Prolonged weightlessness and calcium loss in man

Data have been accumulated from a series of studies in which men have been subjected to weightlessness in orbital space flight for periods of up to 12 weeks. These data are used to predict the long term consequences of weightlessness upon the skeletal system. Space flight induced a loss of calcium which accelerated exponentially from about 50 mg/d at the end of 1 week to approx. 300 mg/d at the end of 12 weeks. The hypercalciuria reached a constant level within 4 weeks while fecal calcium losses continued to increase throughout the period of exposure. This apparent diminution of gastrointestinal absorptive efficiency was accompanied by a slight decline in the plasma level of parathyroid hormone and a slight elevation in the plasma level of calcium and phosphorus. Although losses in mineral from the calcaneus were closely correlated with the calcium imbalance, no changes were detected in the mineral mass of the ulna and radius. From the data presented it is concluded that the process of demineralization observed in space flight is more severe than would be predicted on the basis of observations in immobilized, bed rested, or paralyzed subjects. It is, moreover, suggested that the process may not be totally reversible.     

Mineral and nitrogen balance study: results of metabolic observations on Skylab II 28-day orbital mission

Prediction that the various stresses of flight, particularly weightlessness, would bring about significant derangements in the metabolism of the musculoskeletal system has been based on various observations of long-term immobilized or inactive bed rest. The only attempt at controlled measurement of metabolic changes in space prior to Skylab, a study during the 14-day Gemini VII flight, revealed rather modest losses of important elements. The three astronauts of Skylab II consumed a planned day-by-day, quite constant, dietary intake of major metabolic elements in mixed foods and beverages and provided virtually complete collections of excreta for 31 days preflight, during the 28 days inflight, and for 17 days postflight. Analyses showed that, in varying degree among the crewmen, urinary calcium increased gradually during flight in a pattern similar to that observed in bed-rest studies: the mean plateau peak of urinary calcium excretion in the latter part of flight was double preflight levels. Fecal calcium excretion did not change significantly, but calcium balance, owing to the urinary calcium rise, became either negative or less positive than in preflight measurement. Increased excretion and negative balance of nitrogen and phosphorus indicated appreciable loss of muscle tissue in all three crewmen. Significant losses also occurred inflight in potassium, sodium, and magnesium. Based on the similarity in pattern and degree between these observations and those in bed rest of the losses in calcium, phosphorus, and nitrogen, musculoskeletal integrity would not be threatened in space flights of up to at least 3 months. However, if similar changes occur, indicative of continuing losses of these elements, in the planned Skylab flights for considerably more than 28 days, concern for capable musculoskeletal function should be serious for flights of very many months' duration, and greater research attention will need to be given to development of protective counter-measures.     

Bone and body mass changes during space flight

Long duration space flight has shown us that humans have significant bone loss and mineral changes because they are living in microgravity. Skylab and the longer Salyut and Mir missions, are providing us useful data and allowing us to explore the mechanism involved in skeletal turnover. Bone redistribution occurs throughout space flight with bone loss predominately in the weight bearing bones of posture and locomotion. The primary health hazards which may occur during space flight induced by skeletal changes include signs and symptoms of hypercalcemia, and the risk of kidney stones and metastatic calcification. After flight lengthy recovery of bone mass and the possible increase in the risk of bone fracture should be considered. Continued research studies are being directed toward determining the mechanisms by which bone is lost in space and developing more effective countermeasures by both the US (Schneider and McDonald, 1984 and Schneider, LeBlanc & Huntoon, 1993) and Russian (Grigoriev et. al., 1989) space programs.     

