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Early and late renin and ANP modifications induced by bedrest.

A number of studies have been devoted to better understand the cardiovascular adaptation to space flights. These studies included hemodynamic and hormonal studies, but few investigations of the rhythms exist in the literature. However, the importance of the modifications of rhythms in true or simulated weightlessness was underlined in some published works. Several factors are probably associated to modify the circadian rhythms. First, there is a reduction or an absence of gravity, an important environmental factor: second, space missions or bed rest simulations are conducted under confinement conditions which may influence many psychological functions. The resulting instability of the circadian state will affect other physiological systems, because circadian variations are a fundamental feature of many biological systems (sleep, endocrine and cardiovascular functions). The present study was undertaken to study the effect of as well as a continuous 28-day bed rest on the rhythms of circulating PRA and ANP, the modification of rhythmicity of systolic and diastolic blood pressure and heart rate during bed rest.

Atrial Natriuretic Factor↗

Telescience testbed in human space physiology.

The present telescience testbed study was conducted to evaluate the feasibility of physiological experimentation under restricted conditions such as during simulated weightlessness induced by using a water immersion facility, a reduced capacity of laboratory facilities, a delay and desynchronization of communication between investigator and operator, restrictions of different kinds of experiments practiced by only one operator following a limited time line and so on. The three day's experiments were carried out following the same protocols. The operators were changed every day, but was the same the first and the third day. The operators were both medical doctors but not all round experts in the physiological experimentation. The experimental objectives were: 1) ECG changes by changing water immersion levels, 2) blood pressure changes, 3) ultrasonic Echo-cardiographic changes, 4) laser Doppler skin blood flowmetry in a finger, 5) blood sampling to examine blood electrolytic and humoral changes. The effectiveness of the testbed experiment was assessed by evaluating the quality of the obtained data and estimating the friendliness of the operation of the telescience to investigators and operators.

Aerospace Medicine↗

Effects of hypergravity on adherent human cells.

In recent years, accumulating evidence has shown that microgravity or hypergravity may affect cell growth and differentiation. Since it is not easy to carry out researches in space or to simulate weightlessness on earth, we conducted experiments on simulated hypergravity (2 to 15 g) by using a centrifuge (radius: 80 cm; speed motor: 180 rpm). We looked for the effects of chronic hypergravity (7 to 10 days) on cultures of three human cell lines: lung or dermic fibroblasts and lung adenocarcinoma A 549 cells. The results showed a significant decrease (10-20%, P<0.05) in cell proliferation connected to a significant decrease (20-50%, P<0.01) in culture DNA content under hypergravity, but only for lung fibroblasts. The protein content was never disturbed. Dermic fibroblast elastase activity was enhanced (8-13%, P<0.02) under 15 g. Total phospholipid content as well as relative amounts of phospholipid components, analysed by thin layer chromatography, were unchanged in A 549 cells.

Adenosarcoma↗

Human muscle atrophy in supportlessness: effects of short-term exposure to dry immersion.

Atrophy of skeletal muscle is a response that is considered as the most consistent under conditions of real and simulated weightlessness. Microgravity is transformed in the motor system into a number of factors, the most important of them are considered axial unloading and support unloading. The effects of support stimulus may be evaluated in studies under conditions of dry immersion (DI) which provides the equal distribution of the mechanical pressure (e.g. hydrostatic pressure) throughout the surface of the body. Thus the deprivation of the gradient of the mechanical pressure simulates the supportless conditions. The study was aimed to test if the support unloading simulated in dry immersion induces not only functional but also structural alterations in human postural muscles.

Adult↗

Comparison of the effects of spaceflight and hindlimb-suspension on rat pituitary vasopressin and brainstem norepinephrine content.

