Maximal Isometric Force Production Research Articles

Consequences of sarcolemma fatigue on maximal muscle strength production in patients with myalgic encephalomyelitis/chronic fatigue syndrome

BackgroundMyalgic encephalomyelitis is an invalidating chronic disease often associated with exercise-induced alterations of muscle membrane excitability (M wave). No simultaneous measurements of maximal isometric force production and sarcolemma fatigue in the same muscle group have been previously reported. We hypothesized that M wave alterations could be partly responsible for the reduced muscle force present in this invalidating disease. MethodsThis retrospective study compared two groups of patients who presented (n = 30) or not (n = 28) alterations of M waves evoked by direct muscle stimulation during and after a cycling exercise bout. The maximal handgrip strength was measured before and after exercise, concomitantly with electromyogram recordings from flexor digitorum longus muscle. The patients also answered a questionnaire to identify eventual exacerbation of their clinical symptoms following the exercise test. FindingsThe M wave amplitude significantly decreased in muscles and the M wave duration significantly increased in the group of patients with M wave alterations after exercise. Resting values of handgrip were significantly lower in patients with exercise-induced M-wave alterations than in patients without M-wave abnormalities. In patients with exercise-induced M-wave alterations, handgrip significantly decreased after exercise and the changes in handgrip and M wave were positively correlated. The frequency of post-exertion malaise, increased fatigue, myalgia, headache and cognitive dysfunction was significantly higher in patients with M-wave alterations and variations in handgrip after exercise. InterpretationThese data suggest that post-exercise sarcolemma fatigue often measured in patients with myalgic encephalomyelitis could be the cause of muscle failure.

Influence of Force-Length Relationship and Task-Specific Constraints on Finger Force-Generating Capacities.

Grip strength loss in extended and flexed wrist postures has been explained by reduced force-generating capacities of extrinsic finger flexor resulting from non-optimal length, owing to the force-length relationship. Recent works suggested that other muscles, especially wrist extensors, participate in this grip strength loss. The objective of this study was to clarify the role of the force-length relationship in finger force production. 18 participants performed maximal isometric finger force production during pinch grip (Pinch) and four-finger pressing (Press) tasks in four different wrist postures (extended, flexed, neutral, spontaneous). The maximum finger force (MFF), finger and wrist joint angles, as well as activation of four muscles were determined using dynamometry, motion capture, and electromyography. The force and length of the four muscles were estimated from joint angles and muscle activation using a musculoskeletal model. MFF decreased for flexed wrist during Pinch but remained stable across wrist postures during Press. The results suggested that the loss of pinch grip force in deviated wrist posture is partially related to force-length relationship of finger extensors. In opposition, MFF during Press was not influenced by the modulation of muscle capacities but was probably first limited by mechanical and neural factors related to finger interdependence.

People with mild Parkinson's disease have impaired force production in upper limb muscles: A cross-sectional study.

There has been little examination of force production of the upper limb in people with Parkinson's disease (PD), despite its impact on activities of daily living and clear evidence that force production is significantly reduced in lower limb muscle groups. The aim of this study was to determine the force production of the major muscle groups of the upper limb in people with PD during the "on" phase after medication, compared with aged-matched neurologically-normal controls. A cross-sectional study was carried out. Thirty people with mild PD (Hoehn Yahr mean 1.1) and 24 age-matched neurologically-normal controls. Maximum isometric force production of the shoulder flexors, extensors, abductors, adductors, internal rotators and external rotators, elbow flexors and extensors, wrist flexors and extensors and hand grip using dynamometry. There was a significant impairment in force production in all upper limb muscle groups, compared with control participants, except in the wrist flexors. On average the deficit in force production was 22%, despite people with PD having mild disease, being physically active and being measured during the "on" phase of medication. The most severely affected muscle groups were the upper limb extensors. People with PD have a significant deficit in force production of the upper limb muscle groups compared with age-matched neurologically normal controls. Regular assessment of strength of the upper limb should be considered by clinicians and strengthening interventions could be implemented if a deficit is identified.