A mathematical and experimental simulation of the hematological response to weightlessness

Two ground-based methods of weightlessness simulation--a computer model of erythropoiesis feedback regulation and bedrest--were used to investigate the mechanisms which lead to loss of red cell mass during spaceflight. Both methods were used to simulate the first Skylab mission of 28 days. Human bedrest subjects lose red cell mass linearly with time and in this study the loss was 6.7% at the end of four weeks (compared to 14% in Skylab). Postbedrest recovery of red cell mass was delayed for two weeks during which time a further decline in this quantity was noted. This is consistent with the first Skylab mission but not with the two longer flights of two and three months. Hemoconcentration, observed early in the study, was essentially maintained despite red cell loss because of continued loss of plasma volume. The computer model, using the time-varying hematocrit data to estimate red cell production rates, predicted dynamic behavior of plasma volume and red cell mass that was in close agreement with the measured values. The results support the hypothesis that red cell loss during supine bedrest is a normal physiological feedback process in response to hemoconcentration enhanced tissue oxygenation and suppression of red cell production. In contrast, the delayed postbedrest recovery of red cell mass was more difficult to explain, especially in the light of enhanced reticulocyte indices observed at the onset on ambulation. Model simulation suggested the possibilities, still to be experimentally demonstrated, that this period was marked by some combination of increased oxygen-hemoglobin affinity, small reductions in mean red cell life span, ineffective erythropoiesis, or abnormal reticulocytosis. The question of whether hemoconcentration is the sole contributor to spaceflight red cell losses also remains to be resolved.     

Understanding metabolic alterations in space flight using quantitative models: fluid and energy balance

This report summarizes many of the results obtained during the Skylab program, on metabolic changes during weightlessness. The examination of the data was conducted following an integrated multi-disciplinary and multi-experimental approach. Emphasis is given on several major aspects of metabolic adaptation to space flight: fluid-electrolyte regulation, mechanisms of hormone disturbances, energy balance and etiology of weight loss. The aim is to obtain a composite picture of the fluid, electrolyte and energy response to weightlessness.     

Medical considerations for extending human presence in space

The prospects for extending the length of time that humans can safely remain in space depend partly on resolution of a number of medical issues. Physiologic effects of weightlessness that may affect health during flight include loss of body fluid, functional alterations in the cardiovascular system, loss of red blood cells and bone mineral, compromised immune system function, and neurosensory disturbances. Some of the physiologic adaptations to weightlessness contribute to difficulties with readaptation to Earth's gravity. These include cardiovascular deconditioning and loss of body fluids and electrolytes; red blood cell mass; muscle mass, strength, and endurance; and bone mineral. Potentially harmful factors in space flight that are not related to weightlessness include radiation, altered circadian rhythms and rest/work cycles, and the closed, isolated environment of the spacecraft. There is no evidence that space flight has long-term effects on humans, except that bone mass lost during flight may not be replaced, and radiation damage is cumulative. However, the number of people who have spent several months or longer in space is still small. Only carefully-planned experiments in space preceded by thorough ground-based studies can provide the information needed to increase the amount of time humans can safely spend in space.     

One hundred US EVAs: a perspective on spacewalks

In the 36 years between June 1965 and February 2001, the US human space flight program has conducted 100 spacewalks, or extravehicular activities (EVAs), as NASA officially calls them. EVA occurs when astronauts wearing spacesuits travel outside their protective spacecraft to perform tasks in the space vacuum environment. US EVA started with pioneering feasibility tests during the Gemini Program. The Apollo Program required sending astronauts to the moon and performing EVA to explore the lunar surface. EVA supported scientific mission objectives of the Skylab program, but may be best remembered for repairing launch damage to the vehicle and thus saving the program. EVA capability on Shuttle was initially planned to be a kit that could be flown at will, and was primarily intended for coping with vehicle return emergencies. The Skylab emergency and the pivotal role of EVA in salvaging that program quickly promoted Shuttle EVA to an essential element for achieving mission objectives, including retrieving satellites and developing techniques to assemble and maintain the International Space Station (ISS). Now, EVA is supporting assembly of ISS. This paper highlights development of US EVA capability within the context of the overarching mission objectives of the US human space flight program.     

