Tracking, command, control and data-acquisition of NASA flight programs.
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Spaceflight could provoke formation of kidney stones, in part by causing hypercalciuria and hyperphosphaturia. Applicants for spaceflight who have metabolic or environmental derangements to begin with might be particularly susceptible to stone formation in space. We, therefore, analyzed 24-h urine samples for stone-forming risk factors in 104 male applicants before their selection into the astronaut-mission specialist corps. The urinary environment was abnormally supersaturated with calcium oxalate in 25.0% of applicants, brushite in 36.5%, and monosodium urate in 66.3%, predisposing these applicants to crystallization of stone-forming calcium salts. This high level of supersaturation was caused by both "metabolic" and environmental disturbances. Thus, hypercalciuria was found in 11.5% of applicants, hyperoxaluria in 2.9%, hyperuricosuria in 18.3% and hypocitraturia in 5.8%. Environmental derangements were generally more prominent, as indicated by low urine volume of less than 2 L.d-1 in 84.6%, high urinary phosphate in 24.4%, and high urinary sodium in 10.6% of applicants. The results suggest that most of the abnormal stone risk factors disclosed among applicants for spaceflight programs were environmental in origin.
Horizontal movements of both eyes were recorded simultaneously using scleral search coils in 2 rhesus monkeys before and after the COSMOS 2229 space-flight of 1992-1993. Another 9 monkeys were tested at comparable time intervals and served as controls. Ocular vergence, defined as the difference in horizontal position between the left and right eyes, was measured during off-vertical yaw axis rotation (OVAR) in darkness. Vergence was modulated sinusoidally as a function of head position with regard to gravity during OVAR. The amplitude of peak-to-peak modulation increased with increments in tilt of the angle of the rotational axis (OVAR tilt angle) that ranged from 15 degrees to 90 degrees. Of the 11 monkeys tested, 1 had no measurable modulation in vergence. In the other 10, the mean amplitude of the peak to peak modulation was 5.5 degrees +/- 1.3 degrees at 90 degrees tilt. Each of these monkeys had maximal vergence when its nose was pointed close to upward (gravity back; mean phase: -0.9 degree +/- 26 degrees). After space flight, the modulation in vergence was reduced by over 50% for the two flight monkeys, but the phase of vergence modulation was not altered. The reduction in vergence modulation was sustained for the 11-day postflight testing period. We conclude that changes in vergence are induced in monkeys by the sinusoidal component of gravity acting along the naso-occipital axis during yaw axis OVAR, and that the modulation of the vergence reflex is significantly less sensitive to linear acceleration after space flight.
We combined dual-photon absorptiometry, iliac crest histomorphometry, and backscattered electrons analysis to characterize bone mineralization effects of a spaceflight on young monkeys. Two 4- to 5-kg male rhesus monkeys (Macaca mulatta) were flown during a 11.5-day spaceflight that took place onboard Cosmos 2229 biosatellite (Bion 10). Vivarium (n = 4) and Earth-based chair (n = 4) control situations were studied for comparison. Flight monkeys exhibited lower values of iliac cancellous bone volume, associated with nonsignificantly thinner trabeculae. Bone mineralization rate and the proportion of trabecular bone surface involved in mineralization processes were found markedly reduced after spaceflight. Analysis of embedded sections by backscattered electrons imaging showed a nonsignificant shift to lower mineralization in the flight biopsies vs. postflight mock-up biopsies. These results were in accordance with dual-photon absorptiometry evaluations showing a tendency for decreased bone mineral content during flight and recovery thereafter. The ground simulation experiment performed on the same monkeys more than 1 mo after landing suggests that the observed effects were specifically related to spaceflight and that the animals had only partially recovered. Additional animals on future flights will be required to confirm these findings.
Over the past two decades, it has become apparent that changes in immune parameters occur in cosmonauts and astronauts after spaceflight. Therefore, interest has been generated in the use of animal surrogates to better understand the nature and extent of these changes, the mechanism of these changes, and to allow the possible development of countermeasures. Among the changes noted in animals after spaceflight are alterations in lymphocytic blastogenesis, cytokine function, natural killer cell activity, and colony-stimulating factors. The nature and significance of spaceflight-induced changes in immune responses will be the focus of this review.
