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At least 433 records · Page 24

The bearable lightness of being: bones, muscles, and spaceflight

Bones and muscles support and move the body. Tendons link the two tissues and serve as a mechanism for transfer of forces from muscle to bone. These three tissues interact and respond to periods of activity or inactivity with appropriate alterations in structure and strength. There is substantial evidence that an environment devoid of mechanical stress on the skeleton (such as reduced gravitational forces during spaceflight, a "microgravity environment") produces direct effects on bone structure and function. There is little agreement concerning the biologic mechanisms for these atrophic changes. Changes in fluid balance and distribution coincident to spaceflight also affect muscles and bones by an unknown mechanism. Tendon-bone junctions are presumed to be spared from the effects of spaceflight. However, recent evidence from rodents suggests that spaceflight profoundly effects both the skeleton and the tendon-bone junctions. These effects include cortical bone resorption, which undermines the Sharpey's fibers that anchor the tendon to the bone matrix. The challenge to biomedical scientists is to devise methods for protecting spaceflight crews from these atrophic changes; such protection would allow for longer and more extensive spaceflights.

manned↗

Spaceflight influences on ocular counterrolling and other neurovestibular reactions

Exposure to extended periods of weightlessness in orbital flight has profound effects on the neurovestibular system and influences head and eye movements, postural control, and spatial orientation. The associated space motion sickness is among the earliest of the signs of adaptation to this new environment. This report both reviews the prominent neurovestibular phenomena associated with going into space and returning to earth and relates the issues to vestibular compensation and rehabilitation. New results from the Spacelab SLS-2 mission are included, showing significant reductions in postflight ocular counterrolling and changes in ocular counterrolling left/right asymmetries after 2 weeks in space.

Review↗

Cardiogenic oscillation phase relationships during single-breath tests performed in microgravity

We studied the phase relationships of the cardiogenic oscillations in the phase III portion of single-breath washouts (SBW) in normal gravity (1 G) and in sustained microgravity (microG). The SBW consisted of a vital capacity inspiration of 5% He-1.25% sulfurhexafluoride-balance O2, preceded at residual volume by a 150-ml Ar bolus. Pairs of gas signals, all of which still showed cardiogenic oscillations, were cross-correlated, and their phase difference was expressed as an angle. Phase relationships between inspired gases (e.g., He) and resident gas (n2) showed no change from 1 G (211 +/- 9 degrees) to microG (163 +/- 7 degrees). Ar bolus and He were unaltered between 1 G (173 +/- 15 degrees) and microG (211 +/- 25 degrees), showing that airway closure in microG remains in regions of high specific ventilation and suggesting that airway closure results from lung regions reaching low regional volume near residual volume. In contrast, CO2 reversed phase with He between 1 G (332 +/- 6 degrees) and microG (263 +/- 27 degrees), strongly suggesting that, in microG, areas of high ventilation are associated with high ventilation-perfusion ratio (VA/Q). This widening of the range of VA/Q in microG may explain previous measurements (G.K. Prisk, A.R. Elliott, H.J.B. Guy, J.M. Kosonen, and J.B. West J. Appl. Physiol. 79: 1290-1298, 1995) of an overall unaltered range of VA/Q in microG, despite more homogeneous distributions of both ventilation and perfusion.

Non-NASA Center↗

Multiple-breath washin of helium and sulfur hexafluoride in sustained microgravity

We performed multiple-breath washouts of N2 and simultaneous washins of He and SF6 with fixed tidal volume (approximately 1,250 ml) and preinspiratory lung volume (approximately the subject's functional residual capacity in the standing position) in four normal subjects (mean age 40 yr) standing and supine in normal gravity (1 G) and during exposure to sustained microgravity (microG). The primary objective was to examine the influence of diffusive processes on the residual, nongravitational ventilatory inhomogeneity in the lung in microG. We calculated several indexes of convective ventilatory inhomogeneity from each gas species. A normal degree of ventilatory inhomogeneity was seen in the standing position at 1 G that was largely unaltered in the supine position. When we compared the standing position in 1 G with microG, there were reductions in phase III slope in all gases, consistent with a reduction in convection-dependent inhomogeneity in the lung in microG, although considerable convective inhomogeneity persisted in microG. The reductions in the indexes of convection-dependent inhomogeneity were greater for He than for SF6, suggesting that the distances between remaining nonuniformly ventilated compartments in microG were short enough for diffusion of He to be an effective mechanism to reduce gas concentration differences between them.

