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At least 37 records · Page 2

Thin filament diversity and physiological properties of fast and slow fiber types in astronaut leg muscles

Slow type I fibers in soleus and fast white (IIa/IIx, IIx), fast red (IIa), and slow red (I) fibers in gastrocnemius were examined electron microscopically and physiologically from pre- and postflight biopsies of four astronauts from the 17-day, Life and Microgravity Sciences Spacelab Shuttle Transport System-78 mission. At 2.5-microm sarcomere length, thick filament density is approximately 1,012 filaments/microm(2) in all fiber types and unchanged by spaceflight. In preflight aldehyde-fixed biopsies, gastrocnemius fibers possess higher percentages (approximately 23%) of short thin filaments than soleus (9%). In type I fibers, spaceflight increases short, thin filament content from 9 to 24% in soleus and from 26 to 31% in gastrocnemius. Thick and thin filament spacing is wider at short sarcomere lengths. The Z-band lattice is also expanded, except for soleus type I fibers with presumably stiffer Z bands. Thin filament packing density correlates directly with specific tension for gastrocnemius fibers but not soleus. Thin filament density is inversely related to shortening velocity in all fibers. Thin filament structural variation contributes to the functional diversity of normal and spaceflight-unloaded muscles.

Non-NASA Center↗

Noninvasive markers of bone metabolism in the rhesus monkey: normal effects of age and gender

Measurement of bone turnover in conditions such as osteoporosis has been limited by the need for invasive iliac bone biopsy to reliably determine parameters of bone metabolism. Recent advances in the area of serum and urinary markers of bone metabolism have raised the possibility for noninvasive measurements; however, little nonhuman primate data exist for these parameters. The purpose of this experiment was to define the normal range and variability of several of the newer noninvasive bone markers which are currently under investigation in humans. The primary intent was to determine age and gender variability, as well as provide some normative data for future experiments in nonhuman primates. Twenty-four rhesus macaques were divided into equal groups of male and female according to the following age groupings: 3 years, 5-10 years, 15-20 years, and > 25 years. Urine was collected three times daily for a four-day period and measured for several markers of bone turnoverm including pyridinoline (PYD), deoxypyrodinoline (DPD), hydroxyproline, and creatinine. Bone mineral density measurements of the lumbar spine were performed at the beginning and end of the study period. Serum was also obtained at the time of bone densitometry for measurement of osteocalcin levels by radioimmunoassay. There were no significant differences in bone mineral density, urine PYD, or urine DPD based on gender. Bone density was lowest in the youngest animals, peaked in the 15-20-year group, but again decreased in the oldest animals. The osteocalcin, PYD, and DPD levels followed an inversely related pattern to bone density. The most important result was the relative age insensitivity of the ratio of PYD:DPD in monkeys up to age 20 years. Since bone density changes take months or years to become measurable and iliac biopsies are invasive, the PYD/DPD marker ratio may have important implications for rapid noninvasive measurement of the effects of potential treatments for osteoporosis in the non-human primate model.

NASA Discipline Musculoskeletal↗

The Artificial Gravity Bed Rest Pilot Project: Effects on Knee Extensor and Plantar Flexor Muscle Groups