To compare actual spaceflight to ground-based simulation (hindlimb-suspension), we measured the norepinephrine (NE) content in A1, A2, A5 and A6 (locus coeruleus) and the vasopressin content in the neurohypophysial system. The experimental period was of 9 days' duration. The NE content in the locus coeruleus decreased significantly in rats flown for 9 days (67%, p < 0.001), but showed no significant changes after hindlimb-suspension. These results demonstrated that suspended rats adapted better to weightlessness-simulation than flown rats to actual microgravity. In rats flown aboard SLS-1, the vasopressin content was significantly increased in the posterior pituitary (71%, p < 0.01), and was decreased in the hypothalamus (49%, p < 0.05). In 9-day suspended rats pituitary vasopressin levels were unchanged, while in the hypothalamus a significant decrease was noted (21%, p < 0.05). It was concluded that spaceflight changes in pituitary vasopressin levels and in the locus coeruleus NE content were consistent with a stress reaction, occurring during and/or after landing. These results confirmed that hindlimb-suspension model constitutes a valid and less stressful [correction of lesstressful] ground-based simulation of microgravity in rats.

Animals↗

Orientation of Paramecium under the conditions of weightlessness.

A cell culture of Paramecium with a precise negative gravitaxis was exposed to 4 x l0(-6) g during a parabolic flight of a sounding rocket for 6 min. Computer image analysis revealed that without gravity stimulus the individual swimming paths remained straight. In addition, three reactions could be distinguished. For about 30 s, paramecia maintained the swimming direction they had before onset of low gravity. During the next 20 s, an approximate reversal of the swimming direction occurred. This period was followed by the expected random swimming pattern. Similar behavior was observed under the condition of simulated weightlessness on a fast-rotating clinostat. Control experiments on the ground under hyper-gravity on a low-speed centrifuge microscope and on a vibration test facility proved that the observed effects were caused exclusively by the reduction of gravity.

Acceleration↗

Early development in aquatic vertebrates in near weightlessness during the D-2 Mission STATEX project.

Aboard the German-Spacelab-Mission D-2 the project "Gravity Perception and Neuronal Plasticity (STATEX II)" was performed. STATEX is for STATolith EXperiment. Objects were growing tadpoles of the South African Toad (Xenopus laevis D.) and a juvenile cichlid fish (Oreochromis mossambicus). The results give a broader base for the understanding of how environmental stimuli (e.g. linear accelerations) affect the development and function of the gravity perceiving systems in these two vertebrates. These systems are accepted as models for the human vestibulum. Results of experiments in hyper-g (up to 5 g), simulated weightlessness (Fast-rotating-clinostat) and parabolic flights are compared and discussed.

Animals↗

Biological effects of weightlessness and clinostatic conditions registered in cells of root meristem and cap of higher plants.

Research in cellular reproduction, differentiation and vital activity, i.e. processes underlying the development and functioning of organisms, plants included, is essential for solving fundamental and applied problems of space biology. Detailed anatomical analysis of roots of higher plants grown on board the Salyut 6 orbital research station show that under conditions of weightlessness for defined duration mitosis, cytokinesis and tissue differentiation in plant vegetative organs occur essentially normally. At the same time, certain rearrangements in the structural organization of cellular organelles--mainly the plastid apparatus, mitochondria, Golgi apparatus and nucleus--are established in the root meristem and cap of the experimental plants. This is evidence for considerable changes in cellular metabolism. The structural changes in the subcellular level arising under spaceflight conditions are partially absent in clinostat experiments designed to simulate weightlessness. Various clinostatic conditions have different influences on the cell structural and functional organization than does space flight. It is suggested that alterations of cellular metabolism under weightlessness and clinostatic conditions occur within existing genetic programs.

Arabidopsis↗

Clinorotation reduces number, but not size, of cartilaginous nodules formed in micromass cultures of mouse limbbud cells.