NASA Discipline Cardiopulmonary↗

Effect of 17 days of bed rest on peak isometric force and unloaded shortening velocity of human soleus fibers

The purpose of this study was to examine the effect of prolonged bed rest (BR) on the peak isometric force (P0) and unloaded shortening velocity (V0) of single Ca(2+)-activated muscle fibers. Soleus muscle biopsies were obtained from eight adult males before and after 17 days of 6 degrees head-down BR. Chemically permeabilized single fiber segments were mounted between a force transducer and position motor, activated with saturating levels of Ca2+, and subjected to slack length steps. V0 was determined by plotting the time for force redevelopment vs. the slack step distance. Gel electrophoresis revealed that 96% of the pre- and 87% of the post-BR fibers studied expressed only the slow type I myosin heavy chain isoform. Fibers with diameter > 100 microns made up only 14% of this post-BR type I population compared with 33% of the pre-BR type I population. Consequently, the post-BR type I fibers (n = 147) were, on average, 5% smaller in diameter than the pre-BR type I fibers (n = 218) and produced 13% less absolute P0. BR had no overall effect on P0 per fiber cross-sectional area (P0/CSA), even though half of the subjects displayed a decline of 9-12% in P0/CSA after BR. Type I fiber V0 increased by an average of 34% with BR. Although the ratio of myosin light chain 3 to myosin light chain 2 also rose with BR, there was no correlation between this ratio and V0 for either the pre- or post-BR fibers. In separate fibers obtained from the original biopsies, quantitative electron microscopy revealed a 20-24% decrease in thin filament density, with no change in thick filament density. These results raise the possibility that alterations in the geometric relationships between thin and thick filaments may be at least partially responsible for the elevated V0 of the post-BR type I fibers.

STS-78 Shuttle Project↗

Microgravity vestibular investigations: perception of self-orientation and self-motion

Four astronauts experienced passive whole-body rotation in a number of test sessions during a 7-day orbital mission. Pitch (Y-axis) and roll (X-axis) rotation required subject orientations on the rotator in which the otolith system was at radius of 0.5 m. Thus subjects experienced a constant -0.22 Gz stimulus to the otoliths during the 60 s constant-velocity segments of "pitch" and "roll" ramp profiles. The Gz stimulus, a radius-dependent vector ranging from -0.22 Gz at the otoliths to +0.36 Gz at the feet, generated sensory information that was not interpreted as inversion in any of the 16 tests carried out in flight (12 in pitch and 4 in roll orientation). None of the subjects was rotated with head off-center during the first 33 h of the mission. In the state of orbital adaptation of these subjects, a -0.22 Gz otolith stimulus did not provide a vertical reference in the presence of a gradient of +Gz stimuli to the trunk and legs.

NASA Experiment Number 284058↗

Effects of 14 days of spaceflight and nine days of recovery on cell body size and succinate dehydrogenase activity of rat dorsal root ganglion neurons

The cross-sectional areas and succinate dehydrogenase activities of L5 dorsal root ganglion neurons in rats were determined after 14 days of spaceflight and after nine days of recovery. The mean and distribution of the cross-sectional areas were similar to age-matched, ground-based controls for both the spaceflight and for the spaceflight plus recovery groups. The mean succinate dehydrogenase activity was significantly lower in spaceflight compared to aged-matched control rats, whereas the mean succinate dehydrogenase activity was similar in age-matched control and spaceflight plus recovery rats. The mean succinate dehydrogenase activity of neurons with cross-sectional areas between 1000 and 2000 microns2 was lower (between 7 and 10%) in both the spaceflight and the spaceflight plus recovery groups compared to the appropriate control groups. The reduction in the oxidative capacity of a subpopulation of sensory neurons having relatively large cross-sectional areas immediately following spaceflight and the sustained depression for nine days after returning to 1 g suggest that the 0 g environment induced significant alterations in proprioceptive function.