Energy utilization rates during shuttle extravehicular activities

The work rates or energy utilization rates during EVA are major factors in sizing of life support systems. These rates also provide a measure of ease of EVA and its cost in crew fatigue. From the first Shuttle EVA on the STS-6 mission in 1983, we have conducted 59 man-EVA and 341 man-hours of EVA. Energy utilization rates have been measured on each of these EVA. Metabolic rate was measured during each EVA using oxygen utilization corrected for suit leakage. From 1981–1987, these data were available for average data over the EVA or over large segments of the EVA. Since 1987, EVA oxygen utilization data were available at 2-minute intervals. The average metabolic rate on Shuttle EVA (194 kcal/hr.) has been significantly lower than metabolic rates during Apollo and Skylab missions. Peak rates have been below design levels, infrequent, and of short duration. The data suggest that the energy cost of tasks may be inversely related to the degree of training for the task. The data provide insight on the safety margins provided by life support designs and on the energy cost of Station construction EVA.     

Bone effects of space flight: analysis by quantum concept of bone remodelling.

During the manned Skylab flights mineral losses from the calcaneum and changes in external calcium balance were in the ranges found for healthy subjects at bedrest. Calcium balance reached a nadir of -200 mg/day by two months with no change thereafter; the negative balance was due to increased urinary excretion with no change in net absorption. The total calcium loss averaged 18 g in the longest flight of 84 days; the densitiometric data suggested that about two-thirds of this came from trabecular bone and about one-third from cortical bone. These data could represent reversible bone loss due to increased birth rate of normal osteoclasts and osteoblasts and consequent increase in bone turnover and in reversible mineral deficit, or irreversible bone loss due to overactive osteoclasts and/or underactive osteoblasts. If the former explanation is correct, significant bone loss is unlikely whatever the duration of future flights, except in older persons already losing bone; if the latter explanation is correct, space flights longer than six months may lead to a significant increase in fracture risk in later life. Neither terrestrial immobilization nor unwilling animals in orbit are ideal models for the effects of space flight on human bone. To choose between reversible and irreversible mechanisms of bone loss, and to determine the effects of space flight on lifelong fracture risk, future astronauts and cosmonauts must undergo adequate histologic study of bone after in vivo tetracycline labeling.     

T cell regulation in microgravity – The current knowledge from in vitro experiments conducted in space,parabolic flights and ground-based facilities

Dating back to the Apollo and Skylab missions, it has been reported that astronauts suffered from bacterial and viral infections during space flight or after returning to Earth. Blood analyses revealed strongly reduced capability of human lymphocytes to become active upon mitogenic stimulation. Since then, a large number of in vitro studies on human immune cells have been conducted in space, in parabolic flights, and in ground-based facilities. It became obvious that microgravity affects cell morphology and important cellular functions. Observed changes include cell proliferation, the cytoskeleton, signal transduction and gene expression. This review gives an overview of the current knowledge of T cell regulation under altered gravity conditions obtained by in vitro studies with special emphasis on the cell culture conditions used. We propose that future in vitro experiments should follow rigorous standardized cell culture conditions, which allows better comparison of the results obtained in different flight- and ground-based experiment platforms.     

Antibody engineering--a valuable asset in preventing closed environment epidemics

Investigations of Mir, Space Shuttle, Skylab and Apollo missions report extensive colonisation of the spacecraft by bacteria and fungi, which can lead to degradative effects on spacecraft equipment and devastating effects on space-grown crops. More than 80% of terrestrial greenhouse epidemics are due to the fungal genera Phytophthora, Pythium and Fusarium, which have been found in life support system test-beds. The advent of recombinant antibody technologies, including ribosome display and phage display, has made it possible to develop antibodies against virtually any toxin or organism and allows for maturation of antibodies by in vitro molecular evolution. These antibodies may play an important role in an integrated pest management regime for life support systems. Efficacy of existing fungal countermeasures could be increased by chemical linkage to antibodies, which target the site of action of the biocide or trap the pathogen in a biofilter. Novel recombinant antibody-biocide fusions can be expressed in situ by plants or symbiotic microbes to create direct disease resistance.     

