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At least 145 records · Page 8

Hindlimb immobilization - Length-tension and contractile properties of skeletal muscle

Casts were placed around rat feet in plantar flexion position to immobilize the soleus muscle in a shortened position, while the other foot was fixed in dorsal flexion to set the extensor digitorum longus in a shortened position. The total muscular atrophy and contractile properties were measured at 1, 2, 4, 7, 14, 21, 28, 35, and 42 days after immobilization, with casts being replaced every two weeks. The slow twitch soleus and the fast-twitch vastus lateralis and longus muscles were excised after termination of the experiment. The muscles were then stretched and subjected to electric shock to elicit peak tetanic tension and peak tetanic tension development. Force velocity features of the three muscles were assayed in a series of afterloaded contractions and fiber lengths were measured from subsequently macerated muscle. All muscles atrophied during immobilization, reaching a new steady state by day 21. Decreases in fiber and sarcomere lengths were also observed.

Witzmann, F. A.↗

The validity of an animal model for experiments related to weightlessness

Animal evolution has witnessed morphological and physiological adaptations to gravitational forces. In the rat, hind limb muscles can be used to illustrate a range of load bearing functions: soleus - gastrocnemius = plantaris - extensor digitorum longus (EDL). A harness suspension apparatus is used to induce hypokinesia and hypodynamia (H&H) and to simulate responses comparable to those seen in weightlessness (i.e., COSMOS experiments). After one and two weeks of suspension H&H, there is muscle atrophy with a loss in muscle mass; the result of loss in muscle protein. Concommitantly, there is a decrease in RNA, but not in DNA content. The effects are greatest in the soleus and least in the EDL. These recent findings, in concert with earlier reports of increased nitrogenous excretion, suggest that both decreased protein synthesis and increased protein catabolism are characteristic of muscle atrophy. Recovery is seen in terms of reversal of these effects after removal from suspension.

Musacchia, X. J.↗

Glucocorticoid sensitivity, disuse, and the regulation of muscle mass

A new noninvasive immobilization procedure to be used on rats has been developed to study immobilization-induced muscle hypersensitivity to normal glucocorticoid concentration, subsequent muscle atrophy, and atrophy recovery. The immobilization procedure involves encasing the hind limb in a light-weight plasticlike cast (10 percent the usual plaster weight), completely resistant to animal gnawing. The effects of right-angle immobilization of the ankle on the slow fiber soleus, and the fast fiber extensor digitorum longus, resemble the effects of weightlessness. The increased concentration of glucocorticoid receptor sites in immobilized and denervated muscle is discussed, along with the chronic loss of muscle mass that occurs in practically all dystrophies. It is concluded that lack of mechanical work in a zero gravity environment is a major cause of glucocorticoid hypersensitivity in the body's musculature.

Almon, R. R.↗

Muscle and the physiology of locomotion

NASA's past, current, and planned research on muscle deterioration at zero gravity and development of countermeasures are reviewed; Soviet studies are discussed as well. A definition of muscle mass and strength regulation factors, and improved measurement methods of muscle atrophy are needed. Investigations of tissue growth factors and their receptors, endogenous and exogenous anabolic protein synthesis stimulation, and a potential neurotropic factor are among the projects in progress or planned. At present, vigorous physical exercise during spaceflight is recommended as the most effective countermeasure against skeletal muscle atrophy.

Rambaut, P. C.↗

The influence of rat suspension-hypokinesia on the gastrocnemius muscle

Hind-limb hypokinesia was induced in rats by the Morey method to characterize the response of the gastrocnemius muscle. A comparison of rats suspended for 2 weeks with weight, sex, and litter-matched control rats indicate no difference in gastrocnemius wet weight, contraction, or one-half relaxation times, but less contractile function as indicated by lowered dP/dt. Myosin ATPase staining identified uniform Type I (slow-twitch) and II (fast-twitch) atrophy in the muscles from 4 of 10 rats suspended for 2 weeks and 1 of 12 rats suspended for 4 weeks; muscles from three other rats of the 4-week group displayed greater Type I atrophy. Other histochemical changes were characteristic of a neuropathy. These data together with recently acquired soleus data (29) indicate the Morey model, like space flight, evokes greater changes in the Type I or slow twitch fibers of the gastrocnemius and soleus muscles.

Templeton, G. H.↗

Nutrition in Space Flight: Some Thoughts

Space flight causes physiological changes related to microgravity and on which nutrition has a bearing. Examples are: muscle atrophy-protein; bone atrophy-calcium; phosphorus, and vitamin D; space sickness-fat; cardiovascular deconditioning-sodium; water, and potassium. The physiological changes are discussed which relate to living in space.