manned↗

Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain

Estrogen deficiency induced bone loss is associated with increased bone turnover in rats and humans. The respective roles of increased bone turnover and altered balance between bone formation and bone resorption in mediating estrogen deficiency-induced cancellous bone loss was investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in the distal femur. However, cancellous bone was preferentially lost in the metaphysis, a site that normally experiences low strain energy. No bone loss was observed in the epiphysis, a site experiencing higher strain energy. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased and decreased in long bones of ovariectomized rats by treadmill exercise and functional unloading, respectively. Functional unloading was achieved during orbital spaceflight and following unilateral sciatic neurotomy. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing loading accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in the unloaded and prevented loss in the loaded limb following unilateral sciatic neurotomy in part by reducing indices of bone turnover. These results suggest that estrogen regulates the rate of bone turnover, but the overall balance between bone formation and bone resorption is influenced by prevailing levels of mechanical strain.

STS-62 Shuttle Project↗

The effects of orbital spaceflight on bone histomorphometry and messenger ribonucleic acid levels for bone matrix proteins and skeletal signaling peptides in ovariectomized growing rats

A 14-day orbital spaceflight was performed using ovariectomized Fisher 344 rats to determine the combined effects of estrogen deficiency and near weightlessness on tibia radial bone growth and cancellous bone turnover. Twelve ovariectomized rats with established cancellous osteopenia were flown aboard the space shuttle Columbia (STS-62). Thirty ovariectomized rats were housed on earth as ground controls: 12 in animal enclosure modules, 12 in vivarium cages, and 6 killed the day of launch for baseline measurements. An additional 18 ovary-intact rats were housed in vivarium cages as ground controls: 8 rats were killed as baseline controls and the remaining 10 rats were killed 14 days later. Ovariectomy increased periosteal bone formation at the tibia-fibula synostosis; cancellous bone resorption and formation in the secondary spongiosa of the proximal tibial metaphysis; and messenger RNA (mRNA) levels for the prepro-alpha2(1) subunit of type 1 collagen, osteocalcin, transforming growth factor-beta, and insulin-like growth factor I in the contralateral proximal tibial metaphysis and for the collagen subunit in periosteum pooled from tibiae and femora and decreased cancellous bone area. Compared to ovariectomized weight-bearing rats, the flight group experienced decreases in periosteal bone formation, collagen subunit mRNA levels, and cancellous bone area. The flight rats had a small decrease in the cancellous mineral apposition rate, but no change in the calculated bone formation rate. Also, spaceflight had no effect on cancellous osteoblast and osteoclast perimeters or on mRNA levels for bone matrix proteins and signaling peptides. On the other hand, spaceflight resulted in an increase in bone resorption, as ascertained from the diminished retention of a preflight fluorochrome label. This latter finding suggests that osteoclast activity was increased. In a follow-up ground-based experiment, unilateral sciatic neurotomy of ovariectomized rats resulted in cancellous bone loss in the unloaded limb in excess of that induced by gonadal hormone deficiency. This additional bone loss was arrested by estrogen replacement. We conclude from these studies that estrogen alters the expression of signaling peptides believed to mediate skeletal adaptation to changes in mechanical usage and likewise modifies the skeletal response to mechanical unloading.

NASA Program Space Physiology and Countermeasures↗

The effect of space flight on monoclonal antibody synthesis in a hybridoma mouse cell line

The hybridoma cell line, 3G10G5, producing a monoclonal antibody to the major capsid protein VP1 from the avian polyomavirus budgerigar fledgling disease virus, was produced from a Balb/C mouse. This cell line was used to test the effects of microgravity on cellular processes, specifically protein synthesis. A time course study utilizing incorporation of [35S]methionine into newly synthesized monoclonal antibody was performed on STS-77. After 5.5 days, it was observed that cell counts for the samples exposed to microgravity were lower than those of ground-based samples. However, radiolabel incorporation of the synthesized monoclonal antibody was similar in both orbiter and ground control samples. Overall, microgravity does not seem to have an effect on this cell line's ability to synthesize IgG protein.

