Impact of capillary and sarcolemmal proximity on mitochondrial structure and energetic function in skeletal muscle.

Mitochondria within skeletal muscle cells are located either between the muscle contractile apparatus (interfibrillar mitochondria, IFM) or beneath the cell membrane (subsarcolemmal mitochondria, SSM), with several structural and functional differences reported between IFM and SSM. However, recent 3D imaging studies demonstrate that mitochondria are particularly concentrated in the proximity of capillaries embedded in sarcolemmal grooves rather than in proximity to the sarcolemma itself (paravascular mitochondria, PVM). To evaluate the impact of capillary vs. sarcolemmal proximity, we compared the structure and function of skeletal muscle mitochondria located either lateral to embedded capillaries (PVM), adjacent to the sarcolemma but not in PVM pools (SSM) or interspersed between sarcomeres (IFM). Mitochondrial morphology and interactions were assessed by 3D electron microscopy coupled with machine learning segmentation, whereas mitochondrial energy conversion was assessed by two-photon microscopy of mitochondrial membrane potential, content, calcium, NADH redox and flux in live, intact cells. Structurally, although PVM and SSM were similarly larger than IFM, PVM were larger, rounder and had more physical connections to neighbouring mitochondria compared to both IFM and SSM. Functionally, PVM had similar or greater basal NADH flux compared to SSM and IFM, respectively, despite a more oxidized NADH pool and a greater membrane potential, signifying a greater activation of the electron transport chain in PVM. Together, these data indicate that proximity to capillaries has a greater impact on resting mitochondrial energy conversion and distribution in skeletal muscle than the sarcolemma alone. KEY POINTS: Capillaries have a greater impact on mitochondrial energy conversion in skeletal muscle than the sarcolemma. Paravascular mitochondria are larger, and the outer mitochondrial membrane is more connected with neighbouring mitochondria. Interfibrillar mitochondria are longer and have greater contact sites with other organelles (i.e. sarcoplasmic reticulum and lipid droplets). Paravascular mitochondria have greater activation of oxidative phosphorylation than interfibrillar mitochondria at rest, although this is not regulated by calcium.

Reorganization of mitochondria-organelle interactions during postnatal development in skeletal muscle.

Skeletal muscle cellular development requires the integrated assembly of mitochondria and other organelles adjacent to the sarcomere in support of muscle contractile performance. However, it remains unclear how interactions among organelles and with the sarcomere relates to the development of muscle cell function. Here, we combine 3D volume electron microscopy, proteomic analyses, and live cell functional imaging to investigate the postnatal reorganization of mitochondria-organelle interactions in skeletal muscle. We show that while mitochondrial networks are disorganized and loosely associated with the contractile apparatus at birth, contact sites among mitochondria, lipid droplets and the sarcoplasmic reticulum are highly abundant in neonatal muscles. The maturation process is characterized by a transition to highly organized mitochondrial networks wrapped tightly around the muscle sarcomere but also to less frequent interactions with both lipid droplets and the sarcoplasmic reticulum. Concomitantly, expression of proteins involved in mitochondria-organelle membrane contact sites decreases during postnatal development in tandem with a decrease in abundance of proteins associated with sarcomere assembly despite an overall increase in contractile protein abundance. Functionally, parallel measures of mitochondrial membrane potential, NADH redox status, and NADH flux within intact cells revealed that mitochondria in adult skeletal muscle fibres maintain a more activated electron transport chain compared with neonatal muscle mitochondria. These data demonstrate a developmental redesign reflecting a shift from muscle cell assembly and frequent inter-organelle communication toward a muscle fibre with mitochondrial structure, interactions, composition and function specialized to support contractile function. KEY POINTS: Mitochondrial network organization is remodelled during skeletal muscle postnatal development. The mitochondrial outer membrane is in frequent contact with other organelles at birth and transitions to more close associations with the contractile apparatus in mature muscles. Mitochondrial energy metabolism becomes more activated during postnatal development. Understanding the developmental redesign process within skeletal muscle cells may help pinpoint specific areas of deficit in muscles with developmental disorders.

Leveraging Emerging Technologies to Expand Accessibility and Improve Precision in Rehabilitation and Exercise for People with Disabilities.

