Beyond power limits: the kinetic energy capacity of skeletal muscle.

Muscle is the universal agent of animal movement, and limits to muscle performance are therefore an integral aspect of animal behaviour, ecology, and evolution. A mechanical perspective on movement makes it amenable to analysis from first principles, and so brings the seeming certitude of simple physical laws to the challenging comparative study of complex biological systems. Early contributions on movement biomechanics considered muscle energy output to be limited by muscle work capacity, Wmax; triggered by seminal work in the late 1960s, it is now held broadly that a complete analysis of muscle energy output is to also consider muscle power capacity, for no unit of work can be delivered in arbitrarily brief time. Here, we adopt a critical stance towards this paradigmatic notion of a power-limit, and argue that the alternative constraint to muscle energy output is instead imposed by a characteristic kinetic energy capacity, Kmax, dictated by the maximum speed with which the actuating muscle can shorten. The two critical energies can now be directly compared, and define the physiological similarity index, Γ=Kmax/Wmax. It is the explanatory power of this comparison that lends weight to a shift in perspective from muscle power to kinetic energy capacity, as is argued through a series of brief illustrative examples. Γ emerges as an important dimensionless number in musculoskeletal dynamics, and sparks novel hypotheses on functional adaptations in musculoskeletal "design" that depart from the parsimonious evolutionary null hypothesis of geometric similarity.

Overarm Training Tolerance: A Pilot Study on the Use of Muscle Oxygen Saturation as a Biomarker.

Ulnar collateral ligament (UCL) tears occur due to the prolonged exposure and overworking of joint stresses, resulting in decreased strength in the flexion and extension of the elbow. Current rehabilitation approaches for UCL tears involve subjective assessments (pain scales) and objective measures such as monitoring joint angles and range of motion. The main goal of this study is to find out if using wearable near-infrared spectroscopy technology can help measure digital biomarkers like muscle oxygen levels and heart rate. These measurements could then be applied to athletes who have been injured. Specifically, measuring muscle oxygen levels will help us understand how well the muscles are using oxygen. This can indicate improvements in how the muscles are healing and growing new blood vessels after reconstructive surgery. Previous research studies demonstrated that there remains an unmet clinical need to measure biomarkers to provide continuous, internal data on muscle physiology during the rehabilitation process. This study's findings can benefit team physicians, sports scientists, athletic trainers, and athletes in the identification of biomarkers to assist in clinical decisions for optimizing training regimens for athletes that perform overarm movements; the research suggests pathways for possible earlier detection, and thus earlier intervention for injury prevention.

High-intensity interval training improves bone remodeling, lipid profile, and physical function in multiple sclerosis patients.

Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease due to an autoimmune chronic inflammatory response, yet the etiology is currently not completely understood. It is already known that physical activity plays an essential role in improving quality of life, especially in neuropathological conditions. The study was aimed to investigate the possible benefits of high-intensity interval training (HIIT) in bone and lipid metabolism markers, and neuromotor abilities in MS patients. 130 participants were recruited; 16 subjects with MS met the inclusion criteria and were included in the data analysis. The patients were randomly assigned to two groups: a Control group (CG) (34.88 ± 4.45 yrs) that didn't perform any physical activity and the Exercise group (EG) (36.20 ± 7.80 yrs) that performed HIIT protocol. The training program was conducted remotely by a kinesiologist. It was performed three times a week for 8 weeks. At the beginning (T0) and the end of the study (T1) physical function tests, bone remodelling markers, and lipid markers analyses were performed. After 8 weeks of training the wall squat (s) (T0 = 27.18 ± 4.21; T1 = 41.68 ± 5.38, p ≤ 0.01) and Time Up and Go test (s) (T0 = 7.65 ± 0.43; T1 = 6.34 ± 0.38 p ≤ 0.01) performances improved; lipid markers analysis showed a decrease in Total (mg/dl) (T0 = 187.22 ± 15.73; T1 = 173.44 ± 13.03, p ≤ 0.05) and LDL (mg/dl) (T0 = 108 ± 21.08; T1 = 95.02 ± 17.99, p < 0.05) cholesterol levels. Additionally, the levels of osteocalcin (µg/L), a marker of bone formation increased (T0 = 20.88 ± 4.22; T1 = 23.66 ± 6.24, p < 0.05), 25-OH Vitamin D (µg/L) improved after 8 weeks (T0 = 21.11 ± 7.11; T1 = 27.66 ± 7.59, p < 0.05). HIIT had an effect on lower limb strength and gait control, improved bone formation, and lipid management, in MS patients.