manned↗

Optomotor behaviour in Xenopus laevis tadpoles as a measure of the effect of gravity on visual and vestibular neural integration

The ability of aquatic vertebrates to maintain their position requires integration of visual and vestibular sensory information. To understand better how aquatic animals integrate such information, we measured the optomotor behaviour of Xenopus laevis tadpoles raised in growth chambers in microgravity (< 10(-3)g), normal gravity (1 g), hypergravity (3 g) and on a slowly rotating clinostat (simulated microgravity). The goal of this research was to determine how development in an altered gravitational force field affects the visual- and vestibular-dependent behaviour of tadpoles. This research represents the first time that the optomotor behaviour of an organism raised from fertilization in microgravity has been tested. Significant differences were observed in the optomotor behaviour among the four gravity treatments. When first exposed to normal gravity, the microgravity-raised tadpoles exhibited the strongest (or most positive) optomotor behaviour, while the 3 g centrifuge tadpoles showed no optomotor response. Some abnormal behaviours (such as erratic swimming, lying motionless and abnormal swimming posture) were observed in the tadpoles raised in altered gravity on the initial day of testing. One day later, the tadpoles raised in hypergravity did not differ significantly in their optomotor behaviour from control tadpoles raised in normal gravity. However, tadpoles raised in microgravity still displayed an exaggerated optomotor response. One week after the tadpoles had been introduced to normal gravity, there was no longer a significant difference in optomotor behaviour among the different gravity treatments. This convergence of optomotor behaviour by tadpoles from the different treatment reflects the acclimation of their vestibular systems to normal gravity.

NASA Discipline Developmental Biology↗

Cytoplasm-to-myonucleus ratios following microgravity

The cytoplasmic volume-to-myonucleus ratio in the tibialis anterior and gastrocnemius muscles of juvenile rats after 5.4 days of microgravity was studied. Three groups of rats (n = 8 each) were used. The experimental group (space rats) was flown aboard the space shuttle Discovery (NASA, STS-48), while two ground-based groups, one hindlimb suspended (suspended rats), one non-suspended (control), served as controls. Single fibre analysis revealed a significant decrease in cross-sectional area (microns2) in the gastrocnemius for both the space and the suspended rats; in the tibialis anterior only the suspended rats showed a significant decrease. Myonuclei counts (myonuclei per mm) in both the tibialis anterior and gastrocnemius were significantly increased in the space rats but not in the suspended rats. The mean myonuclear volume (individual nuclei: microns3) in tibialis anterior fibres from the space rats, and in gastrocnemius fibres from both the space and the suspended rats, was significantly lower than that in the respective control group. Estimation of the total myonuclear volume (microns3 per.mm), however, revealed no significant differences between the three groups in either the tibialis anterior or gastrocnemius. The described changes in the cross-sectional area and myonuclei numbers resulted in significant decreases in the cytoplasmic volume-to-myonucleus ratio (microns3 x 10(3)) in both muscles and for both space and suspended rats (tibialis anterior; 15.6 +/- 0.6 (space), 17.2 +/- 1.0 (suspended), 20.8 +/- 0.9 (control): gastrocnemius; 13.4 +/- 0.4 (space) and 14.9 +/- 1.1 (suspended) versus 18.1 +/- 1.1 (control)). These results indicate that even short periods of unweighting due to microgravity or limb suspension result in changes in skeletal muscle fibres which lead to significant decreases in the cytoplasmic volume-to-myonucleus ratio.