Design of an Isometric End-Point Force Control Task for Electromyography Normalization and Muscle Synergy Extraction From the Upper Limb Without Maximum Voluntary Contraction.

Muscle synergy analysis via surface electromyography (EMG) is useful to study muscle coordination in motor learning, clinical diagnosis, and neurorehabilitation. However, current methods to extract muscle synergies in the upper limb suffer from two major issues. First, the necessary normalization of EMG signals is performed via maximum voluntary contraction (MVC), which requires maximal isometric force production in each muscle. However, some individuals with motor impairments have difficulties producing maximal effort in the MVC task. In addition, the MVC is known to be highly unreliable, with widely different forces produced in repeated measures. Second, synergy extraction in the upper limb is typically performed with a multidirection reaching task. However, some participants with motor impairments cannot perform this task because it requires precise motor control. In this study, we proposed a new isometric rotating task that does not require precise motor control or large forces. In this task, participants maintain a cursor controlled by the arm end-point force on a target that rotates at a constant angular velocity at a designated force level. To relax constraints on motor control precision, the target is widened and blurred. To obtain a reference EMG value for normalization without requiring maximal effort, we estimated a linear relationship between joint torques and muscle activations. We assessed the reliability of joint torque normalization and synergy extraction in the rotating task in young neurotypical individuals. Compared with normalization with MVC, joint torque normalization allowed reliable EMG normalization at low force levels. In addition, the extraction of synergies was as reliable and more stable than with the multidirection reaching task. The proposed rotating task can, therefore, be used in future motor learning, clinical diagnosis, and neurorehabilitation studies.

Alteration of skeletal and cardiac muscles function in DBA/2J mdx mice background: a focus on high intensity interval training.

Duchenne muscular dystrophy (DMD) is a recessive hereditary myopathy due to deficiency of functional dystrophin. Current therapeutic interventions need more investigation to slow down the progression of skeletal and cardiac muscle weakness. In humans, there is a lack of an adapted training program. In animals, the murine Mdx model with a DBA/2J background (D2-mdx) was recently suggested to present pathological features closer to that of humans. In this study, we characterized skeletal and cardiac muscle functions in males and females D2-mdx mice compared to control groups. We also evaluated the impact of high intensity interval training (HIIT) in these muscles in females and males. HIIT was performed 5 times per week during a month on a motorized treadmill. Specific maximal isometric force production and weakness were measured in the tibialis anterior muscle (TA). Sedentary male and female D2-mdx mice produced lower absolute and specific maximal force compared to control mice. Dystrophic mice showed a decline of force generation during repetitive stimulation compared to controls. This reduction was greater for male D2-mdx mice than females. Furthermore, trained D2-mdx males showed an improvement in force generation after the fifth lengthening contraction compared to sedentary D2-mdx males. Moreover, echocardiography measures revealed a decrease in left ventricular end-diastolic volume, left ventricular ejection volume and left ventricular end-diastolic diameter in sedentary male and female D2-mdx mice. Overall, our results showed a serious muscle function alteration in female and male D2-mdx mice compared to controls. HIIT may delay force loss especially in male D2-mdx mice.

Bilateral Deficits during Maximal Grip Force Production in Late Postmenopausal Women

The purpose of this study was to investigate bilateral deficit patterns during maximal hand-grip force production in late postmenopausal women. Twenty late postmenopausal and 20 young premenopausal women performed maximal isometric grip force production tasks with dominant and nondominant hands and both hands, respectively. For late postmenopausal women, pulse wave analysis was used for identifying a potential relationship between maximal hand-grip strength and risk factors of cardiovascular disease. The findings showed that late postmenopausal women produced significantly decreased maximal hand-grip strength in dominant and nondominant and bilateral hand conditions compared to those of premenopausal women. Bilateral deficit patterns appeared in late postmenopausal women. For late postmenopausal women, decreased dominant and bilateral hand-grip forces were significantly related to greater bilateral deficit patterns. Further, less maximal hand-grip strength in unilateral and bilateral hand conditions correlated with greater central pulse pressure. These findings suggested that age-related impairments in muscle strength and estrogen deficiency may interfere with conducting successful activities of bilateral movements. Further, assessing maximal dominant hand-grip strength may predict bilateral deficit patterns and risk of cardiovascular disease in late postmenopausal women.

