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Effect of age on skeletal muscle proteolysis in extensor digitorum longus muscles of B6C3F1 mice.

The purpose of this study was to determine if age-related muscle atrophy is associated with an increased rate of protein degradation in extensor digitorum longus (EDL) muscles from young (YG; 2-4 months), middle-aged (MA; 12-17 months), and aged (AG; 22-24 months) B6C3F1 mice. EDL muscles from AG mice weighed less than EDL muscles from MA mice (p =.01). EDL muscles from MA mice weighed more than EDL muscles from YG mice (p =.02). The rate of protein degradation, as assessed by tyrosine release during in vitro incubations, was higher in EDL muscles from AG mice than it was in those from MA mice (p =.03). The rate of protein degradation was higher in EDL muscles from YG mice than it was in those from MA mice (p =.04). An inverse relationship existed between muscle mass and protein degradation (r = -.67; p =.0001). We conclude that skeletal muscle protein degradation rates decrease with maturation and increase with advancing age.

Aging↗

Overexpression of phospholamban in slow-twitch skeletal muscle is associated with depressed contractile function and muscle remodeling.

The relative amount of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) and its crucial inhibitor phospholamban (PLN) are closely regulated and play a pivotal role in maintaining muscle function. The functional importance of PLN has been intensively investigated in cardiac muscle. However, little is known about the role of PLN in the slow-twitch skeletal muscle, which expresses a significantly lower level of PLN but a similar level of SERCA2a compared with cardiac muscle. Thus, to define the physiological significance of PLN in slow-twitch skeletal muscle, we generated transgenic mice with PLN-specific overexpression in soleus, which is largely composed of slow-muscle fibers. The PLN protein levels and the PLN/SERCA2a ratio in transgenic soleus were comparable with those in cardiac muscle. Assessment of isometric-twitch contractions indicated that PLN overexpression was associated with depressed rates of contraction and relaxation, which were not linked to reduced SERCA2a abundance, although the levels of other key Ca2+-handling proteins, including ryanodine receptor, FKBP12, and L-type Ca2+ channel, were significantly decreased. However, isoproterenol stimulation reversed the inhibitory effects of PLN on the transgenic soleus twitch kinetics. Furthermore, the PLN-overexpressing soleus had smaller muscle size, mass, and cross-sectional area compared with wild-types. Interestingly, the percentage of slow fibers was increased in PLN-overexpressing soleus. Taken together, these findings indicate that increased PLN expression in slow-twitch skeletal muscle is associated with impaired contractile function and muscle remodeling.

Animals↗

The influence of muscle fiber size and type distribution on electromyographic measures of back muscle fatigability.

STUDY DESIGN: This was a cross-sectional study carried out on a group of 31 healthy, consenting volunteers with no history of low back pain (17 men, 14 women). OBJECTIVES: To evaluate the relationship between electromyographic measures of erector spinae fatigability and the muscle's fiber type characteristics. SUMMARY OF BACKGROUND DATA: Using electromyographic techniques, a pronounced fatigability of the muscles of patients with low back pain has been identified. It has been postulated that this is the result of an unfavorable back muscle fiber type distribution, although an association between electromyographic measures of fatigue and the muscle's fiber type characteristics has never been established. METHODS: Two tests of back extensor fatigability were performed (on separate days), each to the limit of endurance: 1) maintenance of 60% total maximum voluntary contraction of the back extensors, and 2) performance of the Biering-Sørensen test. Pairs of surface electrodes were attached to the skin overlying the belly of the erector spinae, bilaterally, at T10 and L3. The median frequency was computed from the electromyographic power spectrum, and fatigability was given by the slope of the linear regression of median frequency on time (MFgrad; %.s-1). One week later, two percutaneous erector spinae muscle biopsy samples were obtained from the same sites described for electromyography (left side only). Samples were prepared for histochemistry for the identification of muscle fiber types. Fiber sizes (cross-sectional areas) were quantified using computerized image analysis. RESULTS: The mean fiber size at each erector spinae region showed a significant correlation with maximum back extensor strength. In the thoracic region, the relative area of the muscle occupied by Type I fibers (which accounts for the relative size and distribution of the fiber types) showed a significant relationship with MFgrad recorded during each fatigue test. A similar relationship was observed for the lumbar region, but for the Biering-Sørensen test only. CONCLUSIONS: The electromyographic changes recorded in back muscles during fatigue appear to be related to the underlying muscle fiber type area distribution. This confirms the usefulness of electromyography in reflecting such muscle characteristics in a noninvasive manner, when monitoring changes in function consequent to the development of, or rehabilitation from, low back pain.

