Immobilization induces a very rapid increase in osteoclast activity

We studied in a randomized, strictly controlled cross-over design, the effects of 6 days 6 degrees head-down tilt bed rest (HDT) in eight male healthy subjects in our metabolic ward. The study consisted of two periods (phases) of 11 days each in order to allow for the test subjects being their own controls. Both study phases were identical with respect to environmental conditions, study protocol and diet. Two days before arriving in the metabolic ward the subjects started with a diet. The diet was continued in the metabolic ward. The metabolic ward period (1l days) was divided into three parts: 4 ambulatory days, 6 days either HDT or control and 1 recovery day. Continuous urine collection started on the first day in the metabolic ward to analyze calcium excretion and bone resorption markers. On the 2nd ambulatory day in the metabolic ward and on the 5th day in HDT or control blood was drawn to analyze serum calcium, parathyroid hormone, and bone formation markers. Urinary calcium excretion was, as early as the first day in immobilization, increased (p<0.01). CTX- and NTX-excretion stayed unchanged in the first 24 h in HDT compared to the control. But already on the 2nd day of immobilization, both bone resorption markers significantly increased. We conclude from these results--pronounced rise of bone resorption markers--that already 24 h of immobilization induce a significant rise in osteoclast activity in healthy subjects. Thus, it appears possible to use short-term bed rest studies as a first step for the development of countermeasures to immobilization.     

Bone mineral measurement: Skylab experiment M-078

The observation that bone mineral is lost in patients who are either immobilized or remain in bed for extended periods of time formed the basis for the concern that large amounts of bone mineral may be lost during long periods of weightlessness. This concern was magnified when early X-ray densitometry studies suggested that rather large amounts of mineral could be lost during rather short periods of weightlessness (4-14 days). Even though these Gemini results have recently been modified, they still reflect substantial losses in the upper extremity. This led to a series of prolonged bed-rest studies (30-36 weeks) which, in addition to careful calcium balance, also employed a newer, more precise method of estimating bone mineral in the radius, ulna, and os calcis. It employed an essentially monoenergetic photon source (125I) and a scintillation detector operating in a rectilinear scanning mode to measure bone mineral by the absorptiometric technique. Bed-rest studies revealed variable mineral losses but suggested that little if any is lost during 4-6 weeks, with variable amounts being lost in 8 weeks. Losses up to 40% were noted in the os calcis after 9 months, with essentially none in the radius and ulna. When this technique was employed during the Apollo 14, 15, and 16 missions, only one crewman (CMP Apollo 15) showed significant losses in the os calcis and none in the radius or ulna. These results were, therefore, in concert with the bed-rest data but at variance with the earlier Gemini data. The variability observed during bed rest was reconciled when it was observed that the rate of loss could be correlated with the initial 24-hour urinary hydroxyproline excretion and the initial os calcis mineral content. Prediction terms were established. Measurements of the SL-II crew after 28 days of weightlessness revealed no significant bone mineral losses. The Skylab data lie within the predicted limits obtained from the bed-rest data. The relevance of the prediction terms to the Skylab and longer missions discussed.     

The effect of hypokinesia on lipid metabolism in adipose tissue

The increase of nonesterified fatty acid (NEFA) concentration in plasma was observed in rats subjected to hypokinesia for 1-60 days. In the period of recovery (7 and 21 days after 60 days immobilization) the content of NEFA returned to control values. The increase of fatty acid release from adipose tissue was observed in hypokinetic rats, however the stimulation of lipolysis by norepinephrine was lower in rats exposed to hypokinesis. The decrease of the binding capacity and a diminished number of beta-adrenergic receptors were found in animals after hypokinesia. The augmentation of the incorporation of glucose into lipids and the marked increase in the stimulation of lipogenesis by insulin were found in adipose tissue of rats subjected to long-term hypokinesia. These results showed an important effect of hypokinesia on lipid mobilization, on lipogenesis and on the processes of hormone regulation in adipose tissue.     