The goal of this project was to examine the effects of artificial gravity (2.5 g) on skeletal muscle strength and key anabolic/catabolic markers known to regulate muscle mass. Two groups of subjects were selected for study: 1) a 21 day-bed rest (BR) control (C) group (N=7); and 2) an AG group (N=8), which was exposed to 21 days of bed-rest plus daily 1 hr exposures to AG (2.5 g). This particular experiment was part of an integrated AG Pilot Project sponsored by NASA/Johnson Space Center. The in vivo torque-velocity relationships of the knee extensors and plantar flexors of the ankle were determined pre and post treatment. Also, pre- and post treatment biopsy samples were obtained from both the vastus lateralis and soleus muscles and were used, in part, for a series of analyses on gene expression (mRNA abundance) of key factors implicated in the anabolic versus catabolic state of the muscle. Post/Pre toque-velocity determinations revealed greater decrements in knee extensor performance in the C versus AG group (P less than 0.04). The plantar flexor muscle group of the AG subjects actually demonstrated a net gain in torque-velocity relationship; whereas, in the C group the overall post/pre responses declined (AG vs C; P less than 0.001). Measurements of muscle fiber cross-sectional area (for both muscles) demonstrated a loss of approx. 20% in the C group while no losses were evident in the AG group. RT-PCR analyses of muscle biopsy specimens demonstrated that markers of growth and cytoskeletal integrity (IGF-1, IGF-1 BP4, mechano growth factor, total RNA, and pro-collagen 3a) were higher in the AG group, whereas catabolic markers (myostatin and atrogen) were elevated in the C group. Importantly, these patterns were seen in both muscles. Based on these observations we conclude that paradigms of AG have the potential to maintain the functional, biochemical, and structural homeostasis of skeletal muscle in the face of chronic unloading states. These findings also warrant further studies since it is likely that other robust paradigms of AG that employ various exercise strategies may be more effective in counteracting long duration unloading states as anticipated on the platforms of the Moon and Mars.

Caiozzo, V. J.↗

T2 vertebral bone marrow changes after space flight

Bone biopsies indicate that during immobilization bone marrow adipose tissue increases while the functional cellular fraction decreases. One objective of our Spacelab flight experiment was to determine, using in vivo volume-localized magnetic resonance spectroscopy (VLMRS), whether bone marrow composition was altered by space flight. Four crew members of a 17 day Spacelab mission participated in the experiment. The apparent cellular fraction and transverse relaxation time (T2) were determined twice before launch and at several times after flight. Immediately after flight, no significant change in the cellular fraction was found. However, the T2 of the cellular, but not the fat component increased following flight, although to a variable extent, in all crew members with a time course for return to baseline lasting several months. The T2 of seven control subjects showed no significant change. Although these observations may have several explanations, it is speculated that the observed T2 changes might reflect increased marrow osteoblastic activity during recovery from space flight.

NASA Experiment Number 284054↗

Disproportionate loss of thin filaments in human soleus muscle after 17-day bed rest

Previously we reported that, after 17-day bed rest unloading of 8 humans, soleus slow fibers atrophied and exhibited increased velocity of shortening without fast myosin expression. The present ultrastructural study examined fibers from the same muscle biopsies to determine whether decreased myofilament packing density accounted for the observed speeding. Quantitation was by computer-assisted morphometry of electron micrographs. Filament densities were normalized for sarcomere length, because density depends directly on length. Thick filament density was unchanged by bed rest. Thin filaments/microm2 decreased 16-23%. Glycogen filled the I band sites vacated by filaments. The percentage decrease in thin filaments (Y) correlated significantly (P < 0.05) with the percentage increase in velocity (X), (Y = 0.1X + 20%, R2 = 0.62). An interpretation is that fewer filaments increases thick to thin filament spacing and causes earlier cross-bridge detachment and faster cycling. Increased velocity helps maintain power (force x velocity) as atrophy lowers force. Atrophic muscles may be prone to sarcomere reloading damage because force/microm2 was near normal, and force per thin filament increased an estimated 30%.