Adult↗

Effects of a nerve-muscle pedicle on the denervated rat thyroarytenoid muscle.

OBJECTIVES: To evaluate the effects of the nerve-muscle pedicle (NMP) method on the rat thyroarytenoid (TA) muscle after transection of the recurrent laryngeal nerve (RLN). STUDY DESIGN: Quantitative histologic assessment of the TA muscle after NMP implantation. METHODS: Thirty-six Wistar rats were divided into two groups: animals subjected to transection of the left RLN alone (DNV group) and animals subjected to transection of the left RLN followed by immediate transplantation of a NMP flap containing the sternohyoid (SH) muscle and ansa cervicalis nerve branch (NMP group). Animals were killed 2, 4, and 10 weeks after the treatments. The TA muscle stained with hematoxylin-eosin was evaluated quantitatively. The pre- and postsynaptic structures of the neuromuscular junction (NMJ) in the TA muscle were analyzed histochemically. The myosin heavy chain (MyHC) isoforms were evaluated using immunohistochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR). RESULTS: In the NMP group, the TA muscle fiber recovered to almost normal at 10 weeks, and the ratio of the number of synaptophysin-positive nerve terminals to that of alpha-bungarotoxin-positive acetylcholine receptors recovered to 79.8 +/- 11.8% (P < .05, compared with the control). Immunohistochemistry and the RT-PCR method after laser capture microdissection revealed the expression of MyHC isoforms type 2B and type 2A; the latter was detected in the SH muscle but not in the normal or denervated TA muscle. CONCLUSION: The NMP method was effective for recovering from the atrophic changes of the TA muscle after transection of the RLN. This was attributed to successful reinnervation by reconstruction of the NMJ, which might change MyHC isoform expression.

Animals↗

Functional neuromuscular stimulation controlled by surface electromyographic signals produced by volitional activation of the same muscle: adaptive removal of the muscle response from the recorded EMG-signal.

In order to use the volitional electromyography (EMG) as a control signal for the stimulation of the same muscle, it is necessary to eliminate the stimulation artifacts and the muscle responses caused by the stimulation. The stimulation artifacts, caused by the electric field in skin and tissue generated by the stimulation current, are relatively easy to eliminate by shutting down the EMG-amplifier at the onset of the stimulation pulses. The muscle response is a nonstationary signal, therefore, an adaptive linear prediction filter is proposed. The filter is implemented and for three filter lengths tested on both simulated and real data. The filter performance is compared with a conventional fixed comb filter. The simulations indicate that the adaptive filter is relatively insensitive to variations in amplitude of the muscle responses, and for all filter lengths produces a good filtering. For variations in shape of the muscle responses and for real data, an increased filter performance can be achieved by increasing the filter length. Using a filter length of up to seven stimulation periods, it is possible to reduce real muscle responses to a level comparable with the background noise. Using the shut-down circuit and the adaptive filter both the stimulation artifacts and the muscle responses can be effectively eliminated from the EMG signal from a stimulated muscle. It is therefore possible to extract the volitional EMG from a partly paralyzed muscle and use it for controlling the stimulation of the same muscle.

Artifacts↗

The effect of muscle contraction on the regulation of adenosine formation in rat skeletal muscle cells.