Physical rehabilitation and exercise training have emerged as promising solutions for improving health, restoring function, and preserving quality of life in populations that face disparate health challenges related to disability. Despite the immense potential for rehabilitation and exercise to help people with disabilities live longer, healthier, and more independent lives, people with disabilities can experience physical, psychosocial, environmental, and economic barriers that limit their ability to participate in rehabilitation, exercise, and other physical activities. Together, these barriers contribute to health inequities in people with disabilities, by disproportionately limiting their ability to participate in health-promoting physical activities, relative to people without disabilities. Therefore, there is great need for research and innovation focusing on the development of strategies to expand accessibility and promote participation in rehabilitation and exercise programs for people with disabilities. Here, we discuss how cutting-edge technologies related to telecommunications, wearables, virtual and augmented reality, artificial intelligence, and cloud computing are providing new opportunities to improve accessibility in rehabilitation and exercise for people with disabilities. In addition, we highlight new frontiers in digital health technology and emerging lines of scientific research that will shape the future of precision care strategies for people with disabilities.

Skeletal Muscle Dysfunction in People With Multiple Sclerosis: A Physiological Target for Improving Physical Function and Mobility.

Impaired mobility is amongst the most debilitating symptoms reported by people with multiple sclerosis (MS). Historically, it has been viewed that walking impairments in people with MS are directly caused by the physical damage to the neurons in the central nervous system (CNS) which results from the immunopathology of MS. However, research from over the past 4 decades has revealed that physical function in people with MS is also affected by skeletal muscle dysfunction characterized by a reduced capacity to produce, regulate, and sustain the force-generating muscle contractions that propel human movement. While the immediate CNS damage caused by MS can alter the neural activation of muscle by disrupting neuromotor transmission, chronic reductions in mobility and extreme fatigue can lead to physically inactive lifestyles that negatively affect skeletal muscle through mechanisms of deconditioning. Consequently, people with MS can experience alterations in activation patterns, muscle mass and tissue composition, contractility, metabolism, and perfusion that contribute to reductions in muscle function that ultimately impair key physical functions such as walking. This article provides an overview of the cellular mechanisms that contribute to skeletal muscle dysfunction in people with MS and a discussion of the current evidence suggesting that skeletal muscle may be a key physiological target for interventions aiming to improve mobility in this population. We specifically highlight recent evidence demonstrating the potential for rehabilitation and exercise interventions to induce muscle plasticity in people with MS who have moderate to severe levels of disability. In conclusion, we discuss future directions in basic science and clinical research that may advance our understanding of muscle dysfunction in MS and lead to the development of more precise and effective treatment strategies.

Mitochondrial network configuration influences sarcomere and myosin filament structure in striated muscles.

Sustained muscle contraction occurs through interactions between actin and myosin filaments within sarcomeres and requires a constant supply of adenosine triphosphate (ATP) from nearby mitochondria. However, it remains unclear how different physical configurations between sarcomeres and mitochondria alter the energetic support for contractile function. Here, we show that sarcomere cross-sectional area (CSA) varies along its length in a cell type-dependent manner where the reduction in Z-disk CSA relative to the sarcomere center is closely coordinated with mitochondrial network configuration in flies, mice, and humans. Further, we find myosin filaments near the sarcomere periphery are curved relative to interior filaments with greater curvature for filaments near mitochondria compared to sarcoplasmic reticulum. Finally, we demonstrate variable myosin filament lattice spacing between filament ends and filament centers in a cell type-dependent manner. These data suggest both sarcomere structure and myofilament interactions are influenced by the location and orientation of mitochondria within muscle cells.

Prediction of future falls among full-time wheelchair and scooter users with multiple sclerosis: A prospective study.