Minocycline Treatment Reduces Mass and Force Output From Fast-Twitch Mouse Muscles and Inhibits Myosin Production in C2C12 Myotubes.

Minocycline, a tetracycline-class of antibiotic, has been tested with mixed effectiveness on neuromuscular disorders such as amyotrophic lateral sclerosis, autoimmune neuritis and muscular dystrophy. The independent effect of minocycline on skeletal muscle force production and signalling remain poorly understood. Our aim here is to investigate the effects of minocycline on muscle mass, force production, myosin heavy chain abundance and protein synthesis. Mice were injected with minocycline (40 mg/kg i.p.) daily for 5 days and sacrificed at day six. Fast-twitch EDL, TA muscles and slow-twitch soleus muscles were dissected out, the TA muscle was snap-frozen and the remaining muscles were attached to force transducer whilst maintained in an organ bath. In C2C12 myotubes, minocycline was applied to the media at a final concentration of 10 μg/mL for 48 h. In minocycline treated mice absolute maximal force was lower in fast-twitch EDL while in slow-twitch soleus there was an increase in the time to peak and relaxation of the twitch. There was no effect of minocycline treatment on the other contractile parameters measured in isolated fast- and slow-twitch muscles. In C2C12 cultured cells, minocycline treatment significantly reduced both myosin heavy chain content and protein synthesis without visible changes to myotube morphology. In the TA muscle there was no significant changes in myosin heavy chain content. These results indicate that high dose minocycline treatment can cause a reduction in maximal isometric force production and mass in fast-twitch EDL and impair protein synthesis during myogenesis in C2C12 cultured cells. These findings have important implications for future studies investigating the efficacy of minocycline treatment in neuromuscular or other muscle-atrophy inducing conditions.

Review of the methods used for calculating physiological cross-sectional area (PCSA) for ecological questions.

This review examines literature that used physiological cross-sectional area (PCSA) as a representative measure of an individual muscle's maximal isometric force production. PCSA is used to understand the muscle architecture and how a trade-off between muscle force and muscle contractile velocity reflect adaptations of the musculoskeletal system as a reflection of functional demands. Over the decades, methods have been developed to measure muscle volume, fascicle lengths, and pennation angle to calculate PCSA. The advantages and limitations of these methods (especially the inclusion/elimination of pennation angle) are discussed frequently; however, these method descriptions are scattered throughout the literature. Here, we reviewed and summarised the different approaches to collecting and recording muscle architectural properties to subsequently calculate PCSA. By critically discussing the advantages and limitations of each methodology, we aim to provide readers with an overview of repeatable methods to assess muscle architecture. This review may serve as a guide to facilitate readers searching for the appropriate techniques to calculate PCSA and measure muscle architecture to be applied in ecomorphology research. RESEARCH HIGHLIGHTS: Discuss the theories behind PCSA in a synthesised review to inform researchers about PCSA methodology.

Cerebellar Transcranial Direct Current Stimulation Improves Maximum Isometric Force Production during Isometric Barbell Squats.