1. The present study examined the effect of muscle contraction on the rate of extracellular adenosine formation and on the distribution of 5' nucleotidase in primary rat skeletal muscle cells in culture. Experiments were also performed to determine whether the muscle cells release a metabolite upon contraction which may influence the extracellular production of adenosine. 2. Muscle contraction, induced by electrical stimulation, increased (P < 0.05) the rate of adenosine formation in the presence of physiological concentrations (2 and 5 microM) of adenosine monophosphate (AMP). Muscle contraction also led to an increase (P < 0.05) in the maximal rate of extracellular adenosine formation from 4.09 +/- 0.19 to 7.04 +/- 0.27 micromol (g protein)-1 min-1. Similarly, homogenates of contracted muscle cells had a higher (by 19.5 +/- 10.5 %; P < 0.05) AMP 5' nucleotidase activity than homogenates of control cells. 3. Addition of buffer from contracted cells to control cells induced an elevation (18.4 +/- 5.3 %; P < 0.05) in the rate of adenosine formation. The rate of adenosine formation was also increased with decreased intracellular adenylate charge (P < 0.05). 4. Cell homogenates treated with detergent had a higher (by 58.0 +/- 16.3 %; P < 0.05) AMP 5' nucleotidase activity than untreated homogenates, suggesting the existence of an enclosed pool of 5' nucleotidase within the muscle cells. The rate of adenosine formation in the detergent-treated homogenates was similar for electrically stimulated and non-electrically stimulated cells. 5. The present data show that muscle contraction induces an enhanced extracellular adenosine production via an increase in the activity of ecto AMP 5' nucleotidase. The activity of 5' nucleotidase can be elevated via a compound released by muscle cells during contraction and by alteration in intracellular adenylate charge. It is furthermore proposed that the extracellular adenosine formation is increased by translocation of 5' nucleotidase from an enclosed intracellular pool to the muscle membrane.

5'-Nucleotidase↗

Lactate transport in rat sarcolemmal vesicles and intact skeletal muscle, and after muscle contraction.

To determine whether it was possible to measure lactate transport rates into intact skeletal muscles, the transport of lactate (zero-trans) was determined in soleus muscle strips incubated in vitro and compared with lactate transport in sarcolemmal vesicles. In addition, the effects of muscle contractility on lactate transport were investigated in electrically-stimulated soleus muscle strips. In both the intact muscle and the sarcolemmal preparations the rates of transport were saturable, stereospecific, and inhibitable by monocarboxylates (pyruvate, alpha-cyano-4-hydroxycinnamate) and a protein modifier (N-ethylmaleimide; P < 0.05). The anion exchange inhibitor SITS had no effect on lactate uptake (P > 0.05). In both preparations lactate transport followed an inwardly directed proton gradient. Relative comparisons (%) between the preparations indicated a similar slope of increasing transport rates with increasing lactate concentrations and similar responses to a changing pH environment. These characterizations of L-lactate transport into isolated sarcolemmal vesicles and muscle strips revealed that both preparations yielded similar conclusions regarding the transmembrane movement of L-lactate. By using this more physiological muscle preparation, contractile activity, induced by electrical stimulation, did not increase lactate uptake in skeletal muscle in the post-exercise period whereas under similar conditions a marked increase in 2-deoxy-D-glucose uptake occurred (+ 47%; P < 0.05). These data suggest that the transport of glucose and lactate in contracting muscle is regulated differently. These studies also show that the incubated muscle strip preparation may be useful for studying lactate transport in an intact cell system during physiological experiments.

Animals↗

Oxygen exchange in muscle of young and old rats: muscle-vascular-pulmonary coupling.