Non-NASA Center↗

Subacute diabetic proximal neuropathy

OBJECTIVE: To evaluate the clinical, electrophysiologic, autonomic, and neuropathologic characteristics and the natural history of subacute diabetic proximal neuropathy and its response to immunotherapy. MATERIAL AND METHODS: For the 12-year period from 1983 to 1995, we conducted a retrospective review of medical records of Mayo Clinic patients with diabetes who had subacute onset and progression of proximal weakness. The responses of treated versus untreated patients were compared statistically. RESULTS: During the designated study period, 44 patients with subacute diabetic proximal neuropathy were encountered. Most patients were middle-aged or elderly, and no sex preponderance was noted. The proximal muscle weakness often was associated with reduced or absent lower extremity reflexes. Associated weight loss was a common finding. Frequently, patients had some evidence of demyelination on nerve conduction studies, but it invariably was accompanied by concomitant axonal degeneration. The cerebrospinal fluid protein concentration was usually increased. Diffuse and substantial autonomic failure was generally present. In most cases, a sural nerve biopsy specimen suggested demyelination, although evidence of an inflammatory infiltrate was less common. Of 12 patients who received treatment (with prednisone, intravenous immune globulin, or plasma exchange), 9 had improvement of their conditions, but 17 of 29 untreated patients (59%) with follow-up also eventually had improvement, albeit at a much slower rate. Improvement was usually incomplete. CONCLUSION: We suggest that the entity of subacute diabetic proximal neuropathy is an extensive and severe variant of bilateral lumbosacral radiculoplexopathy, with some features suggestive of an immune-mediated cause. It differs from chronic inflammatory demyelinating polyradiculoneuropathy in that most cases have a more restricted distribution and seem to be monophasic and self-limiting. The efficacy of immunotherapy is unproved, but such intervention may be considered in the severe and progressive cases or ones associated with severe neuropathic pain.

Non-NASA Center↗

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↗

Glutamate and aspartate are decreased in the skin in amyotrophic lateral sclerosis

We measured the levels of amino acids in biopsied skin from eight patients with amyotrophic lateral sclerosis (ALS) and seven controls. The most conspicuous changes in ALS patients were as follows. First, the contents of the acidic amino acids glutamate and aspartate were significantly decreased in ALS, and were negatively and significantly associated with the duration of illness. Second, the levels of the collagen-associated amino acids hydroxyproline, proline, glycine, alanine, and hydroxylysine were significantly decreased in ALS, and correlated inversely with the duration of illness. These results suggest that there are abnormalities of acidic amino acids and collagen-associated amino acids in the skin of patients with ALS. These changes may underlie the pathogenesis of ALS.

NASA Discipline Musculoskeletal↗

Color-televised medical microscopy

Color television microscopy used at laboratory range magnifications, reproduces a slide image with sufficient fidelity for medical laboratory and instructional use. The system is used for instant pathological reporting between operating room and remotely located pathologist viewing a biopsy through this medium.

Heath, M. A.↗

Evaluation of the hazard from exposure to electron irradiation simulating that in the synchronous orbit

The electron spectrum predicted for the synchronous orbit was simulated to determine the effects that might occur to astroscientists exposed to such irradiation while on a prolonged space station mission in that region. Miniature pigs were exposed to monoenergetic and spectral-fractionated irradiations with 0.5 to 2.1 MeV electrons. Clinical and pathological alterations observed in biopsies were correlated with depth-dose pattern and length of post irradiation period up to one year. With monoenergetic electrons, the lowest dose causing a recognizable lesion was 1450 rad and with increasing dose lesions appeared earlier and were more severe. At the highest dose given, 2650 rad, ulceration extending into the dermis was present by twenty one days and required about four months for complete healing. Spectral-fractionated irradiations, in which the total dose range was essentially comparable to that of the monoenergetic series, resulted in very minimal outer dermis edema at 1790 rad and at no dose employed did necrosis of epidermis or ulceration into dermis occur.

Lippincott, S. W.↗

Prevention of disuse osteoporosis: Effect of sodium fluoride during five weeks of bed rest

An attempt was made to modify factors which promote disuse osteoporosis and thereby prevent it from occurring. Since fluoride is currently used to enhance bone formation in the treatment of low turnover osteoporosis, it was hypothesized that if the fluoride ion was available over a long period of time that it would slow the demonstrated loss of calcium by inhibiting bone resorption and enhancing bone formation. This study was used to determine whether oral medication with sodium F will modify or prevent 5 weeks of bed rest induced disuse osteoporosis, to determine the longitudinal effects of 5 weeks of bed rest on PTH, CT and calcitriol, to measure muscle volume changes and metabolic activity by magnetic resonance imaging and magnetic resonance spectroscopy during prolonged bed rest, to measure changes in peak muscle strength and fatigability, and to measure bone turnover in bone biopsies. Subjects were studied during 1 week of equilibration, 4 weeks of control ambulation, 5 weeks of bed rest, and 1 week of reambulation.

