Effect of exercise on cardiac tissue oxidative and inflammatory mediators in chronic kidney disease.

BACKGROUND: Chronic renal failure (CRF) results in diminished physical activity and increased risk of cardiovascular disease (CVD). CVD risk factors are raised by sedentary life style and ameliorated by physical fitness in the general population. Accordingly, exercise improves hypertension, endothelial dysfunction, insulin resistance, dyslipidemia, inflammation and oxidative stress in high-risk populations. This study was designed to explore the effect of exercise on oxidative and inflammatory mediators in the left ventricle (LV) of CRF rats. METHODS AND RESULTS: One week after 5/6 nephrectomy female rats were housed in either regular cages or cages equipped with running wheels for 4 weeks. Sham-operated rats housed in regular cages served as controls. Sedentary CRF rats exhibited azotemia, hypertension, anemia, oxidative stress, activation of NF-kappaB and upregulations of reactive oxygen species-generating enzyme, NAD(P)H oxidase, MCP-1, cyclooxygenase-2 (COX-2), and PAI-1 in LV. The CRF rats assigned to the exercise group ran 6.8 +/- 0.7 km/day and 72 +/- 8 min/day. Voluntary exercise reversed NF-kappaB activation and lowered NAD(P)H oxidase, PAI-1, MCP-1 and COX-2 abundance, increased LV mass by raising myofibrillar proteins and ameliorated anemia without affecting renal function or arterial pressure. CONCLUSIONS: CRF resulted in upregulation of prooxidant/proinflammatory pathways in LV. These changes were ameliorated by exercise, which indicates the potential cardiovascular benefit of exercise in renal insufficiency.

Skeletal muscle growth in young rats is inhibited by chronic exposure to IL-6 but preserved by concurrent voluntary endurance exercise.

Childhood diseases are often accompanied by chronic inflammation, which is thought to negatively impact growth. Interleukin-6 (IL-6) is typically cited as an indicator of inflammation and is linked to impaired growth. This study was designed to isolate and identify potential effects of chronic IL-6 exposure on skeletal muscle growth during development. A second aim was to determine if endurance exercise, thought to antagonize chronic inflammation, would interact with any effects of IL-6. The muscles of one leg of rapidly growing rats were exposed to IL-6 or vehicle for 14 days. Subgroups of IL-6-infused rats were provided access to running wheels. Local IL-6 infusion resulted in approximately 13% muscle growth deficit (myofibrillar protein levels). Exercise (>4,000 m/day) prevented this deficit. IL-6 infusion increased mRNA for suppressor of cytokine signaling-3 (SOCS3) and tumor necrosis factor-alpha (TNF-alpha), and this was not prevented by exercise. IL-6 infusion increased the mRNAs for atrogin, insulin-like growth factor-I (IGF-I), and IGF binding protein-4 (IGFBP4), and these effects were mitigated by exercise. Exercise stimulated an increase in total RNA ( approximately 19%) only in the IL-6-infused muscle, suggesting that a compensatory increase in translational capacity was required to maintain muscle growth. This study indicates that IL-6 exposure during periods of rapid growth in young animals can retard growth possibly via interactions with key growth factors. Relatively high volumes of endurance-type exercise do not exacerbate the negative effects of IL-6 and in fact were found to be beneficial in protecting muscle growth.

Combined isometric, concentric, and eccentric resistance exercise prevents unloading-induced muscle atrophy in rats.

