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Age‐related loss of strength is disproportionally greater than the loss of mass, suggesting maladaptations in the neuro‐myo‐tendinous system. Myofibers are often misshaped in aged and diseased muscle, but systematic analyses of large sample sets are lacking. Our aim was to investigate myofiber shape in relation to age, exercise, myofiber type, species and sex. Vastus lateralis muscle biopsies (n= 265) from 197 males and females, covering an age span of 20–97 years, were examined. The gastrocnemius and soleus muscles of 11 + 22‐month‐old male C57BL/6 mice were also examined. Immunofluorescence and ATPase stainings of muscle cross‐sections were used to measure myofiber cross‐sectional area (CSA) and perimeter. From these, a shape factor index (SFI) was calculated in a fibre‐type‐specific manner (type I/II in humans; type I/IIa/IIx/IIb in mice), with higher values indicating increased deformity. Heavy resistance training (RT) was performed three times per week for 3–4 months by a subgroup (n= 59). Correlation analyses were performed comparing SFI and CSA with age, muscle mass, maximal voluntary contraction (MVC), rate of force development and specific force (MVC/muscle mass). In human muscle, SFI was positively correlated with age for both type I (R2= 0.20) and II (R2= 0.38) myofibers. When subjects were separated into age cohorts, SFI was lower for type I (4%, P< 0.001) and II (6%, P< 0.001) myofibers in young (20–36) compared with old (60–80) and higher for type I (5%, P< 0.05) and II (14%, P< 0.001) myofibers in the oldest old (>80) compared with old. The increased SFI in old muscle was observed in myofibers of all sizes. Within all three age cohorts, type II myofiber SFI was higher than that for type I myofiber (4–13%, P< 0.001), which was also the case in mice muscles (8–9%, P< 0.001). Across age cohorts, there was no difference between males and females in SFI for either type I (P= 0.496/0.734) or II (P= 0.176/0.585) myofibers. Multiple linear regression revealed that SFI, after adjusting for age and myofiber CSA, has independent explanatory power for 8/10 indices of muscle mass and function. RT reduced SFI of type II myofibers in both young and old (3–4%, P< 0.001). Here, we identify type I and II myofiber shape in humans as a hallmark of muscle ageing that independently predicts volumetric and functional assessments of muscle health. RT reverts the shape of type II myofibers, suggesting that a lack of myofiber recruitment might lead to myofiber deformity.

Morphological studies of skeletal muscle tissue provide insights into the architecture of muscle fibers, the surrounding cells, and the extracellular matrix (ECM). However, a spatial proteomics analysis of the skeletal muscle including the muscle-tendon transition zone is lacking. Here, we prepare cryotome muscle sections of the mouse soleus muscle and measure each slice using short liquid chromatography-mass spectrometry (LC-MS) gradients. We generate 3,000 high-resolution protein profiles that serve as the basis for a network analysis to reveal the complex architecture of the muscle-tendon junction. Among the protein profiles that increase from muscle to tendon, we find proteins related to neuronal activity, fatty acid biosynthesis, and the renin-angiotensin system (RAS). Blocking the RAS in cultured mouse tenocytes using losartan reduces the ECM synthesis. Overall, our analysis of thin cryotome sections provides a spatial proteome of skeletal muscle and reveals that the RAS acts as an additional regulator of the matrix within muscle-tendon junctions.

Background and Purpose. Muscle-specific strength training has previously been shown to be effective in the rehabilitation of chronic neck muscle pain in women. The aim of this study was to determine the level of activation of the neck and shoulder muscles using surface electromyography (EMG) during selected strengthening exercises in women undergoing rehabilitation for chronic neck muscle pain (defined as a clinical diagnosis of trapezius myalgia). Subjects. The subjects were 12 female workers (age=30-60 years) with a clinical diagnosis of trapezius myalgia and a mean baseline pain intensity of 5.6 (range=3-8) on a scale of 0 to 9. Method. Electromyographic activity in the trapezius and deltoid muscles was measured during the exercises (lateral raises, upright rows, shrugs, one-arm rows, and reverse flys) and normalized to EMG activity recorded during a maximal voluntary static contraction (MVC). Results. For most exercises, the level of muscle activation was relatively high (>60% of MVC), highlighting the effectiveness and specificity of the respective exercises. For the trapezius muscle, the highest level of muscle activation was found during the shrug (102 ± 11% of MVC), lateral raise (97 ± 6% of MVC), and upright row (85 ± 5% of MVC) exercises, but the latter 2 exercises required smaller training loads (3-10 kg) compared with the shrug exercise (20-30 kg). Discussion and Conclusion. The lateral raise and upright row may be suitable alternatives to shrugs during rehabilitation of chronic neck muscle pain. Several of the strength exercises had high activation of neck and shoulder muscles in women with chronic neck pain. These exercises can be used equally in the attempt to achieve a beneficial treatment effect on chronic neck muscle pain., Musculoskeletal pain is the most common condition L treated by physical therapists and contributes substantially to health care costs and sick leave. The occurrence of neck muscle pain has been [...]

Study was conducted to examine muscle and blood metabolites during soccer match play and relate it to possible changes in sprint performance. The study demonstrated that sprint performance is reduced temporarily both during and towards the end of a soccer game.

A study to better understand how immobilization and surgery affect muscle size and function in the elderly and to identify effective training regimes is presented. An investigation of whether elderly patients who had undergone the hip-replacement surgery could benefit from additional training in the early postoperative phase and more specifically what training modality would be most effective is made.

This article discusses the relationship between exercise and adipose tissue blood flow in older women. An analysis of body composition, oxygen consumption, and blood glycerol is presented.

A study is presented that shows that functional electrical stimulation cycle training of the legs of paralyzed individuals helps increase insulin sensitivity. Because of inactivity, spinal cord injury patients are susceptible to hyperinsulinemia.

This article examines changes in body temperature related to cycling induced by electrical muscle stimulation in people with disabling spinal cord injuries. Results indicate that electrically induced exercise resulted in an increase in core and muscle temperature while skin surface temperature remained constant.

Objective During skeletal growth, the articular cartilage expands to maintain its cover of bones in joints, however, it is unclear when and how cartilage grows. We aim to determine the expanding growth pattern and timing across the tibia plateau in human knees.Design Six human tibia plateaus (2 healthy, 2 with osteoarthritis, and 2 with posttraumatic osteoarthritis) were used for full-depth cartilage sampling systematically across the joint surface at 12 medial and 4 lateral sites. Methodologically, we took advantage of the performed nuclear bomb tests in the years 1955 to 1963, which increased the atmospheric 14C that was incorporated into human tissues. Cartilage was treated enzymatically to extract collagen, analyzed for 14C content, and year at formation was determined from historical atmospheric 14C concentrations.Results By age-determination, each tibia condyle had central points of formation surrounded by later-formed cartilage toward the periphery. Furthermore, the tibia plateaus contained collagen with 14C levels corresponding to mean donor age of 11.7 years (±3.8 SD). Finally, the medial condyle had lower 14C levels corresponding to formation 1 year later than the lateral condyle (P= 0.009).Conclusions Human cartilage on the tibia plateau contains collagen that has experienced little if any turnover since school-age. The cartilage formation develops from 2 condyle centers and radially outward with the medial condyle finishing slightly later than the lateral condyle. This suggests a childhood programmed cartilage formation with a very limited adulthood collagen turnover.