The prevention of adverse physiological change in Space Station crewmembers

Various physiological countermeasures, consisting primarily of isotonic and isometric exercises but also including prescribed nutrient intake, have been used in all manned spaceflights exceeding about one month in duration. So consistent has been this practice that the effects of weightlessness on the human, unconfounded by the use of countermeasures, are difficult to discern. Equally elusive, in the absence of control studies conducted in weightlessness, is an accurate assessment of the efficacy of the countermeasures themselves. Changes in body composition occurring during and following flights from Gemini through Shuttle, when compared with changes during and following bedrest, demonstrate certain mitigating effects that may be attributable to countermeasures and which provide some rationale for the choice of countermeasures in the Space Station.     

Space motion sickness medications: interference with biomedical parameters

The possibility that drugs administered to Skylab 3 (SL-3) and 4 (SL-4) crewmen for space motion sickness may have interfered with their biomedical evaluation in space was investigated. Healthy volunteers received combinations of Scopolamine/Dexedrine for four days in regimens similar to those used in these missions. Urine samples, heart rate, body temperature, mood and performance were analyzed for drug-related changes. Twenty-four hour urine samples were analyzed by the same procedures as those used to analyze the flight samples. Hormone concentrations determined included cortisol, epinephrine, norepinephrine, aldosterone and antidiuretic hormone (ADH). In addition, volume, specific gravity, osmolarity, sodium (Na), potassium (K), calcium (Ca), magnesium (Mg), chloride (Cl), inorganic phosphate, uric acid and creatinine were measured. Performance was not affected by the Scopolamine/Dexedrine. The drug combination increased daily mean heart rate (HR) significantly in all the subjects and daily mean rectal temperature (RT) in some of the subjects. A 2-4 hr phase shift in the HR circadian rhythm was also observed which indicates that internal circadian synchrony was disturbed by the drugs. Psychological and subjective evaluation indicated that the subjects could usually identify which days they were given the drugs by an increase in tension and anxiety, decreased patience, restlessness, decreased appetite, difficulty in sleeping and feelings of increased heart rate and body temperature. Urinary electrolytes were not changed significantly by the drug, but marked and significant changes occurred in urine volume and hormone excretion patterns. Scopolamine/Dexedrine caused consistent elevations in urinary cortisol and epinephrine and a transient elevation in ADH. Norepinephrine excretion was decreased, but there was no significant change in aldosterone excretion or in 24 hr urine volume. A comparison of these findings with the first four days of inflight data from the SL-3 and SL-4 missions leads to the conclusion that the dramatic increases in aldosterone excretion during the first three days of spaceflight probably can be directly attributed to weightlessness, whereas the antimotion sickness medication could have substantially contributed to the early increased excretion of epinephrine and cortisol during these missions.     

美国航天器交会技术研究

美国交会对接技术的发展可分为三个阶段：＂双子座＂与＂阿波罗＂飞船,航天飞机,以及后航天飞机时代的项目。自主交会技术的发展,首先基于多种制导和导航敏感器的研发,特别是用于最终逼近段的激光敏感器。制导、导航与控制系统的冗余,以及故障检测与隔离的方法,在轨迹安全性中起重要作用。文章研究美国自主交会方案,包括＂双子座＂,＂阿波...     

Bone loss during long term space flight is prevented by the application of a short term impulsive mechanical stimulus

In long term space flight, the mechanical forces applied to the skeleton are substantially reduced and are altered in character. This reduced skeletal loading results in a reduction in bone mass. Exercise techniques currently used in space can maintain muscle mass but the mechanical stimulus provided by this exercise does not prevent bone loss. By applying an external impulsive load for a short period each day, which is intended to mimic the heel strike transient, to the lower limb of an astronaut during a long term space flight (5 months), this study tests the hypothesis that the bone cells can be activated by an appropriate external mechanical stimulus to maintain bone mass throughout prolonged periods of weightlessness. A mechanical loading device was developed to produce a loading of the os-calcis similar to that observed during the heel strike transient. The device is activated by the astronaut to provide a transient load to the heel of one leg whilst providing an equivalent exercising load to the other leg. During the EUROMIR95 mission on the MIR space station, an astronaut used this device for a short period daily throughout the duration of the mission. Pre- and post-flight measurements of bone mineral density (BMD) of the os-calcis and femoral neck of the astronaut were made to determine the efficacy of the device in preventing loss of bone mineral during the mission. On the os-calcis which received the mechanical stimulus, BMD was maintained throughout the period of the flight, while it was reduced by up to 7% on the os-calcis which received no stimulus. Post-flight, BMD in both the stimulated and non-stimulated os-calcis reduces, the extent of this reduction however is less in the stimulated os-calcis. For the femoral neck, the mechanical stimulation does not produce a positive effect.     

