Down-Regulation of Mitochondrial Metabolism after Tendon Release Primes Lipid Accumulation in Rotator Cuff Muscle.

Atrophy and fat accumulation are debilitating aspects of muscle diseases and are rarely prevented. Using a vertical approach combining anatomic techniques with omics methodology in a tenotomy-induced sheep model of rotator cuff disease, we tested whether mitochondrial dysfunction is implicated in muscle wasting and perturbed lipid metabolism, speculating that both can be prevented by the stimulation of ß-oxidation with l-carnitine. The infraspinatus muscle lost 22% of its volume over the first 6 weeks after tenotomy before the area-percentage of lipid increased from 8% to 18% at week 16. Atrophy was associated with the down-regulation of mitochondrial transcripts and protein and a slow-to-fast shift in muscle composition. Correspondingly, amino acid levels were increased 2 weeks after tendon release, when the levels of high-energy phosphates and glycerophospholipids were lowered. l-Carnitine administration (0.9 g/kg per day) prevented atrophy over the first 2 weeks, and mitigated alterations of glutamate, glycerophospholipids, and carnitine levels in released muscle, but did not prevent the level decrease in high-energy phosphates or protein constituents of mitochondrial respiration, promoting the accumulation of longer lipids with an increasing saturation. We conclude that the early phase of infraspinatus muscle degeneration after tendon release involves the elimination of oxidative characteristics associated with an aberrant accumulation of lipid species but is largely unrelated to the prevention of atrophy with oral l-carnitine administration.

The Cardiovascular Response to Interval Exercise Is Modified by the Contraction Type and Training in Proportion to Metabolic Stress of Recruited Muscle Groups.

BACKGROUND: Conventional forms of endurance training based on shortening contractions improve aerobic capacity but elicit a detriment of muscle strength. We hypothesized that eccentric interval training, loading muscle during the lengthening phase of contraction, overcome this interference and potentially adverse cardiovascular reactions, enhancing both muscle metabolism and strength, in association with the stress experienced during exercise. METHODS: Twelve healthy participants completed an eight-week program of work-matched progressive interval-type pedaling exercise on a soft robot under predominately concentric or eccentric load. RESULTS: Eccentric interval training specifically enhanced the peak power of positive anaerobic contractions (+28%), mitigated the strain on muscle's aerobic metabolism, and lowered hemodynamic stress during interval exercise, concomitant with a lowered contribution of positive work to the target output. Concentric training alone lowered blood glucose concentration during interval exercise and mitigated heart rate and blood lactate concentration during ramp exercise. Training-induced adjustments for lactate and positive peak power were independently correlated (p < 0.05, |r| > 0.7) with indices of metabolic and mechanical muscle stress during exercise. DISCUSSION: Task-specific improvements in strength and muscle's metabolic capacity were induced with eccentric interval exercise lowering cardiovascular risk factors, except for blood glucose concentration, possibly through altered neuromuscular coordination.

Human vestibular perceptual thresholds - A systematic review of passive motion perception.

BACKGROUND: The vestibular system detects head accelerations within 6 degrees of freedom. How well this is accomplished is described by vestibular perceptual thresholds. They are a measure of perceptual performance based on the conscious evaluation of sensory information. This review provides an integrative synthesis of the vestibular perceptual thresholds reported in the literature. The focus lies on the estimation of thresholds in healthy participants, used devices and stimulus profiles. The dependence of these thresholds on the participants clinical status and age is also reviewed. Furthermore, thresholds from primate studies are discussed. RESULTS: Thresholds have been measured for frequencies ranging from 0.05 to 5 Hz. They decrease with increasing frequency for five of the six main degrees of freedom (inter-aural, head-vertical, naso-occipital, yaw, pitch). No consistent pattern is evident for roll rotations. For a frequency range beyond 5 Hz, a U-shaped relationship is suggested by a qualitative comparison to primate data. Where enough data is available, increasing thresholds with age and higher thresholds in patients compared to healthy controls can be observed. No effects related to gender or handedness are reported. SIGNIFICANCE: Vestibular thresholds are essential for next generation screening tools in the clinical domain, for the assessment of athletic performance, and workplace safety alike. Knowledge about vestibular perceptual thresholds contributes to basic and applied research in fields such as perception, cognition, learning, and healthy aging. This review provides normative values for vestibular thresholds. Gaps in current knowledge are highlighted and attention is drawn to specific issues for improving the inter-study comparability in the future.