In previous studies we used a ground based model to investigate the cellular responses to microgravity by exposing micromass cultures of embryonic limb cells to simulated weightlessness on a clinostat. Cultures set up in T-flasks and rotated at 30 rpm showed that clinostatted cultures had less chondrocyte differentiation than stationary or rotation controls, as assessed by number of nodules/culture stained with cartilage specific Alcian blue. In the current study, nodule size and shape of these nodules was assessed by interactive measurement of area, perimeter, circularity, and equivalent diameters, using the Optimas imaging software. Results show no significant difference in any of the measurements, indicating that clinorotation has no effect on expansion of the nodules either by differentiation of cells within the nodule, or by recruitment of cells into the nodule. The reduction in number of nodules without an alteration in size and shape indicates that the effect of simulated microgravity is to reduce the cell interactions required for the initial condensation of cells into a nodule, probably by interference with cell adhesion molecules.

Animals↗

Hindlimb-suspension and spaceflight both alter cGMP levels in rat choroid plexus.

Effects of actual and simulated weightlessness on choroidal guanylate cyclase activity were evaluated by assaying the production of cyclic guanosine monophosphate (cGMP), a second messenger involved in mechanisms regulating the secretion of cerebrospinal fluid (CSF) in choroid plexus. Cyclic cGMP was measured, using radio-immunoassay, in choroidal extracts of hindlimb-suspended rats (HLS rats), adapted to an anti-orthostatic restraint for 30 min., or for 3, 9 or 14 days and after a 17-day spaceflight (Life and Microgravity SpaceLab experiment; LMS). Basal cGMP levels were slightly but significantly decreased in the first 30 min. of the HLS experiment, whereas they were significantly increased in rats adapted to longer anti-orthostatic restraints. LMS flight rats demonstrated a similar increase in the choroidal cGMP baseline. After natriuretic peptide stimulation, i.e. using ANP (atrial natriuretic peptide) or BNP (brain natriuretic peptide), choroidal cGMP contents were typically increased (by 1.5-2 times; p<0.05) in control rats (LMS and HLS experiments), but not significantly elevated in suspended rats, except for those adapted to HLS for 14 days. In these animals the ANP-dependent cGMP production was significantly increased (by about 3 times; p<0.005). The ANP- or BNP-dependent responses were similarly abolished in LMS flight rats, which were dissected 4-6 hours after return to Earth's gravity. The role of corticosteroids was also investigated during the LMS experiment. Results on choroidal functions revealed a lack of significant change of cGMP levels between adrenalectomized and sham-operated rats. For the first time, it is reported that both basal and ANP- stimulated cGMP levels are dramatically changed over the first 14 days of suspension, i.e. with experiments known to simulate some effects of weightlessness. Basal choroidal cGMP levels are also increased after 17 days in space, suggesting that space adaptation also impacts choroidal guanylate cyclase activities. However, the absence of ANP-dependent cGMP increase, observed in LMS flight animals, suggests that HLS could not simulate all the spaceflight effects. Thus, these preliminary results seem to show that a natriuretic peptides-independent s stem is involved in choroidal adaptation to spaceflight.

Adaptation, Physiological↗

Effect of posture on arterial baroreflex control of heart rate in humans.

Altered baroreflex function may contribute to the cardiovascular changes associated with weightlessness. Since central blood volume (CBV) increases during simulated weightlessness we have examined the possibility that acute changes in CBV may modify baroreceptor function. We used graded head-up tilt (HUT) and head-down tilt (HDT) to induce changes in CBV, and neck suction to stimulate carotid baroreceptors, in 6 subjects. The increase in pulse interval induced by a negative pressure of 8.2 kPa (62 mm Hg) imposed for 10 s while supine was compared with the increase while tilted for 8 min at +/- 15 degrees, +/- 30 degrees and +/- 45 degrees. During HDT at 15 degrees the pulse interval over the first 5 cardiac cycles following suction onset was 51 +/- (SEM) 18 ms longer (p less than 0.05), at 30 degrees it was 61 +/- 20 ms longer (p less than 0.05), and at 45 degrees it was 74 +/- 35 ms longer (p less than 0.01), compared with supine. During HUT at 15 degrees the pulse interval was 25 +/- 9 ms shorter (p less than 0.05) than when supine, but was not significantly different at 30 degrees and 45 degrees. These responses occurred independently of changes in brachial blood pressure. Attenuation was also observed after 5 min (56 +/- 17 ms; less than 0.05), and after 40 min (25 +/- 9 ms; p less than 0.05) of 60 degrees HUT compared with supine. We conclude that posture does modify arterial baroreflex control of heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Ultrasonic studies and calcium content of the bones in experimental animals during limited mobility and weightlessness].