Tendon is a highly organized, dense connective tissue that has been demonstrated to have very little turnover. In spite of the low turnover, tendon can grow in response to loading, which may take place primarily at the periphery. Tendon injuries and recurrence of injuries are common in both humans and animals in sports. It is unclear why some areas of the tendon are more susceptible to such injuries and whether this is due to intrinsic regional differences in extracellular matrix (ECM) production or tissue turnover. This study aimed to compare populations of tenocytes derived from the tendon core and periphery. Tenocytes were isolated from equine superficial digital flexor tendons (SDFTs), and the proliferation capacity was determined. ECM production was characterized by immuno- and histological staining and by liquid chromatography-mass spectrometry-based proteomics. Core and periphery SDFT cultures exhibited comparable proliferation rates and had very similar proteome profiles, but showed biological variation in collagen type I deposition. In conclusion, the intrinsic properties of tenocytes from different regions of the tendon are very similar, and other factors in the tissue may contribute to how specific areas respond to loading or injury.

ObjectivesBone and other human tissues remodel through life, for example, as a response to increasing load, and this prevents permanent destruction of the tissue. Non-traumatic meniscal rupture is a common musculoskeletal disease, but it is unknown if it is caused by inability of the menisci to remodel. The aim of this study was to determine whether meniscal collagen is remodelling throughout life.MethodsThe life-long turnover of the human meniscal collagens was explored by the 14C bomb pulse method. 14C levels were determined in menisci from 18 patients with osteoarthritis and 7 patients with healthy knees.ResultsThere was a negligible turnover of the meniscal collagen in adults. This low turnover was observed in menisci from patients with knee osteoarthritis and in healthy menisci.ConclusionThis study provides evidence that essentially no remodelling occurs in the adult human meniscal collagen structure and explains the clinical degeneration that is often seen in menisci of middle-aged and elderly persons. It suggests that strengthening of the collagen structure of menisci, as response to physical activity, may occur during childhood, while it is not possible in the adult population.

Several studies are conducted to explain the various effects of regular strength training on the telemore length in skeletal muscle of the athletes with exercise-associated fatigue. The results prove that the abnormal shortening of the telemores is not associated with the long-term training.

A study was conducted to determine the effects of the maximal muscle contraction force and muscle mass among the elderly who had undergone life-long training. Results revealed those who had undergone training managed to maintain their muscle mass and functions better until old age.

The articles main hypothesis is, following Vilém Flusser, that modern imagery in general is ‘technical’, which means its images are images of concepts. As such they are difficult to distinguish phenomenologically and semiotically from their environment and therefore difficult to identify as images. From this outset the main argument is that certain modern images are capable of revealing this technicality by confronting the viewer with a concrete visibility forcing discursive relocations of the knowledge integral to perceiving them. The article develops this argument via the understanding of images of Gottfried Boehm and Michel Foucault in connection with analyses of photographs of the Russian artist Alexander Rodchenko and paintings by the Danish painters J. F. Willumsen and Erik Hoppe.

Objective.The morphology of articular cartilage (AC) enables painless movement. Aging and mechanical loading are believed to influence development of osteoarthritis (OA), yet the connection remains unclear.Methods.This narrative review describes the current knowledge regarding this area, with the literature search made on PubMed using appropriate keywords regarding AC, age, and mechanical loading.Results.Following skeletal maturation, chondrocyte numbers decline while increasing senescence occurs. Lower cartilage turnover causes diminished maintenance capacity, which produces accumulation of fibrillar crosslinks by advanced glycation end products, resulting in increased stiffness and thereby destruction susceptibility.Conclusion.Mechanical loading changes proteoglycan content. Moderate mechanical loading causes hypertrophy and reduced mechanical loading causes atrophy. Overloading produces collagen network damage and proteoglycan loss, leading to irreversible cartilage destruction because of lack of regenerative capacity. Catabolic pathways involve inflammation and the transcription factor nuclear factor-κB. Thus, age seems to be a predisposing factor for OA, with mechanical overload being the likely triggering cause.

Skeletal muscle possesses adaptability to mechanical loading and regenerative potential following muscle injury due to muscle stem cell activity. So far, it is known that muscle stem cell activity is supported by the roles of several interstitial cells within skeletal muscle in response to muscle damage. The adjacent tendon is also exposed to repetitive mechanical loading and possesses plasticity like skeletal muscle. However, the interplay between the skeletal muscle and adjacent tendon tissue has not been fully investigated. Here, we tested whether factors released by three-dimensional (3D) engineered human tendon constructs in response to uniaxial tensile loading can stimulate the proliferation and differentiation of human-derived myogenic cells (myoblasts). Tendon constructs were subjected to repetitive mechanical loading (4% strain at 0.5 Hz for 4 h) and non- repetitive loading (0% strain at 0 Hz for 4 h), and the conditioned media from mechanically loaded and non-mechanically loaded control constructs were applied to myoblasts. Immunofluorescence analysis revealed both an increase of myotube fusion index (≥ 5 nuclei within one desmin+ myotube) and the myotube diameter when conditioned medium from mechanically loaded tendon constructs was applied. MSTN, MYH7, and AXIN2 gene expressions were down-regulated in myotubes treated with conditioned medium from mechanically loaded tendon constructs. However, proliferative potential (number of Ki67+ and BrdU+ myoblasts) did not differ between the two groups. These results indicate that tendon fibroblasts enhance myotube formation by mechanical loading-induced factors. Our finding suggests that mechanical loading affects the signaling interplay between skeletal muscle and tendon tissue and is thus important for musculoskeletal tissue development and regeneration in humans.

From 19th to 22nd November 2018, 26 researchers representing nine countries and a variety of academic disciplines met in Snekkersten, Denmark, to reach evidence-based consensus about physical activity and older adults. It was recognised that the term ‘older adults’ represents a highly heterogeneous population. It encompasses those that remain highly active and healthy throughout the life-course with a high intrinsic capacity to the very old and frail with low intrinsic capacity. The consensus is drawn from a wide range of research methodologies within epidemiology, medicine, physiology, neuroscience, psychology and sociology, recognising the strength and limitations of each of the methods. Much of the evidence presented in the statements is based on longitudinal associations from observational and randomised controlled intervention studies, as well as quantitative and qualitative social studies in relatively healthy community-dwelling older adults. Nevertheless, we also considered research with frail older adults and those with age-associated neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease, and in a few cases molecular and cellular outcome measures from animal studies. The consensus statements distinguish between physical activity and exercise. Physical activityis used as an umbrella term that includes both structured and unstructured forms of leisure, transport, domestic and work-related activities. Physical activity entails body movement that increases energy expenditure relative to rest, and is often characterised in terms of intensity from light, to moderate to vigorous. Exerciseis defined as a subset of structured physical activities that are more specifically designed to improve cardiorespiratory fitness, cognitive function, flexibility balance, strength and/or power. This statement presents the consensus on the effects of physical activity on older adults’ fitness, health, cognitive functioning, functional capacity, engagement, motivation, psychological well-being and social inclusion. It also covers the consensus on physical activity implementation strategies. While it is recognised that adverse events can occur during exercise, the risk can be minimised by carefully choosing the type of activity undertaken and by consultation with the individual’s physician when warranted, for example, when the individual is frail, has a number of co-morbidities, or has exercise-related symptoms, such as chest pain, heart arrhythmia or dizziness. The consensus was obtained through an iterative process that began with the presentation of the state-of-the-science in each domain, followed by group and plenary discussions. Ultimately, the participants reached agreement on the 30-item consensus statements.