Sustained performance of muscular exercise is contingent upon increasing muscle O(2) delivery (Qo2; the product of blood flow and arterial O(2) content, i.e. Q X Cao2) and utilization (Vo2m ) rapidly at exercise onset and sustaining necessary conductive and diffusive O(2) fluxes throughout exercise. A tight co-ordination of pulmonary, cardiovascular and muscle system responses is therefore required to prevent muscle microvascular O(2) pressures (P(mvO(2))) from falling to levels that impair blood-muscle O(2) exchange and/or impact metabolic control and reduce exercise tolerance. Microvascular O(2) pressures are determined by the balance between and Qo2 and Vo2m, and emerging evidence indicates that this balance is regulated differently across muscle fibre types and also in aged muscle. Moreover, disease states such as diabetes (type I and II) and chronic heart failure (CHF) also impact P(mvO(2)). This brief review primarily examines evidence obtained in animals that ageing: (1) redistributes exercising away from highly oxidative muscles and muscle fibres; (2) alters muscle capillary haemodynamics; and (3) reduces the O(2) pressure head within the microcirculation (P(mvO(2))) that serves to facilitate blood-muscle O(2) transfer. In many respects, these alterations found in healthy ageing animals bear a striking resemblance to those present in some chronic diseases (e.g. diabetes, CHF) and may help explain the compromised exercise tolerance present in aged individuals. Putative mechanistic insights are explored within the context of current knowledge and future investigative approaches.

Aging↗

The responses of human muscle spindle endings to vibration of non-contracting muscles.

1. In micro-electrode recordings from the human peroneal and tibial nerves, the responses of thirty-two primary spindle endings, thirteen secondary spindle endings and three Golgi tendon organs were studied during vibration of the tendons of the receptor-bearing muscles in the leg. The amplitude of the applied vibration was 1-5 mm and the frequency was varied from 20 to 220 Hz. As checked with e.m.g. and torque measurements, the muscles of the leg were relaxed during the sequences analysed. 2. Providing that the vibrator was accurately applied, all endings responded with discharges phase-locked to the vibration cycles, the discharge rates being at the vibration frequency or at subharmonics of that frequency. The response to vibration was of abrupt onset and offset, was maintained for the duration of vibration, and was not subject to fluctuation with changes in attention or with remote muscle contraction. 3. The maximal discharge rate that could be achieved varied from one ending to the next, and increased with the length of the receptor-bearing muscle. For endings driven at their maximal rate an increase in vibration frequency produced a decrease in discharge rates as the ending changed to a subharmonic pattern of response. The converse occurred on decreasing vibration frequency. 4. For any given muscle length, primary endings could generally be driven to higher rates than secondary endings but there was a wide range of responsiveness within each group and a significant overlap between the groups. At medium muscle length, the most responsive primary endings could be driven up to 220 Hz but secondary endings did not reach discharge rates higher than 100 Hz. 5. With combined vibration and passive movements, primary endings exhibited maximal vibration responsiveness during the stretching phases, sometimes firing twice per vibration cycle. During the shortening phases, however, they usually ceased responding to the vibratory stimulus. The vibration responsiveness of secondary endings was not potentiated to the same extent by on-going muscle stretch or reduced to the same extent by on-going muscle shortening. Thus, during shortening, secondary endings may be more responsive than primary endings. 6. The responses of primary endings to tendon taps were reduced during muscle vibration, a reduction which probably contributes to vibration-induced suppression of tendon jerks. Additionally, as the muscle shortened after tendon percussion, there was a transient pause in the response to vibration.

Action Potentials↗

Effect of muscle acidity on muscle metabolism and fatigue during intense exercise in man.

