Optimizing physical performance is a major goal in current physiology. However, basic understanding of combining high sprint and endurance performance is currently lacking. This study identifies critical determinants of combined sprint and endurance performance using multiple regression analyses of physiologic determinants at different biologic levels. Cyclists, including 6 international sprint, 8 team pursuit, and 14 road cyclists, completed a Wingate test and 15-km time trial to obtain sprint and endurance performance results, respectively. Performance was normalized to lean body mass 2/3 to eliminate the influence of body size. Performance determinants were obtained from whole-body oxygen consumption, blood sampling, knee-extensor maximal force, muscle oxygenation, wholemuscle morphology, and muscle fiber histochemistry of musculus vastus lateralis. Normalized sprint performance was explained by percentage of fast-type fibers and muscle volume (R 2 = 0.65; P < 0.001) and normalized endurance performance by performance oxygen consumption (Vȯ 2 ), mean corpuscular hemoglobin concentration, and muscle oxygenation (R 2 = 0.92; P < 0.001). Combined sprint and endurance performance was explained by gross efficiency, performance Vȯ 2 , and likely by muscle volume and fascicle length (P = 0.056; P = 0.059). High performance Vȯ 2 related to a high oxidative capacity, high capillarization 3 myoglobin, and small physiologic cross-sectional area (R 2 = 0.67; P < 0.001). Results suggest that fascicle length and capillarization are important targets for training to optimize sprint and endurance performance simultaneously.-Van der Zwaard, S., van der Laarse, W. J., Weide, G., Bloemers, F. W., Hofmijster, M. J., Levels, K., Noordhof, D. A., de Koning, J. J., de Ruiter, C. J., Jaspers, R. T. Critical determinants of combined sprint and endurance performance: an integrative analysis from muscle fiber to the human body. FASEB J. 32, 2110FASEB J. 32, -2123FASEB J. 32, (2018 Many sports require a combination of sprint and endurance performance. During the past decades, physiologic determinants of physical performance have been the subject of intensive investigation (e.g., in cycling, 1-11). Studies focused on determinants of either sprint (e.g., 8-18) or endurance performance (e.g., 1-7, 19-23), even though physical performance is rarely a dichotomous function of only sprint or only endurance. Generally, a limited number of whole-body determinants of sprint or endurance performance have been studied, although there are many physical performance determinants at different levels (i.e., molecular, cellular, whole-muscle, organ, and whole ABBREVIATIONS: 3D, 3-dimensional; CAF, capillaries around the fiber; CD, capillary density; C/F, capillary-to-fiber ratio; FCSA, fiber cross-sectional area; fVȯ 2max , fiber maximal oxygen consumption; [Hb], hemoglobin concentration; Hct, hematocrit; [HHbMb], deoxygenated hemoglobin and myoglobin concentration; iSDH activity, spatially integrated SDH activity, SDH activity 3 FCSA; KE, k...

Cerebral palsy (CP), the single largest cause of childhood physical disability, is characterized firstly by a lesion in the immature brain, and secondly by musculoskeletal problems that progress with age. Previous research reported altered muscle properties, such as reduced volume and satellite cell (SC) numbers and hypertrophic extracellular matrix compared to typically developing (TD) children (>10 years). Unfortunately, data on younger CP patients are scarce and studies on SCs and other muscle stem cells in CP are insufficient or lacking. Therefore, it remains difficult to understand the early onset and trajectory of altered muscle properties in growing CP children. Because muscle stem cells are responsible for postnatal growth, repair and remodeling, multiple adult stem cell populations from young CP children could play a role in altered muscle development. To this end, new methods for studying muscle samples of young children, valid to delineate the features and to elucidate the regenerative potential of muscle tissue, are necessary. Using minimal invasive muscle microbiopsy, which was applied in young subjects under general anaesthesia for the first time, we aimed to isolate and characterize muscle stem cell-derived progenitors of TD children and patients with CP. Data of 15 CP patients, 3-9 years old, and 5 aged-matched TD children were reported. The muscle microbiopsy technique was tolerated well in all participants. Through the explant technique, we provided muscle stem cell-derived progenitors from the Medial Gastrocnemius. Via fluorescent activated cell sorting, using surface markers CD56, ALP, and PDGFRa, we obtained SC-derived progenitors, mesoangioblasts and fibro-adipogenic progenitors, respectively. Adipogenic, skeletal, and smooth muscle differentiation assays confirmed the cell identity and ability to give rise to different cell types after appropriate stimuli. Myogenic differentiation in CP SC-derived progenitors showed enhanced fusion index and altered myotube formation based on MYOSIN HEAVY CHAIN expression, as well as disorganization of nuclear spreading, which were not observed in TD myotubes.