Development of an integrated countermeasure device for use in long-duration spaceflight

Prolonged weightlessness is associated with declines in musculoskeletal, cardiovascular, and sensorimotor health. Consequently, in-flight countermeasures are required to preserve astronaut health. We developed and tested a novel exercise countermeasure device (CCD) for use in spaceflight with the aim of preserving musculoskeletal and cardiovascular health along with an incorporated balance training component. Additionally, the CCD features a compact footprint, and a low power requirement. Methods: After design and development of the CCD, we carried out a training study to test its ability to improve cardiovascular and muscular fitness in healthy volunteers. Fourteen male and female subjects (41.4±9.0 years, 69.5±15.4 kg) completed 12 weeks (3 sessions per week) of concurrent strength and endurance training on the CCD. All training was conducted with the subject in orthostasis. When configured for spaceflight, subjects will be fixed to the device via a vest with loop attachments secured to subject load devices. Subjects were tested at baseline and after 12 weeks for 1-repetition max leg press strength (1RM), peak oxygen consumption (VO_2peak), and isokinetic joint torque (ISO) at the hip, knee, and ankle. Additionally, we evaluated subjects after 6 weeks of training for changes in VO_2peak and 1RM. Results: VO_2peak and 1RM improved after 6 weeks, with additional improvements after 12 weeks (1.95±0.5, 2.28±0.5, 2.47±0.6 L min^?1, and 131.2±63.9,182.8±75.0, 207.0±75.0 kg) for baseline, 6 weeks, and 12 weeks, respectively. ISO for hip adduction, adduction, and ankle plantar flexion improved after 12 weeks of training (70.3±39.5, 76.8±39.2, and 55.7±21.7 N m vs. 86.1±37.3, 85.1±34.3, and 62.1±26.4 N m, respectively). No changes were observed for ISO during hip flexion, knee extension, or knee flexion. Conclusions: The CCD is effective at improving cardiovascular fitness and isotonic leg strength in healthy adults. Further, the improvement in hip adductor and abductor torque provides support that the CCD may provide additional protection for the preservation of bone health at the hip.     

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.     

Ion regulatory function of the human kidney in prolonged space flights.

Ten cosmonauts, who performed 30-175-day space flights aboard Salyut-4 and Salyut-6, and over 60 test subjects who were exposed to bed rest of up to 182 days and immersion of up to 56 days, were examined. The renal excretion of potassium and calcium increased, reaching a maximum by the 4-6th weeks in prolonged space flights and simulation studies. During the load tests with potassium and calcium salt, excretion postflight was much higher than preflight. During potassium chloride load tests a positive correlation between the blood content of aldosterone and potassium excretion existed, whereas during calcium lactate load tests an increased calcium excretion was accompanied by a decrease in blood parathyroid hormone concentration. The most probable cause of the negative ion balance in weightlessness is the reduced capacity of tissues to retain electrolytes due to the decreased ion pool capacity. Different exercises have been shown to exert a beneficial effect on electrolyte metabolism.     

Effects of repeated long duration +2Gz load on man's cardiovascular function

Usefulness of a short-arm human centrifuge is expected when it is used in space as a countermeasure against cardiovascular deconditioning, problem of bone-calcium metabolism, etc. However, nothing is solidly established regarding the most desirable program for artificial G application. Accordingly, this study was designed to analytically evaluate the effects of repeated long duration +Gz load on human cardiovascular function. Recently heart rate spectral analysis has been recognized as a powerful tool for quantitatively evaluating parasympathetic and sympathetic activity separately in human. It is reported that power of the high frequency component (HF-p) is mediated selectively by parasympathetic activity and the power ratio of low to high frequency components(LF/HF) is indicative of cardiac sympathetic activity or cardiac sympathovagal balance. Sequence method is developed to examine spontaneous baroreceptor reflex sensitivity (BRS). We studied cardiovascular control function by using these methods in 9 healthy men before and after 7 days of daily repeated 1hour +2Gz load. When compared with the data of pre-G load period, post-G load period, decrease of HR, increases of HF-p and BRS were statistically significant. SBP, DBP and LF/HF tended to decrease, however, these changes were not statistically significant. This results indicate that repeated +2Gz load increases parasympathetic activity and arterial baroreceptor-cardiac reflex sensitivity. In recent years, many investigators suggest that space flight and head-down bedrest leads to impaired baroreceptor-cardiac reflex responses and decrease of parasympathetic activity, which may contribute to orthostatic intolerance. So our results suggest that daily repeated 1hour +2Gz load would be useful in preventing post-flight orthostatic intolerance.     

