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At least 19 records

Interaction of Mechanical Load with Growth Hormone (GH) and Insulin-Like Growth Factor I (IGF-I) on Slow-Twitch Skeletal Muscle and Bone

Exogenous humoral growth factors, combined with increased mechanical loading, reportedly induce hypertrophy of fast-, but not slow-twitch skeletal muscles, and have little effect in attenuating atrophy of slow-twitch muscle associated with exposure to microgravity in animals with intact neuroendocrine systems. These observations suggest that anabolic adjuvants and muscle tension do not interact to stimulate growth or maintenance of slow-twitch skeletal muscle. The purpose of the present study was to determine whether a chronic increase in mechanical loading (synergistic ablation) or hindlimb unweighting (hindlimb suspension) interact with exogenous GH and IGF-I (Genentech, So San Francisco, CA) in the slow-twitch soleus muscles of female rats (approx. 250 g). Bilateral ablation of the plantaris and gastrocnemius muscles induced 38% and 40% increases in the absolute (mg/pair) and relative (mg/100 g body weight) weights of the soleus, respectively (p less than or = 0.05), in ambulatory rats. GH and IGF-I interacted with chronic loading to increase absolute soleus mass an additional 20% (p less than or = 0.05), and mixed and myofibrillar protein contents an additional 12% and 7%, respectively (NS). In contrast, hindlimb suspension (HLS) resulted in 20% and 18% decreases in the absolute and relative weights of the soleus, respectively (p less than or = 0.05); GH and IGF-I did not spare loss of soleus mass or protein content in HLS rats. HLS decreased tibial plate thickness approx. 11% (p less than or = 0.05), but not weights of the tibia or femus. GH and IGF-I increased tibial plate thickness approx. 30% (p less than or = 0.05), in ambulatory and HLS rats, and increased femur and tibial weights 12% (p less than or = 0.05) and 8% (NS), respectively, in ambulatory rats, but had no effect in HLS rats. Results of the present investigation suggest that GH and IGF-I can stimulate hypertrophy of slow-twitch skeletal muscle when chronically overloaded, but can also stimulate growth of hindlimb bones in the absence of mechanical load.

Linderman, Jon K.↗

Adaptive responses of GLUT-4 and citrate synthase in fast-twitch muscle of voluntary running rats

Glucose transporter (GLUT-4) protein, hexokinase, and citrate synthase (proteins involved in oxidative energy production from blood glucose catabolism) increase in response to chronically elevated neuromuscular activity. It is currently unclear whether these proteins increase in a coordinated manner in response to this stimulus. Therefore, voluntary wheel running (WR) was used to chronically overload the fast-twitch rat plantaris muscle and the myocardium, and the early time courses of adaptative responses of GLUT-4 protein and the activities of hexokinase and citrate synthase were characterized and compared. Plantaris hexokinase activity increased 51% after just 1 wk of WR, whereas GLUT-4 and citrate synthase were increased by 51 and 40%, respectively, only after 2 wk of WR. All three variables remained comparably elevated (+50-64%) through 4 wk of WR. Despite the overload of the myocardium with this protocol, no substantial elevations in these variables were observed. These findings are consistent with a coordinated upregulation of GLUT-4 and citrate synthase in the fast-twitch plantaris, but not in the myocardium, in response to this increased neuromuscular activity. Regulation of hexokinase in fast-twitch muscle appears to be uncoupled from regulation of GLUT-4 and citrate synthase, as increases in the former are detectable well before increases in the latter.

Non-NASA Center↗

Adaptation of fibers in fast-twitch muscles of rats to spaceflight and hindlimb suspension

The adaptation of single fibers in medial gastrocnemius (MG), a fast-twitch extensor, and in tibialis anterior (TA), a fast-twitch flexor, was studied after 14 days of spaceflight onboard Cosmos 2044 or hindlimb suspension. Quantitative myosin ATPase activities of single fibers were measured in flight and suspended rats. Each of the enzyme and size measurements were directly correlated within each fiber with respect to its qualitative myosin ATPase staining properties and its expression of fast, slow, or both myosin heavy chains (MHC). The percentage of slow- and fast-twitch fibers of the MG and TA were found to be unchanged. Mean fiber size of all fibers was unaffected after flight or suspension. The ATPase activity in the MG was higher in flight than in control or suspended rats. In comparison to Cosmos 1887 spaceflight, the adaptations in the muscle fibers of the MG were more moderate.