Rowers need to combine high sprint and endurance capacities. Muscle morphology largely explains muscle power generating capacity, however, little is known on how muscle morphology relates to rowing performance measures. The aim was to determine how muscle morphology of the vastus lateralis relates to rowing ergometer performance, sprint and endurance capacity of Olympic rowers. Eighteen rowers (12♂, 6♀, who competed at 2016 Olympics) performed an incremental rowing test to obtain maximal oxygen consumption, reflecting endurance capacity. Sprint capacity was assessed by Wingate cycling peak power. M. vastus lateralis morphology (volume, physiological cross-sectional area, fascicle length and pennation angle) was derived from 3-dimensional ultrasound imaging. Thirteen rowers (7♂, 6♀) completed a 2000-m rowing ergometer time trial. Muscle volume largely explained variance in 2000-m rowing performance (R = 0.85), maximal oxygen consumption (R = 0.65), and Wingate peak power (R = 0.82). When normalized for differences in body size, maximal oxygen consumption and Wingate peak power were negatively related in males (r = -0.94). Fascicle length, not physiological cross-sectional area, attributed to normalized peak power. In conclusion, vastus lateralis volume largely explains variance in rowing ergometer performance, sprint and endurance capacity. For a high normalized sprint capacity, athletes may benefit from long fascicles rather than a large physiological cross-sectional area.

Using a cross-sectional design, the purpose of this study was to determine how pennate gastrocnemius medialis (GM) muscle geometry changes as a function of adolescent age. Sixteen healthy adolescent males (aged 10-19 years) participated in this study. GM muscle geometry was measured within the mid-longitudinal plane obtained from a 3D voxel-array composed of transverse ultrasound images. Images were taken at footplate angles corresponding to standardised externally applied footplate moments (between 4 Nm plantar flexion and 6 Nm dorsal flexion). Muscle activity was recorded using surface electromyography (EMG), expressed as a percentage of maximal voluntary contraction (%MVC). To minimise the effects of muscle excitation, EMG inclusion criteria were set at < 10% of MVC. In practice, however, normalised EMG levels were much lower. For adolescent subjects with increasing ages, GM muscle (belly) length increased due to an increase in the length component of the physiological cross-sectional area measured within the mid-longitudinal plane. No difference was found between fascicles at different ages, but the aponeurosis length and pennation angle increased by 0.5 cm year À1 and 0.5°per year, respectively. Footplate angles corresponding to externally applied 0 and 4 Nm plantarflexion moments were not associated with different adolescent ages. In contrast, footplate angles corresponding to externally applied 4 and 6 Nm dorsal flexion moments decreased by 10°between 10 and 19 years. In conclusion, we found that in adolescents' pennate GM muscles, longitudinal muscle growth is mediated predominantly by increased muscle fascicle diameter.

The developmental goal of 3D ultrasound imaging (3DUS) is to engineer a modality to perform 3D morphological ultrasound analysis of human muscles. 3DUS images are constructed from calibrated freehand 2D B-mode ultrasound images, which are positioned into a voxel array. Ultrasound (US) imaging allows quantification of muscle size, fascicle length, and angle of pennation. These morphological variables are important determinants of muscle force and length range of force exertion. The presented protocol describes an approach to determine volume and fascicle length of m. vastus lateralis and m. gastrocnemius medialis. 3DUS facilitates standardization using 3D anatomical references. This approach provides a fast and cost-effective approach for quantifying 3D morphology in skeletal muscles. In healthcare and sports, information on the morphometry of muscles is very valuable in diagnostics and/or follow-up evaluations after treatment or training.

Treatment strategies and training regimens, which induce longitudinal muscle growth and increase the muscles’ length range of active force exertion, are important to improve muscle function and to reduce muscle strain injuries in clinical populations and in athletes with limited muscle extensibility. Animal studies have shown several specific loading strategies resulting in longitudinal muscle fiber growth by addition of sarcomeres in series. Currently, such strategies are also applied to humans in order to induce similar adaptations. However, there is no clear scientific evidence that specific strategies result in longitudinal growth of human muscles. Therefore, the question remains what triggers longitudinal muscle growth in humans. The aim of this review was to identify strategies that induce longitudinal human muscle growth. For this purpose, literature was reviewed and summarized with regard to the following topics: (1) Key determinants of typical muscle length and the length range of active force exertion; (2) Information on typical muscle growth and the effects of mechanical loading on growth and adaptation of muscle and tendinous tissues in healthy animals and humans; (3) The current knowledge and research gaps on the regulation of longitudinal muscle growth; and (4) Potential strategies to induce longitudinal muscle growth. The following potential strategies and important aspects that may positively affect longitudinal muscle growth were deduced: (1) Muscle length at which the loading is performed seems to be decisive, i.e., greater elongations after active or passive mechanical loading at long muscle length are expected; (2) Concentric, isometric and eccentric exercises may induce longitudinal muscle growth by stimulating different muscular adaptations (i.e., increases in fiber cross-sectional area and/or fiber length). Mechanical loading intensity also plays an important role. All three training strategies may increase tendon stiffness, but whether and how these changes may influence muscle growth remains to be elucidated. (3) The approach to combine stretching with activation seems promising (e.g., static stretching and electrical stimulation, loaded inter-set stretching) and warrants further research. Finally, our work shows the need for detailed investigation of the mechanisms of growth of pennate muscles, as those may longitudinally grow by both trophy and addition of sarcomeres in series.