Linking in vivo muscle dynamics to force-length and force-velocity properties reveals that guinea fowl lateral gastrocnemius operates at shorter than optimal lengths.

The isometric force-length (F-L) and isotonic force-velocity (F-V) relationships characterize the contractile properties of skeletal muscle under controlled conditions, yet it remains unclear how these properties relate to in vivo muscle function. Here, we map the in situ F-L and F-V characteristics of guinea fowl (Numida meleagris) lateral gastrocnemius (LG) to the in vivo operating range during walking and running. We test the hypothesis that muscle fascicles operate on the F-L plateau, near the optimal length for force (L0) and near velocities that maximize power output (Vopt) during walking and running. We found that in vivo LG velocities are consistent with optimizing power during work production, and economy of force at higher loads. However, LG does not operate near L0 at higher loads. LG length was near L0 at the time of electromyography (EMG) onset but shortened rapidly such that force development during stance occurred on the ascending limb of the F-L curve, around 0.8L0. Shortening across L0 in late swing might optimize potential for rapid force development near the swing-stance transition, providing resistance to unexpected perturbations that require rapid force development. We also found evidence of in vivo passive force rise in late swing, without EMG activity, at lengths where in situ passive force is zero, suggesting that dynamic viscoelastic effects contribute to in vivo force development. Comparison of in vivo operating ranges with F-L and F-V properties suggests the need for new approaches to characterize muscle properties in controlled conditions that more closely resemble in vivo dynamics.

Intermittent swimming and muscle power output in brook trout, Salvelinus fontinalis.

Slow and sustainable intermittent swimming has recently been described in several Centrarchid fishes, such as bluegill and largemouth bass. This swimming behavior involves short periods of body-caudal fin undulation alternating with variable periods of coasting. This aerobic muscle powered swimming appears to reduce energetic costs for slow, sustainable swimming, with fish employing a "fixed-gear" or constant tailbeat frequency and modulating swimming speed by altering the length of the coasting period. We asked if this swimming behavior was found in other fish species by examining volitional swimming by brook trout in a static swimming tank. Further, we employed muscle mechanics experiments to explore how intermittent swimming affects muscle power output in comparison to steady swimming behavior. Brook trout regularly employ an intermittent swimming form when allowed to swim volitionally, and consistently showed a tailbeat frequency of ~2 Hz. Coasting duration had a significant, inverse relationship to swimming speed. Across a range of slow, sustainable swimming speeds, tailbeat frequency increased modestly with speed. The duration of periods of coasting decreased significantly with increasing speed. Workloop experiments suggest that intermittent swimming reduces fatigue, allowing fish to maintain high power output for longer compared to continuous activity. This study expands the list of species that employ intermittent swimming, suggesting this behavior is a general feature of fishes.

Sexual dimorphisms in skeletal muscle: current concepts and research horizons.

The complex compositional and functional nature of skeletal muscle makes this organ an essential topic of study for biomedical researchers and clinicians. An additional layer of complexity is added with the consideration of sex as a biological variable. Recent research advances have revealed sexual dimorphisms in developmental biology, muscle homeostasis, adaptive responses, and disorders relating to skeletal muscle. Many of the observed sex differences have hormonal and molecular mechanistic underpinnings, whereas others have yet to be elucidated. Future research is needed to investigate the mechanisms dictating sex-based differences in the various aspects of skeletal muscle. As such, it is necessary that skeletal muscle biologists ensure that both female and male subjects are represented in biomedical and clinical studies to facilitate the successful testing and development of therapeutics for all patients.

