCI subjects demonstrated greater central activation ratio (CAR) values during lengthening (i.e., eccentric) maximal voluntary contractions (MVCs), compared with during isometric or shortening (i.e., concentric) MVCs. In contrast, healthy controls demonstrated lower lengthening CAR values compared with their isometric and shortening CARs. For the present investigation, we hypothesized SCI subjects would again produce their highest CAR values during lengthening MVCs, and that these increases in central activation were partially attributable to greater efficacy of Ia-α motoneuron transmission during muscle lengthening following SCI. Results show SCI subjects produced higher CAR values during lengthening vs. isometric or shortening MVCs (all P < 0.001). H-reflex testing revealed normalized H-reflexes (maximal SOL H-reflex-to-maximal M-wave ratios) were greater for SCI than controls during passive (P = 0.023) and active (i.e., 75% MVC; P = 0.017) lengthening, suggesting facilitation of Ia transmission post-SCI. Additionally, measures of spinal reflex excitability (passive lengthening maximal SOL H-reflex-to-maximal M-wave ratio) in SCI were positively correlated with soleus electromyographic activity and CAR values during lengthening MVCs (both P < 0.05). The present study presents evidence that patterns of dynamic muscle activation are altered following SCI, and that greater central activation during lengthening contractions is partly due to enhanced efficacy of Ia-α motoneuron transmission.

Achilles tendon displacement patterns during passive stretch and eccentric loading are altered in middle-aged adults

The purpose of this study was to investigate middle-age effects on Achilles displacement patterns under passive stretch and eccentric loading. Healthy young (24.1 ± 1.4 years, n = 9) and middle-aged (49.0 ± 3.1 years, n = 9) adults were positioned prone and the ankle was cyclically dorsiflexed (0.5 Hz, 25° range) during passive stretch and active lengthening. Achilles displacements were tracked in cine ultrasound using 2D speckle tracking. Displacements were found to be non-uniform, with mid and deep portions of the tendon displacing more than superficial portions. However, the degree of non-uniformity was significantly reduced in middle-aged adults, suggesting a potential age-related reduction in inter-fascicle sliding or a shift in loading sharing between plantarflexors. Eccentric loading reduced displacement magnitudes, likely reflecting distal tendon stretch induced via active muscle contractions. Changes in tendon displacement with active loading were greater in middle-aged adults, which could reflect greater tendon compliance. The observed age-related changes in Achilles tendon behavior may have implications for both plantarflexor performance and injury risk.

The stretch-shortening cycle (SSC) revisited: residual force enhancement contributes to increased performance during fast SSCs of human m. adductor pollicis.

The stretch-shortening cycle (SSC) occurs in most everyday movements, and is thought to provoke a performance enhancement of the musculoskeletal system. However, mechanisms of this performance enhancement remain a matter of debate. One proposed mechanism is associated with a stretch-induced increase in steady-state force, referred to as residual force enhancement (RFE). As yet, direct evidence relating RFE to increased force/work during SSCs is missing. Therefore, forces of electrically stimulated m. adductor pollicis (n = 14 subjects) were measured during and after pure stretch, pure shortening, and stretch-shortening contractions with varying shortening amplitudes. Active stretch (30°, ω = 161 ± 6°s−1) caused significant RFE (16%, P < 0.01), whereas active shortening (10°, 20°, and 30°; ω = 103 ± 3°s−1, 152 ± 5°s−1, and 170 ± 5°s−1) resulted in significant force depression (9–15%, P < 0.01). In contrast, after SSCs (that is when active stretch preceded active shortening) no force depression was found. Indeed for our specific case in which the shortening amplitude was only 1/3 of the lengthening amplitude, there was a remnant RFE (10%, P < 0.01) following the active shortening. This result indicates that the RFE generated during lengthening affected force depression when active lengthening was followed by active shortening. As conventional explanations, such as the storage and release of elastic energy, cannot explain the enhanced steady-state force after SSCs, it appears that the stretch-induced RFE is not immediately abolished during shortening and contributes to the increased force and work during SSCs.

The series elastic shock absorber: tendon elasticity modulates energy dissipation by muscle during burst deceleration.

