Association between Levocarnitine Treatment and the Change in Knee Extensor Strength in Patients Undergoing Hemodialysis: A Post-Hoc Analysis of the Osaka Dialysis Complication Study (ODCS)

Carnitine deficiency is prevalent in patients undergoing hemodialysis, and it could result in lowered muscle strength. So far, the effect of treatment with levocarnitine on lower limb muscle strength has not been well described. This observational study examined the association between treatment with levocarnitine with the change in knee extensor strength (KES) in hemodialysis patients. Eligible patients were selected from the participants enrolled in a prospective cohort study for whom muscle strength was measured annually. We identified 104 eligible patients for this analysis. During the one-year period between 2014 to 2015, 67 patients were treated with intravenous levocarnitine (1000 mg per shot, thrice weekly), whereas 37 patients were not. The change in KES was significantly higher (p = 0.01) in the carnitine group [0.02 (0.01–0.04) kgf/kg] as compared to the non-carnitine group [−0.02 (−0.04 to 0.01) kgf/kg]. Multivariable-adjusted regression analysis showed the positive association between the change in KES and the treatment with levocarnitine remained significant after adjustment for the baseline KES and other potential confounders. Thus, treatment with intravenous levocarnitine was independently and positively associated with the change in KES among hemodialysis patients. Further clinical trials are needed to provide more solid evidence.

Training History-Dependent Functional Role of EMG Model-Predicted Antagonist Moments in Knee Extensor Moment Generation in Healthy Young Adults

Resistance training (RT) improves the skeletal muscle’s ability to generate maximal voluntary force and is accompanied by changes in the activation of the antagonist muscle which is not targeted primarily by RT. However, the nature and role of neural adaptation to RT in the antagonist muscle is paradoxical and not well understood. We compared moments, agonist muscle activation, antagonist activation, agonist-antagonist coactivation, and electromyographic (EMG) model-predicted moments generated by antagonist hamstring muscle coactivation during isokinetic knee extension in leg strength-trained (n = 10) and untrained (n = 11) healthy, younger adults. Trained vs. untrained adults were up to 58% stronger. During knee extension, hamstring activation was 1.6-fold greater in trained vs. untrained adults (p = 0.022). This hamstring activation produced 2.6-fold greater model-predicted antagonist moments during knee extension in the trained (42.7 ± 19.55 Nm) vs. untrained group (16.4 ± 12.18 Nm; p = 0.004), which counteracted (reduced) quadriceps knee extensor moments ~43 Nm (0.54 Nm·kg−1) and by ~16 Nm (0.25 Nm·kg−1) in trained vs. untrained. Antagonist hamstring coactivation correlated with decreases and increases, respectively, in quadriceps moments in trained and untrained. The EMG model-predicted antagonist moments revealed training history-dependent functional roles in knee extensor moment generation.

Reproducibility of knee extensor and flexor contraction velocity in healthy men and women assessed using tensiomyography: A study protocol

Tensiomyography measures the radial displacement of a muscle during an electrically evoked twitch contraction. The rate of muscle displacement is increasingly reported to assess contractile properties. Several formulas currently exist to calculate the rate of displacement during the contraction phase of the maximal twitch response. However, information on the reproducibility of these formulas is scarce. Further, different rest intervals ranging from 10 s to 30 s are applied between consecutive stimuli during progressive electrical stimulation until the maximum twitch response. The effect of different rest intervals on the rate of displacement has not been investigated so far. The first aim of this study is to investigate the within and between-day reliability of the most frequently used formulas to calculate the rate of displacement. The second aim is to investigate the effect of changing the inter-stimulus interval on the rate of displacement. We will determine the rectus femoris and biceps femoris rate of displacement of twenty-four healthy subjects’ dominant leg on two consecutive days. The maximum displacement curve will be determined two times within three minutes on the first day and a third time 24 h later. On day two, we will also apply three blocks of ten consecutive stimuli at a constant intensity of 50 mA. Inter-stimuli intervals will be 10 s, 20 s or 30 s in each block, respectively, and three minutes between blocks. The order of inter-stimulus intervals will be randomized. This study will allow a direct comparison between the five most frequently used formulas to calculate the rate of displacement in terms of their reproducibility. Our data will also inform on the effect of different inter-stimulus intervals on the rate of displacement. These results will provide helpful information on methodical considerations to determine the rate of displacement and may thus contribute to a standardized approach.