Fecal incontinence patients categorized based on anal pressure and electromyography: Anal sphincter damage and clinical symptoms.

BACKGROUND: Disruption of external anal sphincter muscle (EAS) is an important factor in the multifactorial etiology of fecal incontinence (FI). OBJECTIVES: We categorize FI patients into four groups based on the location of lesion in neuromuscular circuitry of EAS to determine if there are differences with regards to fecal incontinence symptoms severity (FISI) score, age, BMI, obstetrical history, and anal sphincter muscle damage. METHODS: Female patients (151) without any neurological symptoms, who had undergone high-resolution manometry, anal sphincter EMG, and 3D ultrasound imaging of the anal sphincter were assessed. Patients were categorized into four groups: Group 1 (normal)-normal cough EMG (>10 µV), normal squeeze EMG (>10 µV), and normal anal squeeze pressure (>124 mmHg); Group 2 (cortical apraxia, i.e., poor cortical activation)-normal cough EMG, low squeeze EMG, and low anal squeeze pressure; Group 3 (muscle damage)-normal cough EMG, normal squeeze EMG, and low anal squeeze pressure; and Group 4 (pudendal nerve damage)-low cough EMG, low squeeze EMG, and low anal squeeze pressure. RESULTS: The four patient groups were not different with regards to the patient's age, BMI, parity, and FISI scores. 3D ultrasound images of the anal sphincter complex revealed significant damage to the internal anal sphincter, external anal sphincter, and puborectalis muscles in all four groups. CONCLUSION: The FI patients are a heterogeneous group; majority of these patients have significant damage to the muscles of the anal sphincter complex. Whether biofeedback therapy response is different among different patient groups requires study.

Cox7a1 controls skeletal muscle physiology and heart regeneration through complex IV dimerization.

The oxidative phosphorylation (OXPHOS) system is intricately organized, with respiratory complexes forming super-assembled quaternary structures whose assembly mechanisms and physiological roles remain under investigation. Cox7a2l, also known as Scaf1, facilitates complex III and complex IV (CIII-CIV) super-assembly, enhancing energetic efficiency in various species. We examined the role of Cox7a1, another Cox7a family member, in supercomplex assembly and muscle physiology. Zebrafish lacking Cox7a1 exhibited reduced CIV2 formation, metabolic alterations, and non-pathological muscle performance decline. Additionally, cox7a1-/- hearts displayed a pro-regenerative metabolic profile, impacting cardiac regenerative response. The distinct phenotypic effects of cox7a1-/- and cox7a2l-/- underscore the diverse metabolic and physiological consequences of impaired supercomplex formation, emphasizing the significance of Cox7a1 in muscle maturation within the OXPHOS system.

Comparison of Blood Flow Restriction Interventions to Standard Rehabilitation After an Anterior Cruciate Ligament Injury: A Systematic Review.

BACKGROUND: Blood flow restriction training (BFR-t) data are heterogeneous. It is unclear whether rehabilitation with BFR-t after an anterior cruciate ligament (ACL) injury is more effective in improving muscle strength and muscle size than standard rehabilitation. PURPOSE: To review outcomes after an ACL injury and subsequent reconstruction in studies comparing rehabilitation with and without BFR-t. STUDY DESIGN: Systematic review. Level of evidence, 3. METHODS: A search of English-language human clinical studies published in the past 20 years (2002-2022) was carried out in 5 health sciences databases, involving participants aged 18-65 undergoing rehabilitation for an ACL injury. Outcomes associated with muscle strength, muscle size, and knee-specific patient-reported outcome measures (PROMs) were extracted from studies meeting inclusion criteria and compared. RESULTS: The literature search identified 279 studies, of which 5 met the selection criteria. Two studies suggested that BFR-t rehabilitation after an ACL injury improved knee or thigh muscle strength and muscle size compared with rehabilitation consisting of comparable and higher load resistance training, with two studies suggesting the opposite. The single study measuring PROMs showed improvement compared to traditional rehabilitation, with no difference in muscle strength or size. CONCLUSION: BFR-t after an ACL injury seems to benefit muscle strength, muscle size, and PROM scores compared with standard rehabilitation alone. However, only 1 large study included all these outcomes, which has yet to be replicated in other settings. Further studies utilizing similar methods with a common set of outcome measures are required to confirm the effects of BFR-t on ACL rehabilitation.