Maximum voluntary contraction force (MVC) is an important predictor of athletic performance as well as physical fitness throughout life. Many everyday life activities involve multi-joint or whole-body movements that are determined in part through optimized muscle strength. Transcranial direct current stimulation (tDCS) has been reported to enhance muscle strength parameters in single-joint movements after its application to motor cortical areas, although tDCS effects on maximum isometric voluntary contraction force (MIVC) in compound movements remain to be investigated. Here, we tested whether anodal tDCS and/or sham stimulation over primary motor cortex (M1) and cerebellum (CB) improves MIVC during isometric barbell squats (iBS). Our results provide novel evidence that CB stimulation enhances MIVC during iBS. Although this indicates that parameters relating to muscle strength can be modulated through anodal tDCS of the cerebellum, our results serve as an initial reference point and need to be extended. Therefore, further studies are necessary to expand knowledge in this area of research through the inclusion of different tDCS paradigms, for example investigating dynamic barbell squats, as well as testing other whole-body movements.

Changes in Early and Maximal Isometric Force Production in Response to Moderate- and High-Load Strength and Power Training.

Comfort, P, Jones, PA, Thomas, C, Dos'Santos, T, McMahon, JJ, and Suchomel, TJ. Changes in early and maximal isometric force production in response to moderate- and high-load strength and power training. J Strength Cond Res 36(3): 593-599, 2022-The aims of this study were to determine the changes in early (50-, 100-, 150-, 200-, 250 ms) and maximal isometric force production, in response to a 4-week period of moderate-load resistance training (60-82.5% 1 repetition maximum [1RM]), followed by a 4-week period of high-load (80-90% 1RM) resistance training. Thirty-four subjects (age 19.5 ± 2.8 years; height 1.72 ± 0.08 m; body mass 69.9 ± 11.4 kg; maximal power clean 0.92 ± 0.03 kg·kg-1) participated in this study. Only trivial-to-moderate (0.2-2.7%, d = 0.00-0.88) and nonsignificant (p > 0.05) changes in early isometric force production were observed in response to the moderate-load training period, whereas very large (9.2-14.6%, d = 2.71-4.16), significant (p ≤ 0.001) increases in early isometric force production were observed in response to high-load training. In contrast, there was a very large, significant increase in peak force (PF) across the moderate-load phase (7.7 ± 11.8%, d = 2.02, p = 0.003), but only a moderate significant increase in PF (3.8 ± 10.6%, d = 1.16, p = 0.001) across the high-load phase. The results of this study indicate that high-load multijoint resistance training, that follows moderate-load training, results in superior increases in early multi-joint force production, compared with the changes observed after moderate-load resistance training.

Active recovery shows favorable IGF-I and IGF binding protein responses following heavy resistance exercise compared to passive recovery

IGF-I and IGFBPs have important physiological modulatory effects and this study sought to examine the influence of active vs. passive recovery following a heavy resistance exercise on IGF-I and IGF binding protein (IGFBP) recovery responses. It was hypothesized that increased IGF-I and decreased inhibitory IGFBPs during active recovery may be reflective of cascades promoting physiological recovery. 18 untrained men ((AR n = 7, PR n = 11), age: 26 ± 4 years, height: 174 ± 8 cm, body mass: 75 ± 13 kg) performed either a protocol-specific 10 × 10 × 30% 1RM active (AR) or passive recovery (PR) session following a heavy resistance exercise session performed on a leg press device (10 × 10 1RM). Maximal isometric force production (MVC) and IGF- and IGFBPs were measured pre, post, 1-hr post, and next morning. A significantly greater relative response in IGF-I was observed in AR than in PR at post recovery and next morning (p < .01 and statistical trend, respectively) while absolute concentrations of IGFBP-1 at next morning were significantly higher in PR than AR (p < .05), and relative IGFBP-1 response from control to next morning in PR was significantly greater than in AR (p < .001). IGFBP-1 may be inhibitory to IGF-I biological action, thus the lower concentration of IGFBP-1 after AR may be considered favorable in terms of recovery due to its positive relationship with glucose metabolism and maintaining metabolic homeostasis. These results suggest that some of the benefits of an active recovery bout may be mediated by favorable IGF-I system responses (increased IGF-I and decreased IGFBP-1) in the hormonal milieu that may assist facilitating the cascade of physiological recovery processes following acute heavy resistance loading exercise.