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Plasma volume is reduced by 10-20% within 24-48 h of exposure to simulated or actual microgravity. The clinical importance of microgravity induced hypovolemia is manifested by its relationship with orthostatic intolerance and reduced maximal oxygen uptake (VO2max) after return to one gravity (1G). Since there is no evidence to suggest that plasma volume reduction during microgravity is associated with thirst or renal dysfunctions, a diuresis induced by an immediate blood volume shift to the central circulation appears responsible for microgravity-induced hypovolemia. Since most astronauts choose to restrict their fluid intake before a space mission, absence of increased urine output during actual space flight may be explained by low central venous pressure (CVP) which accompanies dehydration. Compelling evidence suggests that prolonged reduction in CVP during exposure to microgravity reflects a "resetting" to a lower operating point, which acts to limit plasma volume expansion during attempts to increase fluid intake. In ground based and space flight experiments, successful restoration and maintenance of plasma volume prior to returning to an upright posture may depend upon development of treatments that can return CVP to its baseline IG operating point. Fluid-loading and lower body negative pressure (LBNP) have not proved completely effective in restoring plasma volume, suggesting that they may not provide the stimulus to elevate the CVP operating point. On the other hand, exercise, which can chronically increase CVP, has been effective in expanding plasma volume when combined with adequate dietary intake of fluid and electrolytes. The success of designing experiments to understand the physiological mechanisms of and development of effective counter measures for the control of plasma volume in microgravity and during return to IG will depend upon testing that can be conducted under standardized controlled baseline conditions during both ground-based and space flight investigations.
Spacelab Life Sciences-1 and -2 provided skeletal muscles from rats dissected in flight for the first time and 2 h to 14 days postflight. The muscles permitted the distinguishing of primary adaptations to microgravity from secondary reloading-induced alterations. In microgravity, rats adopted bipedal forelimb locomotion with the hindlimbs relegated to grasping activities. On landing day, body posture was abnormally low and walking was stilted at a rate one-third of normal. The adductor longus (AL) and soleus muscles exhibited decreased myofiber areas that did not recover 14 days postflight. Doubling of the nonmyofiber area indicated interstitial edema in AL muscles 2.3 h postflight. Solei did not manifest edema postflight, and neither muscle showed edema in flight. Sarcomere eccentric contraction-like lesions were detected in 2.6% of AL myofibers 4.5 h postflight; lesions were absent earlier postflight and in flight. At 9 days postflight, these lesions were repaired but regenerating AL myofibers were present, which suggests that myofiber necrosis occurred 1-2 days postflight. These studies demonstrate that muscle atrophy occurs in microgravity, whereas interstitial edema and sarcomere lesions are postflight phenomena.
The effects of 14 days of spaceflight on myonuclear number, fiber size, and myosin heavy chain (MHC) expression in isolated rat soleus muscle fiber segments were studied. Single soleus muscle fibers from rats flown on the Spacelab Life Sciences-2 14-day mission were compared with those from age-matched ground-based control rats by using confocal microscopy and gel electrophoresis. Spaceflight resulted in a significant reduction in the number of fibers expressing type I MHC and an increase in the number of fibers expressing type IIx or IIa MHC. Space-flight also resulted in an increase in the percentage of fibers coexpressing more than one MHC and in the reexpression of the neonatal isoform of MHC in some fibers. Fiber cross-sectional area was significantly reduced in pure type I MHC-expressing fibers and in fibers coexpressing type I+II MHC but not in fibers expressing one or more type II MHC in the flight rats. The number of myonuclei per millimeter was significantly reduced in type I MHC-expressing fibers from the flight rats but was not significantly different in type I+II and type II MHC-coexpressing fibers. Fibers expressing neonatal MHC were similar in size to control fibers but had significantly fewer myonuclei per millimeter than flight fibers not expressing neonatal MHC. In type I MHC-expressing fibers, the reduction in fiber cross-sectional area was greater than the reduction in myonuclear number; thus the average cytoplasmic volume per myonucleus was significantly lower in flight than in control fibers. The reduction in both myonuclear number and fiber size of fibers expressing type I MHC after 14 days of spaceflight supports the hypothesis that changes in the number of myonuclei may be a contributing factor to the reduction in fiber size associated with chronic unloading of the musculature.
The circadian timing system (CTS) coordinates an animal's physiology and behavior both internally and with the 24-h day. Previous studies have suggested that the CTS is sensitive to changes in gravity. To examine this question, the expression of the CTS in four juvenile male rhesus macaques (Macaca mulatta) were studied in space. These animals were flown on the Cosmos 2044 and 2229 missions. Activity, heart rate, and axillary and brain (Cosmos 2229) temperatures were recorded. In both flights, the subjects exhibited delays in the phasing of their temperature rhythms and a decrease in mean heart rate compared with ground control studies. These data are in support of other studies that demonstrate that the CTS is sensitive to changes in the gravitational environment. Furthermore, the data also support the concept of a multioscillator organization of the primate CTS due to the differential responses of the rhythms measured.