Rheumatoid arthritis (RA) is often associated with diminished muscle mass, reflecting an imbalance between protein synthesis and protein breakdown. To investigate the anabolic potential of both exercise and nutritional protein intake we investigated the muscle protein synthesis rate and anabolic signaling response in patients with RA compared to healthy controls. Thirteen RA patients (age range 34–84 years; diagnosed for 1–32 years, median 8 years) were individually matched with 13 healthy controls for gender, age, BMI and activity level (CON). Plasma levels of C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured using enzyme-linked immunosorbent assay (ELISA) in resting blood samples obtained on two separate days. Skeletal muscle myofibrillar and connective tissue protein fractional synthesis rate (FSR) was measured by incorporation of the amino acid 13C6-phenylalanine tracer in the overnight fasted state for 3 hours (BASAL) and 3 hours after intake of whey protein (0.5 g/kg lean body mass) alone (PROT, 3 hrs) and in combination with knee-extensor exercise (EX) with one leg (8 × 10 reps at 70 % of 1RM; PROT + EX, 3 hrs). Expression of genes related to inflammatory signaling, myogenesis and muscle growth/atrophy were analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). CRP was significantly higher in the RA patients (2.25 (0.50) mg/l) than in controls (1.07 (0.25) mg/l; p= 0.038) and so was TNF-α (RA 1.18 (0.30) pg/ml vs. CON 0.64 (0.07) pg/ml; p= 0.008). Muscle myofibrillar protein synthesis in both RA patients and CON increased in response to PROT and PROT + EX, and even more with PROT + EX (p< 0.001), with no difference between groups (p> 0.05). The gene expression response was largely similar in RA vs. CON, however, expression of the genes coding for TNF-α, myogenin and HGF1 were more responsive to exercise in RA patients than in CON. The study demonstrates that muscle protein synthesis rate and muscle gene expression can be stimulated by protein intake alone and in combination with physical exercise in patients with well-treated RA to a similar extent as in healthy individuals. This indicates that moderately inflamed RA patients have maintained their muscle anabolic responsiveness to physical activity and protein intake.

Macrophages (MPs) exert either beneficial or deleterious effects on tissue repair, depending on their activation/polarization state. They are crucial for adult skeletal muscle repair, notably by acting on myogenic precursor cells. However, these interactions have not been fully characterized. Here, we explored both in vitro and in vivo, in human, the interactions of differentially activated MPs with myogenic precursor cells (MPCs) during adult myogenesis and skeletal muscle regeneration. We showed in vitro that through the differential secretion of cytokines and growth factors, proinflammatory MPs inhibited MPC fusion while anti‐inflammatory MPs strongly promoted MPC differentiation by increasing their commitment into differentiated myocytes and the formation of mature myotubes. Furthermore, the in vivo time course of expression of myogenic and MP markers was studied in regenerating human healthy muscle after damage. We observed that regenerating areas containing proliferating MPCs were preferentially associated with MPs expressing proinflammatory markers. In the same muscle, regenerating areas containing differentiating myogenin‐positive MPCs were preferentially coupled to MPs harboring anti‐inflammatory markers. These data demonstrate for the first time in human that MPs sequentially orchestrate adult myogenesis during regeneration of damaged skeletal muscle. These results support the emerging concept that inflammation, through MP activation, controls stem cell fate and coordinates tissue repair. STEMCELLS2013;31:384–396

To outline different approaches of how protein breakdown can be quantified and to present a new approach to determine the fractional breakdown rate of individual slow turnover proteins in vivo.

Tendons are designed to withstand considerable loads. Mechanical loading of tendon tissue results in upregulation of collagen expression and increased synthesis of collagen protein, the extent of which is probably regulated by the strain experienced by the resident fibroblasts (tenocytes). This increase in collagen formation peaks around 24 h after exercise and remains elevated for about 3 days. The degradation of collagen proteins also rises after exercise, but seems to peak earlier than the synthesis. Despite the ability of tendons to adapt to loading, repetitive use often results in injuries, such as tendinopathy, which is characterized by pain during activity, localized tenderness upon palpation, swelling and impaired performance. Tendon histological changes include reduced numbers and rounding of fibroblasts, increased content of proteoglycans, glycosaminoglycans and water, hypervascularization and disorganized collagen fibrils. At the molecular level, the levels of messenger RNA for type I and III collagens, proteoglycans, angiogenic factors, stress and regenerative proteins and proteolytic enzymes are increased. Tendon microrupture and material fatigue have been suggested as possible injury mechanisms, thus implying that one or more 'weak links' are present in the structure. Understanding how tendon tissue adapts to mechanical loading will help to unravel the pathogenesis of tendinopathy.

The prevalence of neck muscle pain has steadily increased and especially pain from the descending part of the trapezius muscle has been associated with monotonous work tasks such as computer work. Physical exercise is generally recommended as treatment, but it is unclear which type of training is most effective. Our objective was to determine the effectiveness of specific strength training of the painful muscle versus general fitness training without direct involvement of the painful muscle (leg bicycling) on work‐related neck muscle pain.We conducted a randomized controlled trial and recruited subjects from 7 workplaces characterized by monotonous jobs (e.g., computer‐intensive work). Forty‐eight employed women with chronic neck muscle pain (defined as a clinical diagnosis of trapezius myalgia) were randomly assigned to 10 weeks of specific strength training locally for the affected muscle, general fitness training performed as leg bicycling with relaxed shoulders, or a reference intervention without physical activity. The main outcome measure was an acute and prolonged change in intensity of neck muscle pain (100‐mm visual analog scale [VAS]).A decrease of 35 mm (∼79%; P < 0.001) in the worst VAS pain score over a 10‐week period was seen with specific strength training, whereas an acute and transient decrease in pain (5 mm; P < 0.05) was found with general fitness training.Specific strength training had high clinical relevance and led to marked prolonged relief in neck muscle pain. General fitness training showed only a small yet statistically significant acute pain reduction.

Background and aims:Restricted physical activity as a consequence of chronic disease or injury is a predictor of functional decline. The aim of this study was to test the hypothesis that a 6-month multidimensional training program would have sustained beneficial effects upon the physiological, functional and psychological condition of old women with a recent history of falls. Methods:Participants were 65 home-dwelling women (70–90 years) identified from hospital records as having had an accidental fall. After assessment of muscle strength, balance performance, walking speed, balance confidence, and physical activity level, the participants were randomly assigned to a control group (n=33) or a training group (n=32), who performed a multidimensional training program including moderate resistance exercise and balance exercise twice weekly for 6 months. Measurements were repeated after 6 and 12 months. Results:Six months of multidimensional training resulted in significant improvements and between-group differences in isometric knee extension strength (p<0.05), trunk extension/flexion strength (p<0.001), habitual/maximal walking speed (p<0.001) and balance performance (p<0.001). At follow-up, 6 months after intervention, these improvements were preserved in the training group and there was also a significant between-group difference with regard to balance confidence. No between-group differences were found concerning number of falls or physical activity level during the one-year study period. Conclusions:A multi-dimensional training program produced significant improvements in physiological and functional risk factors for falls and disability in women aged 70–90 years with a recent history of falls.

Ageing is associated with a loss in both muscle mass and in the metabolic quality of skeletal muscle. This leads to sarcopenia and reduced daily function, as well as to an increased risk for development of insulin resistance and type 2 diabetes. A major part, but not all, of these changes are associated with an age-related decrease in the physical activity level and can be counteracted by increased physical activity of a resistive nature. Strength training has been shown to improve insulin-stimulated glucose uptake in both healthy elderly individuals and patients with manifest diabetes, and likewise to improve muscle strength in both elderly healthy individuals and in elderly individuals with chronic disease. The increased strength is coupled to improved function and a decreased risk for fall injuries and fractures. Elderly individuals have preserved the capacity to improve muscle strength and mass with training, but seem to display a reduced sensitivity towards stimulating protein synthesis from nutritional intake, rather than by any reduced response in protein turnover to exercise.