Short-Term Low Choline Intake May Not Negatively Affect Strength Gains in Older Adults

PURPOSE: The micronutrient choline is a precursor to acetylcholine (ACh), which mediates skeletal muscle contraction and force production. We previously reported that 12 weeks of low choline consumption (~50% of Adequate Intake [AI]) impaired strength gains in older adults in response to resistance exercise training. The purpose of this study was to investigate whether low choline consumption for a shorter period of time has negative effects on muscle responses to resistant exercise (RE) in older adults. METHODS: Thirty one, 50-to-65-year-old, generally healthy men and women were randomly assigned to one of three choline intake groups (Low, 3.6 ± 0.6 mg/kg/d, n=10; Med, 6.0 ± 0.6 mg/kg/d, n=11; High, 8.8 ± 0.8 mg/kg/d, n=10) and underwent 3 weeks of diet and RE intervention (leg press and extension, 2x/week, 3 sets, 8-12 reps, 75% of maximum strength [1RM]; 4 bouts of maximal isometric force production on leg extension). 1RM and EMG tests were performed before and after intervention. RESULTS: While all three groups experienced significant increases in strength, there was no difference between choline groups in changes in 1RMs (Leg press, Low: 12.4 ± 12.0%, Med: 17.5 ± 10.7%, High: 15.8 ± 10.7%, p=0.588; Leg extension, Low: 17.9 ± 13.0%, Med: 15.3 ± 18.8%, High: 5.9 ± 12.2%, p=0.209). Similarly, no differences were observed in EMG amplitudes or average/peak isometric force outputs between groups. CONCLUSION: These data suggest that less than a month of low or high choline intake may not affect strength gains in older adults. It appears that only a prolonged period of low choline intake may have negative effects on muscle responses to RE.

The dual CCR2/CCR5 chemokine receptor antagonist Cenicriviroc reduces macrophage infiltration and disease severity in Duchenne muscular dystrophy (Dmdmdx-4Cv) mice.

Duchenne muscular dystrophy (DMD) is characterized by progressive muscle weakness which is ultimately fatal, most often due to involvement of the diaphragm. Macrophage infiltration of dystrophic muscles has been strongly linked to muscle damage and fibrosis in DMD. We hypothesized that cenicriviroc (CVC), a dual chemokine receptor (CCR2/CCR5) antagonist currently under clinical evaluation for other diseases, could prevent macrophage accumulation and blunt disease progression in the diaphragms of mdx mice (genetic homologue of DMD). Treatment with CVC (20 mg/kg/day intraperitoneally) or vehicle was initiated in mdx mice at 2 weeks of age (prior to the onset of muscle necrosis) and continued for 4 weeks. Flow cytometry to assess inflammatory cell subsets as well as histological and force generation parameters were determined in mdx diaphragms at the conclusion of the treatment. CVC therapy induced a major (3.9-fold) reduction in total infiltrating macrophages, whereas total numbers of neutrophils and T lymphocytes (CD4+ and CD8+) were unaffected. No changes in macrophage polarization status (inflammatory versus anti-inflammatory skewing based on iNOS and CD206 expression) were observed. Muscle fiber size and fibrosis were not altered by CVC, whereas a significant reduction in centrally nucleated fibers was found suggesting a decrease in prior necrosis-regeneration cycles. In addition, maximal isometric force production by the diaphragm was increased by CVC therapy. These results suggest that CVC or other chemokine receptor antagonists which reduce pathological macrophage infiltration may have the potential to slow disease progression in DMD.

Strength improvements through occlusal splints? The effects of different lower jaw positions on maximal isometric force production and performance in different jumping types.