During downhill running, manoeuvring, negotiation of obstacles and landings from a jump, mechanical energy is dissipated via active lengthening of limb muscles. Tendon compliance provides a 'shock-absorber' mechanism that rapidly absorbs mechanical energy and releases it more slowly as the recoil of the tendon does work to stretch muscle fascicles. By lowering the rate of muscular energy dissipation, tendon compliance likely reduces the risk of muscle injury that can result from rapid and forceful muscle lengthening. Here, we examine how muscle-tendon mechanics are modulated in response to changes in demand for energy dissipation. We measured lateral gastrocnemius (LG) muscle activity, force and fascicle length, as well as leg joint kinematics and ground-reaction force, as turkeys performed drop-landings from three heights (0.5-1.5 m centre-of-mass elevation). Negative work by the LG muscle-tendon unit during landing increased with drop height, mainly owing to greater muscle recruitment and force as drop height increased. Although muscle strain did not increase with landing height, ankle flexion increased owing to increased tendon strain at higher muscle forces. Measurements of the length-tension relationship of the muscle indicated that the muscle reached peak force at shorter and likely safer operating lengths as drop height increased. Our results indicate that tendon compliance is important to the modulation of energy dissipation by active muscle with changes in demand and may provide a mechanism for rapid adjustment of function during deceleration tasks of unpredictable intensity.

Modulation of soleus H-reflex during shortening and lengthening muscle actions in young and older adults.

The H-reflex is dependently modulated during isometric and anisometric muscle actions. However, the manner of the H-reflex modulation during dynamic muscle movements in relation to ageing is less stated in the literature. This study was designed to investigate the effects of ageing on soleus (SOL) H-reflex modulation during dynamic muscle actions. Twenty young (24 ± 4 years of age) and 20 older adults (73 ± 5 years of age) voluntarily participated in the study. The SOL H-reflex was measured during passive and active shortening and lengthening muscle actions in a sitting position. The older group showed a lower ratio of the maximal amplitude of H-reflex to M-wave (SOL Hmax/Mmax) during the passive lengthening than that during the passive shortening (shortening: 0.40 ± 0.22 vs. lengthening: 0.15 ± 0.10, P < 0.05), whereas the SOL Hmax/Mmax ratio of the young group was significantly higher during the shortening than that during the lengthening contractions at maximal effort (shortening: 0.51 ± 0.26 vs. lengthening: 0.37 ± 0.18, P < 0.05). These results suggested different modulations of group Ia afferent inputs to the SOL motoneurons during passive and active dynamic muscle actions between young and older adults.

Active regulation of longitudinal arch compression and recoil during walking and running.

The longitudinal arch (LA) of the human foot compresses and recoils in response to being cyclically loaded. This has typically been considered a passive process, however, it has recently been shown that the plantar intrinsic foot muscles have the capacity to actively assist in controlling LA motion. Here we tested the hypothesis that intrinsic foot muscles, abductor hallucis (AH), flexor digitorum brevis (FDB) and quadratus plantae (QP), actively lengthen and shorten during the stance phase of gait in response to loading of the foot. Nine participants walked at 1.25 m s⁻¹ and ran at 2.78 and 3.89 m s⁻¹ on a force-instrumented treadmill while foot and ankle kinematics were recorded according to a multisegment foot model. Muscle-tendon unit (MTU) lengths, determined from the foot kinematics, and intramuscular electromyography (EMG) signals were recorded from AH, FDB and QP. Peak EMG amplitude was determined during the stance phase for each participant at each gait velocity. All muscles underwent a process of slow active lengthening during LA compression, followed by a rapid shortening as the arch recoiled during the propulsive phase. Changes in MTU length and peak EMG increased significantly with increasing gait velocity for all muscles. This is the first in vivo evidence that the plantar intrinsic foot muscles function in parallel to the plantar aponeurosis, actively regulating the stiffness of the foot in response to the magnitude of forces encountered during locomotion. These muscles may therefore contribute to power absorption and generation at the foot, limit strain on the plantar aponeurosis and facilitate efficient foot ground force transmission.

Dose-dense Paclitaxel in Advanced Ovarian Cancer

Carboplatin and paclitaxel, delivered on a 3-weekly basis, is the historical standard for the management of advanced epithelial ovarian cancers (EOC). Increased dose intensity, the inclusion of additional active cytotoxic agents and lengthening treatment duration have failed to improve the outcomes seen with standard doses of carboplatin and paclitaxel in the treatment of EOC. Dose-dense (i.e. weekly) delivery of paclitaxel may exploit anticancer mechanisms such as anti-angiogenesis and the induction of apoptosis. Tumour regrowth may be more effectively impaired by the dose-dense delivery of paclitaxel. Non-randomised studies of dose-dense chemotherapy in EOC have been promising, particularly in heavily pretreated and platinum-resistant disease, with reported response rates as high as 60%. Dose-dense paclitaxel also seems to be well tolerated. These observations led to a number of comparative trials of dose-dense paclitaxel chemotherapy, three have been reported and four are ongoing. This review explores the rationale behind dose-dense delivery of paclitaxel and evaluates the results of completed phase III trials.