薄壁加筋壳强度变差系数仿真预估方法研究

针对运载火箭结构价格昂贵，通过试验获取强度变差系数困难问题，提出了基于产品实测数据仿真预估强度变差系数方法。以轴压载荷作用下的1 m直径薄壁正交网格加筋圆柱壳试验件为对象，开展了实现技术途径及试验验证研究。测量并统计试验产品材料性能、结构尺寸及几何形貌不确定性；应用双重傅立叶级数对实测几何形貌表征，将其引入到结构理想有限元分析模型，实现极限强度精确仿真分析；采用混沌多项式展开（Polynomial Chaos Expansion，PCE）代理模型，实现考虑关键参数不确定性的极限强度高效模拟打靶和强度总体变差系数预估；并开展了3个试验件的轴压强度破坏试验验证。结果表明，预估的强度变差系数可很好包络试验样本变差系数，具有较高可靠性的同时，相对历史统计数据有较大降低，对实现结构可靠性安全系数的精确量化设计，挖掘现代先进结构承载潜力有重要意义。     

Physical–chemical properties of plasma membrane and function of erythrocytes of cosmonauts after long-term space flight

We studied microfluidity and selective ion permeability of plasma membranes and O₂-binding properties of erythrocytes of cosmonauts during early rehabilitation after a long-term space flight (LTSF). Microfluidity of plasma membranes in surface regions was found to undergo a reversible decrease during 13–15 days following LTSF, which was accompanied by a reversible increase in relative cholesterol content. Cosmonauts’ erythrocytes revealed an increased activity of Na/H-exchanger and K_Ca-channel as well as a decrease in number of discocytes and increase in number of echinocytes, stomatocytes and knizocytes. Total hemoglobin content as well as oxyhemoglobin content were lowered after the LTSF, while the affinity of hemoglobin to O₂ was advanced. It is suggested that the changes in Hb properties, microfluidity and selective permeability of plasma membranes following the elevated cholesterol content in the membranes can decrease tissue supply with O₂.     

Effect of weightlessness on sympathetic-adrenomedullary activity of rats.

Three cosmic experiments were performed in which rats spent 18-20 days in space on board the biosatellites "COSMOS 782", "COSMOS 936" and "COSMOS 1129". The following indicators of the sympathetic-adrenomedullary system (SAS) activity were measured: tissue and plasma catecholamines (CA), CA-synthesizing enzymes--tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), phenylethanolamine-N-methyltransferase (PNMT)--as well as CA-degrading enzymes-monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). Adrenal epinephrine (EPI) and norepinephrine (NE) as well as CA-synthesizing and degrading enzymes were not significantly changed in the animals after flight on COSMOS 782. On the other hand, a significant increase was found in heart CA, the indicator which is usually decreased after stress. 26 days after landing all values were at control levels. The results obtained, compared to our previous stress experiments on Earth, suggest that prolonged weightlessness does not appear to be a pronounced stressful stimulus for the SAS. Heart and plasma CA, mainly NE, were increased both in the group living in the state of weightlessness and the group living in a centrifuge and exposed to artificial gravitation 1 g (COSMOS 936), suggesting again that prolonged weightlessness is not an intensive stressful stimulus for the SAS. The animals exposed after space flight on COSMOS 1129 to repeated immobilization stress on Earth showed a significant decrease of adrenal EPI and an expressive increase of adrenal TH activity compared to stressed animals which were not in space. Thus, the results corroborate that prolonged state of weightlessness during space flight though not representing by itself an intensive stressful stimulus for the sympathetic-adrenomedullary system, was found to potentiate the response of "cosmic rats" to stress exposure after return to Earth.     

