Impact of treadmill locomotor training on skeletal muscle IGF1 and myogenic regulatory factors in spinal cord injured rats

The objective of this study was to determine the impact of treadmill locomotor training on the expression of insulin-like growth factor I (IGF1) and changes in myogenic regulatory factors (MRFs) in rat soleus muscle following spinal cord injury (SCI). Moderate, midthoracic (T₈) contusion SCIs were produced using a NYU (New York University) impactor. Animals were randomly assigned to treadmill training or untrained groups. Rats in the training group were trained starting at 1 week after SCI, for either 3 bouts of 20 min over 1.5 days or 10 bouts over 5 days. Five days of treadmill training completely prevented the decrease in soleus fiber size resulting from SCI. In addition, treadmill training triggered increases in IGF1, MGF and IGFBP4 mRNA expression, and a concurrent reduction of IGFBP5 mRNA in skeletal muscle. Locomotor training also caused an increase in markers of muscle regeneration, including small muscle fibers expressing embryonic myosin and Pax7 positive nuclei and increased expression of the MRFs, myogenin and MyoD. We concluded that treadmill locomotor training ameliorated muscle atrophy in moderate contusion SCI rats. Training-induced muscle regeneration and fiber hypertrophy following SCI was associated with an increase in IGF1, an increase in Pax7 positive nuclei, and upregulation of MRFs.     

Clenbuterol has a greater influence on untrained than on previously trained skeletal muscle in rats

The effects of clenbuterol, a selectiveβ ₂-adrenergic agonist, and of exercise training on the properties of skeletal muscle were studied in the hindlimb of sedentary and trained rats. A 2-week training programme, consisting of climbing on a grid with a load attached to the tail, did not increase the muscle mass of the soleus, the plantaris and the gastrocnemius muscles or modify the isometricin situ contractile properties of the medial gastrocnemius muscle. The only change observed in a 12-week training regimen was a significant increase in contractile forces (expressed in grams per gram of muscle) of the medial gastrocnemius muscle at sub-tetanic stimulating frequencies (twitch 42%, 25Hz 45% and 50Hz 47%). Both training programmes significantly increased fatigue resistance of the medial gastrocnemius muscle. A 2-week oral treatment with clenbuterol significantly increased the muscle mass of the soleus (19.8%), plantaris (16.9%) and gastrocnemius (15.3%) muscles in all animals treated with the agonist. However, clenbuterol had different effects in animals beginning their training programme than in animals that had been trained for the previous 10 weeks. Specifically, clenbuterol caused a significant increase in gastrocnemius muscle mass in the former group but not in the latter. These results suggest that the responses to the combination of clenbuterol and training in previously trained skeletal muscles are not as marked as those observed in untrained muscles.     

Regenerative responses in slow- and fast-twitch muscles following moderate contusion spinal cord injury and locomotor training

The aim of this study was to use the rat moderate spinal cord contusion model to investigate the effects of incomplete spinal cord injury (SCI) on the muscle regeneration process, comparing regeneration of slow-twitch plantarflexor soleus muscle and fast-twitch dorsiflexor tibialis anterior (TA) muscle. Additionally, we wanted to examine the effect of a week of locomotor training following incomplete SCI on the muscle regeneration process in these muscles and also determine if a week of similar locomotor training is sufficient to initiate muscle regeneration in control, non-injured rats. Thirty-two, adult, female, Sprague–Dawley rats were chosen for the study. Moderate, midthoracic contusion SCIs were produced using a NYU (New York University) impactor in all rats except controls. Animals were randomly assigned to treadmill training or untrained groups. Rats in the treadmill training group were manually treadmill trained starting at 1 week after SCI, for 10 bouts (2 sessions of 20 min of actual stepping) over 5 days and control rats in the training group received similar training. Our results indicate that a muscle regenerative response was initiated only in the slow-twitch soleus muscle in the initial 2 weeks following SCI, the addition of 1 week of locomotor treadmill training led to a significant increase in soleus regenerative process. No significant regenerative process was observed in the fast-twitch TA. Increased muscle regeneration in soleus is suggested by our findings of increased expression of (1) insulin-like growth factor-1, involved in the activation of satellite cells; (2) Pax7, a marker of satellite cell activation; (3) myogenin, a muscle regulatory protein; and (4) embryonic myosin, an indicator of new muscle fiber formation. Locomotor training in control, non-injured animals did not induce similar changes towards the regenerative process.     