1. The aim of this study was to examine the effect of muscle pH on muscle metabolism and development of fatigue during intense exercise. 2. Seven subjects performed intense exhaustive leg exercise on two occasions: with and without preceding intense intermittent arm exercise leading to high or moderate (control) blood lactate concentrations (HL and C, respectively). Prior to and immediately after each exercise bout, a muscle biopsy was taken from m. vastus lateralis of the active leg. Leg blood flow was measured and femoral arterial and venous blood samples were collected before and frequently during the exhaustive exercises. 3. The duration of the exercise was shorter in HL than in C (3.46 +/- 0.28 vs. 4.67 +/- 0.55 min; means +/- S.E.M.; P < 0.05). Before exercise muscle pH was the same in C and HL (7.17 vs. 7.10), but at the end of exercise muscle pH was lower in HL than in C (6.82 vs. 6.65; P < 0.05). The release of potassium during exercise was higher (P < 0.05) in HL compared with C, but the arterial and femoral venous plasma potassium concentrations were the same at exhaustion in HL and C. 4. Muscle lactate concentration was higher in HL compared with C (3.7 +/- 0.4 vs. 1.6 +/- 0.2 mmol (kg wet weight)-1; P < 0.05), but the same at exhaustion (26.5 +/- 2.7 vs. 25.4 +/- 2.4 mmol (kg wet weight)-1). Total release of lactate in HL was lower than in C (18.7 +/- 4.5 vs. 50.4 +/- 11.0 mmol; P < 0.05), but rate of lactate production was not different (9.0 +/- 1.0 vs. 10.2 +/- 1.3 mmol (kg wet weight)-1 min-1). The rate of muscle glycogen breakdown was the same in C and HL (8.1 +/- 1.2 vs. 8.2 +/- 1.0 mmol (kg wet weight)-1 min-1). 5. The present data suggest that elevated muscle acidity does not reduce muscle glycogenolysis/glycolysis and is not the only cause of fatigue during intense exercise in man. Instead, accumulation of potassium in muscle interstitium may be an important factor in the development of fatigue.

Adult↗

Desmin knockout muscles generate lower stress and are less vulnerable to injury compared with wild-type muscles.

The functional role of the skeletal muscle intermediate filament system was investigated by measuring the magnitude of muscle force loss after cyclic eccentric contraction (EC) in normal and desmin null mouse extensor digitorum longus muscles. Isometric stress generated was significantly greater in wild-type (313 +/- 8 kPa) compared with knockout muscles (276 +/- 13 kPa) before EC (P < 0.05), but 1 h after 10 ECs, both muscle types generated identical levels of stress ( approximately 250 kPa), suggesting less injury to the knockout. Differences in injury susceptibility were not explained by the different absolute stress levels imposed on wild-type versus knockout muscles (determined by testing older muscles) or by differences in fiber length or mechanical energy absorbed. Morphometric analysis of longitudinal electron micrographs indicated that Z disks from knockout muscles were more staggered (0.36 +/- 0. 03 microm) compared with wild-type muscles (0.22 +/- 0.03 microm), which may indicate that the knockout cytoskeleton is more compliant. These data demonstrate that lack of the intermediate filament system decreases isometric stress production and that the desmin knockout muscle is less vulnerable to mechanical injury.

Age Factors↗

Muscle cooling delays activation of the muscle metaboreflex in humans.

Elevation of muscle temperature has been shown to increase muscle sympathetic nerve activity (MSNA) during isometric exercise in humans. The purpose of the present study was to evaluate the effect of muscle cooling on MSNA responses during exercise. Eight subjects performed ischemic isometric handgrip at 30% of maximal voluntary contraction to fatigue followed by 2 min of postexercise muscle ischemia (PEMI), with and without local cooling of the forearm. Local cooling of the forearm decreased forearm muscle temperature from 31.8 +/- 0.4 to 23.1 +/- 0.8 degrees C (P = 0.001). Time to fatigue was not different during the control and cold trials (156 +/- 11 and 154 +/- 5 s, respectively). Arterial pressures and heart rate were not significantly affected by muscle cooling during exercise, although heart rate tended to be higher during the second minute of exercise (P = 0.053) during muscle cooling. Exercise-induced increases in MSNA were delayed during handgrip with local cooling compared with control. However, MSNA responses at fatigue and PEMI were not different between the two conditions. These findings suggest that muscle cooling delayed the activation of the muscle metaboreflex during ischemic isometric exercise but did not prevent its full expression during fatiguing contraction. These results support the concept that muscle temperature can play a role in the regulation of MSNA during exercise.