Association of malignant hyperthermia and exertional heat illness in young athletes: An analysis of awareness among clinical and athletic first responders.

Background: Malignant hyperthermia (MH), a rare inherited condition seen almost exclusively in the perioperative setting, is triggered by volatile anesthetics or an intravenous paralytic drug, succinylcholine. It can, however, occur without any exposure to anesthetic drugs, being associated with heat illness and rhabdomyolysis, thus presenting a little-known risk to young athletes exercising in hot environments. Objective: This study aimed to determine the first responder awareness of MH and its association with heat illness in young athletes within athletic and clinical environments. Methods: Awareness within the clinical milieu was assessed by an institutional chart review of 3296 charts. The identified heat illness cases were examined for treatment consistent with the management of a suspected episode of MH. Awareness among first responders in an athletic setting was examined by a survey administered to a total of 1,500 coaches and athletic trainers at the high school level along with emergency medical services providers across the United States. Results: No treatment consistent with the suspicion of MH was noted among clinical first responders, suggesting a lack of awareness. Survey administration also revealed a limited amount of knowledge of MH and its potential role in heat illness. Conclusion: The results point to lack of awareness among pre-hospital and hospital-based first responders of the relationship between MH and heat illness in young athletes. An effort to educate these members of the healthcare community can contribute to an expeditious and life-saving intervention. Clinical Relevance: First responders who may interact with a young athlete have low knowledge of MH and its relationship to heat illness. Similar lack of awareness exists among hospital personnel who care for young individuals with heat illness. Educating the first responders about this condition can speed up the time to intervene and save lives.

Investigating the Contraction Pattern of the Zygomaticus Major Muscle and its Clinical Relevance: A Functional MRI Study.

BACKGROUND: Our understanding of facial anatomy has significantly evolved, yet the detailed contraction patterns of facial muscles and their presentation during clinical imaging remain largely unexplored. Understanding the contraction patterns and visual presentation of these muscles, particularly the zygomaticus major could enhance pre-surgical facial assessments and the development of new treatment strategies. METHODS: A total of 34 healthy young individuals (17 female, 17 male) with a mean age of 23.6 (2.4) years [range: 20-30] were investigated regarding the length, thickness, width, and angle of the zygomaticus major muscle in five different facial expressions (i.e., repose, anger, joy, surprise, and sadness) utilizing MR imaging. RESULTS: Joyful expressions caused a reduction in muscle length to 85.6% of its original length and an increase in width (103.4%), thickness (108.4%), and facial angle (2.72°) when compared to that in repose, suggesting isotonic contraction. Conversely, expressions of anger, surprise, and sadness generally led to muscle stretching, seen through changes in length (98.9%, 104.3%, and 102.7%, respectively), width (98.8%, 96.5%, and 99.4%, respectively), and thickness (91.2%, 91.0%, and 102.7%, respectively), with variable alterations in facial angle (0.55°, 1.85°, and 1.00°, respectively) depending on the specific expression. CONCLUSION: This MRI-based study indicates that the zygomaticus major muscle experiences isotonic contraction, characterized by decreased length and increased width and thickness. The findings underline the importance of muscle thickness as a reliable parameter in assessing facial muscle function and offer valuable guidance for practitioners in accurately evaluating muscle performance during different facial expressions. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Electrical impedance myography in healthy volunteers.