Decay of force transients following active stretch is slower in older than young men: Support for a structural mechanism contributing to residual force enhancement in old age

Following active lengthening of muscle, force reaches an isometric steady state above that which would be achieved for a purely isometric contraction at the same muscle length. This fundamental property of muscle, termed “residual force enhancement (RFE),” cannot be predicted by the force-length relationship, and is unexplained by the cross-bridge theory of muscle contraction. Recently, we showed that older adults experience higher RFE than young for the ankle dorsiflexors primarily owing to a greater reliance on passive force enhancement (PFE) and similar RFE for the knee extensors but a greater contribution of PFE to total RFE. Natural adult aging may prove a useful model in exploring mechanisms of RFE which may reside in the dissipation of force transients following stretch. A post-hoc analysis was conducted on previously described RFE experiments in young (~26 years) and old (~77 years) men for the dorsiflexors and knee extensors to fit the force following stretch with a biexponential decay. In both muscle groups the decay half-life of the first exponential was two times slower in the older compared with young men. There were significant associations between PFE and the decay in force, suggesting a greater “non-active” contribution to total RFE across muscles in older compared with young men. The greater “non-active” component of RFE in older adults could be due to structural age-related changes causing increased muscle stiffness during and following stretch.

Variation in isometric force after active shortening and lengthening and their mechanisms: a review

Introduction The isometric force history dependence of skeletal muscle has been studied along the last one hundred years. Several theories have been formulated to explain and establish the causes of the phenomenon, but not successfully, as they have not been fully accepted and demonstrated, and much controversy on such a subject still remains. Objective To present a systematic literature review on the dynamics of the mechanisms of force depression and force enhancement after active shortening and lengthening, respectively, identifying the key variables involved in the phenomenon, and to date to present the main theories and hypothesis developed trying to explaining it. Method The procedure of literature searching complied the major databases, including articles either, those which directly investigated the phenomena of force depression and force enhancement or those which presented possible causes and mechanisms associated with their respective events, from the earliest studies published until the year of 2010. Results 97 references were found according to the criteria used. Conclusion Based on this review, it is suggested that the theory of stress inhibition of actin-myosin cross-bridges is that better explain the phenomenon of force depression. Whereas regarding the force enhancement phenomenon, one theory have been well accepted, the increased number of actin-myosin cross-bridges in strong binding state influenced by the recruitment of passive elastic components, which hole is attributed to the titin filament.

A comparison of muscle energy models for simulating human walking in three dimensions

The popular Hill model for muscle activation and contractile dynamics has been extended with several different formulations for predicting the metabolic energy expenditure of human muscle actions. These extended models differ considerably in their approach to computing energy expenditure, particularly in their treatment of active lengthening and eccentric work, but their predictive abilities have never been compared. In this study, we compared the predictions of five different Hill-based muscle energy models in 3D forward dynamics simulations of normal human walking. In a data-tracking simulation that minimized muscle fatigue, the energy models predicted metabolic costs that varied over a three-fold range (2.45–7.15J/m/kg), with the distinction arising from whether or not eccentric work was subtracted from the net heat rate in the calculation of the muscle metabolic rate. In predictive simulations that optimized neuromuscular control to minimize the metabolic cost, all five models predicted similar speeds, step lengths, and stance phase durations. However, some of the models predicted a hip circumduction strategy to minimize metabolic cost, while others did not, and the accuracy of the predicted knee and ankle angles and ground reaction forces also depended on the energy model used. The results highlights the need to clarify how eccentric work should be treated when calculating muscle energy expenditure, the difficulty in predicting realistic metabolic costs in simulated walking even with a detailed 3D musculoskeletal model, the potential for using such models to predict energetically-optimal gait modifications, and the room for improvement in existing muscle energy models and locomotion simulation frameworks.