Reliability of panoramic ultrasound imaging and agreement with magnetic resonance imaging for the assessment of lumbar multifidus anatomical cross-sectional area.

The aim of this study was to investigate the reliability of panoramic ultrasound (US) imaging and agreement with magnetic resonance imaging (MRI) for assessing the average lumbar multifidus anatomical cross-sectional area between the lumbar vertebral bodies L3-L5 (i.e., LMF ACSAL3-L5). US and MRI scans of 20 male youth competitive alpine skiers were collected. To test the intra- and interrater reliability of US, transversal panoramic scans were analyzed on two different days by the same rater and the analysis of the first day was compared with the analysis of a second rater. To examine the agreement between US and MRI, Bland-Altman analysis was performed. Intrarater reliability was excellent, and interrater reliability was weak to good for both sides. The bias between MRI and US was - 0.19 ± 0.90 cm2 (2.68 ± 12.30%) for the left side and - 0.04 ± 0.98 cm2 (- 1.11 ± 12.93%) for the right side (i.e., for both sides US slightly overestimated LMF ACSAL3-L5 on average). The limits of agreement were - 1.95 to 1.57 cm2 (- 26.70 to 21.30%) for the left side and - 1.95 to 1.88 cm2 (- 26.46 to 24.24%) for the right side. Panoramic US imaging may be considered a method with excellent intrarater and weak to good interrater reliability for assessing LMF ACSAL3-L5. Comparison with MRI showed large individual differences in some cases, but an acceptable bias between the two imaging modalities.

Three-dimensional mapping of ultrasound-derived skeletal muscle shear wave velocity.

Introduction: The mechanical properties of skeletal muscle are indicative of its capacity to perform physical work, state of disease, or risk of injury. Ultrasound shear wave elastography conducts a quantitative analysis of a tissue's shear stiffness, but current implementations only provide two-dimensional measurements with limited spatial extent. We propose and assess a framework to overcome this inherent limitation by acquiring numerous and contiguous measurements while tracking the probe position to create a volumetric scan of the muscle. This volume reconstruction is then mapped into a parameterized representation in reference to geometric and anatomical properties of the muscle. Such an approach allows to quantify regional differences in muscle stiffness to be identified across the entire muscle volume assessed, which could be linked to functional implications. Methods: We performed shear wave elastography measurements on the vastus lateralis (VL) and the biceps femoris long head (BFlh) muscle of 16 healthy volunteers. We assessed test-retest reliability, explored the potential of the proposed framework in aggregating measurements of multiple subjects, and studied the acute effects of muscular contraction on the regional shear wave velocity post-measured at rest. Results: The proposed approach yielded moderate to good reliability (ICC between 0.578 and 0.801). Aggregation of multiple subject measurements revealed considerable but consistent regional variations in shear wave velocity. As a result of muscle contraction, the shear wave velocity was elevated in various regions of the muscle; showing pre-to-post regional differences for the radial assessement of VL and longitudinally for BFlh. Post-contraction shear wave velocity was associated with maximum eccentric hamstring strength produced during six Nordic hamstring exercise repetitions. Discussion and Conclusion: The presented approach provides reliable, spatially resolved representations of skeletal muscle shear wave velocity and is capable of detecting changes in three-dimensional shear wave velocity patterns, such as those induced by muscle contraction. The observed systematic inter-subject variations in shear wave velocity throughout skeletal muscle additionally underline the necessity of accurate spatial referencing of measurements. Short high-effort exercise bouts increase muscle shear wave velocity. Further studies should investigate the potential of shear wave elastography in predicting the muscle's capacity to perform work.

Lumbar Multifidus Morphology in Youth Competitive Alpine Skiers and Associated Sex, Age, Biological Maturation, Trunk Stability, and Back Complaints.