ObjectiveThe influence of the jaw position on postural control, body posture, walking and running pattern has been reported in the literature. All these movements have in common that a relatively small, but well controlled muscle activation is required. The induced effects on motor output through changed jaw positions have been small. Therefore, it has been questioned if it could still be observed in maximal muscle activation.MethodTwenty-three healthy, mid age recreational runners (mean age = 34.0 ± 10.3 years) participated in this study. Three different jump tests (squat jump, counter movement jump, and drop jumps from four different heights) and three maximal strength tests (trunk flexion and extension, leg press of the right and left leg) were conducted. Four different dental occlusion conditions and an additional familiarization condition were tested. Subjects performed the tests on different days for which the four occlusion conditions were randomly changed.ResultsNo familiarization effect was found. Occlusion conditions with a relaxation position and with a myocentric condylar position showed significantly higher values for several tests compared to the neutral condition and the maximal occlusion position. Significance was found in the squat jump, countermovement jump, the drop jump from 32cm and 40cm, trunk extension, leg press force and rate of force development. The effect due to the splint conditions is an improvement between 3% and 12% (min and max). No influence of the jaw position on symmetry or balance between extension and flexion muscle was found.ConclusionAn influence of occlusion splints on rate of force development (RFD) and maximal strength tests could be confirmed. A small, but consistent increase in the performance parameters could be measured. The influence of the occlusion condition is most likely small compared to other influences as for example training status, age, gender and circadian rhythm.

Pharmacological inhibition of myostatin protects against skeletal muscle atrophy and weakness after anterior cruciate ligament tear.

Anterior cruciate ligament (ACL) tears are among the most frequent knee injuries in sports medicine, with tear rates in the US up to 250,000 per year. Many patients who suffer from ACL tears have persistent atrophy and weakness even after considerable rehabilitation. Myostatin is a cytokine that directly induces muscle atrophy, and previous studies rodent models and patients have demonstrated an upregulation of myostatin after ACL tear. Using a preclinical rat model, our objective was to determine if the use of a bioneutralizing antibody against myostatin could prevent muscle atrophy and weakness after ACL tear. Rats underwent a surgically induced ACL tear and were treated with either a bioneutralizing antibody against myostatin (10B3, GlaxoSmithKline) or a sham antibody (E1-82.15, GlaxoSmithKline). Muscles were harvested at either 7 or 21 days after induction of a tear to measure changes in contractile function, fiber size, and genes involved in muscle atrophy and hypertrophy. These time points were selected to evaluate early and later changes in muscle structure and function. Compared to the sham antibody group, 7 days after ACL tear, myostatin inhibition reduced the expression of proteolytic genes and induced the expression of hypertrophy genes. These early changes in gene expression lead to a 22% increase in muscle fiber cross-sectional area and a 10% improvement in maximum isometric force production that were observed 21 days after ACL tear. Overall, myostatin inhibition lead to several favorable, although modest, changes in molecular biomarkers of muscle regeneration and reduced muscle atrophy and weakness following ACL tear. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2499-2505, 2017.

Functional Changes after Recombinant Human Growth Hormone Replacement in Patients with Chronic Traumatic Brain Injury and Abnormal Growth Hormone Secretion.

We explored the effects of recombinant human growth hormone (rhGH) replacement on physical and cognitive functioning in subjects with a moderate-to-severe traumatic brain injury (TBI) with abnormal growth hormone (GH) secretion. Fifteen individuals who sustained a TBI at least 12 months prior to study enrollment were identified as having abnormal GH secretion by glucagon stimulation testing (maximum GH response less than 8 ng/mL). Peak cardiorespiratory capacity, body composition, and muscle force testing were assessed at baseline and one year after rhGH replacement. Additionally, standardized neuropsychological tests that assess memory, processing speed, and cognitive flexibility, as well as self-report inventories related to depression and fatigue, were administered at baseline and 1 year after rhGH replacement. Comparison tests were performed with proper post hoc analyses. All analyses were carried out at α < 0.05. Peak O2 consumption, peak oxygen pulse (estimate of cardiac stroke volume), and peak ventilation all significantly increased (p < 0.05). Maximal isometric and isokinetic force production were not altered. Skeletal muscle fatigue did not change but the perceptual rating of fatigue was reduced by ∼25% (p = 0.06). Cognitive performance did not change significantly over time, whereas self-reported symptoms related to depression and fatigue significantly improved. The observed changes suggest that rhGH replacement has a positive impact on cardiorespiratory fitness and a positive impact on perceptual fatigue in survivors of TBI with altered GH secretion.