Geared up to stretch: pennate muscle behavior during active lengthening

Many locomotor activities require muscles to actively lengthen, dissipate energy and decelerate the body. These eccentric contractions can disrupt cytoskeletal structures within myofibrils and reduce force output. We examined how architectural features of pennate muscles can provide a protective mechanism against eccentric muscle damage by limiting fascicle lengthening. It has been previously shown that the angled fibers of pennate muscles change orientation when shortening. This change in fiber orientation can amplify fascicle shortening, resulting in a velocity advantage at the level of the muscle-tendon unit (MTU) that is characterized by a gear ratio (MTU velocity/fascicle velocity). A muscle's architectural gear ratio (AGR) has been shown to vary as a function of force during shortening, while AGR during lengthening remains largely unknown. We independently measured fascicle length and MTU length in vitro in the bullfrog plantaris. We characterized the muscle's force-velocity curve and AGR during both shortening and lengthening across a broad range of forces (10-190% peak isometric force). AGR was measured during the isotonic portion of each contraction, to eliminate possible contributions of series elasticity to MTU length changes. We found that gear ratio varies with force during both shortening and lengthening contractions. The highest AGR was observed during lengthening contractions, indicating that lengthening of the MTU can occur with relatively little stretch of the fascicle. As fascicle strain is considered an important determinant of muscle damage, a high gear ratio may afford pennate muscles protection against the damaging effects of active lengthening.

Modulation of spinal excitability by a sub-threshold stimulation of M1 area during muscle lengthening

It is well known that the H-reflex amplitude decreases during passive muscle lengthening in comparison with passive shortening. However, this decrease in spinal synaptic efficacy observed during passive lengthening seems to be lesser during eccentric voluntary contraction. The aim of the present study was to examine whether spinal excitability during lengthening condition could be modulated by magnetic brain stimulation. H reflexes of the triceps surae muscles were elicited on 10 young healthy subjects, and conditioned by a sub-threshold transcranial magnetic stimulation (TMS). The conditioning stimulation was applied over the M1 area of triceps surae muscles at an intensity below motor threshold with a conditioning-test interval of 5ms. Conditioned and non-conditioned H-reflexes were elicited at rest, during passive lengthening and shortening, and during submaximal contractions (concentric, eccentric and isometric). During passive and active lengthening, H reflexes conditioned by a sub-threshold TMS pulse increased on average by 50% compared with non-conditioned responses. No significant effect was found during isometric and concentric conditions. Activation of the corticospinal pathway would partially cancel inhibitions caused by muscle stretch, and according to the time-delayed effect, this result suggested the existence of a specific polysynaptic pathway. In additional experiments, H responses were conditioned by cervico-medullary stimulations, showing that the modulation described by the previous results involves subcortical mechanisms. This study provides further evidences that the modulation of the final cortico-spinal command reaching the muscle depends on a central mechanism that controls peripheral input, such as Ia afference discharge during lengthening.

Conceptual Framework for Strengthening Exercises to Prevent Hamstring Strains

High-speed running accounts for the majority of hamstring strains in many sports. The terminal swing phase is believed to be the most hazardous as the hamstrings are undergoing an active lengthening contraction in a long muscle length position. Prevention-based strength training mainly focuses on eccentric exercises. However, it appears crucial to integrate other parameters than the contraction type. Therefore, the aim of this study is to present a conceptual framework based on six key parameters (contraction type, load, range of motion, angular velocity, uni-/bilateral exercises, kinetic chain) for the hamstring's strength exercise for strain prevention. Based on the biomechanical parameters of sprinting, it is proposed to use high-load eccentric contractions. The movement should be performed at a slow to moderate angular velocity and focused at the knee joint, while the hip is kept in a large flexion position in order to reach a greater elongation stress of the hamstrings than in the terminal swing phase. In this way, we believe that, during sprinting, athletes would be better trained to brake the knee extension effectively in the whole range of motion without overstretch of the hamstrings. Finally, based on its functional application, unilateral open kinetic chain should be preferred.

Peak power is reduced following lengthening contractions despite a maintenance of shortening velocity