Comparative effects of hindlimb suspension and exercise on skeletal muscle myosin isozymes in rats

Summary The purpose of this study was to ascertain the time course of changes, whilst suspending the hindlimb and physical exercise training, of myosin light chain (LC) isoform expression in rat soleus and vastus lateralis muscles. Two groups of six rats were suspended by their tails for 1 or 2 weeks, two other groups of ten rats each were subjected to exercise training on a treadmill for 9 weeks, one to an endurance training programme (1-h running at 20 m · min^–1 5 days · week^–1), and the other to a sprint programme (30-s bouts of running at 60 m · min^–1 with rest periods of 5 min). At the end of these experimental procedures, soleus and vastus lateralis superficialis muscles were removed for myosin LC isoform determination by two-dimensional gel electrophoresis. Hindlimb suspension for 2 weeks significantly increased the proportion of fast myosin LC and decreased slow myosin LC expression in the soleus muscle. The pattern of myosin LC was unchanged in the vastus lateralis muscle. Sprint training or endurance training for 9 weeks increased the percentage of slow myosin LC in vastus lateralis muscle, whereas soleus muscle myosin LC was not modified. These data indicate that hindlimb suspension influences myosin LC expression in postural muscle, whereas physical training acts essentially on phasic muscle. There were no differences in myosin LC observed under the influence of sprint- or endurance-training programme.     

Rapid assessment of quantitative T1, T2 and T2* in lower extremity muscles in response to maximal treadmill exercise

MRI provides a non‐invasive diagnostic platform to quantify the physical and physiological attributes of skeletal muscle at rest and in response to exercise. MR relaxation parameters (T₁, T₂ and T₂*) are characteristic of tissue composition and metabolic properties. With the recent advent of quantitative techniques that allow rapid acquisition of T₁, T₂ and T₂* maps, we posited that an integrated treadmill exercise–quantitative relaxometry paradigm can rapidly characterize exercise‐induced changes in skeletal muscle relaxation parameters. Accordingly, we investigated the rest/recovery kinetics of T₁, T₂ and T₂* in response to treadmill exercise in the anterior tibialis, soleus and gastrocnemius muscles of healthy volunteers, and the relationship of these parameters to age and gender. Thirty healthy volunteers (50.3 ± 16.6 years) performed the Bruce treadmill exercise protocol to maximal exhaustion. Relaxometric maps were sequentially acquired at baseline and for approximately 44 minutes post‐exercise. Our results show that T₁, T₂ and T₂* are significantly and differentially increased immediately post‐exercise among the leg muscle groups, and these values recover to near baseline within 30–44 minutes. Our results demonstrate the potential to characterize the kinetics of relaxation parameters with quantitative mapping and upright exercise, providing normative values and some clarity on the impact of age and gender. Copyright © 2015 John Wiley & Sons, Ltd.     

Soleus H-reflex modulation during body weight support treadmill walking in spinal cord intact and injured subjects

The soleus H-reflex modulation pattern was investigated in ten spinal cord intact subjects during treadmill walking at varying levels of body weight support (BWS), and nine spinal cord injured (SCI) subjects at a BWS level that promoted the best stepping pattern. The soleus H-reflex was elicited by tibial nerve stimulation with a single 1-ms pulse at an intensity that the M-waves ranged from 4 to 8% of the maximal M-wave (M_max). During treadmill walking, the H-reflex was elicited every four steps, and stimuli were randomly dispersed across the gait cycle which was divided into 16 equal bins. EMGs were recorded with surface electrodes from major left and right hip, knee, and ankle muscles. M-waves and H-reflexes at each bin were normalized to the M_max elicited at 60–100 ms after the test reflex stimulus. For every subject, the integrated EMG area of each muscle was established and plotted as a function of the step cycle phase. The H-reflex gain was determined as the slope of the relationship between H-reflex and soleus EMG amplitudes at 60 ms before H-reflex elicitation for each bin. In spinal cord intact subjects, the phase-dependent H-reflex modulation, reflex gain, and EMG modulation pattern were constant across all BWS (0, 25, and 50) levels, while tibialis anterior muscle activity increased with less body loading. In three out of nine SCI subjects, a phase-dependent H-reflex modulation pattern was evident during treadmill walking at BWS that ranged from 35 to 60%. In the remaining SCI subjects, the most striking difference was an absent H-reflex depression during the swing phase. The reflex gain was similar for both subject groups, but the y-intercept was increased in SCI subjects. We conclude that the mechanisms underlying cyclic H-reflex modulation during walking are preserved in some individuals after SCI.     