Johnson, P. C., Jr.↗

Thymic involution in the suspended rat model for weightlessness - Decreased glucocorticoid receptor concentration

Hindlimb muscle atrophy, thymic involution and adrenal hypertrophy in rats during spaceflight can be simulated using suspension models. Skeletal muscle and thymus are sensitive to gluco-corticoids (GC), and previous studies have demonstrated that muscle atrophy in suspended rats is associated with increased GC receptor concentration. The objectives were to confirm thymic involution during suspension, and determine if involution correlated with increased GC receptor concentration. Seven days of antiorthostatic (AO) suspension of rats produced a significant (P less than 0.001) reduction in thymic wet weight not associated with an alteration of percent water content. GC receptor concentration (pmol/mg protein) decreased 20 percent (P less than 0.025) in thymus glands from 7 day AO suspended rats. Suspension, therefore, is associated with involution of the thymus, but this is not dependent upon AO positioning. Thymus GC receptor concentrations were depressed in 7-day suspended rats, in contrast with previous observations on skeletal muscle, suggesting that different mechanisms may underlie these responses.

Steffen, J. M.↗

In vivo nuclear magnetic resonance imaging

During the past year the Woodlands Baylor Magnetic Resonance Imaging (MRI) facility became fully operational. A detailed description of this facility is given. One significant instrument addition this year was the 100 MHz, 40cm bore superconducting imaging spectrometer. This instrument gives researchers the capability to acquire high energy phosphate spectra. This will be used to investigate ATP, phosphocreatinine and inorganic phosphate changes in normal and atrophied muscle before, during and after exercise. An exercise device for use within the bore of the imaging magnet is under design/construction. The results of a study of T sub 1 and T sub 2 changes in atrophied muscle in animals and human subjects are given. The imaging and analysis of the lower leg of 15 research subjects before and after 5 weeks of complete bedrest was completed. A compilation of these results are attached.

Leblanc, A.↗

Adaptation and readaptation medical concerns of a Mars trip

The ability of the human body to adapt to microgravity environments and to later readapt to a gravity environment was examined. Issues specifically relating to the effects of long duration space flight on the adaptation/readaptation process are discussed. The need for better health prediction techniques is stressed in order to be able to better anticipate crew health problems and to perform corrective actions. Several specific examples are discussed of latent diseases which could occur during a long duration space mission, even after having subjected the crew to thorough premission checkups. The need for learning how to prevent or ameliorate such problems as space adaptation syndrome, bone and muscle (and possibly tissue) atrophy, immune system atrophy, and heart arrythmias is also discussed. The implications of the age of the crew, the influence of an onboard low level gravity field, and drugs are briefly addressed as factors in the adaptation/readaptation process.

Johnson, Philip C.↗

Periodic weight support effects on rat soleus fibers after hindlimb suspension

The morphological and histochemical properties of rat soleus muscles were investigated following one week of hindlimb suspension. Short-duration daily weight support activity is shown to ameliorate, but not prevent, soleus atrophy induced by hindlimb suspension. The results indicate that fiber cross-sectional area is more responsive to periodic weight support in dark than light ATPas fibers, and that muscle fiber atrophy need not be associated with a loss in succinate dehydrogenase activity.

Hauschka, Edward O.↗

Effects of immobilization on rat hind limb muscles under non-weight-bearing conditions

The effect of stretched and unstretched immobilization of a hind limb on the concentration and the metabolism of proteins in the hind-limb muscles of rats was investigated. The animals were divided into three groups: (1) weight-bearing controls, (2) tail-cast-suspended, and (3) suspended, with one hind limb immobilized with the ankle in dorsiflexion (30-40 deg angle) and the other freely moving. It was found that unloading the hind limbs for 6 days by tail cast suspension caused soleus to atrophy and reduced growth of the gastrocnemius and plantaris muscles; unloading resulted in a higher degradation rate and lower synthesis rate in both in vitro and in vivo. Chronic stretch of the unloaded soleus not only prevented its atrophy but led to significant hypertrophy, relative to weight-bearing controls, with increases in both the sarcoplasmic and myofibrillar protein fractions. Immobilizing one ankle in dorsiflexion prevented the inhibition of growth in the plantaris and gastrocnemius muscles due to unloading.