INTRODUCTION/AIMS: Electrical impedance myography (EIM) is a noninvasive technique being used in clinical studies to characterize muscle by phase, reactance, and resistance after application of a low-intensity current. The aim of this study was to obtain 50-kHz EIM data from healthy volunteers (HVs) for use in future clinical and research studies, perform reliability tests on EIM outcome measures, and compare findings with muscle ultrasound variables. METHODS: Four arm and four leg muscles of HVs were evaluated using an EIM device with two sensors, P/N 20-0045 and P/N 014-009. Muscles were evaluated individually and eight-muscle average (8MU), four-muscle upper extremity average, and four-muscle lower extremity average. An intraclass correlation coefficient (ICC) was applied to assess interrater, intrarater, and intersensor reliability using a subset of HVs. Ultrasound studies on muscle thickness and elastography were also performed on a subset of HVs. RESULTS: For the P/N 20-0045 sensor, the 8MU EIM mean and standard deviation (n = 41) was 14.54 ± 3.31 for phase, 7.04 ± 1.22 for reactance, and 28.91 ± 7.63 for resistance. Reliability for 8MU phase (n = 22) was good to excellent for both interrater (n = 22, ICC = 0.920, 95% CI 0.820 to 0.966) and intrarater (n = 22, ICC = 0.950, 95% CI 0.778 to 0.983). The P/N 014-009 sensor had similar reliability findings. Correlation analyses showed no association between EIM and muscle thickness. DISCUSSION: EIM is a reproducible measure of muscle physiology. Obtaining EIM values from HVs allows us to gain a better understanding how EIM may be altered in diseased muscle.

Head posture impacts mammalian hyoid position and suprahyoid muscle length: implication for swallowing biomechanics.

Instantaneous head posture (IHP) can extensively alter resting hyoid position in humans, yet postural effects on resting hyoid position remain poorly documented among mammals in general. Clarifying this relationship is essential for evaluating interspecific variation in hyoid posture across evolution, and understanding its implications for hyolingual soft tissue function and swallowing motor control. Using Didelphis virginiana as a model, we conducted static manipulation experiments to show that head flexion shifts hyoid position rostrally relative to the cranium across different gapes. IHP-induced shifts in hyoid position along the anteroposterior axis are comparable to in vivo hyoid protraction distance during swallowing. IHP also has opposite effects on passive genio- and stylohyoid muscle lengths. High-speed biplanar videoradiography suggests Didelphis consistently swallows at neutral to flexed posture, with stereotyped hyoid kinematics across different head postures. IHP change can affect suprahyoid muscle force production by shifting their positions on the length-tension curve, and redirecting lines of action and the resultant force from supra- and infrahyoid muscles. We hypothesize that demands on muscle performance may constrain the range of swallowing head postures in mammals. This article is part of the theme issue 'Food processing and nutritional assimilation in animals'.

Meta-analysis data of skeletal muscle slow fiber content across mammalian species.

Herein, the dataset generated for Queeno et al. [1] is presented and described. Mammalian skeletal muscle slow (MyHC-I) fiber composition data was collated from 269 eligible studies identified via a systematic literature search and meta-analysis, following a structure similar to PRISMA [2]. Academic search systems were queried with terms relating to mammalian skeletal muscle fiber content and reference lists of selected articles were thoroughly investigated for additional studies. Eligible studies were those that provided skeletal muscle fiber composition data from mammalian species that were not subjected to experimental manipulations. Taxonomic information, sex, age, number of individuals sampled, average body mass (kg), average slow fiber content (%) of each skeletal muscle under investigation and fiber-typing methodology were collated from eligible studies when available. Muscle fiber composition data was collected from more than 200 skeletal muscles across 174 mammalian species, which will be of value to those interested in muscle physiology, interspecific muscle comparisons, and connections between muscle physiology, taxonomy, body mass, ecomorphology and locomotor strategy (among others).

Mitochondrial Properties in Skeletal Muscle Fiber.