NASA Discipline Cell Biology↗

Animal models and their importance to human physiological responses in microgravity

Two prominent theories to explain the physiological effects of microgravity relate to the cascade of changes associated with the cephalic shifts of fluids and the absence of tissue deformation forces. One-g experiments for humans used bed rest and the head-down tilt (HDT) method, while animal experiments have been conducted using the tail-suspended, head-down, and hindlimbs non-weightbearing model. Because of the success of the HDT approach with rats to simulate the gravitational effects on the musculoskeletal system exhibited by humans, the same model has been used to study the effects of gravity on the cardiopulmonary systems of humans and other vertebrates. Results to date indicate the model is effective in producing comparable changes associated with blood volume, erythropoiesis, cardiac mass, baroreceptor responsiveness, carbohydrate metabolism, post-flight VO2max, and post-flight cardiac output during exercise. Inherent with these results is the potential of the model to be useful in investigating responsible mechanisms. The suspension model has promise in understanding the capillary blood PO2 changes in space as well as the arterial PO2 changes in subjects participating in a HDT experiment. However, whether the model can provide insights on the up-or-down regulation of adrenoreceptors remains to be determined, and many investigators believe the HDT approach should not be followed to study gravitational influences on pulmonary function in either humans or animals. It was concluded that the tail-suspended animal model had sufficient merit to study in-flight and post-flight human physiological responses and mechanisms.

NASA Discipline Cardiopulmonary↗

Life sciences space missions. Overview

It has been known for many years that weightlessness induces changes in numerous physiological systems: the cardiovascular system declines in both aerobic capacity and orthostatic tolerance; there is a reduction in fluid and electrolyte balance, hematocrit, and certain immune parameters; bone and muscle mass and strength are reduced; various neurological responses include space motion sickness and posture and gate alterations. These responses are caused by the hypokinesia of weightlessness, the cephalic fluid shift, the unloading of the vestibular system, stress, and the altered temporal environment.

NASA Center HQS↗

Effects of spaceflight on rat peripheral blood leukocytes and bone marrow progenitor cells

The white blood cell (WBC) elements and the bone marrow myeloid progenitor cell populations were analyzed to ascertain adaptation to micro-gravity and subsequent readaptation to 1 G in rats flown on the 14-day Spacelab Life Sciences-2 (SLS-2) mission. Bone marrow cells were harvested from one group of rats killed inflight (FD13) and blood was drawn from three other groups at various times. The WBC level was normal on FD14 with the exception of neutrophilia. On FD13, numbers of colony-forming units-granulocyte (CFU-G), CFU-GM, and CFU-M from flight animals were decreased compared with ground controls when incubated with recombinant rat interleukin-3 (rrIL-3) alone or in combination with recombinant human erythropoietin (rhEpo). On recovery (R + 0), flight rats had decreased numbers of total leukocytes and absolute numbers of lymphocytes and monocytes with elevated neutrophils compared with control rats. They had lower numbers of CD4, CD8, CD2, CD3, and B cells in the peripheral blood but no differences in spleen lymphocytes.

NASA Discipline Number 00-00↗

Microgravity in the STS-29 space shuttle discovery affected the vestibular system of chick embryos

Out of 32 embryos flown (16 @ E2 + 16 @ E9) for 5 days, 16 survived. All sixteen E2 were dead at landing. Eight were opened and eight were incubated at 1.0G. Autopsy showed that 4 E2 survived over 24 hours in space. Eight E14 hatched without anatomical malformations, and 8 E14 were fixed. The height of the macular epithelia was 31 mu m (mean) in control and 26 mu m in flight chicks. The cross-sectional area of macular nuclei of control was 17 mu m(2) for hair cells and 14 mu m(2) in supporting cells. In flight, cross-sectional area was 17 mu m(2) in hair cells and 15 mu m(2) in supporting cells (n=250). The shape factor of cartilage cells (1.0 = perfect circle) between control (mean = 0.70) and flight (mean = 0.72), and the area of cartilaginous cells between controls (mean = 9 mu m(2)) and flight (mean = 9 mu m(2)) did not differ (n=300). The nuclei of support cells were closer to the basement membrane in flight than in control chicks. The immunoreactivity of otoconia with anti keratan, fibronectin or chrondroitin sulfate was not different between flight and control ears. There were more afferent fibers inside the macular epithelia of flight (p<0.05) than control. Three of 8 flight animals had elevated vestibular thresholds (VT), with normal mean response amplitudes and latencies. Modified afferent innervation patterns requiring weeks to compensate are sufficient to elevate VT, and should be investigated further. Other reversible (sublethal) microgravity effects on sensory epithelia (vacuoles, swelling, etc) require quantification.

Flight Experiment↗