The aim of the present study was to simultaneously examine skeletal muscle heat production and ATP turnover in humans during dynamic exercise with marked differences in aerobic metabolism. This was done to test the hypothesis that efficiency is higher in anaerobic than aerobic ATP resynthesis. Six healthy male subjects performed 90 s of low intensity knee‐extensor exercise with (OCC) and without thigh occlusion (CON‐LI) as well as 90 s of high intensity exercise (CON‐HI) that continued from the CON‐LI bout. Muscle heat production was determined by continuous measurements of muscle heat accumulation and heat release to the blood. Muscle ATP production was quantified by repeated measurements of thigh oxygen uptake as well as blood and muscle metabolite changes. All temperatures of the thigh were equalized to ≈37 °C prior to exercise by a water‐perfused heating cuff. Oxygen uptake accounted for 80 ± 2 and 59 ± 4 %, respectively, of the total ATP resynthesis in CON‐LI and CON‐HI, whereas it was negligible in OCC. The rise in muscle temperature was lower (P< 0.05) in OCC than CON‐LI (0.32 ± 0.04 vs.0.37 ± 0.03 °C). The mean rate of heat production was also lower (P< 0.05) in OCC than CON‐LI (36 ± 4 vs.57 ± 4 J s−1). Mechanical efficiency was 52 ± 4 % after 15 s of OCC and remained constant, whereas it decreased (P< 0.05) from 56 ± 5 to 32 ± 3 % during CON‐LI. During CON‐HI, mechanical efficiency transiently increased (P< 0.05) to 47 ± 4 %, after which it decreased (P< 0.05) to 36 ± 3 % at the end of CON‐HI. Assuming a fully coupled mitochondrial respiration, the ATP turnover per unit of work was calculated to be unaltered during OCC (≈20 mmol ATP kJ−1), whereas it increased (P< 0.05) from 21 ± 4 to 29 ± 3 mmol ATP kJ−1during CON‐LI and further (P< 0.05) to 37 ± 3 mmol ATP kJ−1during CON‐HI. The present data confirm the hypothesis that heat loss is lower in anaerobic ATP resynthesis than in oxidative phosphorylation and can in part explain the finding that efficiency declines markedly during dynamic exercise. In addition, the rate of ATP turnover apparently increases during constant load low intensity exercise. Alternatively, mitochondrial efficiency is lowered as exercise progresses, since ATP turnover was unaltered during the ischaemic exercise bout.

Paretic human muscle rapidly loses strength and oxidative endurance, and electrical stimulation training may partly reverse this. We evaluated the effects of two training protocols on the contractile and metabolic properties of the wrist extensor in 12 C‐5/6 tetraplegic individuals. The wrist extensor muscles were stimulated for 30 min/day, 5 days/week, for 12 weeks, using either a high‐resistance (Hr) or a low‐resistance (Lr) protocol. Total work output was similar in both protocols. The nontrained arm was used as a control. Maximum voluntary torque increased in the Hr (P< 0.05) but not the Lr group. Electrically stimulated peak tetanic torque at 15 HZ, 30 HZ, and 50 HZwere unchanged in the Lr group and tended to increase only at 15 HZ(P< 0.1) in the Hr group. Resistance to fatigue, however, increased (P< 0.05) in both Hr (42%) and Lr (41%) groups. Muscle metabolism was evaluated by 31P nuclear magnetic resonance spectroscopy (31P‐NMRS) during and following a continuous 40‐s 10‐HZcontraction. In the Hr group the cost of contraction decreased by 38% (P< 0.05) and the half‐time of phosphocreatine (PCr) recovery was shortened by 52% (P< 0.05). Thus, long‐term electrically induced stimulation of the wrist extensor muscles in spinal cord injury (SCI) increases fatigue resistance independent of training pattern. However, only the Hr protocol increased muscle strength and was shown to improve muscle aerobic metabolism after training. Muscle Nerve 27: 72–80, 2003

The influence of initial training status on the response of circulating insulin-like growth factor (IGF) and its binding proteins (IGFBP) to prolonged physical training was studied in young men. It was hypothesized that highly standardized training would result in more extensive changes in the circulating IGF system in untrained subjects because of lower fitness level. Seven untrained (UT) and 12 well-trained (WT) individuals performed 11 wk of intense physical training (2–4 h daily). Fasting serum samples were analyzed for total and free IGF-I and -II, for IGFBP-1 to -4, as well as for IGFBP-3 proteolysis. Eleven weeks of physical training resulted in decreased levels of total IGF-I, free IGF-I, and IGFBP-4 in both the UT and WT groups. In the UT group, IGFBP-2 increased, IGFBP-3 decreased [from 4,255 ± 410 (baseline) to 3,896 ± 465 (SD) μg/l (week 4);P< 0.05], and IGFBP-3 proteolysis increased [from 28 ± 8% (baseline) to 37 ± 7% (week 4) and 39 ± 12% (week 11); P< 0.05], whereas no significant changes were found in the WT group. In conclusion, intense physical training results in a marked influence on the IGF system and its binding proteins with generally more extensive changes seen in the untrained individuals. Also, prolonged physical training resulted in increased IGFBP-3 proteolysis in previously untrained individuals only, indicating that intense physical training affects trained and untrained individuals differently.

The vascular endothelium is an important mediator of tissue vasodilatation, yet the role of the specific substances, nitric oxide (NO) and prostaglandins (PG), in mediating the large increases in muscle perfusion during exercise in humans is unclear. Quadriceps microvascular blood flow was quantified by near infrared spectroscopy and indocyanine green in six healthy humans during dynamic knee extension exercise with and without combined pharmacological inhibition of NO synthase (NOS) and PG by l‐NAME and indomethacin, respectively. Microdialysis was applied to determine interstitial release of PG. Compared to control, combined blockade resulted in a 5‐ to 10‐fold lower muscle interstitial PG level. During control incremental knee extension exercise, mean blood flow in the quadriceps muscles rose from 10 ± 0.8 ml (100 ml tissue)−1min−1at rest to 124 ± 19, 245 ± 24, 329 ± 24 and 312 ± 25 ml (100 ml tissue)−1min−1at 15, 30, 45 and 60 W, respectively. During inhibition of NOS and PG, blood flow was reduced to 8 ± 0.5 ml (100 ml tissue)−1min−1at rest, and 100 ± 13, 163 ± 21, 217 ± 23 and 256 ± 28 ml (100 ml tissue)−1min−1at 15, 30, 45 and 60 W, respectively (P< 0.05 vs.control). In conclusion, combined inhibition of NOS and PG reduced muscle blood flow during dynamic exercise in humans. These findings demonstrate an important synergistic role of NO and PG for skeletal muscle vasodilatation and hyperaemia during muscular contraction.

Plasma interleukin‐6 (IL‐6) concentration has been shown to increase with exercise and various cell types and tissues have been suggested to be responsible for this increase. At present no studies have measured the interstitial concentration of IL‐6 in skeletal muscle and connective tissue. The present study represents the first attempt to simultaneously measure IL‐6 in plasma, skeletal muscle and peritendinous connective tissue in response to prolonged exercise. Six healthy well‐trained volunteers completed a 36 km run (flat, 12 km h−1). IL‐6 was measured before, 2 h post‐exercise and 24 h, 48 h, 72 h and 96 h post‐exercise in both the medial gastrocnemius muscle (not measured at rest due to risk of disabling the subsequent exercise, and 24 h and 72 h post‐exercise) and the peritendinous tissue around the Achilles tendon using microdialysis catheters with a high molecular mass cut‐off value (3000 kDa). The plasma concentration of IL‐6 was measured simultaneously, and in addition every hour during the exercise, by enzyme‐linked immunosorbent assay (ELISA). The plasma concentration of IL‐6 was found to increase throughout the exercise, reaching peak values immediately after completion of the run (50‐fold increase). Using the microdialysis technique, the interstitial concentration of IL‐6 was found to increase dramatically from 0 ± 0 pg ml−1to 3618 ± 1239 pg ml−1in the peritendinous tissue in the hours following the exercise. The pattern of changes was similar in plasma and peritendinous tissue, although approximately 100‐fold higher in the latter. For comparison the interstitial muscle concentration was found to be 465 ± 176 pg ml−1when measured 2 h post‐exercise and 223 ± 113 pg ml−1and 198 ± 96 pg ml−148 h and 96 h post‐exercise, respectively. The present study demonstrates that the connective tissue around the human Achilles tendon produces significant amounts of IL‐6 in response to prolonged physical activity, which might contribute to the exercise‐induced increase in IL‐6 found in plasma.

