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Mineral and nitrogen metabolic studies on Skylab flights and comparison with effects of earth long-term recumbency.

A metabolic study of the effects of space flight on various chemical elements, particularly those with special relevance to the musculo-skeletal system, was carried out on the nine astronauts who participated in the three Skylab flights of 28, 59 and 84 days in 1973-1974. The study required of the cooperating crewmen constant dietary intake, continuous 24-hour urine collections and total fecal collections for 21-31 days before each flight, throughout each flight and for 17-18 days post-flight. Increases in urinary calcium and negative calcium balances during space flight were generally similar to those found in previous immobilization and bedrest studies. The persistence of these alterations in calcium metabolism throughout the flights suggested that calcium losses would continue in weightlessness for a very long time. Significant losses of nitrogen and phosphorus occurred, associated with observed reduction in muscle tissue. Both mineral and muscle losses occurred despite vigorous exercise regimens in flight. It was concluded that unless protective measures can be developed, capable musculo-skeletal function is likely to be impaired in space flights, ultimately to be conducted to Mars, of 11/2 to 3 years duration.

Bed Rest↗

Amino acid spectrum of human blood plasma during space flight and in antiorthostatic hypokinesia.

The paper summarizes results of experiments on the influence of space flight and anti-orthostatic hypokinesia on the amino acids spectrum of human blood plasma. Our findings give evidence for: (i) A specific norm of the content of free amino acids in plasma during training and (ii) consistent changes of plasma aminograms during space flight related to its duration and to individual features of cosmonauts. The content of free amino acids in the plasma of bed-rested subjects varied phasically and tended to increase practically at every experimental stage. The paper discusses the findings and possible mechanisms of the detected changes.

Amino Acids↗

Deconditioning during prolonged immersion and possible countermeasures.

Test subjects covered with a waterproof highly elastic cloth were exposed to 13-day water immersion up to the neck. They were divided into two groups. The first (control) group consisting of six persons was exposed to immersion alone and the second (experimental) group was exposed daily to accelerations of 0.6-2 Gz for 60-90 min during the last 6 days of immersion. Before and after immersion all the test subjects were exposed to +3 Gz for 5 min which served as a provocative test. These experiments give evidence that the use of dry immersion allows experimentation during prolonged immersion without concomitant complications. Variations in the physiological parameters (cardiovascular system, fluid-electrolyte balance, blood-coagulatory system) are indicative of the preventive effect of periodic accelerations during 13-day immersion.

Acceleration↗

[Effect of extremity cuffs as a countermeasure against the cardiovascular deconditioning during 21 d head-down bedrest].

OBJECTIVE: To affirm the protective effect of inflated cuffs. METHOD: The protective effect against the cardiovascular deconditioning of inflated cuffs on the upper parts of thighs and arms during the 1st through 10th days of 21 d bedrest has been reported previously. The effect of the cuffs during the rest of the 21 d bedrest were studied in this paper. Five subjects in cuffs group whose orthostatic tolerance were well maintained continued bed rest for 7 d without inflated cuffs. For the last 4 days of this period, inflated cuffs were again applied. Orthostatic tolerance of subjects in cuffs group with and without cuffs were measured. RESULT: Two of the five subjects suffered orthostatic intolerance on the 17th day. No sign of orthostatic intolerance were observed by the end of bedrest. CONCLUSION: (1) the cardiovascular deconditioning developed when inflated cuffs were not used, and (2) the use of inflated cuffs for 4 d improves the orthostatic tolerance.

Adolescent↗

[Effects of lower body negative pressure in the first and last week during 21 d head-down bed rest on orthostatic tolerance and cardiac function].

OBJECTIVE: To investigate the changes of orthostatic tolerance and cardiac function during 21 d head-down tilt (HDT) bed rest and effect of lower body negative pressure (LBNP) in the first and the last weeks in humans. METHOD: Twelve healthy male volunteers were exposed to -6 degrees HDT bed rest for 21 d. Six subjects received -30 mmHg LBNP sessions for 1 h/d from the 1st to the 7th day and from the 15th to the 21st day of the HDT, and the other six who did not receive LBNP served as control. Orthostatic tolerance was assessed by means of standard tilt test. The cardiac pumping function and cardiac systolic function were measured before and during HDT. RESULT: Before HDT, all the subjects in the two groups completed the tilt tests. After 10 d and 21 d of HDT, all the subjects of the control group and one subject of the LBNP group could not complete the tilt test due to presyncopal or syncopal symptoms. The mean time of upright standing in the control group (15.0 +/- 3.2 min) was significantly shorter than those in the LBNP group (19.7 +/- 0.9 min). The stroke volume and cardiac output decreased significantly in the control group on days 3 and 10 of HDT, but remained unchanged throughout HDT in the LBNP group. A significant increase in preejection period (PEP)/left ventricular ejection time (LVET) was observed on days 3 and 14 of HDT in both groups. The PEP/LVET in the LBNP group was significantly lower than those in the control group on days 3 of HDT, while LVET in LBNP group was significantly higher than those in the control group on days 3, 7 and 14 of HDT. CONCLUSION: It is suggested that the brief daily LBNP sessions in the first and the last weeks were effective in preventing orthostatic intolerance and the reduction of cardiac pumping function and cardiac systole function induced by 21 d HDT bed rest.