BACKGROUND: The lumbar multifidus (LMF), as a dynamic stabilizer of the lumbar spine, may play an important role in the prevention of overuse-related back complaints. HYPOTHESIS: LMF morphology is associated with trunk stability and differs between symptomatic and asymptomatic skiers. STUDY DESIGN: Cohort study. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 85 youth skiers (28 females, mean age, 14.7 ± 0.7 years; 57 males, mean age, 14.9 ± 0.5 years) underwent anthropometric assessments, an estimation of biological maturation, a magnetic resonance imaging- and ultrasound-based examination of LMF morphology, and a biomechanical quantification of deadbug bridging stabilization performance. Athletes were categorized as symptomatic if they had registered at least 1 significant overuse-related back complaint episode in the 12 months before the main examination. RESULTS: Male skiers showed a greater LMF size (ie, anatomical cross-sectional area [ACSA]) than female skiers, except for vertebral body L5, where no difference was found (8.8 ± 1.8 cm2 vs 8.3 ± 1.4 cm2, P = 0.18). Conversely, female skiers displayed longer fascicles than male skiers (5.8 ± 0.8 cm vs 5.4 ± 0.8 cm, P = 0.03). Skiers aged under 16 years (U16) skiers had greater values for LMF size and fascicle length than U15 skiers. Maturity offset was associated with L5 LMF size (R2 = 0.060, P = 0.01), fascicle length (R2 = 0.038, P = 0.04), and muscle thickness (R2 = 0.064, P = 0.02). L5 LMF size was associated with trunk stability (R2 = 0.068, P = 0.01). Asymptomatic skiers showed on average a 12.8% greater value for L5 LMF size compared with symptomatic skiers (P = 0.04). CONCLUSION: There are sex- and age-related differences in LMF morphology in youth competitive alpine skiers. Moreover, the ACSA at the level of the lumbar vertebral body L5 undergoes changes during biological maturation, shows a small, but significant association with trunk stability, and differs between symptomatic and asymptomatic skiers with back complaints. CLINICAL RELEVANCE: The observed association of muscle structure (ie, L5 LMF ACSA) with functional aspects (ie, trunk stabilization capacity) and clinical representation (ie, overuse-related back complaints) further highlights the important role of the multifidus muscle for training and injury prevention in youth competitive alpine skiers around the growth spurt.

Estimating Vestibular Perceptual Thresholds using a Six-Degree-of-Freedom Motion Platform.

Vestibular perceptual thresholds refer to the motion intensity required to enable a participant to detect or discriminate a motion based on vestibular input. Using passive motion profiles provided by six degree-of-motion platforms, vestibular perceptual thresholds can be estimated for any kind of motion and thereby target each of the sub-components of the vestibular end-organ. Assessments of vestibular thresholds are clinically relevant as they complement diagnostic tools such as caloric irrigation, the head impulse test (HIT), or vestibular evoked myogenic potentials (VEMPs), which only provide information on sub-components of the vestibular system, but none of them allow for assessing all components. There are several methods with different advantages and disadvantages for estimating vestibular perceptual thresholds. In this article, we present a protocol using an adaptive staircase algorithm and sinusoidal motion profiles for an efficient estimation procedure. Adaptive staircase algorithms consider the response history to determine the peak velocity of the next stimuli and are the most commonly used algorithms in the vestibular domain. We further discuss the impact of motion frequency on vestibular perceptual thresholds.

Biceps femoris long head morphology in youth competitive alpine skiers is associated with age, biological maturation and traumatic lower extremity injuries.