The tibialis anterior muscle of nine paraplegic men was chronically stimulated (2–6 h per day; at 10 Hz, 5 s on, 5 s off) under isometric loading conditions for 5 days per week for 4 weeks. After 4 weeks of training, muscle fatigue resistance in an electrically evoked test had increased by an average of 75% (P< .01, n= 9), but there were no changes in the relative composition of the three myosin heavy chain (MHC) isoforms. Five of the subjects continued training for an additional 5 weeks (2 h per day, 3 days per week). Although there was a tendency for twitch time to peak torque to increase after this additional period, no change occurred in relative MHC isoform content. However, in situ hybridization analysis revealed that even after 2 weeks of stimulation, there was evidence of upregulation of the mRNA for the MHC‐I isoform and downregulation of the MHC‐IIX isoform, a development that continued in weeks 4 and 9. This study provides evidence, at the level of gene transcription, that a fast‐to‐slow change in MHC isoform composition may be possible in human muscle when its usage is significantly increased. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000–000, 2002

Subcutaneous adipose tissue lipolysis was studied in vivo by Fick's arteriovenous (a-v) principle using either calculated (microdialysis) or directly measured (catheterization) adipose tissue venous glycerol concentration. We compared results during steady-state (rest and prolonged continuous exercise), as well as during non-steady-state (onset of exercise and early exercise) experimental settings. Fourteen healthy women [age: 74 ± 1 (SE) yr] were studied at rest and during 60-min continuous bicycling at 60% of peak O2uptake. Calculated and measured subcutaneous abdominal adipose tissue venous glycerol concentrations increased substantially from rest to exercise but were similar both at rest and during later stages of exercise. In contrast, during the initial ∼40 min of exercise, calculated glycerol concentration was significantly lower (∼40%) than measured adipose tissue venous glycerol concentration. Despite several methodological limitations inherent to both techniques, the results strongly suggest that microdialysis and catheterization provide similar estimates of subcutaneous adipose tissue lipolysis in steady-state experimental settings like rest and continuous prolonged exercise. However, during shorter periods of exercise (<40 min), the results from the two techniques may differ quantitatively in the studied subjects. Caution should, therefore, be taken when lipolysis is evaluated, based on results obtained by the two techniques under non-steady-state conditions.

1It has been established that pulmonary oxygen uptake is greater during cycle exercise in humans at high compared to low contraction frequencies. However, it is unclear whether this is due to more work being performed at the high frequencies and whether the energy turnover of the working muscles is higher. The present study tested the hypothesis that human skeletal muscle oxygen uptake and energy turnover are elevated during exercise at high compared to low contraction frequency when the total power output is the same.2Seven subjects performed single‐leg dynamic knee‐extensor exercise for 10 min at contraction frequencies of 60 and 100 r.p.m. where the total power output (comprising the sum of external and internal power output) was matched between frequencies (54 ± 5 vs.56 ± 5 W; mean ±s.e.m.). Muscle oxygen uptake was determined from measurements of thigh blood flow and femoral arterial–venous differences for oxygen content (a–v O2diff). Anaerobic energy turnover was estimated from measurements of lactate release and muscle lactate accumulation as well as muscle ATP and phosphocreatine (PCr) utilisation based on analysis of muscle biopsies obtained before and after each exercise bout.3Whilst a–v O2diff was the same between contraction frequencies during exercise, thigh blood flow was higher (P< 0.05) at 100 compared to 60 r.p.m. Thus, muscle V̇O2was higher (P< 0.05) during exercise at 100 r.p.m. Muscle V̇O2increased (P< 0.05) by 0.06 ± 0.03 (12 %) and 0.09 ± 0.03 l min−1(14 %) from the third minute to the end of exercise at 60 and 100 r.p.m., respectively, but there was no difference between the two frequencies.4Muscle PCr decreased by 8.1 ± 1.7 and 9.1 ± 2.0 mmol (kg wet wt)−1, and muscle lactate increased to 6.8 ± 2.1 and 9.8 ± 2.5 mmol (kg wet wt)−1during exercise at 60 and 100 r.p.m., respectively. The total release of lactate during exercise was 48.7 ± 8.8 and 64.3 ± 10.6 mmol at 60 and 100 r.p.m. (not significant, NS). The total anaerobic ATP production was 47 ± 8 and 61 ± 12 mmol kg−1, respectively (NS).5Muscle temperature increased (P< 0.05) from 35.8 ± 0.3 to 38.2 ± 0.2 °C at 60 r.p.m. and from 35.9 ± 0.3 to 38.4 ± 0.3 °C at 100 r.p.m. Between 1 and 7 min muscle temperature was higher (P< 0.05) at 100 compared to 60 r.p.m.6The estimated mean rate of energy turnover during exercise was higher (P< 0.05) at 100 compared to 60 r.p.m. (238 ± 16 vs.194 ± 11 J s−1). Thus, mechanical efficiency was lower (P< 0.05) at 100 r.p.m. (24 ± 2 %) compared to 60 r.p.m. (28 ± 3 %). Correspondingly, efficiency expressed as work per mol ATP was lower (P< 0.05) at 100 than at 60 r.p.m. (22.5 ± 2.1 vs.26.5 ± 2.5 J (mmol ATP)−1).7The present study showed that muscle oxygen uptake and energy turnover are elevated during dynamic contractions at a frequency of 100 compared with 60 r.p.m. It was also observed that muscle oxygen uptake increased as exercise progressed in a manner that was not solely related to the increase in muscle temperature and lactate accumulation.

1The relative roles of sympathetic nerve activity and circulating catecholamines for adipose tissue lipolysis during exercise are not known.2Seven paraplegic spinal cord injured (SCI, injury level T3‐T5) and seven healthy control subjects were studied by microdialysis and 133xenon washout in clavicular (Cl) and in umbilical (Um) (sympathetically decentralized in SCI) subcutaneous adipose tissue during 1 h of arm cycling exercise at ∼60 % of the peak rate of oxygen uptake.3During exercise, adipose tissue blood flow (ATBF) and interstitial glycerol, lactate and noradrenaline concentrations increased significantly in both groups. Plasma catecholamine levels increased significantly less with exercise in SCI than in healthy subjects. The exercise‐induced increase in interstitial glycerol concentration in subcutaneous adipose tissue was significantly lower in SCI compared with healthy subjects (SCI: 25 ± 12 % (Cl), 36 ± 20 % (Um); healthy: 60 ± 17 % (Cl), 147 ± 45 % (Um)) and the increase in ATBF was significantly lower (Cl) or similar (Um) in SCI compared with healthy subjects (SCI: 1.2 ± 0.3 ml (100 g)−1min−1(Cl), 1.0 ± 0.3 ml (100 g)−1min−1(Um); healthy: 2.8 ± 0.7 ml (100 g)−1min−1(Cl), 0.6 ± 0.3 ml (100 g)−1min−1(Um)). Accordingly, in both adipose tissues lipolysis increased less in SCI compared with healthy subjects, indicating that circulating catecholamines are important for the exercise‐induced increase in subcutaneous adipose tissue lipolysis. In SCI subjects, the exercise‐induced increase in subcutaneous adipose tissue lipolysis was not lower in decentralized than in sympathetically innervated adipose tissue. During exercise the interstitial noradrenaline and adrenaline concentrations were lower in SCI compared with healthy subjects (P< 0.05) and always lower than arterial plasma catecholamine concentrations (P< 0.05).4It is concluded that circulating catecholamines are important for the exercise‐induced increase in subcutaneous adipose tissue lipolysis while sympathetic nerve activity is not.