Effect of endurance training and acute exercise on sarcoplasmic reticulum function in rat fast- and slow-twitch skeletal muscles

Following 10 weeks of endurance training and in age-matched sedentary rats, sarcoplasmic reticulum (SR) Ca²⁺-uptake, Ca²⁺-release, and Ca²⁺-stimulated adenosinetriphosphatase (ATPase) activity were examined in homogenates of the plantaris and soleus muscles from rats subjected to moderate-intensity treadmill running to exhaustion. In order to examine the effects of acute exercise and/or training on SR Ca²⁺-handling capacity, comparisons between exhausted and non-exercised rats and between trained and untrained rats were performed. Our data confirm that Ca²⁺-sequestration by the SR from fast-twitch muscles is depressed after training. Immediately after exhaustive running, decreases in SR function occurred in both muscles, but were more pronounced in the soleus. In the plantaris, reductions in SR Ca²⁺-uptake rate and Ca²⁺-ATPase activity were observed in untrained rats only, while in the soleus they were adversely affected irrespective of training status. Although the average run time to exhaustion varied markedly between untrained and trained animals (untrained: 253.0 min; trained: 559.4 min), no differences existed with regard to the magnitude of decreases in SR function in the soleus after exercise. The mean rate of decline in SR Ca²⁺-handling capacity during acute exercise, as estimated from the run time and the extent of the decline, was more than twofold higher in untrained than in trained soleus. From the present study, it is unclear whether there exists a causal relationship between muscular fatigue and SR function because the run time to exhaustion was not significantly correlated with any of parameters indicative of SR Ca²⁺-handling capacity, but suggested that endurance training may be capable of delaying a progression of the deterioration in SR function that occurs during exercise. Electronic Publication     

Effect of aerobic training on 99mTc-methoxy isobutyl isonitrile (99mTc-sestamibi) uptake by myocardium and skeletal muscle: implication for noninvasive assessment of muscle metabolic profile

Aim: The effect of long‐term endurance training on skeletal muscle and myocardial uptake of ^99mTc‐sestamibi, a radiopharmaceutical accumulating in the mitochondria, was investigated. Methods: Twenty‐six Wistar rats were divided into a trained (5 days week^?1 endurance running for 14 weeks) and an untrained group. On completion of training, ^99mTc‐sestamibi was administered and, 2 h post‐injection, the myocardium and the soleus, extensor digitorum longus (EDL) and medial gastrocnemius (MG) muscles were removed for the measurement of cytochrome c oxidase (CCO) activity and ^99mTc‐sestamibi uptake. Tissue ^99mTc‐sestamibi kinetics was preliminarily studied in 16 other rats for up to 2 h post‐injection. Results: Two hours post‐injection ^99mTc‐sestamibi uptake was either stable (myocardium) or still rising (skeletal muscles). Both CCO activity and ^99mTc‐sestamibi uptake decreased in the same order (myocardium, soleus, EDL, MG) in the tissues examined. The CCO activity of the EDL and MG muscles was higher (P < 0.05) in the trained compared to the untrained group. ^99mTc‐sestamibi uptake in the soleus and EDL muscles was higher (P < 0.05) in the trained compared to the untrained rats, whereas the difference in MG was marginally significant (P = 0.06) in favour of the trained group. Conclusions: Long‐term endurance training, resulting in elevated skeletal muscle CCO activity, is also associated with a similar increase in ^99mTc‐sestamibi uptake. This finding suggests that ^99mTc‐sestamibi could be used in imaging assessment of skeletal muscle metabolism with possible applications in both clinical and sports medicine settings.     