The velocity of ultrasonic propagation, calcium content, and femur size of rats exposed to actual and simulated weightlessness were investigated. The exposure slowed down the ultrasonic velocity in bones. The effect of the calcium content on the ultrasonic velocity in various bone sites was different: as a rule, there was a positive correlation in diaphyses and a negative correlation in epiphyses. These specific features should be taken into consideration when new methods of bone ultrasonic diagnostics will be developed.

Animals↗

[Tolerance of +Gx-loads by females before and after a 120-day hypokinesia].

The goal of the work was to study female tolerance of g-loads before and after simulated weightlessness, and evaluate the effectiveness of countermeasures and anti-g means proposed for space flight. Centrifuge with a 7.25 m arm was used for 29 runs of 8 female subjects. The subjects were exposed to the transverse loads (+GX) at 8.2 g on a special regimen with the total run time of 9 min to simulate the ballistic descent from orbit in a SOYUZ-TM vehicle. Baseline tolerance of the females to transverse loads up to +8GX was good and satisfactory. Following 120 days of bed rest without the countermeasures or the anti-g suit g-tolerance was significantly lowered as evidenced by visual disorders in 67% of cases and exaggerated, if compared with the pre-hypokinesia levels, heart and respiration rates, i.e. 20% and 23.5%, respectively. The countermeasures and anti-g suit Centaur maintained g-tolerance at essentially the baseline level and precluded visual disorders. Results of the study speak in favor of the countermeasures and anti-g means used by the females in simulated long-duration weightlessness which can be recommended for the final phase of extended space mission.

Adaptation, Physiological↗

[Can a tail-suspension model be applied to simulate the reproduction system under weightlessness?].

A tail-suspension model to simulate weightlessness is widely used for studies on physiological changes not only of the musculoskeletal system but also of the cardiovascular system. In the present study, we applied this model to investigate whether or not it is possible for male spermatogenesis to occur, and for female rats to maintain pregnancy in this model. Two male rats were suspended with the right inguinal canal ligated loosely for 14 days, and female rats were suspended after copulation (the day when spermatozoa were identified on a smear from the female rat, was referred to as Day 0 for her in this paper). The duration of suspension was chosen dependent upon events to be confirmed during the course of pregnancy. To demonstrate the effects of suspension on implantation, the first and second groups consisted respectively of non-suspended rats penetrated at the base of the tail in the same way as suspended rats, and rats suspended during the former half of pregnancy (Days 0-12, and 0-14). The third group consisted of rats suspended during the latter half (Days 10-20, 10-21, 10-26, and 10-28), and in the final group a rat suspended throughout pregnancy (Days 0-22) was placed. Histological analysis of the male rat testes showed that the testes on the ligated side were scarcely impaired, while the others became degenerated presenting similar appearances of cryptorchidism. The levels of serum testosterone were lower than the control values. As for the female rats, one animal in the final group was successful in parturition, and implantation appeared to be delayed in the second group. A tail-suspended rat, if it is acclimatized to its environment, could succeed in parturition. By employing this model, we can certainly elucidate some new aspects of mammalian reproduction in space.

Animals↗

[Peripheral effector mechanism hypothesis on cardiovascular dysfunction after spaceflight].