BACKGROUND: Seventy-five percent (75%) of full-time wheelchair or scooter users with multiple sclerosis (MS) experience at least one fall in a period of 6 months. Falls are detrimental for the independence, quality of life, and community participation. No previous prospective study has evaluated fall risk factors in this segment of MS community. OBJECTIVE: To develop a multivariable falls risk prediction model for people with MS (PwMS) who use a wheelchair or scooter full-time. METHODS: This prospective cohort study is a secondary data analysis that recruited PwMS from the community across the US. Forty-eight adults with MS who use a wheelchair or scooter as their main form of mobility were included. Dependent variable was fall incidence over 3-month recorded through diaries. Dependent variable was categorized as fallers (≥ 1 fall) and non-fallers (0 fall). Predictors were demographics, history of falls in the past 6 months, measures of fear of falling, Spinal Cord Injury- Falls Concern Scale, California Verbal Learning Test II, and Multiple Sclerosis Quality of Life- mental health. Multivariable logistic regression analyses were conducted to identity predictors of future falls. RESULTS: In total, 63 falls (range 0 - 8) were reported over the 3-month period from a total of 26 fallers (54%). Multivariate logistic regression analyses indicated that the risk factor with the best predictive ability of future falls included history of falls in the past 6 months (sensitivity 77%, specificity 54%, and area under the receiving operating curve statistic = 0.76, 95% CI 0.62 to 0.89). CONCLUSION: Findings highlight the importance of asking full-time wheelchair and scooter users with MS if they have fallen in the past 6 months to quickly identify those who are at increased fall risk and in need of follow up assessment and intervention to identify and address modifiable risk factors. More attention to fall risks among full-time wheelchair or scooter users with MS is suggested to increase the understanding among clinicians and researchers of modifiable risk factors.

Regulation of the evolutionarily conserved muscle myofibrillar matrix by cell type dependent and independent mechanisms.

Skeletal muscles play a central role in human movement through forces transmitted by contraction of the sarcomere. We recently showed that mammalian sarcomeres are connected through frequent branches forming a singular, mesh-like myofibrillar matrix. However, the extent to which myofibrillar connectivity is evolutionarily conserved as well as mechanisms which regulate the specific architecture of sarcomere branching remain unclear. Here, we demonstrate the presence of a myofibrillar matrix in the tubular, but not indirect flight (IF) muscles within Drosophila melanogaster. Moreover, we find that loss of transcription factor H15 increases sarcomere branching frequency in the tubular jump muscles, and we show that sarcomere branching can be turned on in IF muscles by salm-mediated conversion to tubular muscles. Finally, we demonstrate that neurochondrin misexpression results in myofibrillar connectivity in IF muscles without conversion to tubular muscles. These data indicate an evolutionarily conserved myofibrillar matrix regulated by both cell-type dependent and independent mechanisms.

Subcellular Specialization of Mitochondrial Form and Function in Skeletal Muscle Cells.

Across different cell types and within single cells, mitochondria are heterogeneous in form and function. In skeletal muscle cells, morphologically and functionally distinct subpopulations of mitochondria have been identified, but the mechanisms by which the subcellular specialization of mitochondria contributes to energy homeostasis in working muscles remains unclear. Here, we discuss the current data regarding mitochondrial heterogeneity in skeletal muscle cells and highlight potential new lines of inquiry that have emerged due to advancements in cellular imaging technologies.

The Functional Impact of Mitochondrial Structure Across Subcellular Scales.

Mitochondria are key determinants of cellular health. However, the functional role of mitochondria varies from cell to cell depending on the relative demands for energy distribution, metabolite biosynthesis, and/or signaling. In order to support the specific needs of different cell types, mitochondrial functional capacity can be optimized in part by modulating mitochondrial structure across several different spatial scales. Here we discuss the functional implications of altering mitochondrial structure with an emphasis on the physiological trade-offs associated with different mitochondrial configurations. Within a mitochondrion, increasing the amount of cristae in the inner membrane improves capacity for energy conversion and free radical-mediated signaling but may come at the expense of matrix space where enzymes critical for metabolite biosynthesis and signaling reside. Electrically isolating individual cristae could provide a protective mechanism to limit the spread of dysfunction within a mitochondrion but may also slow the response time to an increase in cellular energy demand. For individual mitochondria, those with relatively greater surface areas can facilitate interactions with the cytosol or other organelles but may be more costly to remove through mitophagy due to the need for larger phagophore membranes. At the network scale, a large, stable mitochondrial reticulum can provide a structural pathway for energy distribution and communication across long distances yet also enable rapid spreading of localized dysfunction. Highly dynamic mitochondrial networks allow for frequent content mixing and communication but require constant cellular remodeling to accommodate the movement of mitochondria. The formation of contact sites between mitochondria and several other organelles provides a mechanism for specialized communication and direct content transfer between organelles. However, increasing the number of contact sites between mitochondria and any given organelle reduces the mitochondrial surface area available for contact sites with other organelles as well as for metabolite exchange with cytosol. Though the precise mechanisms guiding the coordinated multi-scale mitochondrial configurations observed in different cell types have yet to be elucidated, it is clear that mitochondrial structure is tailored at every level to optimize mitochondrial function to meet specific cellular demands.