Following repetitive lengthening contractions, power (the product of torque and velocity) is impaired during shortening contractions. However, the relative contribution of each component to power loss and the underlying factors are unclear. We investigated neuromuscular properties of the dorsiflexors in 8 males (27 ± 3 years) and 8 females (26 ± 4 years) for a potential sex-related difference before, during, and after 150 unaccustomed maximal lengthening actions. Velocity-dependent power was determined from shortening contractions at 8 levels (1 N · m to 70% of maximum voluntary isometric contraction (MVC)) before, after, and throughout recovery assessed at 0-30 min, 24 h, and 48 h. Immediately following task termination, both sexes displayed similar impairments of 30%, 4%, and 10% in MVC torque, shortening velocity, and overall peak power, respectively (P < 0.05). Peak rate of isometric torque development (RTD) was reduced by 10% in males, but females exhibited a 35% reduction (P < 0.05). Rate of torque development for the MVC remained depressed in both sexes throughout the 30 min recovery period; however, the RTD returned to normal by 24 h in males but did not recover by 48 h in females. Power was reduced preferentially at higher loads (i.e., 60% MVC), with a greater loss in females (65%) than males (45%). For lower loads (<20% MVC), power was impaired minimally (4%-8%; P < 0.05) and recovered within 30 min in both groups. The reduction in maximal angular velocity persisted until 30 min of recovery, and peak power did not recover until 24 h for both sexes. Unaccustomed lengthening contractions decreased power preferentially at higher loads, whereas peak power was reduced minimally owing to maintenance of maximal shortening velocity.

Prenatal smoke exposure: Effects on infant auditory system and placental gene expression

Prenatal smoke exposure has been shown to change cochlear echo response amplitudes and auditory brainstem response (ABR) wave latencies in newborns. Since gene expression changes are often synchronized in different tissue types, the goal of the present work was to determine the relationships between prenatal smoke exposure induced changes in hearing responses with changes in placental gene expression. Results showed significant cotinine level elevations in mothers who smoked ≥10cigarettes/day during their pregnancy compared to no detectable cotinine in nonsmoking mothers. Cochlear echo response amplitudes in the 2–8kHz range and ABR wave latencies, specifically wave V and interpeak interval I–V, were also significantly reduced in newborns of smoking mothers. Functional pathway analysis of upregulated placental genes using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online software showed significant enrichment of terms associated with neurodevelopmental processes including glutamatergic and cholinergic systems and a number of wingless type proteins in the top two tiers with corrected enrichment p-values of ≤0.05. Other relevant functional pathways were significant at unadjusted enrichment p-values of 0.001–0.11 and included calcium signaling, neurotransmission/neurological processes and oxidative stress. The neurological process clusters included 7 genes (EML2, OTOR, SLC26A5, TBL1X, TECTA, USH1C and USH1G) known to modulate cochlear outer hair cell motility. We localized proteins encoded by the top two regulated genes, TBL1X and USH1C, using immunohistochemistry to placental stem and anchoring villi associated with active contractile function. These placental genes may mediate active contraction and relaxation in the placental villi, for example, during maternal–fetal perfusion matching, similar to the active lengthening and shortening of the cochlear outer hair cells during sensory transduction. Thus, the functional consequence of their alteration in the cochlea would be reflected as a decline in cochlear echoes as shown in this study. Such parallel changes suggest the potential utility of placental gene expression as a surrogate for evaluating changes in the developing cochlea related to potential aberrant cochlear function in newborns with prenatal smoke exposure.

Muscle fascicle strains in human gastrocnemius during backward downhill walking

Extensive muscle damage can be induced in isolated muscle preparations by performing a small number of stretches during muscle activation. While typically these fiber strains are large and occur over long lengths, the extent of exercise-induced muscle damage (EIMD) observed in humans is normally less even when multiple high-force lengthening actions are performed. This apparent discrepancy may be due to differences in muscle fiber and tendon dynamics in vivo; however, muscle and tendon strains have not been quantified during muscle-damaging exercise in humans. Ultrasound and an infrared motion analysis system were used to measure medial gastrocnemius fascicle length and lower limb kinematics while humans walked backward, downhill for 1 h (inducing muscle damage), and while they walked briefly forward on the flat (inducing no damage). Supramaximal tibial nerve stimulation, ultrasound, and an isokinetic dynamometer were used to quantify the fascicle length-torque relationship pre- and 2 h postexercise. Torque decreased ~23%, and optimal fascicle length shifted rightward ~10%, indicating that EIMD occurred during the damage protocol even though medial gastrocnemius fascicle stretch amplitude was relatively small (~18% of optimal fascicle length) and occurred predominantly within the ascending limb and plateau region of the length-torque curve. Furthermore, tendon contribution to overall muscle-tendon unit stretch was ~91%. The data suggest the compliant tendon plays a role in attenuating muscle fascicle strain during backward walking in humans, thus minimizing the extent of EIMD. As such, in situ or in vitro mechanisms of muscle damage may not be applicable to EIMD of the human gastrocnemius muscle.