Jiang, Bian↗

Coexistence of twitch potentiation and tetanic force decline in rat hindlimb muscle

The effect of whole-muscle fatigue on the isometric twitch was investigated in various hindlimb muscles of anesthetized rats, using an experimental protocol designed to assess the levels of fatigability in motor units. The results of EMG and force measurements revealed the existence of a linear relationship between fatigability and the magnitude of the twitch force following the fatigue test in both soleus and extensor digitorum longus muscles.

Rankin, Lucinda L.↗

cAMP levels in fast- and slow-twitch skeletal muscle after an acute bout of aerobic exercise

The present study examined whether exercise duration was associated with elevated and/or sustained elevations of postexercise adenosine 3',5'-cyclic monophosphate (cAMP) by measuring cAMP levels in skeletal muscle for up to 4 h after acute exercise bouts of durations that are known to either produce (60 min) or not produce (10 min) mitochondrial proliferation after chronic training. Treadmill-acclimatized, but untrained, rats were run at 22 m/min for 0 (control), 10, or 60 min and were killed at various postexercise (0, 0.5, 1, 2, and 4 h) time points. Fast-twitch white and red (quadriceps) and slow-twitch (soleus) muscles were quickly excised, frozen in liquid nitrogen, and assayed for cAMP with a commercial kit. Unexpectedly, cAMP contents in all three muscles were similar to control (nonexercise) at most (21 of 30) time points after a single 10- or 60-min run. Values at 9 of 30 time points were significantly different from control (P < 0.05); i.e., 3 time points were significantly higher than control and 6 were significantly less than control. These data suggest that the cAMP concentration of untrained skeletal muscle after a single bout of endurance-type exercise is not, by itself, associated with exercise duration.

NASA Discipline Musculoskeletal↗

Effect of spaceflight on the maximal shortening velocity, morphology, and enzyme profile of fast- and slow-twitch skeletal muscle fibers in rhesus monkeys

Weightlessness has been shown to cause limb muscle wasting and a reduced peak force and power in the antigravity soleus muscle. Despite a reduced peak power, Caiozzo et al. observed an increased maximal shortening velocity in the rat soleus muscle following a 14-day space flight. The major purpose of the present investigation was to determine if weightlessness induced an elevated velocity in the antigravity slow type I fibers of the rhesus monkey (Macaca mulatta), as well as to establish a cellular mechanism for the effect. Spaceflight or models of weightlessness have been shown to increase glucose uptake, elevate muscle glycogen content, and increase fatigability of the soleus muscle. The latter appears to be in part caused by a reduced ability of the slow oxidative fibers to oxidize fats. A second goal of this study was to establish the extent to which weightlessness altered the substrate profile and glycolytic and oxidative enzyme capacity of individual slow- and fast-twitch fibers.

Bion 11 Project↗

Contractile properties of rat fast-twitch skeletal muscle during reinnervation - Effects of testosterone and castration

The peroneal nerve of subject rats were crushed 1 cm from the muscle in order to examine the isometric contractile properties of skeletal muscle in the recovery sequency during reinnervation of normal, castrated, and testosterone-treated rats. The particular muscle studied was the extensor digitorum longus, with functional reinnervation first observed 8-9 days after nerve crush. No evidence was found that either castration or testosterone injections altered the process of reinnervation after the nerve crush, with the conclusion being valid at the 0.05 p level. The most reliable index of reinnervation was found to be the twitch:tetanus ratio, a factor of use in future studies of the reinnervation of skeletal muscle.