1Acute exercise is found to increase collagen type I formation locally in peritendinous connective tissue of the Achilles' tendon in humans, as determined from changes in interstitial concentrations of collagen propeptide (PICP) and a collagen degradation product (ICTP) by the use of microdialysis catheters. However, the local collagen type I turnover response to training is unknown.2Nineteen young males were studied before and after 4 and 11 weeks of physical training. Microdialysis catheters with a high molecular mass cut‐off value (3000 kDa), allowing the determination of PICP and ICTP, were placed in the peritendinous space ventral to the Achilles' tendon, under ultrasound guidance, in both legs. The catheters were perfused with a Ringer‐acetate solution containing 3H‐labelled human type IV collagen for in vivorecovery determination (relative recovery: 79 ± 2 %, mean ±s.e.m.).3The PICP concentration in the peritendinous tissue increased in response to training (from 5 ± 1 to 35 ± 5 μg l−1(4 weeks), P <0.05) and remained elevated throughout the training period (28 ± 6 μg l−1, 11 weeks). Tissue ICTP only rose transiently with training (from 2.2 ± 0.1 to 2.8 ± 0.2 μg l−1(4 weeks), P <0.05, and 2.5 ± 0.2 μg l−1(11 weeks), P >0.05 vs.basal). Plasma PICP was unchanged whereas plasma ICTP declined by 17 % in response to training.4The findings indicate that physical training results in an increased turnover of collagen type I in local connective tissue of the peritendinous Achilles' region. Early in the process both synthesis and degradation are elevated, whereas later, the anabolic processes are dominating causing a net synthesis of type I collagen in tendon‐related tissue in humans.

1The present investigation measured the load‐displacement and stress‐strain characteristics of the proximal and distal human triceps surae aponeurosis and tendon in vivoduring graded voluntary 10 s isometric plantarflexion efforts in five subjects.2During the contractions synchronous real‐time ultrasonography of aponeurosis displacement, electromyography of the gastrocnemius, soleus and dorsiflexor muscles, and joint angular rotation were obtained. Tendon cross‐sectional area and moment arm were obtained from magnetic resonance (MR) images. Force and electromyography data from dorsiflexion efforts were used to examine the effect of coactivation.3Tendon force was calculated from the joint moments and tendon moment arm, and stress was obtained by dividing force by cross‐sectional area. Aponeurosis and tendon strain were obtained from the displacements normalised to tendon length.4Tendon force was 3171 ± 201 N, which corresponded to 2.6 % less than the estimated force when coactivation was accounted for (3255 ± 206 N). Aponeurosis displacement (13.9‐ 12.9 mm) decreased 30 % (9.6‐10.7 mm) when accounting for joint angular rotation (3.6 deg). Coactivation and angular rotation‐corrected stiffness yielded a quadratic relationship, R2= 0.98± 0.01, which was similar for the proximal (467 N mm−1) and distal (494 N mm−1) aponeurosis and tendon. Maximal strain and stress were 4.4‐5.6 % and 41.6 ± 3.9 MPa, respectively, which resulted in a Young's modulus of 1048‐1474 MPa.5The mechanical properties of the human triceps surae aponeurosis and tendon in vivowere for the first time examined. The stiffness and Young's modulus exceeded those previously reported for the tibialis anterior tendon in vivo, but were similar to those obtained for various isolated mammalian and human tendons.

1Changes in the concentration of interstitial K+surrounding skeletal muscle fibres ([K+]I) probably play some role in the regulation of cardiovascular adjustments to muscular activity, as well as in the aetiology of muscle pain and fatigue during high‐intensity exercise. However, there is very little information on the response of [K+]Ito exercise in human skeletal muscle.2Five young healthy subjects performed plantar flexion exercise for four 5 min periods at increasing power outputs (≈1‐6 W) with 10 min intervening recovery periods, as well as for two 5 min periods with ischaemia at ≈1 and ≈3 W. Microdialysis probes were inserted into the gastrocnemius medialis muscle of the right leg to measure [K+]I, and K+release from the plantar flexors during and after incremental exercise was calculated from plasma flow and arterial‐venous differences for K+. Calf muscle pain was assessed using a visual analogue scale.3On average, [K+]Iwas 4.4 mmol l−1at rest and increased during minutes 3‐5 of incremental exercise by ≈1‐7 mmol l−1as a positive function of power output. K+release also increased as a function of exercise intensity, although there was a progressive increase by ≈1‐6 mmol l−1in the [K+] gradient between the interstitium and arterial‐venous plasma.4[K+]Iwas lower during ischaemic exercise than control exercise. In contrast to this effect of ischaemia on [K+]I, muscle pain was relatively higher during ischaemic exercise, which demonstrates that factors other than changes in [K+]Iare responsible for ischaemic muscle pain.5In conclusion, this study has demonstrated that during 5 min of dynamic exercise, [K+]Iincreases during the later period of exercise as a positive function of exercise intensity, ischaemia reduces [K+]Iduring rest and exercise, and the increase in [K+]Iis not responsible for muscle pain during ischaemic exercise.

Using near-infrared spectroscopy (NIRS) and the tracer indocyanine green (ICG), we quantified blood flow in calf muscle and around the Achilles tendon during plantar flexion (1–9 W). For comparison, blood flow in calf muscle was determined by dye dilution in combination with magnetic resonance imaging measures of muscle volume, and, for the peritendon region, blood flow was measured by 133Xe washout. From rest to a peak load of 9 W, NIRS-ICG blood flow in calf muscle increased from 2.4 ± 0.2 to 74 ± 5 ml · 100 ml tissue−1· min−1, similar to that measured by reverse dye (77 ± 6 ml · 100 ml tissue−1· min−1). Achilles peritendon blood flow measured by NIRS-ICG rose with exercise from 2.2 ± 0.5 to 15.1 ± 0.2 ml · 100 ml−1· min−1, which was similar to that determined by 133Xe washout (2.0 ± 0.6 to 14.6 ± 0.3 ml · 100 ml tissue−1· min−1). This is the first study using NIRS and ICG to quantify regional tissue blood flow during exercise in humans. Due to its high spatial and temporal resolution, the technique may be useful for determining regional blood flow distribution and regulation during exercise in humans.