Previously, we reported that an isometric resistance training program that was effective in stimulating muscle hypertrophy in ambulatory rats could not completely prevent muscle atrophy during unloading (Haddad F, Adams GR, Bodell PW, Baldwin KM. J Appl Physiol 100: 433-441, 2006). These results indicated that preventing muscle atrophy does not appear to be simply a function of providing an anabolic stimulus. The present study was undertaken to determine if resistance training, with increased volume (3-s contractions) and incorporating both static and dynamic components, would be effective in preventing unloading-induced muscle atrophy. Rats were exposed to 5 days of muscle unloading via tail suspension. During that time one leg received electrically stimulated resistance exercise (RE) that included an isometric, concentric, and eccentric phase. The results of this study indicate that this combined-mode RE provided an anabolic stimulus sufficient to maintain the mass and myofibril content of the trained but not the contralateral medial gastrocnemius (MG) muscle. Relative to the contralateral MG, the RE stimulus increased the amount of total RNA (indicative of translational capacity) as well as the mRNA for several anabolic/myogenic markers such as insulin-like growth factor-I, myogenin, myoferlin, and procollagen III-alpha-1 and decreased that of myostatin, a negative regulator of muscle size. The combined-mode RE protocol also increased the activity of anabolic signaling intermediates such as p70S6 kinase. These results indicate that a combination of static- and dynamic-mode RE of sufficient volume provides an effective stimulus to stimulate anabolic/myogenic mechanisms to counter the initial stages of unloading-induced muscle atrophy.

Similar acute molecular responses to equivalent volumes of isometric, lengthening, or shortening mode resistance exercise.

The present study was undertaken to test the hypothesis that the contraction mode of action [static-isometric (Iso), shortening-concentric (Con), or lengthening-eccentric (Ecc)] used to stress the muscle provides a differential mechanical stimulus eliciting greater or lesser degrees of anabolic response at the initiation of a resistance training program. We performed an acute resistance training study in which different groups of rodents completed four training sessions in either the Iso, Con, or Ecc mode of contraction under conditions of activation and movement specifically designed to elicit equivalent volumes of force accumulation. The results of this experiment indicate that the three modes of contraction produced nearly identical cell signaling, indicative of an anabolic response involving factors such as increased levels of mRNA for IGF-I, procollagen III alpha1, decreased myostatin mRNA, and increased total RNA concentration. The resulting profiles collectively provide evidence that pure mode of muscle action, in and of itself, does not appear to be a primary variable in determining the efficacy of increased loading paradigms with regard to the initiation of selected muscle anabolic responses.

Isometric resistance exercise fails to counteract skeletal muscle atrophy processes during the initial stages of unloading.

This study tested the hypothesis that an isometric resistance training paradigm targeting the medial gastrocnemius of adult rodents is effective in preventing muscle atrophy during the early stages of hindlimb unloading by maintaining normal activation of the insulin receptor substrate-1 (IRS-1)/phosphoinositide-3 kinase (PI3K)/Akt signaling pathway. This pathway has been shown to simultaneously create an anabolic response while inhibiting processes upregulating catabolic processes involving expression of key enzymes in the ubiquitination of proteins for degradation. The findings show that during the 5 days of unloading 1) absolute medial gastrocnemius muscle weight reduction occurred by approximately 20%, but muscle weight corrected to body weight was not different from normal weight-bearing controls (P < 0.05); 2) normalized myofibril fraction concentration and content were decreased; and 3) a robust isometric training program, known to induce a hypertrophy response, failed to maintain the myofibril protein content. This response occurred despite fully blunting the increases in the mRNA for of atrogin-1, MURF-1, and myostatin, e.g., sensitive gene markers of an activated catabolic state. Analyses of the IRS-1/PI3K/Akt markers indicated that abundance of IRS-1 and phosphorylation state of Akt and p70S6 kinase were decreased relative to normal control rats, and the resistance training failed to maintain these signaling markers at normal regulatory level. Our findings suggest that to fully prevent muscle atrophy responses affecting the myofibril system during unloading, the volume of mechanical stress must be augmented sufficiently to maintain optimal activity of the IRS-1/PI3K/Akt pathway to provide an effective anabolic stimulus on the muscle.

IL-6-induced skeletal muscle atrophy.