The effects of high-intensity exercise on skeletal muscle neutrophil myeloperoxidase in untrained and trained rats

The primary purpose of this study was to examine the effects of high-intensity acute exercise on neutrophil infiltration in different muscle fiber types of untrained rats and to compare postexercise neutrophil accumulation in muscles of untrained and trained animals. The effect of high-intensity acute exercise on blood neutrophil degranulation reaction in trained animals was also elucidated. Neutrophil enzyme myeloperoxidase (MPO) was determined as a measure of neutrophil migration into muscles and blood neutrophil degranulation. Male albino rats were subjected to acute exercise and 5 weeks of training. The used model of intensive acute exercise consisted of 5, 15, and 25 intermittent swimming bouts with the addition of weight (8% of total body mass) for 1-min each, followed by 1.5-min rest intervals. MPO was analyzed in quadriceps muscle (white and red portion) and in soleus muscle 24 h after acute exercise. MPO content in resting blood plasma and neutrophils was determined 48-h following the completion of a training process. In addition, MPO content in the trained rats was measured immediately (in blood plasma and neutrophils) after and 24 h (in muscles) following a single-bout of exercise to exhaustion. The remaining two-third of the trained animals were exposed to a single-bout of nonstop swimming with the addition of 6% body mass until exhaustion. These animals were sacrificed immediately and 24 h after loaded swimming to analyze leukocyte count, MPO content in blood plasma and neutrophils and in muscles, respectively. About 24 h after exercise MPO concentrations in the red portion of quadriceps muscle and in soleus muscle were 4–7-fold higher as compared to the white portion of m. quadriceps. There was an association between the quantity of repetitive bouts of swimming and MPO content in the muscles. The duration of swimming to exhaustion of trained rats was 3.8-fold longer than untrained sedentary control. At rest, plasma MPO concentration was found to be 40% higher in trained rats compared to untrained controls (P < 0.05). Postexercise plasma MPO concentrations were significantly higher both in untrained (+137%; P < 0.05) and trained (+81%; P < 0.05) rats compared to resting values. At rest neutrophil MPO concentration was found to be 33% lower in trained rats compared to untrained controls (P < 0.05). There were no significant differences in muscle MPO concentrations between untrained and trained rats at rest. A single-bout of exercise to exhaustion produced a greater increase in MPO content in untrained compared to trained rats. The data suggest that postexercise neutrophil infiltration is more intensive in red fibers types compared to white fiber types. A smaller neutrophil infiltration in muscles of trained animals after exhaustive exercise suggests a protective effect of previous training to muscle injury.Portions of this paper were presented by V. Morozov in 2003 at the 6th ISEI Symposium on Exercise Muscle Metabolism and Immune Function, Copenhagen.     

T2 mapping provides multiple approaches for the characterization of muscle involvement in neuromuscular diseases: a cross‐sectional study of lower leg muscles in 5–15‐year‐old boys with Duchenne muscular dystrophy

Skeletal muscles of children with Duchenne muscular dystrophy (DMD) show enhanced susceptibility to damage and progressive lipid infiltration, which contribute to an increase in the MR proton transverse relaxation time (T₂). Therefore, the examination of T₂ changes in individual muscles may be useful for the monitoring of disease progression in DMD. In this study, we used the mean T₂, percentage of elevated pixels and T₂ heterogeneity to assess changes in the composition of dystrophic muscles. In addition, we used fat saturation to distinguish T₂ changes caused by edema and inflammation from fat infiltration in muscles. Thirty subjects with DMD and 15 age‐matched controls underwent T₂‐weighted imaging of their lower leg using a 3‐T MR system. T₂ maps were developed and four lower leg muscles were manually traced (soleus, medial gastrocnemius, peroneal and tibialis anterior). The mean T₂ of the traced regions of interest, width of the T₂ histograms and percentage of elevated pixels were calculated. We found that, even in young children with DMD, lower leg muscles showed elevated mean T₂, were more heterogeneous and had a greater percentage of elevated pixels than in controls. T₂ measures decreased with fat saturation, but were still higher (P < 0.05) in dystrophic muscles than in controls. Further, T₂ measures showed positive correlations with timed functional tests (r = 0.23–0.79). The elevated T₂ measures with and without fat saturation at all ages of DMD examined (5–15 years) compared with unaffected controls indicate that the dystrophic muscles have increased regions of damage, edema and fat infiltration. This study shows that T₂ mapping provides multiple approaches that can be used effectively to characterize muscle tissue in children with DMD, even in the early stages of the disease. Therefore, T₂ mapping may prove to be clinically useful in the monitoring of muscle changes caused by the disease process or by therapeutic interventions in DMD. Copyright © 2012 John Wiley & Sons, Ltd.     