Effect of the Knee and Hip Angles on Knee Extensor Torque: Neural, Architectural, and Mechanical Considerations

This study examined the influence of knee extensors’ hip and knee angle on force production capacity and their neuromuscular and architectural consequences. Sixteen healthy men performed sub-maximal and maximal voluntary isometric contractions (MVIC) of knee extensors with four different combinations of the knee and hip angles. Muscle architecture, excitation-contraction coupling process, muscular activity, and corticospinal excitability were evaluated on the vastus lateralis (VL) and rectus femoris (RF) muscles. MVIC and evoked peak twitch (Pt) torques of knee extensors increased significantly (p < 0.05) by 42 ± 12% and 47 ± 16% on average, respectively, under knee flexed positions (110° flexion, 0° = full extension) compared to knee extended positions (20° flexion) but were not different between hip positions (i.e., 0° or 60° flexion). Knee flexion also affected VL and RF muscle and fascicle lengths toward greater length than under knee extended position, while pennation angle decreased for both muscles with knee flexion. Pennation angles of the VL muscle were also lower under extended hip positions. Alternatively, no change in maximal muscle activation or corticospinal activity occurred for the VL and RF muscles across the different positions. Altogether these findings evidenced that MVIC torque of knee extensors depended particularly upon peripheral contractile elements, such as VL and RF muscle and fascicle lengths, but was unaffected by central factors (i.e., muscle activation). Furthermore, the hip position can affect the pennation angle of the VL, while VL muscle length can affect the pennation angle of the RF muscle. These elements suggest that the VL and RF muscles exert a mutual influence on their architecture, probably related to the rectus-vastus aponeurosis.

Relationship Between Isokinetic Knee Strength and Single-Leg Drop Jump Performance 9 Months After ACL Reconstruction

Background: Deficits in knee strength after anterior cruciate ligament reconstruction (ACLR) surgery are common. Deficits in the single-leg drop jump (SLDJ), a test of plyometric ability, are also found. Purpose: To examine the relationship between isokinetic knee strength, SLDJ performance, and self-reported knee function 9 months after ACLR. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Knee isokinetic peak torque, SLDJ jump height, contact time, and reactive strength index (RSI), as well as International Knee Documentation Committee (IKDC) scores were assessed in 116 male, field-sport athletes at 9.2 months after ACLR. SLDJ testing took place in a 3-dimensional biomechanics laboratory. Linear regression models were used to analyze the relationship between the variables. Results: A significant relationship was found between ACLR-limb isokinetic knee extensor strength and SLDJ jump height ( P < .001, r 2 = 0.29) and RSI ( P < .001, r 2 = 0.33), and between ACLR-limb isokinetic knee flexor strength and SLDJ jump height ( P < .001, r 2 = 0.12) and RSI ( P < .001, r 2 = 0.15). A significant positive relationship was also found between knee extensor asymmetry and SLDJ jump height asymmetry ( P < .001, r 2 = 0.27) and SLDJ reactive strength asymmetry ( P < .001, r 2 = 0.18). Combined ACLR-limb jump height and contact time best predicted IKDC scores ( P < .001, r 2 = 0.12). Conclusion: Isokinetic knee extension strength explained approximately 30% of SLDJ performance, with a much weaker relationship between knee flexion strength and SLDJ performance. Isokinetic strength and SLDJ performance were weak predictors of variation in IKDC scores.

Skeletal muscle mitochondrial dysfunction and muscle and whole-body functional deficits in cancer patients with weight loss

Reductions in skeletal muscle mass and function are often reported in patients with cancer-associated weight loss and are associated with reduced quality of life, impaired treatment tolerance, and increased mortality. Although cellular changes, including altered mitochondrial function, have been reported in animals, such changes have been incompletely characterized in humans with cancer. Whole body and skeletal muscle physical function, skeletal muscle mitochondrial function and whole-body protein turnover were assessed in 8 patients with cancer-associated weight loss (10.1±4.2% body weight over 6-12 months) and 19 age-, sex-, and BMI-matched healthy controls to characterize skeletal muscle changes at the whole body, muscle, and cellular level. Potential pathways involved in cancer-induced alterations in metabolism and mitochondrial function were explored by interrogating skeletal muscle and plasma metabolomes. Despite similar lean mass compared to control participants, patients with cancer exhibited reduced habitual physical activity (57% fewer daily steps), cardiorespiratory fitness (22% lower VO2peak [mL/kg/min]) and leg strength (35% lower isokinetic knee extensor strength) and greater leg neuromuscular fatigue (36% greater decline in knee extensor torque). Concomitant with these functional declines, patients with cancer had lower mitochondrial oxidative capacity (25% lower State 3 O2 flux [pmol/s/mg tissue]) and ATP production (23% lower State 3 ATP production [pmol/s/mg tissue]) and alterations in phospholipid metabolite profiles indicative of mitochondrial abnormalities. Whole body protein turnover was unchanged. These findings demonstrate mitochondrial abnormalities concomitant with whole-body and skeletal muscle functional derangements associated with human cancer, supporting future work studying the role of mitochondria in the muscle deficits associated with cancer.