Pharmacological Inhibition of Myostatin Protects Against Atrophy and Weakness after ACL Tear

Objectives:Many patients who suffer ACL tears have persistent atrophy and weakness even after rehabilitation. Myostatin is a cytokine that directly induces muscle atrophy, and previous studies using rodent models and patients have demonstrated an up regulation of myostatin after ACL tear. Using a preclinical rat model, our objective was to determine if the use of a bioneutralizing antibody against myostatin could prevent muscle atrophy and weakness after ACL tear.Methods:This study was approved by our IACUC. The left ACL and was transected in 3mo-old male F344 rats. At the time of surgery rats received a single IP injection of either a bioneutralizing antibody against myostatin (10B3, GlaxoSmithKline) or a sham IgG (E1-82.15, GlaxoSmithKline) at a dose of 10mg/kg. Rats (N=8 per group) were sacrificed and tissue was harvested 7 days or 21 days after tear. Contractile force measurements of the extensor digitorum longus (EDL) were performed. The size of muscle fibers in histological sections from the EDL and distal vastus lateralis were also measured. RNA was isolated from the distal rectus femoris and gene expression analysis was performed with RT-qPCR. The expression of each gene was normalized to b actin, and further normalized to the expression of muscles from control, uninjured rats. A two-way ANOVA (alpha=0.05) followed by Holm Sidak post hoc sorting was used to evaluate the effect of time and treatment on measured parameters.Results:Inhibition of myostatin resulted in an increase in muscle fiber size at the 21D time point compared to all other groups (Table 1). While both the sham antibody and myostatin antibody groups increased maximum isometric force production from 7D to 21D, the myostatin antibody group at 21D had a further increase in force compared to the 21D sham group. The muscle E3 ubiquitin ligases atrogin-1 and muscle ring finger 1 (MuRF-1) are the major rate limiting enzymes in muscle protein degradation, and inhibition of myostatin resulted in decreases in the expression of these genes at 7D (Figure 1A). Additionally, IGF-1Ea and IGF-1Eb which are important growth factors that induce muscle protein synthesis, were elevated in the myostatin antibody groups at the 21D time point. For genes related to fibrosis (Figure 1B), although there was no significant difference in MMP-2, there was a significant decrease of MMP-8 expression in the 21D MSTN group when compared to the 21D sham. There were also increases in the expression of TIMP-1 and 2 in the 21D MSTN group.Conclusion:In a preclinical rat model, the targeted inhibition of myostatin protected leg muscles from muscle atrophy and improved force production after ACL tear. While the mechanism of action is not entirely clear, it is possible that the inhibition of myostatin preserves strength by limiting the expression of proteolytic enzymes in the post-acute atrophy phase and increasing protein synthesis in later phases.

Mouse forepaw lumbrical muscles are resistant to age-related declines in force production

A progressive loss of skeletal muscle mass and force generating capacity occurs with aging. Mice are commonly used in the study of aging-associated changes in muscle size and strength, with most models of aging demonstrating 15–35% reductions in muscle mass, cross-sectional area (CSA), maximum isometric force production (Po) and specific force (sPo), which is Po/CSA. The lumbrical muscle of the mouse forepaw is exceptionally small, with corresponding short diffusion distances that make it ideal for in vitro pharmacological studies and measurements of contractile properties. However, the aging-associated changes in lumbrical function have not previously been reported. To address this, we tested the hypothesis that compared to adult (12month old) mice, the forepaw lumbrical muscles of old (30month old) mice exhibit aging-related declines in size and force production similar to those observed in larger limb muscles. We found that the forepaw lumbricals were composed exclusively of fibers with type II myosin heavy chain isoforms, and that the muscles accumulated connective tissue with aging. There were no differences in the number of fibers per whole-muscle cross-section or in muscle fiber CSA. The whole muscle CSA in old mice was increased by 17%, but the total CSA of all muscle fibers in a whole-muscle cross-section was not different. No difference in Po was observed, and while sPo normalized to total muscle CSA was decreased in old mice by 22%, normalizing Po by the total muscle fiber CSA resulted in no difference in sPo. Combined, these results indicate that forepaw lumbrical muscles from 30month old mice are largely protected from the aging-associated declines in size and force production that are typically observed in larger limb muscles.