The unified myofibrillar matrix for force generation in muscle.

Human movement occurs through contraction of the basic unit of the muscle cell, the sarcomere. Sarcomeres have long been considered to be arranged end-to-end in series along the length of the muscle into tube-like myofibrils with many individual, parallel myofibrils comprising the bulk of the muscle cell volume. Here, we demonstrate that striated muscle cells form a continuous myofibrillar matrix linked together by frequently branching sarcomeres. We find that all muscle cells contain highly connected myofibrillar networks though the frequency of sarcomere branching goes down from early to late postnatal development and is higher in slow-twitch than fast-twitch mature muscles. Moreover, we show that the myofibrillar matrix is united across the entire width of the muscle cell both at birth and in mature muscle. We propose that striated muscle force is generated by a singular, mesh-like myofibrillar network rather than many individual, parallel myofibrils.

MUSCLE MITOCHONDRIAL CAPACITY AND ENDURANCE IN ADULTS WITH TYPE 1 DIABETES.

The impact of type 1 diabetes (T1D) on muscle endurance and oxidative capacity is currently unknown. PURPOSE: Measure muscle endurance and oxidative capacity of adults with T1D compared to controls. METHODS: A cross-sectional study design with a control group was used. Subjects (19-37 years old) with T1D (n=17) and controls (n=17) were assessed with hemoglobin A1c (HbA1c) and casual glucose. Muscle endurance was measured with an accelerometer at stimulation frequencies of 2, 4, and 6 Hz for a total of nine minutes. Mitochondrial capacity was measured using near-infrared spectroscopy after exercise as the rate constant of the rate of recovery of oxygen consumption. RESULTS: T1D and control groups were similar in age, sex, height, and race. The T1D group had slightly higher BMI values and adipose tissue thickness over the forearm muscles. Casual glucose was 150±70 mg/dL for T1D and 98±16 mg/dL for controls (P=0.006). HbA1c of T1D subjects was 7.1±0.9% and 5.0±0.4% for controls (P<0.01). Endurance indexes at 2, 4, and 6 Hz were 94.5±5.2%, 81.8±8.4%, and 68.6±13.5% for T1D and 94.6±4.1%, 85.9±6.3%, and 68.7±15.4% for controls (p = 0.97, 0.12, 0.99, respectively). There were no differences between groups in mitochondrial capacity (T1D= 1.9±0.5 min-1 and control=1.8±0.4 min-1, P=0.29) or reperfusion rate (T1D= 8.8±2.8s and control=10.3±3.0s, P=0.88). There were no significant correlations between HbA1c and either muscle endurance, mitochondrial capacity or reperfusion rate. CONCLUSIONS: Adults with T1D did not have reduced oxidative capacity, muscle endurance or muscle reperfusion rates compared to controls. HbA1c also did not correlate with muscle endurance, mitochondrial capacity or reperfusion rates. Future studies should extend these measurements to older people or people with poorly-controlled T1D.

MitoRACE: evaluating mitochondrial function in vivo and in single cells with subcellular resolution using multiphoton NADH autofluorescence.

KEY POINTS: We developed a novel metabolic imaging approach that provides direct measures of the rate of mitochondrial energy conversion with single-cell and subcellular resolution by evaluating NADH autofluorescence kinetics during the mitochondrial redox after cyanide experiment (mitoRACE). Measures of mitochondrial NADH flux by mitoRACE are sensitive to physiological and pharmacological perturbations in vivo. Metabolic imaging with mitoRACE provides a highly adaptable platform for evaluating mitochondrial function in vivo and in single cells with potential for broad applications in the study of energy metabolism. ABSTRACT: Mitochondria play a critical role in numerous cell types and diseases, and structure and function of mitochondria can vary greatly among cells or within different regions of the same cell. However, there are currently limited methodologies that provide direct assessments of mitochondrial function in vivo, and contemporary measures of mitochondrial energy conversion lack the spatial resolution necessary to address cellular and subcellular heterogeneity. Here, we describe a novel metabolic imaging approach that provides direct measures of mitochondrial energy conversion with single-cell and subcellular resolution by evaluating NADH autofluorescence kinetics during the mitochondrial redox after cyanide experiment (mitoRACE). MitoRACE measures the rate of NADH flux through the steady-state mitochondrial NADH pool by rapidly inhibiting mitochondrial energetic flux, resulting in an immediate, linear increase in NADH fluorescence proportional to the steady-state NADH flux rate, thereby providing a direct measure of mitochondrial NADH flux. The experiments presented here demonstrate the sensitivity of this technique to detect physiological and pharmacological changes in mitochondrial flux within tissues of living animals and reveal the unique capability of this technique to evaluate mitochondrial function with single-cell and subcellular resolution in different cell types in vivo and in cell culture. Furthermore, we highlight the potential applications of mitoRACE by showing that within single neurons, mitochondria in neurites have higher energetic flux rates than mitochondria in the cell body. Metabolic imaging with mitoRACE provides a highly adaptable platform for evaluating mitochondrial function in vivo and in single cells, with potential for broad applications in the study of energy metabolism.