Lower extremity injuries are common in competitive alpine skiers, and the knee and lower leg are often affected. The hamstring muscles, especially the biceps femoris long head (BFlh), can stabilize the knee and the hip and may counteract various adverse loading patterns during typical mechanisms leading to severe lower extremity injuries. The aim of the present study was to describe BFlh morphology in youth competitive alpine skiers in relation to sex, age and biological maturation and to investigate its association with the occurrence of traumatic lower extremity injuries in the upcoming season. 95 youth skiers underwent anthropometric measurements, maturity offset estimations and ultrasound assessment, followed by 12-months prospective injury surveillance. Unpaired t tests showed that the two sexes did not differ in BFlh morphology, including fascicle length (Lf), pennation angle (PA), muscle thickness (MT) and average anatomical cross-sectional area (ACSAavg). In contrast, U16 skiers had longer fascicles than U15 skiers (9.5 ± 1.3 cm vs 8.9 ± 1.3 cm, p < 0.05). Linear regression analyses revealed that maturity offset was associated with Lf (R 2 = 0.129, p < 0.001), MT (R 2 = 0.244, p < 0.001) and ACSAavg (R 2 = 0.065, p = 0.007). No association was found between maturity offset and PA (p = 0.524). According to a binary logistic regression analysis, ACSAavg was significantly associated with the occurrence of traumatic lower extremity injuries (Chi-square = 4.627, p = 0.031, RNagelkerke 2 = 0.064, Cohen f = 0.07). The present study showed that BFlh morphology is age- and biological maturation-dependent and that BFlh ACSAavg can be considered a relevant modifiable variable associated with lower extremity injuries in youth competitive alpine skiers.

Implementing Ultrasound Imaging for the Assessment of Muscle and Tendon Properties in Elite Sports: Practical Aspects, Methodological Considerations and Future Directions.

Ultrasound (US) imaging has been widely used in both research and clinical settings to evaluate the morphological and mechanical properties of muscle and tendon. In elite sports scenarios, a regular assessment of such properties has great potential, namely for testing the response to training, detecting athletes at higher risks of injury, screening athletes for structural abnormalities related to current or future musculoskeletal complaints, and monitoring their return to sport after a musculoskeletal injury. However, several practical and methodological aspects of US techniques should be considered when applying this technology in the elite sports context. Therefore, this narrative review aims to (1) present the principal US measures and field of applications in the context of elite sports; (2) to discuss, from a methodological perspective, the strengths and shortcomings of US imaging for the assessment of muscle and tendon properties; and (3) to provide future directions for research and application.

Panoramic ultrasound vs. MRI for the assessment of hamstrings cross-sectional area and volume in a large athletic cohort.

We investigated the validity of panoramic ultrasound (US) compared to magnetic resonance imaging (MRI) for the assessment of hamstrings cross-sectional area (CSA) and volume. Hamstrings CSA were acquired with US (by an expert operator) at four different sites of femur length (FL) in 85 youth competitive alpine skiers (14.8 ± 0.5 years), and successively compared to corresponding scans obtained by MRI, analyzed by a trained vs. a novice rater. The agreement between techniques was assessed by Bland-Altman analyses. Statistical analysis was carried out using Pearson's product moment correlation coefficient (r). US-derived CSA showed a very good agreement compared to MRI-based ones. The best sites were 40% FL (0 = mid patellar point) for biceps femoris long head (r = 0.9), 50% for semitendinosus (r = 0.9), and 30% for semimembranosus (r = 0.86) and biceps femoris short head (BFsh, r = 0.8). US-based vs. MRI-based hamstrings volume showed an r of 0.96. Poorer r values were observed for the novice compared to the trained rater, with the biggest difference observed for BFsh at 50% (r = 0.001 vs. r = 0.50, respectively) and semimembranosus at 60% (r = 0.23 vs. r = 0.42, respectively). Panoramic US provides valid CSA values and volume estimations compared to MRI. To ensure optimal US-vs.-MRI agreement, raters should preferably possess previous experience in imaging-based analyses.

Ultrasound-derived Biceps Femoris Long Head Fascicle Length: Extrapolation Pitfalls.