Jaspers, Stephen R.↗

Experiment K-6-09. Morphological and biochemical investigation of microgravity-induced nerve and muscle breakdown. Part 1: Investigation of nerve and muscle breakdown during spaceflight; Part 2: Biochemical analysis of EDL and PLT muscles

The present findings on rat hindlimb muscles suggest that skeletal muscle weakness induced by prolonged spaceflight can result from a combination of muscle fiber atrophy, muscle fiber segmental necrosis, degeneration of motor nerve terminals and destruction of microcirculatory vessels. Damage was confined to the red adductor longus (AL) and soleus muscles. The midbelly region of the AL muscle had more segmental necrosis and edema than the ends. Macrophages and neutrophils were the major mononucleated cells infiltrating and phagocytosing the cellular debris. Toluidine blue-positive mast cells were significantly decreased in Flight AL muscles compared to controls; this indicated that degranulation of mast cells contributed to tissue edema. Increased ubiquitination of disrupted myofibrils may have promoted myofilament degradation. Overall, mitochondria content and SDH activity were normal, except for a decrease in the subsarcolemmal region. The myofibrillar ATPase activity shifted toward the fast type in the Flight AL muscles. Some of the pathological changes may have occurred or been exacerbated during the 2 day postflight period of readaptation to terrestrial gravity. While simple atrophy should be reversible by exercise, restoration of pathological changes depends upon complex processes of regeneration by stem cells. Initial signs of muscle and nerve fiber regeneration were detected. Even though regeneration proceeds on Earth, the space environment may inhibit repair and cause progressive irreversible deterioration during long term missions. Muscles obtained from Flight rats sacrificed immediately (within a few hours) after landing are needed to distinguish inflight changes from postflight readaptation.

Riley, D. A.↗

Experiment K-6-11. Actin mRNA and cytochrome c mRNA concentrations in the tricepts brachia muscle of rats

It is well known that some skeletal muscles atrophy as a result of weightlessness (Steffen and Musacchia 1986) and as a result of hindlimb suspension (Tischler et al., 1985, Thomason et al., 1987). Because the content of protein is determined by the rates of protein synthesis and degradation, a decrease in protein synthesis rate, or an increase in the protein degradation, or changes in both could produce the atrophy. Indeed, an increased protein degradation (Tischler et al., 1985) and a decreased protein synthesis (Thomason et al., 1988) have been observed in skeletal muscles of suspended hindlimbs of rats. Any decrease in protein synthesis rate could be caused by decreases in mRNA concentrations. Such decreases in the concentration and content of alpha-actin mRNA and cytochrome c mRNA have been noted in skeletal muscles of hindlimb suspended rats (Babij and Booth, 1988). From these findings researchers hypothesized that alpha-actin mRNA and cytochrome c mRNA would decrease in the triceps brachia muscle of Cosmos 1887 rats.

Booth, F. W.↗

Neuromuscular aspects in development of exercise countermeasures

The paper reviews data obtained at the Human Life Sciences Research Program at the Kennedy Space Center on the structural and functional characteristics of the human muscle and on the effects of simulated microgravity (head-down bed rest) and exercise on the muscle. It is shown that prolonged exposure to microgravity induced ultrastructural abnormalities and the atrophy of muscle and impaired muscle functioning (especially upon return to terrestrial gravity) and that ground-based models can be effectively used to study these changes. Results indicate that the incorporation of resistive exercise with a strong emphasis on the use of eccentric muscle action, in addition to concentric action, may provide a very effective countermeasure against muscle atrophy and dysfunction caused by long-duration exposures to microgravity.

Convertino, Victor A.↗

Effect of hindlimb unweighting on tissue blood flow in the rat

This study characterized distribution of blood flow in the rat during hindlimb unweighting (HU), and post-HU standing and exercise. The relationship between reduced hindlimb blood flow and the previously observed elevation in anaerobic metabolism observed with contractile activity in the atrophied soleus muscle was examined (Witzmann et al., 1992). Blood flow was measured during unweighting, normal standing, and running on a treadmill (15 m/min), after 15 days of HU or cage control. For another group blood flow was measured during preexercise treadmill standing and treadmill running. During unweighting, PE standing, and running no difference in soleus blood flow was observed between groups. Muscles composed mainly of fast twitch glycolytic fibers received greater blood flow during chronic unweighting. With exercise blood flow to visceral organs was reduced in control animals, a similar change was not seen in 15 day HU rats. These changes suggest a reduction in the ability of the sympathetic nervous system to distribute cardiac output after chronic HU. A reduction in blood flow to the soleus during exercise was not observed after HU and so does not explain the increased dependence of the atrophied soleus on anerobic energy production during contractile activity.