Schneider, Victor S.↗

Effect of swim exercise training on human muscle fiber function

The effect of swim exercise training on the human muscle fiber function was investigated in swimmers trained in a typical collegiate swim-training program followed by an intensified 10-day training period. The measured parameters included the peak tension (P0), negative log molar Ca(2+) concentration (pCa)-force, and maximal shortening speed (Vmax) of the slow-twitch type I and fast-twitch type II fibers obtained by biopsy from the deltoid muscle. The P0 values were found to be not altered after either the training or the 10-day intensive program. The type I fibers from the trained swimmers showed pCa-force curves shifted to the right, such that higher free Ca(2+) levels were required to elicit a given percent of P0. The training program significantly increased the Vmax in the type I fibers and decreased that of the type II fibers, and the 10-day intensive training produced a further significant decrease of the type II fibers.

Fitts, R. H.↗

A study of the effects of prolonged simulated microgravity on the musculature of the lower extremities in man - An introduction

The experimental approach and the protocol are described for a study designed to investigate the effect of prolonged microgravity (simulated by a continuous exposure of subjects to 30-d-long 6-deg headdown tilt) on the musculature of the lower extremities in humans. The objectives of this study are as follows: (1) to determine changes in the functional characteristics of knee joint flexor and extensor muscle group; (2) to examine changes in the histochemical, biochemical, electron microscopic, and computed tomographic characteristics of skeletal muscle; (3) to determine if functional characteristics of skeletal muscle would be normalized four weeks after the bedrest; and (4) to compare these results to those of spaceflight. Percutaneous muscle biopsy, computed tomography, anthropometry, and in vivo muscle strength measurements are to be used to assess mechanical, structural, and metabolic characteristics of skeletal muscle.

Buchanan, Paul↗

Structural and metabolic characteristics of human skeletal muscle following 30 days of simulated microgravity

The effects of simulated microgravity (30 days of continuous 6-deg headdown bedrest, BR) on the structural and metabolic characteristics of human skeletal muscle were determined. Percutaneous needle biopsy samples obtained from the vastus lateralis and soleus muscles before and after the headdown BR were analyzed for histochemical, biochemical and ultrastructual changes. It was found that headdown BR led to decreases in both fast-twitch and slow-twitch fiber areas in both muscles, and there was evidence of remodeling of the ultrastructure in both muscles. The activities of beta-hydroxyacyl-CoA dehydrogenase and citrate synthase were reduced during BR, but phosphofructokinase and lactate dehydrogenase activities did not change. The results indicate that 30-d exposure to simulated microgravity decreased the capacity for aerobic energy supply of human skeletal muscle and led to a disorganization of the contractile machinery.

Hikida, Robert S.↗

Gravity, Calcium, and Bone: Update, 1989

Some of the results of recent short-term flights and ground-based experiments that have contributed new insights into skeletal adaptation, calcium metabolism, and growth processes in 0 g, are highlighted. After 6 months in space, bone demineralization, invariably involving the os calcis, was found not to extend to the lumbar spine in 4 exercising cosmonauts. A flight experiment in the Space Shuttle crew has documented the early events in the calcium endocrine system during spaceflight. On the ground, brief and long-term bed rest studies of healthy volunteers in the head-down tile (HDT) model of weightlessness were completed. The skeleton of the adult male responds more rapidly to unloading than previously recognized. Regional changes in bone density can be quantified in only 30 days, are highly individual, and follow the direction of gravitational forces in the HDT model during inactivity. Bone biopsy results in healthy volunteers after bed rest differ from results in paraplegics from the same sampling site. Flight experiments in growing rats reveal changes in the composition of bone mineral and matrix in the femur postflight that were found to be highly regional and suggestive of an effect of gravity on mineral distribution. These observations may be relevant to the results from an earlier Cosmos flight where artificial gravity in space was found to maintain bone strength, but not to correct the radial growth deficit.