Adult↗

Muscle grafts overloaded by ablation of synergistic muscles.

We hypothesized that the mass and maximum tetanic tension (Po) of nerve-intact grafts overloaded by ablation of synergistic muscles would be greater than that of standard nerve-intact grafts or of control soleus muscles. Soleus muscles were grafted orthotopically and bilaterally in 35 female rats. Control soleus muscles were obtained from 30 age-matched cohorts. Twenty-eight days following grafting, gastrocnemius muscles were ablated bilaterally in half of the animals. Comparisons were made between 28 and 112 days following grafting. By 112 days the wet mass of the overload nerve-intact grafts was 138% of the standard grafts and 152% of the control soleus muscles, whereas the Po was 161% and 107%, respectively. Specific tension stabilized at approximately 19 +/- 1 N/cm2 for both types of grafts, significantly lower than the value of 24 +/- 1 N/cm2 for control soleus muscles. Ablation of synergistic muscles resulted in a significant and sustained increase in mass and Po in regenerating skeletal muscle autografts. We conclude that provided the appropriate conditioning stimulus small grafts (100-200 mg) are capable of achieving the values for the mass and Po of control muscles.

Animals↗

Effect of testosterone on muscle mass and muscle protein synthesis.

We have studied the effect of a pharmacological dose of testosterone enanthate (3 mg.kg-1.wk-1 for 12 wk) on muscle mass and total-body potassium and on whole-body and muscle protein synthesis in normal male subjects. Muscle mass estimated by creatinine excretion increased in all nine subjects (20% mean increase, P less than 0.02); total body potassium mass estimated by 40K counting increased in all subjects (12% mean increase, P less than 0.0001). In four subjects, a primed continuous infusion protocol with L-[1-13C]leucine was used to determine whole-body leucine flux and oxidation. Whole-body protein synthesis was estimated from nonoxidative flux. Muscle protein synthesis rate was determined by measuring [13C]leucine incorporation into muscle samples obtained by needle biopsy. Testosterone increased muscle protein synthesis in all subjects (27% mean increase, P less than 0.05). Leucine oxidation decreased slightly (17% mean decrease, P less than 0.01), but whole-body protein synthesis did not change significantly. Muscle morphometry showed no significant increase in muscle fiber diameter. These studies suggest that testosterone increases muscle mass by increasing muscle protein synthesis.

Adult↗

Muscle regeneration during hindlimb unloading results in a reduction in muscle size after reloading.

The hindlimb-unloading model was used to study the ability of muscle injured in a weightless environment to recover after reloading. Satellite cell mitotic activity and DNA unit size were determined in injured and intact soleus muscles from hindlimb-unloaded and age-matched weight-bearing rats at the conclusion of 28 days of hindlimb unloading, 2 wk after reloading, and 9 wk after reloading. The body weights of hindlimb-unloaded rats were significantly (P < 0.05) less than those of weight-bearing rats at the conclusion of hindlimb unloading, but they were the same (P > 0.05) as those of weight-bearing rats 2 and 9 wk after reloading. The soleus muscle weight, soleus muscle weight-to-body weight ratio, myofiber diameter, number of nuclei per millimeter, and DNA unit size were significantly (P < 0.05) smaller for the injured soleus muscles from hindlimb-unloaded rats than for the soleus muscles from weight-bearing rats at each recovery time. Satellite cell mitotic activity was significantly (P < 0.05) higher in the injured soleus muscles from hindlimb-unloaded rats than from weight-bearing rats 2 wk after reloading, but it was the same (P > 0.05) as in the injured soleus muscles from weight-bearing rats 9 wk after reloading. The injured soleus muscles from hindlimb-unloaded rats failed to achieve weight-bearing muscle size 9 wk after reloading, because incomplete compensation for the decrease in myonuclear accretion and DNA unit size expansion occurred during the unloading period.

