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Space flight is normally associated with exposure to reduced acceleration (microgravity) and the medical consequences are well described. However, it inevitably also requires periods of increased acceleration during ascent and descent. These periods, although short in comparison to the length of the flight, are classified as long-duration by physiologists. The biological consequences for man [text incomplete]
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To measure the blood flow of a common carotid artery (CCA) during parabolic flight in the rat, we developed an animal double hold box (ADHB) made of styrene expanded form for the anesthetized rat to keep the animal at a proper posture in an aircaft. Twelve anesthetized rats weighing 291-342 g were surgically operated to mount a ultrasound flowmeter probe (1 mm size,1RS:Transonic Systems Inc.) around the right CCA and to insert a catheter into the right axillar artery for blood pressure measurement. These animals were held comfortably in ADHBs which were placed on the rack installed in the aircraft (MU-300). A total of 27 parabolic flights was performed and the blood flow was measured accurately in 9 rats. This special animal holding facility is useful for various types of animal experiments in an aircraft.
Gravitactic orientation was investigated in the unicellular photosynthetic flagellate, Euglena gracilis, under different accelerations between 0 and 1.5 x g during a recent space flight on board the American shuttle Columbia. The threshold for gravitaxis was found at < or = 0.16 x g. Above the threshold the precision of orientation increased with acceleration in a sigmoidal fashion and reached saturation at about 0.32 x g, a behavior typical for physiological receptors. At accelerations above the saturation point the cells were closely aligned with the gravity vector (negative gravitaxis) and deviated more and more as the acceleration decreased. Obviously the gravireceptor responds to an error signal that elicits a course correction, again indicating the involvement of an active physiological gravireceptor. No adaptation of the cells to the conditions of weightlessness could be observed over the duration of the space mission (12 days). After landing, the cells showed a normal gravitactic behavior at 1 x g.
To investigate the effect of loss of consciousness induced by repeated +Gz on the brain and its mechanism, changes of blood-brain barrier (BBB) permeability and brain water content after repeated lower body negative pressure (LBNP) induced loss of consciousness were observed in 30 rats. Rats were anesthetized and exposed to LBNP (-4.0 kPa). The pressure rapidly returned to control level 2 min after EEG became isoelectric. The BBB permeability was measured using lanthanum trace labeling with electron microscopy and brain water content was determined after one or three LBNP exposures. Most tight junctions among endothelial cells opened through which the lanthanum entered into the neurons and extra cellular space and water content in brain tissues increased significantly (P < 0.05) 1 h after 3 LBNP exposures. It demonstrated that 3 exposures to LBNP induced loss of consciousness can result in an increase of BBB permeability in rats, which may play an important role in the development of G-induced brain edema.
Studies of the response of mammalian chondrocytes to gravitational changes in vivo, in organ culture, and in cell culture show that chondrogenesis is reduced in microgravity or by unloading, and increased by low levels of excess g. To investigate the cellular responses to microgravity using a ground based model, micromass cultures were exposed to simulated weightlessness on two clinostats. For rotation on the large clinostat, cultures were set up in Rose chambers, and cells were videotaped and photographed at several time periods after rotation began. For the smaller clinostat, cultures were set up in T-flasks, and two axes of rotation for clinostated cultures were used. Stationary controls [+1 g, -1 g (upside-down), and sideways] as well as rotation controls were employed. Rotation rate was 30 rpm for both clinostatted cultures and rotation controls. Chondrocyte differentiation was assessed by cartilage specific alcian blue staining. Significantly fewer alcian blue stained nodules were present in clinostatted cultures than in stationary controls or rotation controls. Nodules that did not stain with alcian blue, probably due to unsulfated matrix were present in all cultures. The number of nodules in sideways controls was greater than in any other culture (108% of +1 g controls), probably due to ongoing stimulus of the cell via cytoskeletal components. The results show that chondrocytes in culture respond to changes in the gravity vector in a predictable manner, and that carefully controlled clinostat studies can be useful adjuncts to and predictors for spaceflight experiments.
Changes of cardiac function was studied during +Gz exposure in rabbits. Seven New Zealand rabbits were anesthetized and exposed to +2, +4, and +6 Gz (each for 30s, onset rate 1G/s, with 15 min interval in between). The left ventricular systolic pressure (LVSP), peak rate of left ventricular pressure rising (+dp/dtmax) and ECG were recorded. The results showed that during +2, +4 and +6 Gz exposures, LVSP decreased by 62.96% (P<0.01), 63.34% (P<0.01) and 82.01% (P<0.01) respectively, and +dp/dtmax decreased by 58.46% (P<0.01), 53.59% (P<0.01) and 63.06% (P<0.01) respectively, and the left ventricular end diastolic pressure decreased by 67.78 % (P>0.05), 332.74 % (P<0.01) and 500.54% (P<0.01) respectively, as compared with those of control. It is suggested that cardiac function is depressed with +Gz exposure.
Eggs of Xenopus laevis and many other amphibians contain a gradient of yolk platelets along the animal-vegetal axis. Small platelets predominate in the animal hemisphere, and a boundary between medium and large yolk platelets exists near the equator. The blastopore forms at this boundary at the beginning of gastrulation, in the vegetal hemisphere. Does this boundary have a role in determination of the position of the blastopore, or does cortical information predominate? Past experiments using 1g to invert the egg showed a distinct tendency to form the blastopore in the original vegetal hemisphere. Our experiments, however, have used 20g centrifugation to achieve a more complete inversion of the yolk gradient. The blastopore formed in the original animal hemisphere in >95% of surviving gastrulae, if centrifugation was begun at normalized time 0.20-0.25 of the first cell cycle. Nearly normal larvae (DAI grades 4 and 5) form in 64% of cases (ave. DAI = 3.2). These data support the idea that the position of the blastopore depends on the position of the egg's internal contents rather than cortical determinants.