Effect of electromyostimulation training on soleus and gastrocnemii H- and T-reflex properties

When muscle is artificially activated, as with electromyostimulation (EMS), action potentials are evoked in both intramuscular nerve branches and cutaneous receptors, therefore activating spinal motoneurons reflexively. Maximal soleus and gastrocnemii H- and T-reflex and the respective mechanical output were thus quantified to examine possible neural adaptations induced at the spinal level by EMS resistance training. Eight subjects completed 16 sessions of isometric EMS (75 Hz) over a 4-week period. Maximal soleus and gastrocnemii M wave (M_max), H reflex (H_max) and T reflex (T_max) were compared between before and after training, together with the corresponding plantar flexor peak twitch torque. No significant changes were observed for electromechanical properties of H_max reflex following EMS. On the other hand, peak twitch torque produced by T_max, but not by equal-amplitude H reflex, significantly increased as a result of training (+21%, P<0.05). These changes were associated with a trend towards a significant increase for normalized gastrocnemii (+21%, P=0.07) but not soleus T_max reflex. It is concluded that, contrary to results previously obtained after voluntary physical training, EMS training of the plantar flexor muscles did not affect alpha motoneuron excitability and/or presynaptic inhibition, as indicated by H-reflex results. On the other hand, in the absence of change in a control group, T_max electromechanical findings indicated that: (1) equal-amplitude H- and T-reflex adapted differently to EMS resistance training; and (2) EMS had an effect on gastrocnemii but not on soleus muscle, perhaps because of the differences in respective motor unit characteristics (e.g., axon diameter).     

Influence of complete spinal cord injury on skeletal muscle cross-sectional area within the first 6 months of injury

In this study we examined the influence of complete spinal cord injury (SCI) on affected skeletal muscle morphology within 6 months of SCI. Magnetic resonance (MR) images of the leg and thigh were taken as soon as patients were clinically stable, on average 6 weeks post injury, and 11 and 24 weeks after SCI to assess average muscle cross-sectional area (CSA). MR images were also taken from nine able-bodied controls at two time points separated from one another by 18 weeks. The controls showed no change in any variable over time. The patients showed differential atrophy (P?=?0.0001) of the ankle plantar or dorsi flexor muscles. The average CSA of m. gastrocnemius and m. soleus decreased by 24% and 12%, respectively (P?=?0.0001). The m. tibialis anterior CSA showed no change (P?=?0.3644). As a result of this muscle-specific atrophy, the ratio of average CSA of m. gastrocnemius to m. soleus, m. gastrocnemius to m. tibialis anterior and m. soleus to m. tibialis anterior declined (P?=?0.0001). The average CSA of m, quadriceps femoris, the hamstring muscle group and the adductor muscle group decreased by 16%, 14% and 16%, respectively (P?≤?0.0045). No differential atrophy was observed among these thigh muscle groups, thus the ratio of their CSAs did not change (P?=?0.6210). The average CSA of atrophied skeletal muscle in the patients was 45–80% of that of age- and weight-matched able-bodied controls 24 weeks after injury. In conclusion, the results of this study suggest that there is marked loss of contractile protein early after SCI which differs among affected skeletal muscles. While the mechanism(s) responsible for loss of muscle size are not clear, it is suggested that the development of muscular imbalance as well as diminution of muscle mass would compromise force potential early after SCI.     