1Circulation around tendons may act as a shunt for muscle during exercise. The perfusion and oxygenation of Achilles’ peritendinous tissue was measured in parallel with that of calf muscle during exercise to determine (1) whether blood flow is restricted in peritendinous tissue during exercise, and (2) whether blood flow is coupled to oxidative metabolism.2Seven individuals performed dynamic plantar flexion from 1 to 9 W. Radial artery and popliteal venous blood were sampled for O2, peritendinous blood flow was determined by 133Xe‐washout, calf blood flow by plethysmography, cardiac output by dye dilution, arterial pressure by an arterial catheter‐transducer, and muscle and peritendinous O2saturation by spatially resolved spectroscopy (SRS).3Calf blood flow rose 20‐fold with exercise, reaching 44 ± 7 ml (100 g)−1min−1(mean ± s.e.m.) at 9 W, while Achilles’ peritendinous flow increased (7‐fold) to 14 ± 4 ml (100 g)−1min−1, which was 18 % of the maximal flow established during reactive hyperaemia. SRS‐O2saturation fell both in muscle (from 66 ± 2 % at rest to 57 ± 3 %, P< 0.05) and in peritendinous regions (58 ± 4 to 52 ± 4 %, P< 0.05) during exercise along with a rise in leg vascular conductance and microvascular haemoglobin volume, despite elevated systemic vascular resistance.4The parallel rise in calf muscle and peritendinous blood flow and fall in O2saturation during exercise indicate that blood flow is coupled to oxidative metabolism in both tissue regions. Increased leg vascular conductance accompanied by elevated microvascular haemoglobin volume reflect vasodilatation in both muscle and peritendinous regions. However, peak exercise peritendinous blood flow reaches only ≈20 % of its maximal blood flow capacity.

The purpose of this study was to evaluate the effects of spinal cord injury (SCI) and functional electrical stimulation (FES) of paralyzed muscles on type IV collagen content and proteins involving its degradation, which is initiated by matrix metalloproteinase (MMP)-2 and -9 and regulated by their tissue inhibitors (TIMPs)-2 and -1. Ten SCI subjects participated in an 18-month program of functional electrical stimulation (FES) of their leg muscles. Needle biopsies were taken from the vastus lateralis muscle before and at various times during the training period, and from able-bodied controls. Type IV collagen concentration was unaltered. ProMMP-2 level of SCI subjects before the training period tended to be higher than able-bodied controls and was significantly above the control level after FES. MMP-9 concentration was unchanged. The results suggest accelerated type IV collagen turnover in skeletal muscle of SCI individuals especially after FES as a part of adaptive process of the muscle. © 2000 John Wiley & Sons, Inc. Muscle Nerve 23: 580–589, 2000.

In the present study, tissue pressure in the peritendinous area ventral to the human Achilles tendon was determined. The pressure was measured during rest and intermittent isometric calf muscle exercise at three torques (56, 112, and 168 Nm) 20, 40 and 50 mm proximal to the insertion of the tendon in 11 healthy, young individuals. In all experiments a linear significant decrease in pressure was obtained with increasing torque [e.g., at 40 mm: −0.4 ± 0.3 mmHg (rest) to −135 ± 12 mmHg (168 Nm)]. No significant differences were obtained among the three areas measured. On the basis of these observations, microdialysis was performed in the peritendinous region with a colloid osmotic active substance (Dextran 70, 0.1 g/ml) added to the perfusate with the aim of counteracting the negative tissue pressure. Dialysate volume was found to be fully restored (100 ± 4%) during exercise. It is concluded that a marked negative tissue pressure is generated in the peritendinous space around the Achilles tendon during exercise in humans. Negative tissue pressure could lead to fluid shift and could be involved in the increase in blood flow previously noted in the peritendinous tissue during exercise (H. Langberg, J. Bülow, and M. Kjær. Acta Physiol. Scand. 163: 149–153, 1998; H. Langberg, J. Bülow, and M. Kjær. Clin. Physiol. 19: 89–93, 1999).

A long-term paraplegic man presented exclusively (>99%) myosin heavy chain I (MHC I) in the tibialis anterior muscle (TA). This was coupled to a slow speed of contraction, a high resistance to fatigue, and a rapid resynthesis of phosphocreatine after an electrically evoked fatiguing contraction when compared with the TA muscles of 9 other paraplegic individuals. In contrast, the MHC composition of his vastus lateralis, gastrocnemius, and soleus muscles was that expected of a muscle from a spinal cord injured individual. This information may be of clinical importance in terms of the expected morphological and functional adaptations of skeletal muscle to different types of electrical stimulation therapy. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 1731–1737, 1999

1The metabolic processes that occur around the tendon during mechanical loading and exercise are undescribed in man. These processes are important for understanding the development of overuse inflammation and injury.2A microdialysis technique was used to determine interstitial concentrations of glycerol, glucose, lactate, prostaglandin E2(PGE2) and thromboxane B2(TXB2) as well as to calculate tissue substrate balance in the peritendinous region of the human Achilles tendon. Recovery of 48–62% (range) at rest and 70–77% during exercise were obtained for glycerol, glucose and PGE2.3Six young healthy humans were studied at rest, during 30 min of intermittent static plantar flexion of the ankle at a workload corresponding to individual body weight, and during 60 min of recovery. Microdialysis was performed in both legs with simultaneous determination of blood flow by 133Xe washout in the same area, and blood sampling from the radial artery.4With exercise, the net release of lactate as well as of glycerol from the peritendinous space of the Achilles tendon increased 2‐fold (P< 0.05). Furthermore a 100% increase in interstitial concentration of PGE2and TXB2was found, but it was only significant for TXB2(P< 0.05). As peritendinous blood flow increased 2‐ to 3‐fold during intermittent static contractions, this indicates also that the output of these substances from the tissue increased during exercise.5This study indicates that both lipid and carbohydrate metabolism as well as inflammatory activity is accelerated in the peritendinous region of the human Achilles tendon with dynamic loading.

1Physical activity is known to increase type I collagen synthesis measured as the concentration of biomarkers in plasma. By the use of microdialysis catheters with a very high molecular mass cut‐off value (3000 kDa) we aimed to determine local type I collagen synthesis and degradation in the peritendinous region by measuring interstitial concentrations of a collagen propeptide (PICP; 100 kDa) and a collagen degradation product (ICTP; 9 kDa) as well as an inflammatory mediator (PGE2).2Seven trained human runners were studied before and after (2 and 72 h) 3 h of running (36 km). Two microdialysis catheters were placed in the peritendinous space ventral to the Achilles’ tendon under ultrasound guidance and perfused with a Ringer‐acetate solution containing 3H‐labelled human type IV collagen and [15‐3H(N)]PGE2for in vivorecovery determination. Relative recovery was 37–59% (range of the s.e.m. values) for both radioactively labelled substances.3PICP concentration decreased in both interstitial peritendinous tissue and arterial blood immediately after exercise, but rose 3‐fold from basal 72 h after exercise in the peritendinous tissue (55 ± 10 μg l−1, mean ± s.e.m. (rest) to 165 ± 40 μg l−1(72 h), P< 0·05) and by 25% in circulating blood (160 ± 10 μg l−1(rest) to 200 ± 12 μg l−1(72 h), P< 0·05). ICTP concentration did not change in blood, but decreased transiently in tendon‐related tissue during early recovery after exercise only. PGE2concentration increased in blood during running, and returned to baseline in the recovery period, whereas interstitial PGE2concentration was elevated in the early recovery phase.4The findings of the present study indicate that acute exercise induces increased formation of type I collagen in peritendinous tissue as determined with microdialysis and using dialysate fibre with a very high molecular mass cut‐off. This suggests an adaptation to acute physical loading also in non‐bone‐related collagen in humans.

In order to evaluate exercise-induced changes in natural killer (NK) and other immunocompetent cells in spinal cord injured individuals, immunological competent blood cells and stress hormones were followed in five paraplegic and six quadriplegic subjects in relation to 30?min electrically stimulated cycling exercise. The leukocyte and lymphocyte concentrations increased during exercise. In the recovery period, the concentration of neutrophils increased, whereas the lymphocytes decreased. The percentage and concentration of NK cells increased during exercise in the paraplegic group and returned to pre-exercise level 2?h after, whereas no changes were seen in these measures for the quadriplegic group. No changes in activated CD38 + NK cells appeared. Unstimulated and interferon-a or interleukin-2 stimulated NK cell activity increased during exercise and returned to pre-exercise level 2?h after with no distinction between paraplegics and quadriplegics. The concentrations of plasma growth hormone and catecholamines increased during exercise, with the rise in epinephrine being more pronounced in paraplegic than in quadriplegic subjects, indicating a difference between the groups in sympathetic nervous system integrity. The sympathoadrenal activity is concluded to be responsible for recruitment of NK cells to the blood during exercise.