Effects of Treadmill Training on Muscle Oxidative Capacity and Endurance in People with Multiple Sclerosis with Significant Walking Limitations.

BACKGROUND: Exercise can improve muscle function and mobility in people with multiple sclerosis (MS). However, the effects of exercise training on skeletal muscle oxidative capacity and endurance in people with MS remain unclear, and few studies have evaluated muscle plasticity in people with MS who have moderate-to-severe disability. The present study evaluated the effects of treadmill training on muscle oxidative capacity and muscle endurance and examined the relationship to walking function in people with MS who have moderate-to-severe disability. METHODS: Six adults (mean ± SD age, 50 ± 4.9 years) with MS (Expanded Disability Status Scale score, 6.0-6.5) performed treadmill training for 24 minutes approximately twice per week for approximately 8 weeks (16 sessions total) using an antigravity treadmill system. The following measures were taken before and after the intervention phase: muscle oxidative capacity in the medial gastrocnemius using near-infrared spectroscopy after 15 to 20 seconds of electrical stimulation; muscle endurance in the medial gastrocnemius using accelerometer-based mechanomyography during 9 minutes of twitch electrical stimulation in three stages (3 minutes per stage) of increasing frequency (2, 4, and 6 Hz); and walking function using the 2-Minute Walk Test. RESULTS: Mean ± SD muscle oxidative capacity increased from 0.64 ± 0.19 min-1 to 1.08 ± 0.52 min-1 (68.2%). Mean ± SD muscle endurance increased from 80.9% ± 15.2% to 91.5% ± 4.8% at 2 Hz, from 56.3% ± 20.1% to 76.6% ± 15.8% at 4 Hz, and from 29.2% ± 13.1% to 53.9% ± 19.4% at 6 Hz of stimulation in the gastrocnemius. There were no significant improvements in walking function. CONCLUSIONS: Treadmill training can improve muscle oxidative capacity and endurance in people with MS who have moderate-to-severe levels of disability.

Muscle-Specific Endurance of the Lower Back Erectors Using Electrical Twitch Mechanomyography.

Lower back pain is a common symptom potentially associated with skeletal muscle dysfunction. The purpose of this study was to evaluate endurance in the lower back muscles of healthy participants using accelerometer-based mechanomyography. Methods: Young healthy subjects (N = 7) were tested. Surface electrodes and a tri-axial accelerometer were placed over the erector spinae muscle along the T11-L1 Vertebrae. Stimulation was for 3 min each at 2, 4, and 6 Hz, and changes in acceleration were used to calculate an endurance index (EI). Reproducibility of the endurance index measurements was tested on two separate days. Wrist flexor and vastus lateralis muscles were tested for comparison. Near Infrared Spectroscopy (NIRS) was used to measure muscle oxygen levels (O2Hb) (N = 5). EI was 70.3 + 13.4, 32.6 + 8.4, and 19.2 + 6.2% for 2, 4, 6 Hz, respectively. The coefficients of variation were 9.8, 13.9, and 20.3% for 2, 4, 6 Hz, respectively. EI values were lower in the erector spinae muscles compared to the arm and the leg (p < 0.05). O2Hb values were 86.4 + 10.9% at rest and were 77.2 + 15.5, 84.3 + 14.1, and 84.1 + 18.9% for 2, 4, 6 Hz, respectively (p > 0.05, all comparisons). An endurance index can be obtained from the lower back erectors muscles that is reproducible and not influenced by voluntary effort or muscle oxygen levels.

Muscle Dysfunction and Walking Impairment in Women with Multiple Sclerosis.