Chronic, low-level elevation of circulating interleukin (IL)-6 is observed in disease states as well as in many outwardly healthy elderly individuals. Increased plasma IL-6 is also observed after intense, prolonged exercise. In the context of skeletal muscle, IL-6 has variously been reported to regulate carbohydrate and lipid metabolism, increase satellite cell proliferation, or cause muscle wasting. In the present study, we used a rodent local infusion model to deliver modest levels of IL-6, comparable to that present after exercise or with chronic low-level inflammation in the elderly, directly into a single target muscle in vivo. The aim of this study was to examine the direct effects of IL-6 on skeletal muscle in the absence of systemic changes in this cytokine. Data included cellular and molecular markers of cytokine and growth factor signaling (phosphorylation and mRNA content) as well as measurements to detect muscle atrophy. IL-6 infusion resulted in muscle atrophy characterized by a preferential loss of myofibrillar protein (-17%). IL-6 induced a decrease in the phosphorylation of ribosomal S6 kinase (-60%) and STAT5 (-33%), whereas that of STAT3 was increased approximately twofold. The changes seen in the IL-6-infused muscles suggest alterations in the balance of growth factor-related signaling in favor of a more catabolic profile. This suggests that downregulation of growth factor-mediated intracellular signaling may be a mechanism contributing to the development of muscle atrophy induced by elevated IL-6.

Direct relationship between proton T2 and exercise intensity in skeletal muscle MR images.

Exercise selectively increases the signal intensities (SI) of active muscles in T2-weighted magnetic resonance (MR) images. If these SI increases are graded with exercise intensity, the identification of muscle recruitment patterns may be possible using MR imaging. The purpose of this study was to determine the effect of force generation during exercise on muscle T2 values. Also, we examined the effects of extracellular fluid volume (ECV) expansion on muscle T2 values. Transaxial midcalf images were collected before and after exercise on eight volunteers in a 1.5T GE magnet using a standard spin echo sequence. Exercise consisted of three consecutive bouts of ankle dorsiflexion against graded loads. Three subjects also underwent brief bouts of lower leg venous occlusion (ECV expansion) during and in addition to the exercise protocol. T2 values for the dorsiflexors significantly increased after exercise. Greater mean force produced during exercise caused greater increases in T2 after exercise (T2 = 29.6 +/- 0.9 X Force). Exercise and venous occlusion caused equivalent increases in muscle cross-sectional area. These equivalent increases in ECV were not accompanied by equivalent increases in muscle T2; venous occlusion alone caused less than a 5% increase in T2 while exercise caused a 14% to 25% increase. Consequently, a direct relationship between increases in T2 and in ECV after exercise was not established. Venous occlusion during exercise, however, did significantly augment the increase in T2 and ECV of the anterior compartment muscles. Contrast enhancement among muscles after exercise in T2-weighted MR images is dependent on generated force during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationships among IGF-1, DNA content, and protein accumulation during skeletal muscle hypertrophy.

Insulin-like growth factor-1 (IGF-1) is known to have anabolic effects on skeletal muscle cells. This study examined the time course of muscle hypertrophy and associated IGF-1 peptide and mRNA expression. Data were collected at 3, 7, 14, and 28 days after surgical removal of synergistic muscles of both normal and hypophysectomized (HX) animals. Overloading increased the plantaris (Plant) mass, myofiber size, and protein-to-body weight ratio in both groups (normal and HX; P < 0.05). Muscle IGF-1 peptide levels peaked at 3 (normal) and 7 (HX) days of overloading with maximum 4.1-fold (normal) and 6.2-fold (HX) increases. Increases in muscle IGF-1 preceded the hypertrophic response. Total DNA content of the overloaded Plant increased in both groups. There was a strong positive relationship between IGF-1 peptide and DNA content in the overloaded Plant from both groups. These results indicate that 1) the muscles from rats with both normal and severely depressed systemic levels of IGF-1 respond to functional overload with an increase in local IGF-1 expression and 2) this elevated IGF-1 may be contributing to the hypertrophy response, possibly via the mobilization of satellite cells to provide increases in muscle DNA.

Localized infusion of IGF-I results in skeletal muscle hypertrophy in rats.