PURPOSE: This study aimed to compare biceps femoris long head (BFlh) fascicle length (Lf) obtained with different ultrasound-based approaches: 1) single ultrasound images and linear Lf extrapolation, 2) single ultrasound images and one of two different trigonometric equations (termed equations A and B), and 3) extended field of view (EFOV) ultrasound images. METHODS: Thirty-seven elite alpine skiers (21.7 ± 2.8 yr) without a previous history of hamstring strain injury were tested. Single ultrasound images were collected with a 5-cm linear transducer from BFlh at 50% femur length and were compared with whole muscle scans acquired by EFOV ultrasound. RESULTS: The intrasession reliability (intraclass correlation coefficient [ICC3,k]) of Lf measurements was very high for both single ultrasound images (i.e., Lf estimated by linear extrapolation; ICC3,k = 0.96-0.99, SEM = 0.18 cm) and EFOV scans (ICC3,k = 0.91-0.98, SEM = 0.19 cm). Although extrapolation methods showed cases of Lf overestimation and underestimation when compared with EFOV scans, mean Lf measured from EFOV scans (8.07 ± 1.36 cm) was significantly shorter than Lf estimated by trigonometric equations A (9.98 ± 2.12 cm, P < 0.01) and B (8.57 ± 1.59 cm, P = 0.03), but not significantly different from Lf estimated with manual linear extrapolation (8.40 ± 1.68 cm, P = 0.13). Bland-Altman analyses revealed mean differences in Lf obtained from EFOV scans and those estimated from equation A, equation B, and manual linear extrapolation of 1.91 ± 2.1, 0.50 ± 1.0, and 0.33 ± 1.0 cm, respectively. CONCLUSIONS: The typical extrapolation methods used for estimating Lf from single ultrasound images are reliable within the same session, but not accurate for estimating BFlh Lf at rest with a 5-cm field of view. We recommend that EFOV scans are implemented to accurately determine intervention-related Lf changes in BFlh.

Cellular Aspects of Muscle Specialization Demonstrate Genotype - Phenotype Interaction Effects in Athletes.

INTRODUCTION: Gene polymorphisms are associated with athletic phenotypes relying on maximal or continued power production and affect the specialization of skeletal muscle composition with endurance or strength training of untrained subjects. We tested whether prominent polymorphisms in genes for angiotensin converting enzyme (ACE), tenascin-C (TNC), and actinin-3 (ACTN3) are associated with the differentiation of cellular hallmarks of muscle metabolism and contraction in high level athletes. METHODS: Muscle biopsies were collected from m. vastus lateralis of three distinct phenotypes; endurance athletes (n = 29), power athletes (n = 17), and untrained non-athletes (n = 63). Metabolism-, and contraction-related cellular parameters (such as capillary-to-fiber ratio, capillary length density, volume densities of mitochondria and intramyocellular lipid, fiber mean cross sectional area (MCSA) and volume densities of myofibrils) and the volume densities of sarcoplasma were analyzed by quantitative electron microscopy of the biopsies. Gene polymorphisms of ACE (I/D (insertion/deletion), rs1799752), TNC (A/T, rs2104772), and ACTN3 (C/T, rs1815739) were determined using high-resolution melting polymerase chain reaction (HRM-PCR). Genotype distribution was assessed using Chi2 tests. Genotype and phenotype effects were analyzed by univariate or multivariate analysis of variance and post hoc test of Fisher. P-values below 0.05 were considered statistically significant. RESULTS: The athletes demonstrated the specialization of metabolism- and contraction-related cellular parameters. Differences in cellular parameters could be identified for genotypes rs1799752 and rs2104772, and localized post hoc when taking the interaction with the phenotype into account. Between endurance and power athletes these concerned effects on capillary length density for rs1799752 and rs2104772, fiber type distribution and volume densities of myofibrils (rs1799752), and MSCA (rs2104772). Endurance athletes carrying the I-allele of rs1799752 demonstrated 50%-higher volume densities of mitochondria and sarcoplasma, when power athletes that carried only the D-allele showed the highest fiber MCSAs and a lower percentage of slow type muscle fibers. DISCUSSION: ACE and tenascin-C gene polymorphisms are associated with differences in cellular aspects of muscle metabolism and contraction in specifically-trained high level athletes. Quantitative differences in muscle fiber type distribution and composition, and capillarization in knee extensor muscle explain, in part, identified associations of the insertion/deletion genotypes of ACE (rs1799752) with endurance- and power-type Sports.

Concentric and Eccentric Pedaling-Type Interval Exercise on a Soft Robot for Stable Coronary Artery Disease Patients: Toward a Personalized Protocol.