LEVINE, B. D., D. B. FRIEDMAN, K. ENGFRED, B. HANEL, M. KJAER, P. S. CLIFFORD, and N. H. SECHER. The effect of normoxic or hypobaric hypoxic endurance training on the hypoxic ventilatory response. Med. Sci. Sports Exerc., Vol. 24, No. 7, pp. 769–775, 1992. Cross-sectional studies in endurance athletes have demonstrated a diminished hypoxic ventilatory response (HVR) compared with mountaineers or sedentary controls. Conversely, short-term altitude acclimatization may increase the HVR. The longitudinal effect of training, either at sea level or altitude, on HVR has not been previously reported. We therefore studied 21 untrained men and women before and after 5 wk of cycle ergometer training at either sea level or 2,500 m. HVR was determined using the steady-state method (16). Minute ventilation (E) was measured with a Tissot spirometer during the last minute of 5 min breathing room air, 8 and 12 O2, administered in random order. CO2was added at the mouth in an effort to maintain end-tidal CO2at baseline levels. Oxyhemoglobin saturation was measured directly from arterial blood with a hemoximeter (OSM 3). HVR was defined as the positive slope of the line relating Eto O2saturation in l·min-1-1. One group of subjects trained at sea level at 70 maximal oxygen uptake (O2max; N= 7). A second group trained at 2,500 m in a hypobaric chamber, at the same relative exercise intensity (i.e., 70 altitude O2max) or same absolute intensity (same power output) as group 1 (N= 14). Both groups trained on a bicycle ergometer for 45 min-d-1, 5 d·wk-1for 5 wk. In the sea level group, training sufficient to raise sea level VO2maxfrom 3.00 ± 0.27 to 3.41 ± 0.27 1·min-1(mean ± SE, P<0.05) had no effect on HVR (0.36 ± 0.09 to 0.31 ± 0.06 l·min-1-1, P= NS). In the altitude group however, a similar increase in sea level O2max, (3.05 ± 0.19 to 3.42 ± 0.20 l·min-1, P<0.05) was accompanied by an increase in HVR from 0.29 ± 0.06 to 0.41 ± 0.08 l·min-1·-1P< 0.05). We therefore conclude that 5 wk of endurance training at sea level has no effect on HVR. However, when training occurs at altitude, HVR is increased, possibly due to increased chemoreceptor sensitivity.

To establish whether or not hypoxia influences the training-induced adaptation of hormonal responses to exercise, 21 healthy, untrained subjects [26 (2) years, mean (SE)] were studied in three groups before and after 5 weeks' training (cycle ergometer, 45 min· day-1, 5 days· week-1). Group 1 trained at sea level at 70% maximal oxygen uptake ( $$\dot V$$ O2max), group 2 in a hypobaric chamber at a simulated altitude of 2500 m at 70% of altitude $$\dot V$$ O2max, and group 3 at a simulated altitude of 2500 m at the same absolute work rate as group 1. Arterial blood was sampled before, during and at the end of exhaustive cycling at sea level (85% of pretraining of $$\dot V$$ O2max). $$\dot V$$ O2 increased by 12 (2)% with no significant difference between groups, whereas endurance improved most in group 1 (P < 0.05). Training-induced changes in response to exercise of noradrenaline, adrenaline, growth hormone, ß-endorphin, glucagon, and insulin were similar in the three groups. Concentrations of erythropoietin and 2,3-diphosphoglycerate at rest did not change over the training period. In conclusion, within 5 weeks of training, no further adaptation of hormonal exercise responses takes place if intensity is increased above 70% $$\dot V$$ O2max. Furthermore, hypoxia per se does not add to the training-induced hormonal responses to exercise.

We studied whether the previously reported intensified Β-endorphin response to exercise after training might result from a training-induced general increase in anterior pituitary secretory capacity. Identical hypoglycemia was induced by insulin infusion in 7 untrained (Skeletal muscle enzyme activity, fiber composition and in relation to distance running performance 49±4 ml · (kg · min)−1, mean and SE) and 8 physically trained (Skeletal muscle enzyme activity, fiber composition and in relation to distance running performance 65±4 ml · (kg · min)−1) subjects. In response to hypoglycemia, levels of Β-endorphin and prolactin immunoreactivity in serum increased similarly in trained (from 41±2 pg · ml−1 and 6±1 pg · ml−1 before hypoglycemia to 103±11 pg · ml−1 and 43±9 pg · ml−1 during recovery, P<0.05) and untrained (from 35±7 pg · ml−1 and 7±2 pg · ml−1 to 113±18 pg · ml−1 and 31±8 pg · ml−1P<0.05) subjects. Growth hormone (GH) was higher 90 min after glucose nadir in trained (61±13 mU · l−1) than in untrained (25±6 mU · l−1) subjects (P<0.05). Levels of thyrotropin (TSH) changed in neither of the groups. It is concluded that, in contrast to what has been formerly proposed, training does not result in a general increase in secretory capacity of the anterior pituitary gland. TSH responds to hypoglycemia neither in trained nor in untrained subjects. Finally, differences in Β-endorphin responses to exercise between trained and untrained subjects cannot be ascribed to differences in responsiveness to hypoglycemia.

The physiological responses to skating and the incidence of injuries were recorded in young, Danish elite figure skaters (n = 8) over a 1-year period. The skaters' maximum oxygen uptake (VO2 max) ranged from 54.7 to 68.8 ml kg-1 min-1, and work intensity during simulated competitive figure skating corresponded to 89% VO2 max. Before the onset of competitive skating, but after a warm-up, blood lactate (BLa) concentration was measured as 2.0 ± 0.05 mM (x±s.e.). After a 4-min run, BLa increased to 8.0 ± 0.6 mM. The subjects' resting heart rates were measured each morning over a 1-year period and corresponded to 53 ± 2 and 58 ± 3 beats min-1 for the males and females respectively, with no systematic season-related variations. The skaters trained for 15-41 h per week, 60-95 min of this time being spent on warm-up activities. The injury incidence rate during competitive skating was recorded as 1.4 injuries per 1000 h of training, 56% of these being acute and 44% chronic injuries. Of those injuries registered, 83% were recalled by the skaters when a retrospective questionnaire was given to them at the end of the observation period. This study indicates that ice figure skating is associated with high aerobic power. Furthermore, Danish skaters spend large amounts of time on training, including warm-up and stretching. Despite the amount of training and the intensity of ice-skating programmes, injury rates are low compared with other sporting events.

The adrenaline release from the adrenal medulla increases during exercise, but at a given absolute work intensity the magnitude of this response is less pronounced in endurance trained vs sedentary individuals most likely due to a lower sympathetic stimulation of the adrenal medulla. However, when trained and untrained subjects are compared at identical relative work loads as well as in response to numerous non-exercise stimuli, endurance trained athletes have a higher epinephrine secretion capacity compared to sedentary individuals. This indicates a development of a so-called “sports adrenal medulla” as a result of a long term adaption of an endocrine gland to physical training. Such an adaptation is parallel to adaptations taking place in other tissues like skeletal muscle and the heart, and can be advantageous in relation to both exercise performance in the competing athlete and cause a biological rejuvenation in relation to aging.