In the years of 1990's, we systematically studied the adaptational changes in structure and function of both the heart and the vessels during simulated weightlessness. In our serial work, the tail-suspension rat model was used to simulate the microgravity-induced cephalad shift and redistribution of blood. On the basis of the facts we observed and the more recent advances in space and ground-based studies in 1990's, we put forward a hypothesis to offer a possible explanation for the frequent occurrence of postflight cardiovascular dysfunction. It states that, in addition to the factor of hypovolemia, the microgravity-induced adaptational changes in the structure and function of the two main effectors of the cardiovascular system, i.e., the arterial smooth muscle and the cardiac muscle might be one of the most important mechanisms accounting for postflight cardiovascular dysfunction.

Cardiovascular System↗

Autonomic control of cardiovascular dynamics during weightlessness.

Measuring cardiovascular dynamics is a new method of assessing the autonomic regulation of the cardiovascular system, it provides an easily-implemented non-invasive way of monitoring the effects of weightlessness on this regulatory function. The major findings of studies on cardiovascular dynamics during actual or simulated weightlessness are presented, taking into account the recent consensus on this approach. Future improvements of these studies are discussed.

Aerospace Medicine↗

Quantification of left ventricular modification in weightlessness conditions from the spatio-temporal analysis of 2D echocardiographic images.

Two-dimensional echocardiography (2DE) performed during flights with a parabolic trajectory to simulate weightlessness provides a unique means to study left ventricular (LV) modifications to prevent post-flight orthostatic intolerance in astronauts. However, conventional analysis of 2DE is based on manual tracings and depends on experience. Accordingly, the aim was objectively to quantify, from 2DE images, the LV modifications related to different gravity levels, by applying a semi-automated level-set border detection technique. The algorithm validation was performed by the comparison of manual tracing results, obtained by two independent observers with 20 images, with the semi-automated measurements. To quantify LV modifications, three consecutive cardiac cycles were analysed for each gravity phase (1 Gz, 1.8 Gz, 0 Gz). The level-set procedure was applied frame-by-frame to detect the LV endocardial contours and obtain LV area against time curves, from which end-diastolic (EDA) and end-systolic (ESA) areas were computed and averaged to compensate for respiratory variations. Linear regression (y = 0.91x + 1.47, r = 0.99, SEE:0.80cm2) and Bland-Altman analysis (bias = -0.58 cm2, 95% limits of agreement= +/- 2.14cm2) showed excellent correlation between the semi-automatic and manually traced values. Inter-observer variability was 5.4%, and the inter-technique variability was 4.1%. Modifications in LV dimensions during the parabola were found: compared with 1 Gz values, EDA and ESA were significantly reduced at 1.8 Gz by 8.8 +/- 5.5% and 12.1 +/- 10.1%, respectively, whereas, during 0 Gz, EDA and ESA increased by 13.3 +/- 7.3% and 11.6 +/- 5.1%, respectively, owing to abrupt changes in venous return. The proposed method resulted in fast and reliable estimations of LV dimensions, whose changes caused by different gravity conditions were objectively quantified.

Adult↗

Age dependent development of osteopenia in the long bones of tail-suspended mice.

The microgravity, or weightlessness, of space causes measurable bone deterioration in humans and rats. The use of tail-suspension to simulate weightlessness in rats is well-documented. Our studies have focused on mice, as their smaller size suggests more efficient space-based experimentation. Using mice ranging from 1.3-12 months in age, the results of a 2-wk suspension were ascertained through measurement of bone mass and mechanical (3-pt bending) characteristics. Significant differences between tail-suspended (S) and control (C) mice were noted for mice less than 6 months old. Such significance was not observed for the older mice. In addition, for the 1.3 month and 1.7 month old mice, a group of mice were sacrificed (designated PC, or pre-control) with ages matching those of the S mice prior to suspension. These were assayed to determine if the effects of tail-suspension are predominantly on growth-suppression or on bone atrophy. Our results show that tail-suspension effects are best explained by growth-suppression, as both the C and S groups showed growth when compared to the PC groups. 4-wk tail-suspensions of 10 month old mice were implemented to determine if increased suspension time would produce deterioration in older mice. An indication of longer periods of suspension being effective was found, but significant differences like those obtained for younger mice were not seen in the numbers of mice used.

Aging↗