Effects of heavy-resistance strength and balance training on unilateral and bilateral leg strength performance in old adults.

The term “bilateral deficit” (BLD) has been used to describe a reduction in performance during bilateral contractions when compared to the sum of identical unilateral contractions. In old age, maximal isometric force production (MIF) decreases and BLD increases indicating the need for training interventions to mitigate this impact in seniors. In a cross-sectional approach, we examined age-related differences in MIF and BLD in young (age: 20–30 years) and old adults (age: >65 years). In addition, a randomized-controlled trial was conducted to investigate training-specific effects of resistance vs. balance training on MIF and BLD of the leg extensors in old adults. Subjects were randomly assigned to resistance training (n = 19), balance training (n = 14), or a control group (n = 20). Bilateral heavy-resistance training for the lower extremities was performed for 13 weeks (3 × / week) at 80% of the one repetition maximum. Balance training was conducted using predominately unilateral exercises on wobble boards, soft mats, and uneven surfaces for the same duration. Pre- and post-tests included uni- and bilateral measurements of maximal isometric leg extension force. At baseline, young subjects outperformed older adults in uni- and bilateral MIF (all p < .001; d = 2.61–3.37) and in measures of BLD (p < .001; d = 2.04). We also found significant increases in uni- and bilateral MIF after resistance training (all p < .001, d = 1.8-5.7) and balance training (all p < .05, d = 1.3-3.2). In addition, BLD decreased following resistance (p < .001, d = 3.4) and balance training (p < .001, d = 2.6). It can be concluded that both training regimens resulted in increased MIF and decreased BLD of the leg extensors (HRT-group more than BAL-group), almost reaching the levels of young adults.

Reduced muscle fiber force production and disrupted myofibril architecture in patients with chronic rotator cuff tears

A persistent atrophy of muscle fibers and an accumulation of fat, collectively referred to as fatty degeneration, commonly occur in patients with chronic rotator cuff tears. The etiology of fatty degeneration and function of the residual rotator cuff musculature have not been well characterized in humans. We hypothesized that muscles from patients with chronic rotator cuff tears have reduced muscle fiber force production, disordered myofibrils, and an accumulation of fat vacuoles. The contractility of muscle fibers from biopsy specimens of supraspinatus muscles of 13 patients with chronic full-thickness posterosuperior rotator cuff tears was measured and compared with data from healthy vastus lateralis muscle fibers. Correlations between muscle fiber contractility, American Shoulder and Elbow Surgeons (ASES) scores, and tear size were analyzed. Histology and electron microscopy were also performed. Torn supraspinatus muscles had a 30% reduction in maximum isometric force production and a 29% reduction in normalized force compared with controls. Normalized supraspinatus fiber force positively correlated with ASES score and negatively correlated with tear size. Disordered sarcomeres were noted, along with an accumulation of lipid-laden macrophages in the extracellular matrix surrounding supraspinatus muscle fibers. Patients with chronic supraspinatus tears have significant reductions in muscle fiber force production. Force production also correlates with ASES scores and tear size. The structural and functional muscle dysfunction of the residual muscle fibers is independent of the additional area taken up by fibrotic tissue. This work may help establish future therapies to restore muscle function after the repair of chronically torn rotator cuff muscles.