Relationship between muscle T2 * relaxation properties and metabolic state: a combined localized 31P-spectroscopy and 1H-imaging study

A multi-volume ³¹P-magnetic resonance spectroscopy localization procedure was implemented to compare directly muscle metabolism and proton T₂ ^* relaxation properties in the human plantar flexor muscles during exercise. Localized ³¹P-spectra were collected simultaneously from the medial gastrocnemius, lateral gastrocnemius and soleus muscles during exercise using β ₁-insensitive Hadamard Spectroscopic Imaging (HSI). ¹H T₂ ^*-weighted gradient-echo images were acquired at rest and immediately following high-intensity plantar flexion exercise. T₂ ^* mapping of the individual calf muscles showed that plantar flexion with the knee extended produces significant increases (P < 0.0001) in the mean (SEM) T₂ ^* of the medial [35.6 (1.2) ms vs 28.5 (0.5) ms at rest] and lateral gastrocnemius [35.6 (0.9) ms vs 26.2 (0.9) ms at rest], but not in the soleus [26.7 (0.6) ms vs 27.3 (0.8) ms at rest]. In accordance with the changes in T₂ ^*, the ratio of inorganic phosphate to phosphocreatine (P_i:PCr) and the intracellular muscle pH shifted significantly in the gastrocnemii, while the soleus showed no change in muscle pH and only a moderate increase in P_i-to-Ph. Comparison of spectroscopic and relaxation parameters in both gastrocnemius muscles revealed a significant relationship between post-exercise T₂ ^* and intracellular pH (r=0.72–0.76) and P_i-to-Ph ratios (r=0.81–0.88) during exercise. Using an improved method of localization, this study confirms the existence of a strong relationship between transverse relaxation properties and the metabolic state in skeletal muscles engaged in heavy exercise. Accepted: 28 December 1999     

Low-frequency H-reflex depression in trained human soleus after spinal cord injury

After spinal cord injury (SCI), widespread reorganization occurs within spinal reflex systems. Regular muscle activity may influence reorganization of spinal circuitry after SCI. The purpose of this study is to investigate the effects of long-term soleus training on H-reflex depression in humans after SCI. Seven subjects with acute (<7 weeks) SCI (AC group) underwent testing of H-reflex depression at several frequencies of repetitive stimulation. Eight subjects (including 3 from AC) stimulated one soleus muscle daily, leaving the other leg as an untrained within-subject control. Trained limb H-reflexes were assessed during year 1 (TR1) and year 2 (TR2) of training. Untrained limbs were tested during year 2 (UN). H-reflex amplitude was lower at 1, 2 and 5 Hz than at 0.1 or 0.2 Hz (p < 0.05). The pattern of depression differed between AC and UN (p < 0.05), but not between TR2 and UN (p > 0.05) despite significant adaptations in torque and fatigue resistance (p < 0.05). Three subjects who began training very early after SCI retained H-reflex post activation depression, suggesting that early intervention of daily muscular activity may be important.     

Effects of voluntary wheel running and amino acid supplementation on skeletal muscle of mice

The aims of the present study were as follows: (1) to examine the adaptational changes to chronic endurance voluntary exercise and (2) to investigate the effects of amino acid supplementation on the adaptational changes induced by endurance training in hindlimb (gastrocnemius, tibialis, soleus) and respiratory (diaphragm) muscles of mice. Male C57Bl6 mice were divided in four groups: control sedentary, sedentary supplemented with amino acid mixture (BigOne, 1.5 mg g day^–1 in drinking water for 8 weeks), running (free access to running wheels for 8 weeks), and running supplemented with amino acid mixture. Myosin heavy chain (MHC) isoform distribution was determined in all muscles considered. Fiber cross-sectional area (CSA) was measured in the soleus muscle. In all muscles except the tibialis, endurance training was associated with an overall shift towards the expression of slower MHC isoforms. Amino acid supplementation produced a shift towards the expression of faster MHC isoforms in the soleus and diaphragm muscles, and partially antagonized the effects of training. Immunohistochemical analysis of CSA of individual muscle fibers from the soleus muscle suggests that voluntary running produced a decrease in the size of type 1 fibers, and amino acid supplementation during training resulted in an increase in size in both type 1 and type 2A fibers. Collectively, these results suggest that the endurance adaptations induced by voluntary running depend on the muscle type, and that amino acid supplementation is able to modulate both fiber size and MHC isoform composition of skeletal muscles in sedentary and exercised mice.     