Effectiveness of centrifuge-induced artificial gravity with ergometric exercise as a countermeasure during simulated microgravity exposure in humans

To test the effectiveness of centrifuge-induced artificial gravity with ergometric exercise, 12 healthy young men (20.7 +/- 1.9 yr) were exposed to simulated microgravity for 14 days of -6 degrees head-down bedrest. Half the subjects were randomly selected and loaded 1.2 G artificial gravity with 60 W (four out of six subjects) or 40 W (two out of six subjects) of ergometric workload on days 1, 2, 3, 5, 7, 9, 11, 12, 13, 14 (CM group). The rest of the subjects served as the control. Anti-G score, defined as the G-load x running time to the endpoint, was significantly elongated by the load of the centrifuge-ergometer. Plasma volume loss was suppressed (-5.0 +/- 2.4 vs. -16.4 +/- 1.9%), and fluid volume shift was prevented by the countermeasure load. Elevated heart rate and muscle sympathetic nerve activity after bedrest were counteracted, and exaggerated response to head-up tilt was also suppressed. Centrifuge-induced artificial gravity with exercise is effective in preventing cardiovascular deconditioning due to microgravity exposure, however, an effective and appropriate regimen (magnitude of G-load and exercise workload) should be determined in future studies.     

复合材料层合板的低能冲击损伤及剩余拉伸强度研究

针对复合材料层合板的冲击及冲击后的拉伸过程提出了一种全程分析方法。该方法应用三维逐渐累积损伤理论对层合板的冲击及冲击后含损伤层合板在拉伸载荷下损伤破坏的全过程进行分析,分析中没有对冲击后层合板的损伤状态做人为假设,而是把冲击后层合板的实际损伤状态直接用于剩余拉伸强度研究,从而不仅提高了最终失效载荷的预测精度,而且避免了为获得冲击后损伤状态参数所进行的大量试验,同时开发了模拟程序,该程序可以预测任意铺层角度、铺层厚度的层合板在冲击载荷及冲击后拉伸载荷下的逐渐损伤破坏过程和最终失效载荷。通过与已有文献结果进行比较,验证了方法及程序的正确性。     

复合材料层合板热-力作用下的失效研究

碳纤维复合材料力学性能优异,在航空航天等领域广泛使用,其在热-力联合作用下的损伤失效研究对于结构的损伤破坏和强度预测具有重要意义。发展了热力耦合条件下复合材料结构渐进损伤分析方法,建立了三维有限元热烧蚀模型,并验证了计算模型的可靠性;采用三维Hashin失效准则,结合材料刚度突然退化模式,建立了失效分析模型,仿真分析了热-力联合作用下复合材料层合板损伤演化全过程。结果表明,该方法不仅能够较好地模拟复合材料层合板从局部失效的萌生、扩展直至结构完全失效的全过程,而且可以直观地显示结构的损伤失效模式,预测结构在不同条件下的承载能力。     

运载火箭动力系统试验承力环的静力试验

建立了某型号运载火箭动力系统试验用承力环的非破坏性静力试验方案,以评估该承力环的强度和刚度。为模拟发动机关机时的载荷冲击,将静力试验最大载荷设定为发动机额定总推力的2倍,包含水平和垂直两个分量,均分为8个载荷步加载。在承力环上设置了27个三向应变测点和12个轴向位移测点,以监测一些关键点的应力和位移。测量结果显示,在最大载荷下,当量应力达到303 MPa,低于材料屈服强度;轴向变形达到3.16 mm,低于设计许用变形;应力最大点位于支腿销孔处。对销孔孔距的变化进行了测量,并对附近的钢板表面进行了MT探伤。数据结果表明,该承力环在两倍的动力系统试验额定载荷下有足够的强度和刚度,可用于该试验。     

Effects of neurectomy and tenotomy on the bone mineral density and strength of tibiae.

The right hindlimbs of 5 or 6-week old Wistar male rats were sciatic/femoral neurectomized, tenotomized or sham operated. The rats were sacrificed 2 weeks after the surgery and the tibiae were removed. pQCT measurement was performed on total, cortical, and trabecular bone separately at different regions. Reduction of the bone mineral density by unloading was observed more significantly at metaphysis than at diaphysis due to histological heterogeneity between metaphysis and diaphysis; metaphysis is rich in trabecular bone and diaphysis is abundant in cortical bone. Trabecular bone might be more sensitive to unloading because the reduction rate of volumetric bone mineral density in trabecular bone was approximately 10 times and 3 times larger than that of cortical bone in both neurectomy and tenotomy rats, respectively, Unloading also reduced the cross-sectional area and stress strain index at metaphysis.     