Early cardiovascular adaptation to zero gravity simulated by head-down tilt

The early cardiovascular adaptation to zero gravity, simulated by head-down tilt at 5 degrees, was studied in a series of 10 normal young men. The validity of the model was confirmed by comparing the results with data from Apollo and Skylab flights. Tilt produced a significant central fluid shift with a transient increase in central venous pressure, later followed by an increase in left ventricular size without changes in cardiac output, arterial pressure, or contractile state. The hemodynamic changes were transient with a nearly complete return to the control state within 6 hr. The adaptation included a diuresis and a decrease in blood volume, associated with ADH, renin and aldosterone inhibition.     

Quantitative electrocardiography during extended space flight

To assess the effects of prolonged space flight on the electrophysiological properties of the heart, vectorcardiograms (VCG) were obtained on the Skylab crews at regular intervals during flight and the pre- and postflight periods. The VCG signals were telemetered from Skylab and analyzed by digital computer. Conventional 12-lead electrocardiograms were derived from the VCG signals by a lead transformation program. Standardized exercise loads were incorporated into the experiment protocol to increase the sensitivity of the VCG for effects of deconditioning and to detect susceptibility for arrhythmias. In Skylab II, 24 preflight, 21 inflight, and 19 postflight experiments were analyzed. Statistically significant inflight changes observed in two or more crew members included: decreased resting heart rate, increased QRS duration, anterior shift QRS vector, increased QRS vector magnitude, anterior shift T vector, and increased T vector magnitude. One astronaut had occasional premature ventricular contractions (PVC) during the pre- and postflight phases. He had a single episode of multiple PVC's during heavy-load exercise testing in flight. A second astronaut had no arrhythmia during pre- or inflight testing. On postflight day 21 he had multiple PVC's and salvos of ectopic ventricular beats. He has had no recurrence of the arrhythmia. With the exception of the cardiac arrhythmias, no deleterious electrophysiological changes were observed during Skylab II.     

The Skylab sleep monitoring experiment: methodology and initial results

The sleep monitoring experiment permitted an objective evaluation of sleep characteristics during the first two manned Skylab flights. Hardware located onboard the spacecraft accomplished data acquisition, analysis, and preservation, thereby permitting near-real-time evaluation of sleep during the flights and more detailed postmission analysis. The crewman studied during the 28-Day Mission showed some decrease in total sleep time an increase in the percentage of Stage 4 sleep, while the subject in the 59-Day Mission exhibited little change in total sleep time and a small decrease in Stage 4 and REM sleep. Some disruption of sleep characteristics was seen in the final days of both missions, and both subjects exhibited decreases in REM-onset latency in the immediate postflight period. The relatively minor changes seen were not of the type nor magnitude which might be expected to be associated with significant degradation of performance capability.     

Reloading partly recovers bone mineral density and mechanical properties in hind limb unloaded rats

Skeletal unloading results in decreased bone formation and bone mass. During long-term space flight, the decreased bone mass is impossible to fully recover. Therefore, it is necessary to develop the effective countermeasures to prevent spaceflight-induced bone loss. Hindlimb Unloading (HLU) simulates effects of weightlessness and is utilized extensively to examine the response of musculoskeletal systems to certain aspects of space flight. The purpose of this study is to investigate the effects of a 4-week HLU in rats and subsequent reloading on the bone mineral density (BMD) and mechanical properties of load-bearing bones.