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At least 163 records · Page 9
All sourcesNASA NTRSDOE OSTI
NASA NTRS1984

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.↗
NASA NTRS1986

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.↗
NASA NTRS1986

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.↗
NASA NTRS1988

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.↗
NASA NTRS1988

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.↗
NASA NTRS1990

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.↗
NASA NTRS1990

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.↗
NASA NTRS1991

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.↗
NASA NTRS1992

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.↗
NASA NTRS1993

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.↗
NASA NTRS1993

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.↗
NASA NTRS1992

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.↗
NASA NTRS1993

Interaction of various mechanical activity models in regulation of myosin heavy chain isoform expression

The purpose of this study was to determine the effects of a novel combination of mechanical activity paradigms on the isomyosin distribution in rat hindlimb muscles. Thirty female Sprague-Dawley rats were divided into five experimental groups as follows: normal control, functional overload (OV) of the plantaris, OV in conjunction with hindlimb suspension (OV-S), and a combination of OV-S and either static standing weight-bearing activity (OV-SS) or high-incline treadmill exercise (OV-SE). OV of the plantaris resulted in significant hypertrophy and significant fast-to-slow isomyosin shifts. These changes were completely inhibited by the addition of hindlimb suspension (OV-S). Also, neither of the two weight-bearing regimes (OV-SS and OV-SE) was able to attenuate the suspension-induced atrophy. In the vastus intermedius and vastus lateralis, however, OV-SS was able to partially retard the atrophy associated with suspension. In both the plantaris and vastus intermedius, only OV-SS was able to partially reverse the slow-to-fast isomyosin transitions associated with suspension. These results suggest that the type of mechanical activity is important in determining adaptation to altered loading conditions, with OV-SS appearing more effective than OV-SE in reversing the effects of unweighting.

Diffee, Gary M.↗
NASA NTRS1993

Exercise countermeasures for bed-rest deconditioning

The purpose for this 30-day bed rest study was to investigate the effects of short-term, high intensity isotonic and isokinetic exercise training on maintenance of working capacity (peak oxygen uptake), muscular strength and endurance, and on orthostatic tolerance, posture and gait. Other data were collected on muscle atrophy, bone mineralization and density, endocrine analyses concerning vasoactivity and fluid-electrolyte balance, muscle intermediary metabolism, and on performance and mood of the subjects. It was concluded that: The subjects maintained a relatively stable mood, high morale, and high esprit de corps throughout the study. Performance improved in nearly all tests in almost all the subjects. Isotonic training, as opposed to isokinetic exercise training, was associated more with decreasing levels of psychological tension, concentration, and motivation; and improvement in the quality of sleep. Working capacity (peak oxygen uptake) was maintained during bed rest with isotonic exercise training; it was not maintained with isokinetic or no exercise training. In general, there was no significant decrease in strength or endurance of arm or leg muscles during bed rest, in spite of some reduction in muscle size (atrophy) of some leg muscles. There was no effect of isotonic exercise training on orthostasis, since tilt-table tolerance was reduced similarly in all three groups following bed rest. Bed rest resulted in significant decreases of postural stability and self-selected step length, stride length, and walking velocity, which were not influenced by either exercise training regimen. Most pre-bed rest responses were restored by the fourth day of recovery.

Greenleaf, John↗
NASA NTRS1994

Electromyostimulation, circuits and monitoring

One method to determine the benefit of electromyostimulation (EMS) requires an accurate strength assessment of the muscle of interest using a muscle force testing device. Several commercial devices are available. After a pre-EMS muscle assessment, a protocol with accurately controlled stimulation parameters must be applied and monitored. both the actual current and the resultant muscle force must be measured throughout the study. At the conclusion of the study, a reassessment of the muscle strength must be gathered. In our laboratory, electromyostimulation is being studied as a possible countermeasure to the muscle atrophy (degeneration) experienced in space. This muscle loss not only weakens the astronaut, but adversely affects his/her readaptation to 1-g upon return from space. Muscle atrophy is expected to have a more significant effect in long term space flight as anticipated in our space station. Our studies have concentrated on stimulating the four major muscle groups in the leg. These muscles were stimulated sequentially to allow individual muscle force quantification above the knee and ankle. The leg must be restrained in an instrumented brace to allow this measurement and preclude muscle cramping.