Effects of eccentric and concentric training on capillarization and myosin heavy chain contents in rat skeletal muscles after hindlimb suspension

We studied the effects of different protocols of post-disuse rehabilitation on angiogenesis and myosin heavy chain (MHC) content in rat hindlimb muscles after caudal suspension. Thirty female Wistar rats were divided into five groups: (1) Control I, (2) Control II, (3) Suspended, (4) Suspended trained on declined treadmill, and (5) Suspended trained on flat treadmill. Fragments of the soleus and tibialis anterior (TA) muscles were frozen and processed by electrophoresis and immunohistochemistry (CD31 antibody). Hindlimb suspension caused reduction of capillary/fiber (C/F) ratios and contents of MHC type I (MHCI) in the soleus in parallel to increased capillary density. Flat treadmill protocols increased the content of the MHCI isoform. The C/F ratio was increased by concentric training after hypokinesis, but was not modified by eccentric training, which caused a greater reduction of capillary density compared to the other protocols. In the TA muscle, hindlimb suspension caused a non-significant increase in capillary density and C/F ratio with limited changes in MHC. The present data demonstrate that the different training protocols adopted and the functional performance of the muscles analyzed caused specific changes in capillarization and in the content of the various MHC types.     

Different effects of physical training on the morphology of motor nerve terminals in the rat extensor digitorum longus and soleus muscles

Summary The morphology of nerve terminals in the rat extensor digitorum longus and soleus muscles was studied with light microscopy in 13-week-old male animals after 6 weeks of treadmill running and compared with data from untrained controls. The terminals were stained with methylene blue. Physical training tended to increase the area and length of the nerve terminals in relation to the corresponding muscle fiber diameter, and to reduce the density of nerve terminal varicosities, but significant differences between the trained group and the control group were obtained only in the extensor digitorum longus muscle. The different degrees of effect on the nerve terminals in the two muscles may be due to different abilities to respond to the training, but may also be due to differences in work load caused by the training. The effect of training on extensor digitorum longus junctions may reflect some transformation from fast to slow morphological characteristics.     

Surgical manipulation,but not moderate exercise,is associated with increased cytokine mRNA expression in the rat soleus muscle

Interleukin (IL)‐6 production in contracting skeletal muscle and IL‐6 concentration in plasma are increased after prolonged and strenuous exercise. However, as tissue stress or damage are unspecific triggers of increased cytokine levels, we examined whether moderate muscle activity is an independent stimulus for cytokine expression, and to which extent invasive procedures might affectthe results. Soleus muscles were isolated from sedentary rats or from rats that had been running on a treadmill at moderate intensity (70% of maximal oxygen uptake) for 1 h. In another group the soleus muscle was prepared in situ and stimulated intermittently at 5 Hz for 1 h, so that maximal developed force declined by 30%. In situ prepared soleus muscles not subjected to electrical stimulation were used as controls. Messenger RNA (mRNA) expression of 11 cytokines was analysed in the soleus muscles using multiprobe RNAse protection assay, and IL‐6 plasma concentration was measured by enzyme‐linked immunosorbent assay. Treadmill exercise did not affect the mRNA expression of any of the measured cytokines in the soleus muscle. Irrespective of electrical stimulation, mRNA expression of IL‐6 and IL‐1β were significantly increased in the surgically manipulated soleus muscles. Interleukin‐6 plasma concentration was not affected by treadmill running or electrical stimulation. Conclusion, gentle surgical manipulation is a strong stimulus for IL‐6 and IL‐1β mRNA synthesis in skeletal muscle, whereas exercise or electrical muscle stimulation at moderate intensity does not independently affect cytokine mRNA levels in the contracting soleus.     

Age- and training-related changes in the collagen metabolism of rat skeletal muscle

Summary The effects of ageing and life-long endurance training on the collagen metabolism of skeletal muscle were evaluated in a longitudinal study. Wistar rats performed treadmill running 5 days a week for 2 years. The activities of collagen biosynthesis enzymes, prolyl-4-hydroxylase and galactosylhydroxylysyl glucosyltransferase, were highest in the muscles of the youngest animals, decreased up to the age of 2 months and from then on remained virtually unchanged. The enzyme activity in young animals was higher in the slow collagenous soleus muscle than in the rectus femoris muscle. The enzyme activity in the soleus muscle was higher for older trained rats than older untrained rats. The relative proportion of type I collagen increased and that of type III collagen decreased with age, suggesting a more marked contribution by type I collagen to the agerelated accumulation of total muscular collagen. The results show that collagen biosynthesis decreases with maturation and that life-long endurance training maintains a higher level of biosynthesis in slow muscles.