Yeagle, S. P.↗

Disuse Induced Changes in the Cholinergic System of Sciatic Nerve and Slow and Fast Twitch Muscle of Rats

Hindlimb suspension was used as a model of disuse in experiments studing the effects of reduced muscle activity on AChE and its molecular forms, choline acetyltransferase and nicotinic receptor binding in innervated slow and fast muscle. The weight of SOL was reduced to 64% within one week and continued to decrease progressively up to the third week when the weight was reduced to 40% as compared to controls. EDL showed a significant decrease in its weight only at the end of three weeks hypokinesia when it was reduced to 71% of control. Biochemical and histochemical findings are summarized. From these data and from morphological findings it is evident that some properties of skeletal muscles are strongly dependent on patterns and level of loadbearing and on motor unit activiy. With suspension-induced disuse, the usually slow SOL appeared to change its characteristics such as fiber type distribution and AChE activity to one that more resembled a faster muscle. It is important to note that hypokinesia induced changes either physiological, biochemical or morphological, are totally reversible as the induced changes returned to control levels within a week after cessation of disuse.

Dettbarn, W. D.↗

Use and disuse and the control of acetylcholinesterase activity in fast and slow twitch muscle of rat

The role of acetylcholinesterase (AChE) in neuromuscular transmission is relatively well established, little is known, however, of the mechanisms that regulate its synthesis and control its specific distribution in fast and slow muscle. Innervation plays an important role in the regulation of AChE and elimination of the influence of the nerve by surgical denervation results in a loss of AChE. The influences of the nerve and how they are mediated was investigated. It is suggested that muscle usage and other factors such as materials carried by axonal transport may participate in the regulation of this enzyme. The mechanisms that regulate AChE and its molecular forms in two functionally different forms are studied.

Dettbarn, W. D.↗

Size and metabolic properties of fibers in rat fast-twitch muscles after hindlimb suspension

The effect of hind-limb suspension (HS) on single fibers of the medial gastrocnemius (MG) and the tibialis anterior (TA) muscles were studied in rats. Fiber area and the activities of succinate dehydrogenase (SDH) and alpha-glycerophosphate dehydrogenase (GPD) were determined in tissue sections using an image analysis system. After 28 days of HS, the MG atrophied 28 percent, whereas the TA weight was maintained. Both dark- and light-ATPase fibers in the deep region of the MG had decreased cross-sectional areas following HS, with the atrophic response being twice as great in the light-ATPase fibers than in the dark-ATPase fibers. Following HS, mean SDH activities of both fiber types were significantly lower in the MG and TA than in the CON; by contrast, mean GPD activities were either maintained at the CON level or were higher in both MG and TA muscles. The data suggest an independence of the mechanisms determining the muscle fiber size and the metabolic adaptations associated with HS.

Roy, Roland R.↗

A comparison of rat myosin from fast and slow skeletal muscle and the effect of disuse

Certain enzymatic and structural features of myosin, purified from rat skeletal muscles representative of the fast twitch glycolytic (type IIb), the fast twitch oxidative (type IIa), and the slow twitch oxidative (type I) fiber, were determined and the results were compared with the measured contractile properties. Good correlation was found between the shortening velocities and Ca(2+)-activated ATPase activity for each fiber type. Short term hind limb immobilization caused prolongation of contraction time and one-half relaxation time in the fast twitch muscles and a reduction of these contractile properties in slow twitch soleus. Furthermore, the increased maximum shortening velocity in the immobilized soleus could be correlated with increased Ca(2+)-ATPase, but no change was observed in the enzymatic activity of the fast twitch muscles. No alteration in light chain distribution with disuse was observed in any of the fiber types. The myosin from slow twitch soleus could be distinguished from fast twitch myosins on the basis of the pattern of peptides generated by proteolysis of the heavy chains. Six weeks of hind limb immobilization resulted in both an increased ATPase activity and an altered heavy chain primary structure in the slow twitch soleus muscle.