Mcdonald, K. S.↗

Mechanical stimulation of skeletal muscle mitigates glucocorticoid induced decreases in prostaglandin synthesis

The glucocorticoid dexamethasone (Dex) induces a decline in protein synthesis and protein content of tissue cultured, avian skeletal muscle cells, and this atrophy is attenuated by repetitive mechanical stretch. Since the prostaglandin synthesis inhibitor indomethacin mitigated this stretch attenuation of muscle atrophy, the role of prostaglandins as growth modulators in these processes was examined. Dex at 10(exp -8) M reduced PGF(sub 2(alpha)) production 55 percent - 65 percent and PGE(sub 2) production 84 - 90 percent after 24 - 72 h of incubation in static cultures. Repetitive 10 percent stretch-relaxations of the non-Dex treated cultures increased PGF(sub 2(alpha)) efflux 41 percent at 24 h and 276 percent at 72 h and increased PGE(sub 2) production 51 percent at 24 h and 236 percent at 72 h. Mechanical stimulation of Dex treated cultures increased PGF(sub 2(alpha)) production 162 percent after 24 h, thus returning PGF(sub 2(alpha)) efflux to the level of non-Dex treated cultures. At 72 h, stretch increased PGF(sub 2(alpha)) efflux 65 percent in Dex treated cultures, but PGF(sub 2(alpha)) production was 45-84 percent less than non-Dex treated cultures. Mechanical stimulation of Dex treated cultures increased PGE(sub 2) production at 24 h, but not at 72 h. Dex reduced prostaglandin H synthase (PGHS) activity in the muscle cultures by 70 percent after 8 - 24 h of incubation, and mechanical stimulation increased PGHS activity of the Dex treated cultures by 98 percent. It is concluded that repetitive mechanical stimulation attenuates the catabolic effects of Dex on cultured skeletal muscle cells in part by reversing the Dex-induced declines in PGHS activity and prostaglandin production.

Chromiak, Joseph A.↗

Growth factor involvement in tension-induced skeletal muscle growth

Long-term manned space travel will require a better understanding of skeletal muscle atrophy which results from microgravity. Astronaut strength and dexterity must be maintained for normal mission operations and for emergency situations. Although exercise in space slows the rate of muscle loss, it does not prevent it. A biochemical understanding of how gravity/tension/exercise help to maintain muscle size by altering protein synthesis and/or degradation rate should ultimately allow pharmacological intervention to prevent muscle atrophy in microgravity. The overall objective is to examine some of the basic biochemical processes involved in tension-induced muscle growth. With an experimental in vitro system, the role of exogenous and endogenous muscle growth factors in mechanically stimulated muscle growth are examined. Differentiated avian skeletal myofibers can be 'exercised' in tissue culture using a newly developed dynamic mechanical cell stimulator device which simulates different muscle activity patterns. Patterns of mechanical activity which significantly affect muscle growth and metabolic characteristics were found. Both exogenous and endogenous growth factors are essential for tension-induced muscle growth. Exogenous growth factors found in serum, such as insulin, insulin-like growth factors, and steroids, are important regulators of muscle protein turnover rates and mechanically-induced muscle growth. Endogenous growth factors are synthesized and released into the culture medium when muscle cells are mechanically stimulated. At least one family of mechanically induced endogenous factors, the prostaglandins, help to regulate the rates of protein turnover in muscle cells. Endogenously synthesized IGF-1 is another. The interaction of muscle mechanical activity and these growth factors in the regulation of muscle protein turnover rates with our in vitro model system is studied.

Vandenburgh, Herman H.↗

Skeletal muscle responses to unloading with special reference to man

The limited space flight data suggest that exposure to microgravity decreases muscle strength in humans and muscle mass in lower mammals. Several earth-based models have been used to address the effect of unloading on the human neuromuscular system due to the limited access of biological research to long-term space flight. Bedrest eliminates body weight bearing of both lower limbs. Unilateral lower limb suspension (ULLS), where all ambulatory activity is performed on crutches with an elevated sole on the shoe of one foot, has recently been used to unload one lower limb. The results from studies using these two models support their efficacy. The decrease in strength of m. quadriceps femoris, for example, after four to six weeks of bedrest, ULLS or space flight is 20 to 25 percent. The results from the earth-based studies show that this response can be attributed in part to a decrease in the cross-sectional area of the KE which reflects muscle fiber atrophy. The results from the ground based studies also support the limited flight data and show that reductions in strength are larger in lower than upper limbs and in extensor than flexor muscle groups. They also raise issue with the generally held concept that postural muscle is most affected by unweighting. Slow-twitch fibers in lower limb muscles of mixed fiber type composition and muscle composed mainly of slow-twitch fibers do not preferentially atrophy after bedrest or ULLS. Taken together, the data suggest that unloading causes remarkable adaptations in the neuromuscular system of humans. It should be appreciated, however, that this area of research is in its infancy.

Dudley, G. A.↗