Insulin-like growth factor I (IGF-I) peptide levels have been shown to increase in overloaded skeletal muscles (G. R. Adams and F. Haddad. J. Appl. Physiol. 81: 2509-2516, 1996). In that study, the increase in IGF-I was found to precede measurable increases in muscle protein and was correlated with an increase in muscle DNA content. The present study was undertaken to test the hypothesis that direct IGF-I infusion would result in an increase in muscle DNA as well as in various measurements of muscle size. Either 0.9% saline or nonsystemic doses of IGF-I were infused directly into a non-weight-bearing muscle of rats, the tibialis anterior (TA), via a fenestrated catheter attached to a subcutaneous miniosmotic pump. Saline infusion had no effect on the mass, protein content, or DNA content of TA muscles. Local IGF-I infusion had no effect on body or heart weight. The absolute weight of the infused TA muscles was approximately 9% greater (P < 0.05) than that of the contralateral TA muscles. IGF-I infusion resulted in significant increases in the total protein and DNA content of TA muscles (P < 0.05). As a result of these coordinated changes, the DNA-to-protein ratio of the hypertrophied TA was similar to that of the contralateral muscles. These results suggest that IGF-I may be acting to directly stimulate processes such as protein synthesis and satellite cell proliferation, which result in skeletal muscle hypertrophy.

Age dependence of myosin heavy chain transitions induced by creatine depletion in rat skeletal muscle.

This study was designed to test the hypothesis that myosin heavy chain (MHC) plasticity resulting from creatine depletion is an age-dependent process. At weaning (age 28 days), rat pups were placed on either standard rat chow (normal diet juvenile group) or the same chow supplemented with 1% wt/wt of the creatine analogue beta-guanidinopropionic acid [creatine depletion juvenile (CDJ) group]. Two groups of adult rats (age approximately 8 wk) were placed on the same diet regimens [normal diet adult and creatine depletion adult (CDA) groups]. After 40 days (CDJ and normal diet juvenile groups) and 60 days (CDA and normal diet adult groups), animals were killed and several skeletal muscles were removed for analysis of creatine content or MHC distribution. In the CDJ group, creatine depletion (78%) was accompanied by significant shifts toward expression of slower MHC isoforms in two slow and three fast skeletal muscles. In contrast, creatine depletion in adult animals did not result in similar shifts toward slow MHC isoform expression in either muscle type. The results of this study indicate that there is a differential effect of creatine depletion on MHC transitions that appears to be age dependent. These results strongly suggest that investigators contemplating experimental designs involving the use of the creatine analogue beta-guanidinopropionic acid should consider the age of animals to be used.

Time course of changes in markers of myogenesis in overloaded rat skeletal muscles.

During the process of compensatory muscle hypertrophy, satellite cells are thought to proliferate, differentiate, and then fuse with existing myofibers. We hypothesized that early in this process changes occur in the expression of cellular markers indicative of the onset of myogenic processes. The plantaris muscles of rats were overloaded via the unilateral ablation of synergists. Groups of rats were killed at time points from 6 h to 12 days. Changes in muscle gene expression (mRNA) of cyclin D1, p21, myogenin, MyoD, and insulin-like growth factor I (IGF-I, mRNA and peptide) were measured. Cyclin D1 (a cell cycle marker) was increased after 24 h of overloading and corresponded with changes in muscle DNA content. In contrast, p21 and myogenin, markers of cellular differentiation, were increased after just 12 h. Muscle IGF-I peptide levels were also increased at early time points. The results of this study indicate that myogenic processes are activated in response to increased loading at very early time points (e.g., 12 h) and that IGF-I may be modulating this response. Furthermore, these findings suggest that some cells may have been differentiating very early in the adaptation process before events leading to cellular proliferation have been initiated.

Interaction of chronic creatine depletion and muscle unloading: effects on postural locomotor muscles.

In some rodent skeletal muscles, hindlimb non-weight-bearing activity induces a shift in the expression of myosin heavy chains (MHCs) that favors the type II isoforms at the expense of type I. Chemically induced chronic creatine depletion results in isomyosin shifts favoring expression of type I MHCs. In this study, creatine depletion was induced separately and in combination with non-weight-bearing activity to determine if the response to lowering this metabolite would counter the MHC transitions expected from non-weight bearing. Creatine depletion was induced by feeding rats a diet supplemented with the creatine analogue beta-guanidinopropionic acid (beta-GPA). Female Sprague-Dawley rats weighing 247 +/- 8 g were randomly assigned to four groups: 1) normal diet control, 2) beta-GPA control (BC), 3) normal diet suspended (NS), and 4) beta-GPA suspended (BS). BC and BS animals were fed a diet containing the creatine analogue for 68 days. Hindlimb non-weight bearing in BS and NS animals was accomplished by tail suspension for the final 30 days of this period. beta-GPA feeding lowered the creatine content of muscles sampled by 65%. Creatine depletion resulted in a 16% increase in citrate synthase activity in the soleus (SOL) and a 24% increase in the plantaris (PLN). In two postural muscles, the SOL and vastus intermedius (VI), tail suspension resulted in large decreases in the type I MHC expression and increases in type IIx and IIb MHCs. In two locomotor muscles, the PLN and medial gastrocnemius, type I MHC declined and type IIb increased with suspension.(ABSTRACT TRUNCATED AT 250 WORDS)