Arnaud, Sara B.↗

Spaceflight and growth effects on muscle fibers in the rhesus monkey

The effect of a 14-day spaceflight onboard Cosmos 2044 on selected morphological and metabolic properties of single muscle fibers was investigated in a nonhuman primate, Macaca mulatta. It is concluded that the 14-day spaceflight had little impact on fiber size in the soleus (S) and medial gastrocnemius (MG) muscles, whereas it appeared to be a slight decrease in sized in the tibialis anterior (TA). The mean fiber size in the postflight biopsies increased relative to preflight values. The mean fiber succinate dehydrogenase activity was found to decrease in the MG, whereas there was no apparent effect of spaceflight on the s and ta muscles. The differences in response of the S, MG, and TA to spaceflight in monkeys vs rats may be related to a species responsiveness to spaceflight, the manner in which the animals were restrained, and/or the possibility that the ankle musculature was able to function against a load while in space.

Bodine-Fowler, Sue C.↗

Carotid-cardiac baroreflex response and LBNP tolerance following resistance training

The purpose of this study was to examine the effect of lower body resistance training on cardiovascular control mechanisms and blood pressure maintenance during an orthostatic challenge. Lower body negative pressure (LBNP) tolerance, carotid-cardiac baroreflex function (using neck chamber pressure), and calf compliance were measured in eight healthy males before and after 19 wk of knee extension and leg press training. Resistance training sessions consisted of four or five sets of 6-12 repetitions of each exercise, performed two times per week. Training increased strength 25 +/- 3 (SE) percent (P = 0.0003) and 31 +/- 6 percent (P = 0.0004), respectively, for the leg press and knee extension exercises. Average fiber size in biopsy samples of m. vastus lateralis increased 21 +/- 5 percent (P = 0.0014). Resistance training had no significant effect on LBNP tolerance. However, calf compliance decreased in five of the seven subjects measured, with the group average changing from 4.4 +/- 0.6 ml.mm Hg-1 to 3.9 +/- 0.3 ml.mm Hg-1 (P = 0.3826). The stimulus-response relationship of the carotid-cardiac baroreflex response shifted to the left on the carotid pressure axis as indicated by a reduction of 6 mm Hg in baseline systolic blood pressure (P = 0.0471). In addition, maximum slope increased from 5.4 +/- 1.3 ms.mm Hg-1 before training to 6.6 +/- 1.6 ms.mm Hg-1 after training (P = 0.0141). Our results suggest the possibility that high resistance, lower extremity exercise training can cause a chronic increase in sensitivity and resetting of the carotid-cardiac baroreflex.

Tatro, D. L.↗

Skeletal muscle responses to unloading in humans

This study examined the effects of unloading on skeletal muscle structure. Method: Eight subjects walked on crutches for six weeks with a 110 cm elevated sole on the right shoe. This removed weight bearing by the left lower limb. Magnetic resonance imaging of both lower limbs and biopsies of the left m. vastus laterallis (VL) were used to study muscle structure. Results: Unloading decreased (P less than 0.05) muscle cross-sectional areas (CSA) of the knee extensors 16 percent. The knee flexors showed about 1/2 of this response (-7 percent, P less than 0.05). The three vasti muscles each showed decreases (P less than 0.05) of about 15 percent. M. rectus femoris did not change. Mean fiber CSA in VL decreased (P less than 0.05) 14 percent with type 2 and type 1 fibers showing reductions of 15 and 11 percent respectively. The ankle extensors showed a 20 percent decrease (P less than 0.05) in CSA. The reduction for the 'fast' m. gastrocnemius was 27 percent compared to the 18 percent decrease for the 'slow' soleus. Summary: The results suggest that decreases in muscle CSA are determined by the relative change in impact loading history because atrophy was (1) greater in extensor than flexor muscles, (2) at least as great in fast as compared to slow muscles or fibers, and (3) not dependent on single or multi-joint function. They also suggest that the atrophic responses to unloading reported for lower mammals are quantitatively but not qualitatively similar to those of humans.

Dudley, G.↗