Animals↗

Preparation of a skeletal muscle ventricle in sheep: severe damage to the Latissimus dorsi muscle due to mobilization before preconditioning.

As part of a study examining the use of a skeletal muscle ventricle for cardiac assistance in sheep, a new concept of muscle preconditioning was put into practice. We aimed to produce a latissimus dorsi muscle (LDM) capable of performing chronic work immediately after the construction of a skeletal muscle ventricle. The left LDM was detached from the thoracic wall, divided longitudinally and reattached in situ to achieve vascular delay. The right LDM was left unaffected. Thereafter, preconditioning of both LDM was started according to the clinically approved stimulation protocol for cardiomyoplasty. Preconditioning of the unaffected right LDM in situ resulted in a complete muscle fiber transformation with no signs of degeneration or necrosis. Mobilization of the left LDM before preconditioning led to a distinct damage of the muscle. During conditioning, the increase in burst duration from 2 to 3 impulses in sheep A and from 3 to 5 impulses in sheep B resulted in a homogenous degeneration of the muscle fibers of the left LDM. Histomorphological analysis showed a dramatic increase in the percent perimysial and endomysial connective tissue. The applied concept of muscle prefabrication proved to be a failure. Muscle splitting and mobilization followed by vascular delay and in situ conditioning as a concept of muscle prefabrication should be strictly avoided.

Animals↗

Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men--a clinical research center study.

Testosterone replacement in hypogonadism has long been known to promote nitrogen retention and increase body density, but the mechanisms of nitrogen retention and body composition changes are poorly defined. We measured body composition and muscle protein synthesis in five hypogonadal men before and 6 months after initiating testosterone replacement. Body composition was examined using dual energy X-ray absorptiometry. Muscle mass was estimated both by excretion of creatinine on a meat-free diet and from appendicular mass measured using dual energy X-ray absorptiometry. Muscle protein synthesis was assessed by measuring the increment of [13C]leucine in mixed muscle protein and myosin heavy chain during a continuous infusion of L-[l-13C]leucine. In all subjects there was an increase in fat-free mass (average, 15%; range, 10-22%; P = 0.02) and a decrease in fat mass (-11%; range, -0.4% to -22.0%; P = 0.03). Muscle mass also increased in everybody (mean, 20%; range, 11-32%; P = 0.04) such that 65% of the increase in fat-free mass could be attributed to accretion of muscle. The accumulation of muscle was associated with a 56% (P = 0.015) increase in the fractional synthesis rate of mixed skeletal muscle proteins and a trend toward a similar increase in the fractional synthesis rate of myosin heavy chain (46%; P = 0.098). We conclude that testosterone replacement in hypogonadal men enhanced skeletal muscle mass by stimulating the muscle protein synthesis rate.

Amino Acids↗

A modified Hill muscle model that predicts muscle power output and efficiency during sinusoidal length changes.

The power output of a muscle and its efficiency vary widely under different activation conditions. This is partially due to the complex interaction between the contractile component of a muscle and the serial elasticity. We investigated the relationship between power output and efficiency of muscle by developing a model to predict the power output and efficiency of muscles under varying activation conditions during cyclical length changes. A comparison to experimental data from two different muscle types suggests that the model can effectively predict the time course of force and mechanical energetic output of muscle for a wide range of contraction conditions, particularly during activation of the muscle. With fixed activation properties, discrepancies in the work output between the model and the experimental results were greatest at the faster and slower cycle frequencies than that for which the model was optimised. Further optimisation of the activation properties across each individual cycle frequency examined demonstrated that a change in the relationship between the concentration of the activator (Ca2+) and the activation level could account for these discrepancies. The variation in activation properties with speed provides evidence for the phenomenon of shortening deactivation, whereby at higher speeds of contraction the muscle deactivates at a faster rate. The results of this study demonstrate that predictions about the mechanics and energetics of muscle are possible when sufficient information is known about the specific muscle.

Animals↗