Gait of children with spastic paresis (SP) is frequently characterized by a reduced ankle range of motion, presumably due to reduced extensibility of the triceps surae (TS) muscle. Little is known about how morphological muscle characteristics in SP children are affected. The aim of this study was to compare gastrocnemius medialis (GM) muscle geometry and extensibility in children with SP with those of typically developing (TD) children and assess how GM morphology is related to its extensibility. Thirteen children with SP, of which 10 with a diagnosis of spastic cerebral palsy and three with SP of unknown etiology (mean age 9.7 ± 2.1 years; GMFCS: I–III), and 14 TD children (mean age 9.3 ± 1.7 years) took part in this study. GM geometry was assessed using 3D ultrasound imaging at 0 and 4 Nm externally imposed dorsal flexion ankle moments. GM extensibility was defined as its absolute length change between the externally applied 0 and 4 Nm moments. Anthropometric variables and GM extensibility did not differ between the SP and TD groups. While in both groups, GM muscle volume correlated with body mass, the slope of the regression line in TD was substantially higher than that in SP (TD = 3.3 ml/kg; SP = 1.3 ml/kg, p &lt; 0.01). In TD, GM fascicle length increased with age, lower leg length and body mass, whereas in SP children, fascicle length did not correlate with any of these variables. However, the increase in GM physiological cross-sectional area as a function of body mass did not differ between SP and TD children. Increases in lengths of tendinous structures in children with SP exceeded those observed in TD children (TD = 0.85 cm/cm; SP = 1.16 cm/cm, p &lt; 0.01) and even exceeded lower-leg length increases. In addition, only for children with SP, body mass (r = −0.61), height (r = −0.66), muscle volume (r = − 0.66), physiological cross-sectional area (r = − 0.59), and tendon length (r = −0.68) showed a negative association with GM extensibility. Such negative associations were not found for TD children. In conclusion, physiological cross-sectional area and length of the tendinous structures are positively associated with age and negatively associated with extensibility in children with SP.

METHODS: 23 C57BL/6 (WT) and 24 Transgenic (A1) mice were used for this study, with A1 mice overexpressing the protein PGC-1α. Mice were injected with either PBS or Bupivacaine (MAR) at 12 weeks of age. Tibialis anterior (TA) muscle and tibias were excised 3-days post injection. Tissue was immediately frozen for gene expression analysis using RT-qPCR. RESULTS: There was no difference between TAmass/Tibia length ratio in any mice 3-days post injection. PGC-1α gene expression was 13-fold greater in the A1-PBS group compared to the WT-PBS group (p<0.05). The A1-MAR group however, expressed approximately 4-fold less PGC-1a compared to the A1-PBS group 3-days post injection (p<0.05). In WT mice, MyoD gene expression was 1.5 fold greater in the MAR group compared to the PBS group (p<0.05), with no difference between A1 mice. There was a main effect of MAR to increase Myogenin gene expression in both WT and A1 mice. There was a main effect of genotype to decrease LDH-A expression ~50% in both A1 groups (p<0.05). There was a 4-fold increase in LDH-B expression in the A1-PBS group compared to the WT-PBS group (p<0.05). In WT mice, there was no effect of MAR on LDH-B gene expression. However, in A1 mice there was a 50% decrease in the A1-MAR group compared to the A1-PBS group (p<0.05). TNF-α increased approximately 2fold as a main effect of genotype in both A1 groups (p<0.05). CONCLUSION: A surplus of mitochondria may result in more ROS production and higher levels of TNF-α, resulting in altered expression of MyoD. With TNF-α possibly activating NF-κB, a nuclear factor shown to negatively regulate myogenesis. The differential response in LDH-B expression suggests PGC-1α is involved in altering glycolytic energy metabolism at the onset of muscle regeneration.