Adult↗

Neural and neuroendocrine adaptations to microgravity and ground-based models of microgravity.

The functional properties of the motor system of humans and non-human primates are readily responsive to microgravity. There is a growing body of evidence that significant adaptations occur in the spinal cord and muscle in response to prolonged exposure to microgravity. Further, there is evidence that the processing of sensory information from the periphery, particularly that input associated with the function of muscle tendons and joints, is significantly altered as a result of prolonged microgravity. We present evidence that the fundamental neural mechanisms that control the relative activity of the motor pools of a slow and fast extensor muscle is changed such that a slow, postural muscle is less readily activated during locomotion following spaceflight. Another type of change observed in mammals exposed to spaceflight relates to the release of a growth factor, called bioassayable growth hormone, which is thought to be released from the pituitary. When an individual generates a series of isometric plantarflexor contractions, the plasma levels of bioassayable growth hormone increases significantly. This response is suppressed after several days of continuous bedrest or spaceflight. These results suggest a unique neuroendocrine control system and demonstrate its sensitivity to chronic patterns of proprioceptive input associated with load-bearing locomotion.

Adaptation, Physiological↗

Changes in muscle size and architecture following 20 days of bed rest.

Five healthy men carried out a program of head-down bed rest (BR) for 20 days. Before and after BR, a series of cross-sectional scans of the thigh were performed using magnetic resonance imaging, from which volumes of the quadriceps muscles were determined and physiological cross-sectional areas (PCSA) were calculated. Muscle thickness and pennation angles of the triceps brachii, vastus lateralis, and triceps surae muscles were also determined by ultrasonography. During BR, subjects performed unilateral isokinetic knee extension exercises every day. The contralateral limb served as a control. Decrease in PCSA after BR was greater in the control (-10.2 +/- 6.3%) than in the trained limb (-5.2 +/- 4.2%). Among the quadriceps, vastus intermedius in the control limb was predominantly atrophied by BR with respect to the volume and PCSA, and the rectus femoris showed the greatest training effect and retained its size in the trained limb. Decreases in muscle thicknesses in leg muscles were not prevented by the present exercise protocol, suggesting a need for specific exercise training for these muscles. Neither trained nor control muscles showed significant changes in pennation angles in any muscles after BR, suggesting that muscle architecture does not change remarkably by muscle atrophy by up to 10%.

Adult↗

Changes in urinary excretion of deoxypyridinoline in tail-suspended rats: effects of a bisphosphonate, YH529.

Urinary excretion of deoxypyridinoline (D-Pyr) has been shown to be a useful marker for bone resorption. In this study, we investigated whether D-Pyr could be used to monitor the changes in bone resorption of the hind limb induced by tail-suspension. Male Wistar rats 5-weeks old were tail-suspended in a metabolic cage to unload the hind limbs. The control rats were not suspended. YH529 (YH), an inhibitor of bone resorption, or a vehicle (phosphate buffered saline=PBS) was administered daily starting 3 days before the commencement of tail-suspension. In the non-suspended rats receiving PBS, urinary excretion of D-Pyr did not show any significant change during the one-week experimental period. In the non-suspended rats receiving YH, D-Pyr excretion significantly decreased on day 5 and 7 when compared with that observed on day 0, in accordance with the systemic inhibition of bone resorption by YH. In the tail-suspended rats receiving PBS, D-Pyr excretion showed a tendency to increase on day 1, which is in agreement with our previous report that tail-suspension causes an early (on day 1 of suspension) and transient increase in bone-resorption of the hind limbs. In the tail-suspended rats treated with YH, the increase in D-Pyr excretion on day 1 was not observed, and a significantly lower excretion was noted from day 3 to 7 during the tail-suspension. It was suggested that D-Pyr excretion might reflect the transient increase in hind limb bone resorption induced by tail-suspension. As observed in-YH treated rats, D-Pyr excretion could serve as a good marker for the inhibition of systemic bone resorption.

Amino Acids↗

[Change of cerebral blood flow velocity during 4 d head-down tilt bed rest].