Mitochondria are the primary source of energy production and are implicated in a wide range of biological processes in most eukaryotic cells. Skeletal muscle heavily relies on mitochondria for energy supplements. In addition to being a powerhouse, mitochondria evoke many functions in skeletal muscle, including regulating calcium and reactive oxygen species levels. A healthy mitochondria population is necessary for the preservation of skeletal muscle homeostasis, while mitochondria dysregulation is linked to numerous myopathies. In this review, we summarize the recent studies on mitochondria function and quality control in skeletal muscle, focusing mainly on in vivo studies of rodents and human subjects. With an emphasis on the interplay between mitochondrial functions concerning the muscle fiber type-specific phenotypes, we also discuss the effect of aging and exercise on the remodeling of skeletal muscle and mitochondria properties.

Another Way to Confuse Motor Control: Manual Technique Supposed to Shorten Muscle Spindles Reduces the Muscular Holding Stability in the Sense of Adaptive Force in Male Soccer Players.

Sensorimotor control can be impaired by slacked muscle spindles. This was shown for reflex responses and, recently, also for muscular stability in the sense of Adaptive Force (AF). The slack in muscle spindles was generated by contracting the lengthened muscle followed by passive shortening. AF was suggested to specifically reflect sensorimotor control since it requires tension-length control in adaptation to an increasing load. This study investigated AF parameters in reaction to another, manually performed slack procedure in a preselected sample (n = 13). The AF of 11 elbow and 12 hip flexors was assessed by an objectified manual muscle test (MMT) using a handheld device. Maximal isometric AF was significantly reduced after manual spindle technique vs. regular MMT. Muscle lengthening started at 64.93 ± 12.46% of maximal voluntary isometric contraction (MVIC). During regular MMT, muscle length could be maintained stable until 92.53 ± 10.12% of MVIC. Hence, muscular stability measured by AF was impaired after spindle manipulation. Force oscillations arose at a significantly lower level for regular vs. spindle. This supports the assumption that they are a prerequisite for stable adaptation. Reduced muscular stability in reaction to slack procedures is considered physiological since sensory information is misled. It is proposed to use slack procedures to test the functionality of the neuromuscular system, which is relevant for clinical practice.

Task-related differences in peroneus longus muscle fiber conduction velocity.

It has been identified that the peroneus longus presents a regional activity. Specifically, a greater activation of the anterior and posterior compartments has been observed during eversion, whereas a lower activation of the posterior compartment has been reported during plantarflexion. In addition to myoelectrical amplitude, motor unit recruitment can be inferred indirectly from muscle fiber conduction velocity (MFCV). However, there are few reports of MFCV of the regions that make up a muscle, and even less, MFCV of the peroneus longus compartments. This study aimed to analyze the MFCV of peroneus longus compartments during eversion and plantarflexion. Twenty-one healthy individuals were assessed. High-density surface electromyography was recorded from the peroneus longus during eversion and plantarflexion at 10%, 30%, 50%, and 70% of maximal voluntary isometric contraction. The posterior compartment presented a lower MFCV than the anterior compartment during plantarflexion, and both compartments did not show differences in MFCV during eversion; however, the posterior compartment showed an increase in MFCV during eversion compared to plantarflexion. Differences observed in the MFCV of the peroneus longus compartments could support a regional activation strategy and, to some extent, explain different motor unit recruitment strategies of the peroneus longus during ankle movements.

Muscle fascicle and sarcomere adaptation in response to Achilles tendon elongation in an animal model.