Mapping of electrical muscle stimulation using MRI.

The purpose of this study was to map the pattern of muscle contractile activity elicited by electromyostimulation (EMS). A secondary interest was to determine whether EMS evoked a different pattern of contractile activity than voluntary (VOL) efforts. These objectives were addressed by examining the pattern and extent of contrast shift in magnetic resonance (MR) images after isometric actions of the left m. quadriceps of seven subjects had been elicited by EMS (1-s train of 500-microseconds sine wave pulses at 50 Hz) or by VOL means. For both conditions, five sets of 10 muscle actions were executed at each of the three force levels equal to 25, 50, and 75% of maximal VOL isometric torque. There were 1-s, 1.5-min, and 30-min rests between muscle actions, sets, and torque levels, respectively. Transaxial proton MR images (TR/TE = 2,000/30, 60) of m. quadriceps femoris were obtained with a 1.5-T imager at rest and after completion of the five sets of isometric actions at each force level. MR image contrast shift, as indicated by T2 values > 1 SD above the mean resting muscle T2, was calculated per pixel. Torque declined approximately 18% (P < 0.05) during each EMS set independent of the preset relative force level but recovered between sets. EMS increased T2 values above rest (29 +/- 0.2 to 36 +/- 0.5, P < 0.05) in regions of muscle dispersed throughout a given cross section. The pattern of muscle stimulation, as reflected by increased T2 values, varied markedly among subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Myosin heavy chain expression in rodent skeletal muscle: effects of exposure to zero gravity.

This study ascertained the effects of 9 days of zero gravity on the relative (percentage of total) and calculated absolute (mg/muscle) content of isomyosin expressed in both antigravity and locomotor skeletal muscle of ground control (CON) and flight-exposed (FL) rats. Results showed that although there were no differences in body weight between FL and CON animals, a significant reduction in muscle mass occurred in the vastus intermedius (VI) (P < 0.05) but not in the vastus lateralis (VL) or the tibialis anterior. Both total muscle protein and myofibril protein content were not different between the muscle regions examined in the FL and CON groups. In the VI, there were trends for reductions in the relative content of type I and IIa myosin heavy chains (MHCs) that were offset by increases in the relative content of both type IIb and possibly type IIx MHC protein (P > 0.05). mRNA levels were consistent with this pattern (P < 0.05). The same pattern held true for the red region of the VL as examined at both the protein and mRNA level (P < 0.05). When the atrophy process was examined, there were net reductions in the absolute content of both type I and IIa MHCs that were offset by calculated increases in type IIb MHC in both VI and red VL. Collectively, these findings suggest that there are both absolute and relative changes occurring in MHC expression in the "red" regions of antigravity skeletal muscle during exposure to zero gravity that could affect muscle function.

Muscle buffer capacity estimated from pH changes during rest-to-work transitions.