Objective. To investigate the change of cerebral blood flow velocity during 4 d head-down tilt (HDT) bed rest in humans. Method. Eight healthy male volunteers were exposed to -6 degrees HDT bed rest for 4 d. Orthostatic tolerance was assessed by means of standard tilt test. Cerebral blood flow velocity in the right middle cerebral artery was measured by transcranial Doppler sonography before HDT (supine), on days 1, 3 and 4 of HDT and on day 2 post HDT. Result. After 4 d HDT, the frequency of orthostatic intolerance was significantly higher than those before HDT (P<0.05). The systolic, diastolic and mean blood velocities in the middle cerebral artery tended to decrease on days 1 and 3 of HDT, and decreased significantly on day 4 of HDT, compared with pre-HDT, and returned to basal levels on day 2 post HDT. The mean arterial blood pressure and diastolic blood pressure increased significantly, while the body weight decreased significantly during HDT. Conclusion. It is suggested that 4 d HDT may decrease cerebral blood flow velocity and increase the frequency of orthostatic intolerance. This decrease of cerebral blood flow velocity may be partially responsible for the increased risk of orthostatic intolerance.

Adult↗

[Body temperature changes during 7 d -6 degrees head-down bed rest].

Objective. To investigate body temperature changes in man during 7-day -6 degrees head-down bed rest (BR). Method. Body temperatures were measured in the morning (6:00), afternoon (16:00) and evening (20:00) during 7 d BR in 18 healthy males (18-22 years old). Result. Rectal temperature (Tre) in the morning gradually decreased as time (d) of BR increased: after the 4th day of BR (BR4d), Tre significantly reduced compared with the supine control (SC, 36.50 +/- 0.03 degrees C) before BR, and it consistently declined to 36.38 +/- 0.04 degrees C on BR7d; But Tre significantly increased in the afternoon after BR5d and in the evening after BR1d, with the final increments of 0.12 +/- 0.05 degrees C and 0.25 +/- 0.03 degrees C respectively on BR7d. Mean body temperature (Tsk) in the morning was significantly higher from BR2d than its SC, with a final net increase (delta Tsk) of 0.38 +/- 0.14 degrees C on BR7d. And Tsk significantly increased in the afternoon and evening from BR4d, BR2d respectively. Skin temperature on the forehead (Tforehead) elevated in the morning during BR. While in the afternoon and evening, Tforehead were significantly higher from BR7d and BR6d than their SC. Conclusion. Both the difference in time of recording at a BR day and the time (d) of BR have significant influence on Tre, Tsk , and Tforehead (P<0.01). These data suggest that body temperature rhythm, body fluid loss and headward distribution, hypokinesis etc. induced by BR have an impact on human thermal regulation during BR.

Adolescent↗

Culture in vector-averaged gravity environment in a clinostat results in detachment of osteoblastic ROS 17/2.8 cells.

Studies carried out in space flights and in altered gravitational environments have shown that exposure to altered gravity conditions results in alterations in cellular structure and function. In the present study, we used a clinostat to generate a vector-averaged gravity environment, and evaluated the responses of osteoblast-like ROS 17/2.8 cells subsequent to rotation at 50 r.p.m from 24 to 72 hr. We found that the cells started to detach during the first 24 hr of culture in clinostat, but not in stationary and horizontal rotation (the latter serving as a control for turbulence, shear forces and vibrations). At 24 hr, there was a significant decrease in the number of adherent cells under clino-rotation (2.75 +/- 0.5 x 10(5) in stationary culture versus 2.02 +/- 0.27 x 10(5) under clino-rotation), and 19.8% of adherent cells were trypan-blue positive when cultured in 2% fetal bovine serum. All the detached cells were trypan-blue positive. At 72 hr, the cells became confluent in all three groups. These results suggest that vector-averaged gravity could cause the death of osteoblasts during the first 24 hr of clino-rotation. We hypothesize that this cell death might play a role in the pathogenesis of osteoporotic bone loss as observed in actual space flight.

Animals↗

Effects of vector-averaged gravity on NF-kappa B activation in human osteoblast-like cells.

We have recently demonstrated that a transcription factor, nuclear factor kappa B (NF-kappa B), plays a key role in the production of cytokine and cell adhesion molecules in osteoblastic cells. In the present study, we investigated the effects of vector-averaged gravity (clinostat rotation) on tumor necrosis factor (TNF)-alpha-induced activation of NF-kappa B in human osteoblastic HOS-TE85 cells. After a 72-hr clinostat culture, the cells were treated with TNF-alpha for 30 min. Electrophoretic mobility shift assay using the nuclear extracts revealed that the DNA-binding activity of NF-kappa B was substantially reduced in clinostat-cultured cells compared with the stationary control. Concomitantly, the transactivation of NF-kappa B was examined by a transfection study. The cells were transfected with a plasmid expressing a luciferase reporter gene driven by multimerized NF-kappa B sites. They were cultured in the clinostat for 48-hr, followed by a 4-hr treatment with TNF-alpha. Clinostat culture resulted in a significant decrease in the luciferase activities, being consistent with the decreased binding of NF-kappa B. These results indicate that exposure of HOS-TE85 cells to vector-averaged gravity impairs NF-kappa B activation by TNF-alpha.