BACKGROUND: Recent evidence suggests that skeletal muscle dysfunction is involved in disability progression in people with multiple sclerosis (MS). However, the relationship between muscle dysfunction and walking impairments in MS remains unclear. Thus, the cross-sectional relationships between muscle-specific oxidative capacity and walking endurance in women with MS were evaluated. METHODS: Twenty women with MS (11 African American, 9 white) were tested. Muscle oxidative capacity of the medial gastrocnemius was measured using near-infrared spectroscopy after electrical stimulation. Muscle endurance was evaluated using accelerometer-based mechanomyography during electrical stimulation. Muscle strength was measured during maximal voluntary plantarflexion using handheld dynamometry. Walking function was measured using the Timed 25-Foot Walk test and the 6-Minute Walk Test (6MWT). RESULTS: Reduced muscle oxidative capacity (R 2 = 0.68-0.71, P < .01) and muscle endurance (R 2 = 0.59-0.78, P < .01) were associated with lower Timed 25-Foot Walk time and 6MWT distance. Muscle strength was weakly correlated to 6MWT distance (R 2 = 0.21, P = .02). No differences in muscle function or clinical outcome measures were found between African American and white subgroups. Women with moderate-to-severe disability (Expanded Disability Status Scale [EDSS] score, 5.0-6.5) had significantly reduced muscle oxidative capacity, muscle endurance, and walking ability compared with women with mild disability (EDSS score, 2.5-4.5). CONCLUSIONS: Reductions in muscle function in people with MS are related to declines in walking function across all levels of disability. Muscle dysfunction is not differentially related to walking impairment in African American and white women with MS.

Subcellular connectomic analyses of energy networks in striated muscle.

Mapping biological circuit connectivity has revolutionized our understanding of structure-function relationships. Although connectomic analyses have primarily focused on neural systems, electrical connectivity within muscle mitochondrial networks was recently demonstrated to provide a rapid mechanism for cellular energy distribution. However, tools to evaluate organelle connectivity with high spatial fidelity within single cells are currently lacking. Here, we developed a framework to quantitatively assess mitochondrial network connectivity and interactions with cellular sites of energy storage, utilization, and calcium cycling in cardiac, oxidative, and glycolytic muscle. We demonstrate that mitochondrial network configuration, individual mitochondrial size and shape, and the junctions connecting mitochondria within each network are consistent with the differing contraction demands of each muscle type. Moreover, mitochondria-lipid droplet interaction analyses suggest that individual mitochondria within networks may play specialized roles regarding energy distribution and calcium cycling within the cell and reveal the power of connectomic analyses of organelle interactions within single cells.

Case Report: Effect of Antigravity Treadmill Training on Muscle Oxidative Capacity, Muscle Endurance, and Walking Function in a Person with Multiple Sclerosis.

BACKGROUND: Exercise training can improve skeletal muscle metabolism in persons with multiple sclerosis (MS). However, quantification of exercise-mediated improvements in muscle metabolism has been limited, particularly in people with high levels of disability. We evaluated the effect of 9 weeks of antigravity treadmill training on muscle oxidative capacity and muscle endurance and assessed the relationship to walking function in a person with MS. METHODS: One person with MS (Expanded Disability Status Scale score, 6.5) performed treadmill training for 24 minutes approximately twice weekly for 9 weeks (16 sessions) using an antigravity treadmill system. Before and after the intervention phase, we measured muscle oxidative capacity in the medial gastrocnemius using near-infrared spectroscopy after 15 to 20 seconds of electrical stimulation; muscle endurance in the medial gastrocnemius using accelerometer-based mechanomyography during 9 minutes of twitch electrical stimulation in three stages (3 minutes per stage) of increasing frequency (2, 4, and 6 Hz); muscle strength (plantarflexion) using a maximal voluntary contraction; and walking function using the Timed 25-Foot Walk test and the 2-Minute Walk Test. RESULTS: Muscle oxidative capacity increased from 0.73 min-1 to 1.08 min-1 (48%). Muscle endurance increased from 75.9% to 84.0% at 2 Hz, from 67.8% to 76.2% at 4 Hz, and from 13.5% to 44.7% at 6 Hz. Maximal voluntary contraction decreased by 0.68 kg (15%), Timed 25-Foot Walk test speed decreased by 0.19 ft/s (20%), and 2-Minute Walk Test distance increased by 65 m (212%). CONCLUSIONS: Muscle oxidative capacity and muscle endurance, as well as walking function, improved in a person with MS after training on an antigravity treadmill.