Gated phosphorus nuclear magnetic resonance (31P-NMR) spectra were acquired after 5 or 9 s of 5-Hz stimulation in rat and cat skeletal muscles, respectively. Net phosphocreatine (PCr) hydrolysis was associated with an intracellular alkalinization of 0.08 +/- 0.01 and 0.05 +/- 0.003 pH units in isolated perfused cat biceps and soleus, respectively, and 0.12 +/- 0.02 in the superficial predominantly fast-twitch white portion of gastrocnemius of anesthetized rats. The net change in [H+] expected from PCr hydrolysis was calculated, and apparent buffer capacity (beta) in intact muscles was calculated from beta = delta [H+]/delta pH. The beta of the same muscle types was also estimated from titration of muscle homogenates between pH 6.0 and 8.0. The contribution of Pi to total beta of the homogenates was subtracted to ascertain the non-Pi beta for each muscle. The non-Pi beta values were added to the actual amount of Pi present in the stimulated muscles to calculate a predicted beta at pH 7. The apparent beta calculated from PCr and pH changes in intact muscles and the predicted beta from homogenate titrations were in good agreement (38 +/- 9 vs. 38 slykes in cat biceps, 21 +/- 7 vs. 30 in cat soleus, and 30 +/- 6 vs. 27 in rat gastrocnemius). The results indicate that changes in pH during the first few seconds of contraction can be entirely accounted for by proton consumption via net PCr hydrolysis.

Magnetic resonance imaging and electromyography as indexes of muscle function.

Electromyography (EMG) is commonly used to determine the electrical activity of skeletal muscle during contraction. To date, independent verification of the relationship between muscle use and EMG has not been provided. It has recently been shown that relaxation- (e.g., T2) weighted magnetic resonance images (MRI) of skeletal muscle demonstrate exercise-induced contrast enhancement that is graded with exercise intensity. This study was conducted to test the hypothesis that exercise-induced magnetic resonance (MR) contrast shifts would relate to EMG amplitude if both measures reflect muscle use during exercise. Both MRI and EMG data were collected for separate eccentric (ECC) and concentric (CON) exercise of increasing intensity to take advantage of the fact that the rate of increase and amplitude of EMG activity are markedly greater for CON muscle actions. Seven subjects 30 +/- 2 (SE) yr old performed five sets of 10 CON or ECC arm curls with each of four resistances representing 40, 60, 80, and 100% of their 10 repetition maximum for CON curls. There was 1.5 min between sets and 30 min between bouts (5 sets of 10 actions at each relative resistance). Multiple echo, transaxial T2-weighted MR images (1.5 T, TR/TE 2,000/30) were collected from a 7-cm region in the middle of the arm before exercise and immediately after each bout. Surface EMG signals were collected from both heads of the biceps brachii and the long head of the triceps brachii muscles. CON and ECC actions resulted in increased integrated EMG (IEMG) and T2 values that were strongly related (r = 0.99, P < 0.05) with relative resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Running performance and cardiovascular capacity are not impaired in creatine-depleted rats.

Several published reports have indicated that derangement of the phosphocreatine/creatine (Cr) energy-buffering system via Cr analogue feeding results in cardiomyopathy when cardiac performance is assessed in vitro. The present study was designed to examine indexes of cardiac performance in rats that have been chronically Cr depleted. Adult (180 +/- 4 g) rats were assigned to a normal diet (ND) (n = 8) or a Cr-depletion diet (CD) group (n = 10). After 61 +/- 1 days of ad libitum feeding, measurements of steady-state exercise O2 consumption were made. Hemodynamic indexes were then assessed during incremental running to peak sustained levels. Rats were then killed and the left ventricle was excised. In the CD group Cr was depleted 82% and V1 isomyosin decreased while V2 increased. O2 consumption during steady-state running was not different in CD rats. The respiratory exchange ratios of CD rats reflected a bias toward fat utilization during the latter stages of prolonged exercise. The exercise heart rates and peak systolic blood pressures of CD rats were slightly lower than those of ND rats. Both negative and positive rates of left ventricular pressure development were significantly reduced at all running speeds in the CD rats. CD rats were capable of exercise performance equal to that of ND animals. The hemodynamic and metabolic data suggest that the adaptations seen in the CD animals may be similar to those reported after endurance training. These results indicate that chronic Cr depletion does not impair either the circulatory or exercise capacity of rodents.

Skeletal muscle myosin heavy chain composition and resistance training.