BACKGROUND: Cardiovascular diseases are the leading causes of death worldwide, and coronary artery disease (CAD) is one of the most common causes of death in Europe. Leading cardiac societies recommend exercise as an integral part of cardiovascular rehabilitation because it reduces the morbidity and mortality of patients with CAD. Continuous low-intensity exercise using shortening muscle actions (concentric, CON) is a common training modality during cardiovascular rehabilitation. However, a growing clinical interest has been recently developed in high-intensity interval training (HIIT) for stable patients with CAD. Exercise performed with lengthening muscle actions (eccentric, ECC) could be tolerated better by patients with CAD as they can be performed with higher loads and lower metabolic cost than CON exercise. OBJECTIVE: We developed a clinical protocol on a soft robot to compare cardiovascular and muscle effects of repeated and work-matched CON versus ECC pedaling-type interval exercise between patients with CAD during cardiovascular rehabilitation. This study aims to ascertain whether the developed training protocols affect peak oxygen uptake (VO2peak), peak aerobic power output (Ppeak), and parameters of muscle oxygen saturation (SmO2) during exercise, and anaerobic muscle power. METHODS: We will randomize 20-30 subjects to either the CON or ECC group. Both groups will perform a ramp test to exhaustion before and after the training period to measure cardiovascular parameters and SmO2. Moreover, the aerobic skeletal muscle power (Ppeak) is measured weekly during the 8-week training period using a simulated squat jump and a counter movement jump on the soft robot and used to adjust the training load. The pedaling-type interval exercise on the soft robot is performed involving either CON or ECC muscle actions. The soft robotic device being used is a closed kinetic chain, force-controlled interactive training, and testing device for the lower extremities, which consists of two independent pedals and free footplates that are operated by pneumatic artificial muscles. RESULTS: The first patients with CAD, who completed the training, showed protocol-specific improvements, reflecting, in part, the lower aerobic training status of the patient completing the CON protocol. Rehabilitation under the CON protocol, more than under the ECC protocol, improved cardiovascular parameters, that is, VO2peak (+26% vs -6%), and Ppeak (+20% vs 0%), and exaggerated muscle deoxygenation during the ramp test (248% vs 49%). Conversely, markers of metabolic stress and recovery from the exhaustive ramp test improved more after the ECC than the CON protocol, that is, peak blood lactate (-9% vs +20%) and peak SmO2 (+7% vs -7%). Anaerobic muscle power only improved after the CON protocol (+18% vs -15%). CONCLUSIONS: This study indicates the potential of the implemented CON and ECC protocols of pedaling-type interval exercise to improve oxygen metabolism of exercised muscle groups while maintaining or even increasing the Ppeak. The ECC training protocol seemingly provided a lower cardiovascular stimulus in patients with CAD while specifically enhancing the reoxygenation and blood lactate clearance in recruited muscle groups during recovery from exercise. TRIAL REGISTRATION: ClinicalTrials.gov NCT02845063; https://clinicaltrials.gov/ct2/show/NCT02845063.

Inhibition of calpain delays early muscle atrophy after rotator cuff tendon release in sheep.

Chronic rotator cuff (RC) tears are characterized by retraction, fat accumulation, and atrophy of the affected muscle. These features pose an intractable problem for surgical repair and subsequent recovery, and their prevention may be easier than reversal. Using an established ovine model, we tested the hypothesis that inhibition of the protease calpain mitigates m. infraspinatus atrophy by preservation of the myofibers' structural anchors in the sarcolemma (the costameres). Already 2 weeks of distal tendon release led to a reduction in muscle volume (-11.6 ± 9.1 cm3 , P = 0.038) and a 8.3% slow-to-fast shift of the fiber area (P = 0.046), which were both entirely abolished by chronic local administration of the calpain inhibitor calpeptin alone, and in combination with sildenafil. Calpain inhibition blunted the retraction of the muscle-tendon unit by 0.8-1.0 cm (P = 0.020) compared with the control group, and prevented cleavage of the costameric protein talin. Calpain 1 and 2 protein levels increased in the medicated groups after 4 weeks, counteracting the efficacy of calpeptin. Hence atrophic changes emerged after 4 weeks despite ongoing treatment. These findings suggest that the early muscular adaptations in the specific case of RC tear in the ovine model are indistinguishable from the atrophy and slow-to-fast fiber transformation observed with conventional unloading and can be prevented for 2 weeks. Concluding, calpain is a potential target to extend the temporal window for reconstruction of the ruptured RC tendon before recovery turns impossible.