Permanent loss of muscle function seen after an Achilles tendon rupture may partly be explained by tendon elongation and accompanying shortening of the muscle. Muscle fascicle length shortens, serial sarcomere number is reduced, and the sarcomere length is unchanged after Achilles tendon transection (ATT), and these changes are mitigated with suturing. The method involved in this study was a controlled laboratory study. Two groups of rats underwent ATT on one side with a contralateral control (CTRL): A) ATT with 3 mm removal of the Achilles tendon and no suturing (substantial tendon elongation), and B) ATT with suture repair (minimal tendon elongation). The operated limb was immobilized for 2 wk to reduce load. Four weeks after surgery the rats were euthanized, and hindlimbs were analyzed for tendon length, gastrocnemius medialis (GM) muscle mass, length, fascicle length, sarcomere number and length. No differences were observed between the groups, and in both groups the Achilles tendon length was longer (15.2%, P < 0.001), GM muscle mass was smaller (17.5%, P < 0.001), and muscle length was shorter (8.2%, P < 0.001) on the ATT compared with CTRL side. GM fascicle length was shorter (11.2%, P < 0.001), and sarcomere number was lower (13.8%, P < 0.001) on the ATT side in all regions. Sarcomere length was greater in the proximal (5.8%, P < 0.001) and mid (4.2%, P = 0.003), but not distal region on the ATT side. In this animal model, regardless of suturing, ATT resulted in tendon elongation, loss of muscle mass and length, and reduced serial sarcomere number, which resulted in an "overshoot" lengthening of the sarcomeres.NEW & NOTEWORTHY Following acute Achilles tendon rupture, patients are often left with functional deficits. The specific reason remains largely unknown. The shortened muscle leads to reduced fascicle length, in turn leading to adaptation by reduced serial sarcomere numbers. Surprisingly, this adaptation appears to "overshoot" and lead to increased sarcomere length. The present animal model advances understanding of how muscle sarcomeres, which are difficult to measure in humans, are affected when undue elongation takes place after tendon rupture.

Small molecule drugs to improve sarcomere function in those with acquired and inherited myopathies.

Muscle weakness is a hallmark of inherited or acquired myopathies. It is a major cause of functional impairment and can advance to life-threatening respiratory insufficiency. During the past decade, several small-molecule drugs that improve the contractility of skeletal muscle fibers have been developed. In this review, we provide an overview of the available literature and the mechanisms of action of small-molecule drugs that modulate the contractility of sarcomeres, the smallest contractile units in striated muscle, by acting on myosin and troponin. We also discuss their use in the treatment of skeletal myopathies. The first of three classes of drugs discussed here increase contractility by decreasing the dissociation rate of calcium from troponin and thereby sensitizing the muscle to calcium. The second two classes of drugs directly act on myosin and stimulate or inhibit the kinetics of myosin-actin interactions, which may be useful in patients with muscle weakness or stiffness.NEW & NOTEWORTHY During the past decade, several small molecule drugs that improve the contractility of skeletal muscle fibers have been developed. In this review, we provide an overview of the available literature and the mechanisms of action of small molecule drugs that modulate the contractility of sarcomeres, the smallest contractile units in striated muscle, by acting on myosin and troponin.

How to Confuse Motor Control: Passive Muscle Shortening after Contraction in Lengthened Position Reduces the Muscular Holding Stability in the Sense of Adaptive Force.

Adaptation to external forces relies on a well-functioning proprioceptive system including muscle spindle afferents. Muscle length and tension control in reaction to external forces is most important regarding the Adaptive Force (AF). This study investigated the effect of different procedures, which are assumed to influence the function of muscle spindles, on the AF. Elbow flexors of 12 healthy participants (n = 19 limbs) were assessed by an objectified manual muscle test (MMT) with different procedures: regular MMT, MMT after precontraction (self-estimated 20% MVIC) in lengthened position with passive return to test position (CL), and MMT after CL with a second precontraction in test position (CL-CT). During regular MMTs, muscles maintained their length up to 99.7% ± 1.0% of the maximal AF (AFmax). After CL, muscles started to lengthen at 53.0% ± 22.5% of AFmax. For CL-CT, muscles were again able to maintain the static position up to 98.3% ± 5.5% of AFmax. AFisomax differed highly significantly between CL vs. CL-CT and regular MMT. CL was assumed to generate a slack of muscle spindles, which led to a substantial reduction of the holding capacity. This was immediately erased by a precontraction in the test position. The results substantiate that muscle spindle sensitivity seems to play an important role for neuromuscular functioning and musculoskeletal stability.