Doerr, Donald F.↗
NASA NTRS1994

Interactive effects of growth hormone and exercise on muscle mass in suspended rats

Measures to attenuate muscle atrophy in rats in response to simulated microgravity (hindlimb suspension (HS)) have been only partially successful. In the present study, hypophysectomized rats were in HS for 7 days, and the effects of recombinant human growth hormone (GH), exercise (Ex), or GH+Ex on the weights, protein concentrations, and fiber cross-sectional areas (CSAs) of hindlimb muscles were determined. The weights of four extensor muscles, i.e., the soleus (Sol), medial (MG) and lateral (LG) gastrocnemius, and plantaris (Plt), and one adductor, i.e., the adductor longus (AL), were decreased by 10-22% after HS. Fiber CSAs were decreased by 34% in the Sol and by 1 17% in the MG after HS. In contrast, two flexors, i.e., the tibialis anterior (TA) and extensor digitorum longus (EDL), did not atrophy. In HS rats, GH treatment alone maintained the weights of the fast extensors (MG, LG, Plt) and flexors (TA, EDL) at or above those of control rats. This effect was not observed in the slow extensor (Sol) or AL. Exercise had no significant effect on the weight of any muscle in HS rats. A combination of GH and Ex treatments yielded a significant increase in the weights of the fast extensors and in the CSA of both fast and slow fibers of the MG and significantly increased Sol weight and CSA of the slow fibers of the Sol. The AL was not responsive to either GH or Ex treatments. Protein concentrations of the Sol and MG were higher only in the Sol of Ex and GH+Ex rats. These results suggest that while GH treatment or intermittent high intensity exercise alone have a minimal effect in maintaining the mass of unloaded muscle, there is a strong interactive effect of these two treatments.

Grindeland, Richard E.↗
NASA NTRS1994

Experiment K-7-29: Connective Tissue Studies: Changes in Muscle Serine Proteases, Serpins and Matrix Molecules - Part 2

In zero or micro-gravity, type 1 muscle fibers atrophy and lose predominance, especially in slow-twitch muscles. No increase in mononuclear cells has been observed, just as in simple denervation, where both types 1 and 2 fibers atrophy, again without infiltration of cells, but with clear satellite cell proliferation. However, extracellular matrix (ECM) degradation takes place after denervation and if re-innervation is encouraged, functional recovery to near control levels may be achieved. No information is available concerning the ECM milieu, the activation of serine proteases, their efficacy in degrading ECM components and the production of locally-derived natural protease inhibitors (serpins) in effecting surface proteolytic control. In addition, no studies are available concerning the activation of these enzymes in micro- or zero gravity or their response to muscle injury on the ground and what alterations, if any, occur in space. These studies were the basis for the experiments in Cosmos 2044.

Festoff, B. W.↗
NASA NTRS1989

Characteristics and Preliminary Observations of the Influence of Electromyostimulation on the Size and Function of Human Skeletal Muscle During 30 Days of Simulated Microgravity

During 30 days (d) of bedrest, the practicality of using Elec- troMyoStimulation (EMS) as a deterrent to atrophy and strength loss of lower limb musculature was examined. An EMS system was developed that provided variable but quantifiable levels of EMS, and measured torque. The dominant log of three male subjects was stimulated twice daily in a 3-d on/1-d off cycle during bedrest. The non-dominant leg of each subject acted as a control. A stimulator, using a 0.3 ms monophasic 60 Hz pulse waveform, activated muscle tissue for 4 s. The output waveform from the stimulator was sequenced to the Knee Extensors (KE), Knee Flex- ors (KF), Ankle Extensors (AE), and Ankle Flexors (AF), and caused three isometric contractions of each muscle group per minute. Subject tolerance determined EMS Intensity. Each muscle group received four 5-min bouts of EMS each session with a 10 -min rest between bouts. EMS and torque levels for each muscle action were recorded directly an a computer. Overall average EMS Intensity was 197, 197, 195, and 188 mA for the KE, KF, AF, and AE, respectively. Overall average torque development for these muscle groups was 70, 16, 12, and 27 Nm, respectively. EMS intensity doubled during the study, and average torque increased 2.5 times. Average maximum torque throughout a session reached 54% of maximal voluntary for the KE and 29% for the KF. Reductions in leg volume, muscle compartment size, cross-sectional area of slow and fast-twitch fibers, strength, and aerobic enzyme activities, and increased log compliance were attenuated in the legs which received EMS during bedrest. These results indicate that similar EMS levels induce different torques among different muscle groups and that repeated exposure to EMS increases tolerance and torque development. Longer orien- tation periods, therefore, may enhance its effectiveness. Our preliminary data suggest that the efficacy of EMS as an effective countermeasure for muscle atrophy and strength loss during long duration space travel warrants further investigation.

Duvoisin, Marc R.↗