Muscle-specific endurance of the trapezius muscles using electrical twitch mechanomyography.

BACKGROUND: Symptoms of fatigue and pain are often reported for the trapezius muscle in the shoulder. The present study evaluated endurance in the trapezius muscles of healthy participants using electric twitch mechanomyography (ETM). METHODS: Surface electrodes and a tri-axial accelerometer were placed over the left trapezius muscle. Muscles were stimulated for 3 min each at 2 Hz, 4 Hz and 6 Hz. Maintenance of acceleration during muscle twitches was used to calculate an endurance index (EI). Subjects (n = 9) were tested on two separate days to assess reproducibility of the trapezius EI measurements. The endurance measurements were made on the wrist flexor and vastus lateralis muscles for comparison. Near infrared spectroscopy was used to measure muscle oxygenation (HbO2) during the stimulation protocol (n = 8). RESULTS: Mean (SD) EI was 84.9% (8.7%), 63.3% (19.1%) and 41.7% (20.0%) for 2 Hz, 4 Hz and 6 Hz, respectively. The coefficients of variation were 7.4%, 11.3% and 24.0% for 2 Hz, 4 Hz and 6 Hz, respectively. EI values were significantly lower in the trapezius compared to arm and leg muscles (p < 0.05). HbO2 values were unchanged from resting values with electrical stimulation. CONCLUSIONS: The EI as measured by ETM may provide a reproducible method of evaluating function in trapezius muscles that is not influenced by oxygen saturation.

In Vivo Assessment of Mitochondrial Dysfunction in Clinical Populations Using Near-Infrared Spectroscopy.

The ability to sustain submaximal exercise is largely dependent on the oxidative capacity of mitochondria within skeletal muscle, and impairments in oxidative metabolism have been implicated in many neurologic and cardiovascular pathologies. Here we review studies which have demonstrated the utility of Near-infrared spectroscopy (NIRS) as a method of evaluating of skeletal muscle mitochondrial dysfunction in clinical human populations. NIRS has been previously used to noninvasively measure tissue oxygen saturation, but recent studies have demonstrated the utility of NIRS as a method of evaluating skeletal muscle oxidative capacity using post-exercise recovery kinetics of oxygen metabolism. In comparison to historical methods of measuring muscle metabolic dysfunction in vivo, NIRS provides a more versatile and economical method of evaluating mitochondrial oxidative capacity in humans. These advantages generate great potential for the clinical applicability of NIRS as a means of evaluating muscle dysfunction in clinical populations.

Experimental intermittent ischemia augments exercise-induced inflammatory cytokine production.

Acute exercise-induced inflammation is implicated in mediating the beneficial adaptations to regular exercise. Evidence suggests that reduced oxygen and/or blood flow to contracting muscle alters cytokine appearance. However, the acute inflammatory responses to hypoxic/ischemic exercise have been documented with inconsistent results and may not accurately reflect the ischemia produced during exercise in patients with ischemic cardiovascular diseases. Therefore, we determined the extent to which local inflammation is involved in the response to ischemic exercise. Fourteen healthy males performed unilateral isometric forearm contractions for 30 min with and without experimental ischemia. Blood was drawn at baseline, 5 and 10 min into exercise, at the end of exercise, and 30, 60, and 120 min after exercise. Oxygen saturation levels, as measured by near-infrared spectroscopy, were reduced by 10% and 41% during nonischemic and ischemic exercise, respectively. Nonischemic exercise did not affect cytokine values. Ischemia enhanced concentrations of basic fibroblast growth factor, interleukin (IL)-6, IL-10, tumor necrosis factor-alpha, and vascular endothelial growth factor during exercise, but IL-8 was not influenced by ischemic exercise. In conclusion, the present study demonstrates that ischemic, small-muscle endurance exercise elicits local inflammatory cytokine production compared with nonischemic exercise.NEW & NOTEWORTHY We demonstrate that ischemic, small-muscle endurance exercise elicits local inflammatory cytokine production compared with nonischemic exercise. The present study advances our knowledge of the inflammatory response to exercise in a partial ischemic state, which may be relevant for understanding the therapeutic effects of exercise training for people with ischemic cardiovascular disease-associated comorbidities.