Gravity affects cardiac filling pressure and intravascular fluid distribution significantly. A major central fluid shift occurs when all hydrostatic gradients are abolished on entry into microgravity (microG). Understanding the dynamics of this shift requires continuous monitoring of cardiac filling pressure; central venous pressure (CVP) measurement is the only feasible means of accomplishing this. We directly measured CVP in three subjects: one aboard the Spacelab Life Sciences-1 space shuttle flight and two aboard the Spacelab Life Sciences-2 space shuttle flight. Continuous CVP measurements, with a 4-Fr catheter, began 4 h before launch and continued into microG. Mean CVP was 8.4 cmH2O seated before flight, 15.0 cmH2O in the supine legs-elevated posture in the shuttle, and 2.5 cmH2O after 10 min in microG. Although CVP decreased, the left ventricular end-diastolic dimension measured by echocardiography increased from a mean of 4.60 cm supine preflight to 4.97 cm within 48 h in microG. These data are consistent with increased cardiac filling early in microG despite a fall in CVP, suggesting that the relationship between CVP and actual transmural left ventricular filling pressure is altered in microG.
The mean daily energy expenditure rates of three rhesus monkeys (Macaca mulatta) were determined during spaceflight on the joint US-Russian Cosmos 2044 and 2229 missions by the doubly labeled water (2H2(18)O) method. In-flight values were compared with ground data obtained from seven measurements taken from six chair-adapted control monkeys. The mean energy expenditure for the ground control determinations was 94.5 +/- 6.4 kcal.kg-1.day-1 (n = 6). The mean in-flight energy expenditure, 55.1 +/- 8.0 kcal.kg-1.day-1 (n = 3), was significantly less than the mean ground control value (P < 0.05). These data suggest that energy expenditure in restrained rhesus monkeys is significantly reduced during spaceflight.
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The Space Shuttle program has produced a database of information on the cardiovascular responses to spaceflight, based on in-flight as well as pre- and post-flight assessments undertaken as part of the assessment of the health, safety, and efficiency of Shuttle crews. The methods used in routine cardiovascular assessments of Space Shuttle astronauts are reviewed, and the major findings of these investigations are presented.
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Space flight is an environmental condition where astronauts can lose up to 19% of weight-bearing bone during long duration missions. We used the MC3T3-E1 osteoblast to investigate bone cell growth in microgravity (10(-6) to 10(-9)g). Osteoblasts were launched on the STS-56 shuttle flight in a quiescent state with 0.5% fetal calf serum (FCS) medium and growth activation was initiated by adding fresh medium with 10% FCS during microgravity exposure. Four days after serum activation, the cells were fixed before return to normal Earth gravity. Ground controls were treated in parallel with the flight samples in identical equipment. On landing, cell number, cell cytoskeleton, glucose utilization, and prostaglandin synthesis in flight (n = 4) and ground controls (n = 4) were examined. The flown osteoblasts grew slowly in microgravity with total cell number significantly reduced (55 +/- 6 vs 141 +/- 8 cells per microscopic field). The cytoskeleton of the flight osteoblasts had a reduced number of stress fibers and a unique abnormal morphology. Nuclei in the ground controls were large and round with punctate Hoechst staining of the DNA nucleosomes. The flight nuclei were 30% smaller than the controls (P < 0.0001) and oblong in shape, with fewer punctate areas. Due to their reduced numbers, the cells activated in microgravity used significantly less glucose than ground controls (80.2 +/- 0.7 vs 50.3 +/- 3.7 mg of glucose/dl remaining in the medium) and had reduced prostaglandin E2 (PGE2) synthesis when compared to controls (57.3 +/- 17 vs 138.3 +/- 41 pmol/ml). Cell viability was normal since, on a per-cell basis, glucose use and prostaglandin synthesis were comparable for flight and ground samples. Taken together, these data suggest that growth activation in microgravity results in reduced growth, causing reduced glucose utilization and reduced prostaglandin synthesis, with significantly altered actin cytoskeleton in osteoblasts.
Hematologic studies were performed on 21 ground control rats and 21 rats flown during the Spacelab Life Sciences-2 14-day mission. Group A (n = 5) was used to collect blood in flight and 9 days postflight, group B (n = 5) was injected with recombinant human erythropoietin (rhEpo), group C (n = 5) received saline as a control, and group D (n = 6) was killed in flight and tissues were collected. Results indicated no significant changes in peripheral blood erythroid elements between flight and ground control rats. The nonadherent bone marrow on flight day 13 showed a lower number of recombinant rat interleukin-3 (rrIL-3)-responsive and rrIL-3 + rhEpo-responsive blast-forming unit erythroid (BFU-e) colonies in flight rats compared with ground control rats. On landing day, a slight increase in the number of rhEpo + rrIL-3-responsive BFU-e colonies of flight animals compared with ground control rats was evident. Nine days postflight, bone marrow from flight rats stimulated with rhEpo alone or with rhEpo + rrIL-3 showed an increase in the number of colony-forming unit erythroid colonies and a decrease in BFU-e colonies compared with ground control rats. This is the first time that animals were injected with rhEpo and subsequently blood and tissues were collected during the spaceflight to study the regulation of erythropoiesis in microgravity.
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.