Studies from space flights over the past two decades have demonstrated that basic physiological changes occur in humans during space flight. These changes include cephalic fluid shifts, loss of fluid and electrolytes, loss of muscle mass, space motion sickness, anemia, reduced immune response, and loss of calcium and mineralized bone. The cause of most of these manifestations is not known and until recently, the general approach was to investigate general systemic changes, not basic cellular responses to microgravity. Recently analyzed data from the 1973-1974 Skylabs disclose that there is a rise in the systemic hormone, cortisol, which may play a role in bone loss in flight. In two flights where bone growth was measured (Skylabs 3 and 4), the crew members had a significant loss of calcium accompanied by a rise in 24 hour urinary cortisol during the entire flight period. In ground-based work on osteoblasts, we have demonstrated that equivalent amounts of glucocorticoids can inhibit osteoblast cell growth. In addition, this laboratory has recently studied gene growth and activation of mouse osteoblasts (MC3T3-E1) during spaceflight. Osteoblast cells were grown on glass coverslips, loaded in the Biorack plunger boxes 18 hours before launch and activated 19 hours after launch in the Biorack incubator under microgravity conditions. The osteoblasts were launched in a serum deprived state, activated and collected in microgravity. Samples were collected at 29 hours after sera activation (0-g, n=4; 1-g, n=4). The osteoblasts were examined for changes in gene expression and cell morphology. Approximately one day after growth activation, remarkable differences were observed in gene expression in 0-g and 1-g flight samples. The 0-g activated cells had increased c-fos mRNA when compared to flight 1-g controls. The message of immediate early growth gene, cox-2 was decreased in the microgravity activated cells when compared to ground or 1-g flight controls. Cox-1 was not detected in any of the samples. There were no significant differences in the expression of actin mRNA between the 0-g and 1-g samples. These data indicate that quiescent osteoblasts are slower to enter the cell cycle in microgravity, suggesting that the force of gravity itself may be a significant factor in bone loss in spaceflight. Preliminary data from our STS 76 flight experiment support our hypothesis that a basic biological response occurs at the tissue, cellular, and molecular level in 0-g. Here we examine ground-based and space flown data on osteoblast growth in ground-based experiments mimicking space flight conditions and in microgravity to simulate lack of gravity stress to help us understand the mechanism of bone loss by experiments.
In April 1989 the three European scientist astronauts of the D1 Spacelab Mission were exposed to a 1.5 hours +3G centrifuge run in supine position, resulting in a linear acceleration along the subjects' x-axis. Afterwards, severe motion sickness symptoms were provoked by head movements (Sickness Induced by Centrifugation: SIC). The astronauts mentioned close similarities with what they experienced in space during the D1-Spacelab Mission in 1985, where head movements also provoked motion sickness symptoms (Space Adaptation Syndrome: SAS). Moreover, the astronauts agreed that the rank order of their susceptibility to SAS was the same as for SIC. It was therefore postulated that with this method SAS could be simulated on earth. Additionally, in otolith function tests following the centrifuge run, changes in visual-vestibular interaction were observed, which replicated objective findings obtained with the same astronauts immediately after the D1 Spacelab Mission. During the last couple of years a series of experiments has been carried out to determine the nature of the stimulus causing SIC, the incidence of SIC, and the underlying cardio-vascular and/or vestibular mechanisms. These experiments were carried out on several astronauts and some 50 'normal' healthy subjects. In the next sections the main findings of all these experiments and the implications are summarized.
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The Czech Air-Force prepares an introduction of a new generation of aircraft with high maneuvering possibilities. The possibility of making full use of the aircraft flight properties assumes sufficient pilot's +Gz tolerance and also its improvement during the new flight training system. The optimal method to achieve this purpose is the human centrifuge utilization. For the Czech Republic, the building or the renting of a human centrifuge for the pilot's selection is unfortunately very expensive. In our institute we are interested in the analysis of the possibilities of the lower body negative pressure (LBNP) technique for the basic pilot's selection with low level of +Gz tolerance, using the examination of the orthostatic cardiovascular reactions of the pilot's organism.
This experiment was a feasibility study which consisted in investigating arterial blood pressure and heart rate to transient and repeated exposure to microgravity in eight unrestrained rats previously implanted with radio-telemetry transmitter. The aim was to perform such recordings throughout all the phases of a parabola during parabolic flights. This study revealed that it was possible to collect the radio-signal without any interference with electronic or magnetic environment. We observed in microgravity a significant reduction in heart rate (6%) and a significant increase in arterial blood pressure (7%). In conclusion, such a study seems to be feasible during longer exposure to microgravity (space flight) in order to study the cardiovascular adaptation in rat.
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Gravity has always been present during evolution. Through the process of natural selection, contemporary organisms could show evidence of having turned gravity to their advantage as an adjunct to development. In recent time great success has been achieved in description and analysis of gravitaxis mechanism of algae Chara (Sievers et. al., 1991) and Euglena (Hader et. al., l990). The aim of present investigation was the demonstration of gravity-dependent growth and development of algae without distinct gravitaxis and gravitisensor organelles, such as statoliths and amyloplasts.