DNA↗

Effects of bisphosphonate on bone metabolism in tail-suspended rats.

Our previous studies demonstrated that tail suspension causes early, transient increases in osteoclastic activity, followed by a decrease in osteoblastic activity in the hind limbs of rats. To assess whether this early increase in bone resorption is important in the development of disuse atrophy, the effect of YH529, a third generation bisphosphonate, was studied on hind limb atrophy in rats subjected to tail suspension. YH529 (YH group) or PBS (control group) were administered subcutaneously in 5-week-old male Wistar rats suspended for 7 days. In the control group, wet weight, calcium and phosphorus contents decreased significantly in the femur but they did not change in the humerus. In the YH group, however, these parameters did not change significantly in the femur, but both calcium and phosphorus increased significantly in the humerus. These results indicate that the inhibition of bone resorption by YH529 prevents the development of disuse atrophy induced by tail suspension. It is thus suggested that early increases in bone resorption are important for the development of disuse bone atrophy.

Animals↗

Changes in serum concentrations of calcium and its regulating hormones during tail suspension in rats.

To study the effects of mechanical unloading on systemic calcium homeostasis, we determined the changes in serum concentration of calcium, 1,25-dihydroxyvitamin D3 and parathyroid hormone (PTH) during tail-suspension experiments in rats. The serum concentration of ionized calcium significantly increased during the 14 days of the suspension, reflecting increased bone resorption in the hind limbs. This hypercalcemic condition should cause suppression in PTH secretion. Indeed, serum PTH levels decreased on Day 3 of the suspension. This decrease was associated with lower serum levels of 1,25-dihydroxyvitamin [correction of dihyroxyvitamin] D3 probably due to a decrease in the activity of 1 alpha-hydroxylase in the kidneys resulting from a decrease in PTH secretion. Since it is known that 1,25-dihydroxyvitamin D3 stimulates osteoblastic function, it is suggested that endocrine responses evoked by tail suspension aggravate disuse atrophy of the hind limbs.

Amino Acids↗

Percutaneous aspiration of fluid for management of peritonitis in space.

BACKGROUND: As a medical emergency that can affect even well-screened, healthy individuals, peritonitis developing during a long-duration space exploration mission may dictate deviation from traditional clinical practice due to the absence of otherwise indicated surgical capabilities. Medical management can treat many intra-abdominal processes, but treatment failures are inevitable. In these circumstances, percutaneous aspiration under sonographic guidance could provide a "rescue" strategy. HYPOTHESIS: Sonographically guided percutaneous aspiration of intra-peritoneal fluid can be performed in microgravity. METHODS: Investigations were conducted in the microgravity environment of NASA's KC-135 research aircraft (0 G). The subjects were anesthetized female Yorkshire pigs weighing 50 kg. The procedures were rehearsed in a terrestrial animal lab (1 G). Colored saline (500 mL) was introduced through an intra-peritoneal catheter during flight. A high-definition ultrasound system (HDI-5000, ATL, Bothell, WA) was used to guide a 16-gauge needle into the peritoneal cavity to aspirate fluid. RESULTS: Intra-peritoneal fluid collections were easily identified, distinct from surrounding viscera, and on occasion became more obvious during weightless conditions. Subjectively, with adequate restraint of the subject and operators, the procedure was no more demanding than during the 1-G rehearsals. CONCLUSIONS: Sonographically guided percutaneous aspiration of intra-peritoneal fluid collections is feasible in weightlessness. Treatment of intra-abdominal inflammatory conditions in spaceflight might rely on pharmacological options, backed by sonographically guided percutaneous aspiration for the "rescue" of treatment failures. While this risk mitigation strategy cannot guarantee success, it may be the most practical option given severe resource limitations.

Animals↗

Cardiovascular function in the elderly during water immersion.

In attempting to clarify the effects of aging on the regulatory functions of the cardiovascular system, we measured blood pressure, heart rate and stroke volume during thermoneutral head-out water immersion in seven healthy elderly and eight healthy young subjects. In the young subjects water immersion resulted in a marked increase in stroke volume, a deceleration of the heart rate and stable blood pressure values. In the elderly group the blood pressure increased significantly during shoulder-level water immersion. Compared to the young subjects, the elderly presented a less pronounced elevation of the stroke volume, and no change in the heart rate. These results indicate that the vasodepressive mechanisms regulated by baroreflexes diminish with aging, resulting in an elevation of blood pressure.

Adult↗