We recently reported that 19 wk of heavy resistance training caused a decrease in the percentage of type IIb and an increase in the percentage of type IIa fibers as determined by qualitative histochemical analyses of myofibrillar adenosinetriphosphatase activity of biopsies of musculus vastus lateralis (Hather et al. Acta Physiol. Scand. 143: 177-185, 1991). These data were interpreted to suggest that resistance training had caused transformation among the fast-twitch fiber subtypes. To more clearly establish the influence of resistance training on muscle fiber composition, biopsies from the original study were analyzed biochemically for myosin heavy chain (MHC) composition by use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis and histochemically for fiber types by use of myofibrillar adenosinetriphosphatase activity. The results show that after training (n = 13), IIb MHC composition decreased (P < 0.05) from 19 +/- 4 to 7 +/- 1%. IIa MHC, in contrast, increased (P < 0.05) from 48 +/- 3 to 60 +/- 2%. These responses were essentially mirrored by alterations in fiber type distribution. The percentage of type IIb fibers decreased (P < 0.05) from 18 +/- 3 to 1 +/- 1%, whereas the percentage of type IIa fibers increased from 46 +/- 4 to 60 +/- 3% (P < 0.05). Neither I MHC composition nor type I fiber percentage changed with training. The control group (n = 4) showed no changes in MHC composition or fiber type distribution. These results suggest that heavy resistance training alters MHC composition in human skeletal muscle, presumably reflecting a change in genetic expression.

Effects of spaceflight and thyroid deficiency on hindlimb development. I. Muscle mass and IGF-I expression.

Thyroid deficiency (TD) in neonatal rats causes reduced growth of skeletal muscle that is disproportionately greater than that for other tissues (G. R. Adams, S. A. McCue, M. Zeng, and K. M. Baldwin. Am. J. Physiol. Regulatory Integrative Comp. Physiol. 276: R954-R961, 1999). TD depresses plasma insulin-like growth factor I (IGF-I) levels, suggesting a mechanism for this effect. We hypothesized that TD and exposure to spaceflight (SF) would interact to reduce skeletal muscle growth via a reduction in IGF-I levels. Neonatal rats were flown in space for 16 days. There was a similar, nonadditive reduction in the growth of the body ( approximately 50%) and muscle weight (fast muscles, approximately 60%) with either TD or SF. In the soleus muscle, either SF or TD alone resulted in growth reductions that were augmented by SF-TD interactions. There were strong correlations between 1) muscle mass and muscle IGF-I levels and 2) circulating IGF-I and body weight. These results indicate that either hypothyroidism or exposure to SF will limit the somatic and muscle-specific growth of neonatal rats. The impact of these perturbations on skeletal muscle growth is relatively greater than the effect on somatic growth. The mechanisms by which either TD or SF impact growth appear to have a common pathway involving the control of plasma and muscle IGF-I concentrations.

Skeletal muscle responses to lower limb suspension in humans.

Eight subjects participated in a 6-wk unilateral lower limb suspension (ULLS) study to determine the influence of reduced weight bearing on human skeletal muscle morphology. The right shoe was outfitted with a platform sole that prevented the left foot from bearing weight while walking with crutches, yet it allowed freedom of movement about the ankle, knee, and hip. Magnetic resonance images pre- and post-ULLS showed that thigh muscle cross-sectional area (CSA) decreased (P less than 0.05) 12% in the suspended left lower limb, whereas right thigh muscle CSA did not change. Likewise, magnetic resonance images collected post-ULLS showed that muscle CSA was 14% smaller (P less than 0.05) in the left than in the right leg. The decrease in muscle CSA of the thigh was due to a twofold greater response of the knee extensors (-16%, P less than 0.05) than knee flexors (-7%, P less than 0.05). The rectus femoris muscle of the knee extensors showed no change in CSA, whereas the three vastus muscles showed similar decreases of approximately 16% (P less than 0.05). The apparent atrophy in the leg was due mainly to reductions in CSA of the soleus (-17%) and gastrocnemius muscles (-26%). Biopsies of the left vastus lateralis pre- and post-ULLS showed a 14% decrease (P less than 0.05) in average fiber CSA. The decrease was evident in both type I (-12%) and II (-15%) fibers. The number of capillaries surrounding the different fiber types was unchanged after ULLS.(ABSTRACT TRUNCATED AT 250 WORDS)