Cardiac and vascular adaptation to 0g with and without thigh cuffs (Antares 14 and Altair 21 day Mir spaceflights)

Cardiovascular Actaptation was evaluated on 2 astronauts: one wearing thigh cuffs from flight day 1 to 8 (14d flight), the second without cuffs (21d flight). Ultrasound investigations were performed at rest and during LBNP. Results: Without thigh cuffs the cardiovascular Actaptation consists in (1) the development of a hypovolemia with an increase of the heart rate and the cardiac output, (2) the decrease of the vascular tone in the deep (mesenteric and splanchnic) and peripheral (Lower limbs) vascular areas. The use of thigh cuffs maintains the volemia and the cardiac output at the preflight level (without heart rate increase) and prevents the loss of vascular tone in the deep and peripheral areas. Moreover the adaptative process changes since the cuffs are removed and even the volemia seems to be unaffected at this stage the vascular tone decreases to a comparable extend as during the flight without cuffs. Nevertheless during the flight without cuffs or 3 days after removing the cuffs hemodynamic signs of decreased orthostatic tolerance are present during the inflight and the 3 days post flight LBNP. Presently the possible contribution of the thigh cuffs to the reduction of the vascular deconditioning has not been tested yet.     

Serotonin in individual hypothalamic nuclei of rats after space flight on biosatellite Cosmos 1129.

The experiment on Cosmos 1129 was based on our results obtained in rats exposed to single or repeated restrain stress in the laboratory. These results have convincingly demonstrated a significant increase of serotonin concentration (5-HT) in the hypothalamus in acutely stressed rats. This response, which was found also in the isolated hypothalamic nuclei, was diminished in repeatedly (40 times) immobilized rats. While the concentration of 5-HT was unchanged in the majority of the hypothalamic nuclei of animals subjected to cosmic flight, an increase was recorded only in the supraoptic nucleus (NSO) and a decrease in the periventricular nucleus. These findings demonstrate that only few areas of the hypothalamus respond to cosmic flight with changes of 5-HT concentration and suggest either that long-term cosmic flight cannot be an intensive stressor or that during the flight the rats became already adapted to its long-term effect. However, the exposure of flight rats to repeated immobilization stress resulted in a significant increase of 5-HT in the NSO, para-ventricular and dorsomedial (NDM) nuclei. It should be noted that we have never seen any changes of 5-HT concentration, tryptophan hydroxylase and monoamineoxidase activities in repeatedly (40 times) immobilized rats. On the other hand, the increase of 5-HT concentration in the NDM is a typical finding after seven exposures of rats to immobilization on Earth, daily for 150 min. In the experiment COSMOS 1129 such an increase of 5-HT concentration in the NDM was found not only in the flight group but also in the control group of rats subjected to five daily exposures of immobilization stress. With respect to these findings, the increased 5-HT concentrations observed in some isolated hypothalamic nuclei in the flight group of rats exposed after landing to repeated immobilization stress suggest that long-term space flight and the state of weightlessness do not represent a stressogenic factor with respect to the serotoninergic system in the hypothalamus.     

有位移约束结构的可靠性分析

本文从增量载荷法的原理出发，对于具有位移约束的结构体系，通过引入“广义元”的概念，提出了计算其刚度破坏承载能力的方法，使结构体系的可靠性分析范围扩展到强度和刚度要求并存的情况，物理概念清楚，方法有效，通过算例阐述了该方法的应用。     

Postmission plasma volume and red-cell mass changes in the crews of the first two Skylab missions

Red-cell mass determinations were performed before and after the first two Skylab missions. The data showed a 14% mean decrease in red-cell mass after the 28-day mission and a 12% mean decrease after the 59-day mission. The red-cell mass returned to premission levels more slowly after the shorter (28-day) than after the longer mission. Plasma volume decreases were found after each mission. with the crew from the longer mission showing the greater change (13% vs. 8.4%). Postmission decreases in red-cell mass and plasma volume have been a general finding in crewmen who return from short or long spaceflight.