Unsworth, B. R.↗

Contractile function of single muscle fibers after hindlimb suspension

The effects of two weeks of hind-limb suspension (HS) on the functional properties of slow-twitch and fast-twitch single fibers isolated from the predominantly slow-twitch soleus and fast-twitch gastrocnemius of the suspended leg of rats were investigated. Single fibers were suspended between a motor arm and force transducer, and, after their functional properties were studied, the fiber type was established by the myosin heavy chain analysis. It was found that, after HS, the greatest decrease in diameter and a reduction in peak tension occurred in slow-twitch fibers from soleus, followed by slow-twitch fibers from gastrocnemius. Fast-twitch fibers from the red gastrocnemius showed a significant reduction in diameter but no change in peak tension. No effect of HS was observed on the diameter of the fast-twitch fibers from the white gastsrocnemius (which is known to contain 87 percent fast glycolytic fibers).

Gardetto, P. R.↗

Recovery in skeletal muscle contractile function after prolonged hindlimb immobilization

The effect of three-month hindlimb immobilization (IM) in rats on contractile properties of slow-twitch soleus (SOL), fast-twitch extensor digitorum longus, and fast-twitch superficial region of the vastus lateralis were measured after 0, 14, 28, 60, and 90 days of recovery on excized, horizontally suspended muscles stimulated electrically to maximal twitch tension. IM caused decreases in muscle-to-body weight ratios for all muscles, with no complete recovery even after 90 days. The contractile properties of the fast-twitch muscles were less affected by IM than those of the slow-twitch SOL. The SOL isometric twitch duration was shortened, due to reduced contraction and half-relaxation time, both of which returned to control levels after 14 days of recovery. The peak tetanic tension, P(O), g/sq cm,, decreased with IM by 46 percent in the SOL, but recovered by the 28th day. The maximum shortening velocity was not altered by IM in any of the muscles. Thus, normal contractile function could recover after prolonged limb IM.

Fitts, R. H.↗

Models of disuse - A comparison of hindlimb suspension and immobilization

The effects of 1 and 2 weeks of hindlimb suspension (HS) on the contractile properties of fast- and slow-twitch skeletal muscles of male Sprague Dawley rats are studied and compared with hindlimb immobilization (HI) data. The optimal length and contractile properties of the slow-twitch soleus, fast-twitch extensor digitorum longus, and the vastus lateralis are measured. It is observed that HS and HI affect slow-twitch muscles; isometric twitch duration in the slow-twitch soleus is decreased. Soleus muscle mass and peak tetanic tension declines with disuse. A major difference in the influence of HS and HI on the maximal speed of soleus muscle shortening, V(max) is detected; HS produced a twofold increase in V(max) compared to control data and HI had no significant effect on V(max). The relation between V(max) and myosin concentration is analyzed. The data reveal that HS modifies slow-twitch muscle yielding hybrid fibers with elevated shortening velocities and this change may be dependent on the elimination of load-bearing contractions.

Fitts, R. H.↗

Slow to fast alterations in skeletal muscle fibers caused by clenbuterol, a beta(2)-receptor agonist

The effects of a beta(2)-receptor agonist, clenbuterol, and a beta(2) antagonist, butoxamine, on the skeletal muscle fibers of rats were investigated. It was found that chronic treatment of rats with clenbuterol caused hypertrophy of histochemically identified fast-twitch, but not slow-twitch, fibers within the soleus, while in the extensor digitorum longus the mean areas of both fiber types were increased; in both muscles, the ratio of the number of fast-twitch to slow-twitch fibers was increased. In contrast, a treatment with butoxamine caused a reduction of the fast-twitch fiber size in both muscles, and the ratio of the fast-twitch to slow-twitch fibers was decreased.