Knee extensor muscle weakness is a risk factor for the development of knee osteoarthritis: an updated systematic review and meta-analysis including 46 819 men and women

ObjectiveTo update a systematic review on the association between knee extensor muscle weakness and the risk of incident knee osteoarthritis in women and men.DesignSystematic review and meta-analysis.Data sourcesSystematic searches in PubMed, EMBASE, SPORTDiscus, CINAHL, AMED and CENTRAL in May 2021.Eligible criteria for selecting studiesLongitudinal studies with at least 2 years follow-up including baseline measure of knee extensor muscle strength, and follow-up measure of symptomatic or radiographic knee osteoarthritis. Studies including participants with known knee osteoarthritis at baseline were excluded. Risk of bias assessment was conducted using six criteria for study validity and bias. Grading of Recommendations Assessments, Development and Evaluation assessed overall quality of evidence. Meta-analysis estimated the OR for the association between knee extensor muscle weakness and incident knee osteoarthritis.ResultsWe included 11 studies with 46 819 participants. Low quality evidence indicated that knee extensor muscle weakness increased the odds of symptomatic knee osteoarthritis in women (OR 1.85, 95% CI 1.29 to 2.64) and in adult men (OR 1.43, 95% CI 1.14 to 1.78), and for radiographic knee osteoarthritis in women: OR 1.43 (95% CI 1.19 to 1.71) and in men: OR 1.39 (95% CI 1.07 to 1.82). No associations were identified for knee injured populations except for radiographic osteoarthritis in men.DiscussionThere is low quality evidence that knee extensor muscle weakness is associated with incident symptomatic and radiographic knee osteoarthritis in women and men. Optimising knee extensor muscle strength may help to prevent knee osteoarthritis.PROSPERO registration numberCRD42020214976.

A Longitudinal Study of Quantitative Muscle Strength and Functional Motor Ability in Ambulatory Boys with Duchenne Muscular Dystrophy

Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder, that is characterized by progressive muscle degeneration and loss of ambulation between 7–13 years of age. Novel pharmacological agents targeting the genetic defects and disease mechanisms are becoming available; however, corticosteroid (CS) therapy remains the standard of care. Objective: The purpose of this longitudinal study was to elucidate the effect of CS therapy on the rate of muscle strength and gross motor skill decline in boys with DMD and assess the sensitivity of selected outcome measures. Methods: Eighty-four ambulatory boys with DMD (49–180 months), 70 on CS, 14 corticosteroid naïve (NCS), participated in this 8-year multi-site study. Outcomes included; isokinetic dynamometry, the Standing (STD) and Walking/Running/jumping (WRJ) dimensions of the Gross Motor Function Measure (GMFM), and Timed Function Tests (TFTs). Nonlinear mixed modeling procedures determined the rate of change with age and the influence of steroids. Results: Despite CS therapy the rate of decline in strength with age was significant in all muscle groups assessed. CS therapy significantly slowed decline in knee extensor strength, as the NCS group declined at 3x the rate of the CS group. Concurrently, WRJ skills declined in the NCS group at twice the rate of the CS group. 4-stair climb and 10 meter walk/run performance was superior in the boys on CS therapy. Conclusion: CS therapy slowed the rate of muscle strength decline and afforded longer retention of select gross motor skills in boys on CS compared to boys who were NCS. Isokinetic dynamometry, Walk/Run/Jump skills, and select TFTs may prove informative in assessing the efficacy of new therapeutics in ambulatory boys with DMD.

Plantar flexor muscles of kangaroo rats (D. deserti) shorten at a velocity to produce optimal power during jumping

During jumping by kangaroo rats, the musculotendon work contributions across all joints are not well understood. Namely, measures of external joint work do not provide information on the contributions from individual muscles or in-series elastic structures. In this study, we examined the functional roles of a major ankle extensor muscle, lateral gastrocnemius (LG), and of a major knee extensor muscle, vastus lateralis (VL), through in vivo sonomicrometry and electromyography techniques, during vertical jumping by kangaroo rats. Our data showed that both muscles increased shortening and activity with higher jumps. We found that knee angular velocity and VL muscle shortening velocity were coupled in time. In contrast, the ankle angular velocity and LG muscle shortening velocity were decoupled, and rapid joint extension near the end of the jump produced high power outputs at the ankle joint. Further, the decoupling of muscle and joint kinematics allowed the LG muscle to prolong the period of shortening velocity near optimal velocity (Vopt), which likely enabled the muscle to sustain maximal power generation. These observations were consistent with a LG tendon that is much more compliant than that of the VL.