Zeman, Richard J.↗

Relation of systemic and local muscle exercise capacity to skeletal muscle characteristics in men with congestive heart failure

OBJECTIVES. The present study was undertaken to further characterize changes in skeletal muscle morphology and histochemistry in congestive heart failure and to determine the relation of these changes to abnormalities of systemic and local muscle exercise capacity. BACKGROUND. Abnormalities of skeletal muscle appear to play a role in the limitation of exercise capacity in congestive heart failure, but information on the changes in muscle morphology and biochemistry and their relation to alterations in muscle function is limited. METHODS. Eighteen men with predominantly mild to moderate congestive heart failure (mean +/- SEM New York Heart Association functional class 2.6 +/- 0.2, ejection fraction 24 +/- 2%) and eight age- and gender-matched sedentary control subjects underwent measurements of peak systemic oxygen consumption (VO2) during cycle ergometry, resistance to fatigue of the quadriceps femoris muscle group and biopsy of the vastus lateralis muscle. RESULTS. Peak VO2 and resistance to fatigue were lower in the patients with heart failure than in control subjects (15.7 +/- 1.2 vs. 25.1 +/- 1.5 ml/min-kg and 63 +/- 2% vs. 85 +/- 3%, respectively, both p < 0.001). Patients had a lower proportion of slow twitch, type I fibers than did control subjects (36 +/- 3% vs. 46 +/- 5%, p = 0.048) and a higher proportion of fast twitch, type IIab fibers (18 +/- 3% vs. 7 +/- 2%, p = 0.004). Fiber cross-sectional area was smaller, and single-fiber succinate dehydrogenase activity, a mitochondrial oxidative marker, was lower in patients (both p < or = 0.034). Likewise, the ratio of average fast twitch to slow twitch fiber cross-sectional area was lower in patients (0.780 +/- 0.06 vs. 1.05 +/- 0.08, p = 0.019). Peak VO2 was strongly related to integrated succinate dehydrogenase activity in patients (r = 0.896, p = 0.001). Peak VO2, resistance to fatigue and strength also correlated significantly with several measures of fiber size, especially of fast twitch fibers, in patients. None of the skeletal muscle characteristics examined correlated with exercise capacity in control subjects. CONCLUSIONS. These results indicate that congestive heart failure is associated with changes in the characteristics of skeletal muscle and local as well as systemic exercise performance. There are fewer slow twitch fibers, smaller fast twitch fibers and lower succinate dehydrogenase activity. The latter finding suggests that mitochondrial content of muscle is reduced in heart failure and that impaired aerobic-oxidative capacity may play a role in the limitation of systemic exercise capacity.

Non-NASA Center↗

Fatigue and contraction of slow and fast muscles in hypokinetic/hypodynamic rats

The effects of hypokinesia/hypodynamia (H/H) on the fatigability and contractile properties of the rat soleus (S) and gastrocnemius (G) muscles have been investigated experimentally. Whole body suspension for one week was used to induce H/H, and fatigue was brought on by train stimulation for periods of 45 and 16 minutes. Following stimulation, rapid rates of fatigue were observed in the G-muscles of the suspended rats, while minimal fatigue was observed in the S-muscles. The twitch and tetanic contractile properties of the muscles were measured before and after train stimulation. It is found that H/H suspension increased twitch tension in the G-muscles, but did not change any contractile properties in the S-muscles. The peak twitch, train, tetanic tensions and time to peak were unchanged in the S-muscles of the suspended rats. On the basis of the experimental results, it is concluded that 1 wk of muscle atropy induced by H/H significantly increases fatigability in G-muscles, but does not affect the contractile properties of fast-twitch and slow-twitch muscles.

Fell, R. D.↗

Rat soleus muscle fiber responses to 14 days of spaceflight and hindlimb suspension

Morphological and enzymatic responses in fibers of different types were studied in rats after 14 days of spaceflight onboard Cosmos 2044 or hindlimb suspension. Fibers were classified as fast-twitch, slow-twitch, or both fast- and slow-twitch on the basis of the type of myosin heavy chains (MHC). Data obtained indicate that during the 14 days of spaceflight or suspension the protein profiles of 9-14 percents of the slow-twitch fibers reconfigured from typical slow-twitch toward fast switch fibers, while all fibers were dramatically losing total protein. These results were consistent with the data obtained from Cosmos 1887 and Skylab 3. It is suggested that effects of spaceflight on skeletal muscle can be attributed to a dramatic reduction in the level and/or pattern of loading.

Ohira, Yoshi↗