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Recent approaches in the analysis of weightlessness effects on arthropod development.

The concept of Biological Development refers to the extremely complex process by which every biological organism reproduces starting from a huge single cell, the fertilized egg. It includes all aspects of cellular and intercellular structure and function. In spite of many recent advances, especially at the molecular and genetical level, we are still far from fully understanding the details and mechanisms at work in developmental systems. It is even unclear what physical mechanisms are used by the different molecular components resulting in the emergence of these higher levels of organization. Newman and Comper, have extensively discussed the "generic" physical forces potentially involved in pattern formation, arguing that among others, gravitational effects could be involved in the production of cytoplasmic, tissue and extracellular matrix components rearrangements playing a role in morphogenesis. Although plagued with the problem of being a very weak force, specially at the tiny dimensions of cells, gravity is one of the "generic" physical forces that have been continuously operating on biological organisms during evolution. Few scientists would argue against the idea that at least in the early times of evolution, gravity could have been involved in shaping the spatial inhomogeneities behind the initial phases of development.

Animals↗

Cardiopulmonary adaptation to weightlessness.

The lung is profoundly affected by gravity. The absence of gravity (microgravity) removes the mechanical stresses acting on the lung paranchyma itself, resulting in a reduction in the deformation of the lung due to its own weight, and consequently altering the distribution of fresh gas ventilation within the lung. There are also changes in the mechanical forces acting on the rib cage and abdomen, which alters the manner in which the lung expands. The other way in which microgravity affects the lung is through the removal of the gravitationally induced hydrostatic gradients in vascular pressures, both within the lung itself, and within the entire body. The abolition of a pressure gradient within the pulmonary circulation would be expected to result in a greater degree of uniformity of blood flow within the lung, while the removal of the hydrostatic gradient within the body should result in an increase in venous return and intra-thoracic blood volume, with attendant changes in cardiac output, stroke volume, and pulmonary diffusing capacity. During the 9 day flight of Spacelab Life Sciences-1 (SLS-1) we collected pulmonary function test data on the crew of the mission. We compared the results obtained in microgravity with those obtained on the ground in both the standing and supine positions, preflight and in the week immediately following the mission. A number of the tests in the package were aimed at studying the anticipated changes in cardiopulmonary function, and we report those in this communication.

Adaptation, Physiological↗

Functional and cellular adaptations of rodent skeletal muscle to weightlessness.

Microgravity perturbs a wide variety of physiological systems. Specifically, skeletal muscle has been shown to undergo dramatic changes even during spaceflights of short durations. Despite a growing body of knowledge, many critical issues related to sarcomeric gene expression and the translation of this information into muscle function remain relatively unexplored. Ultimately, the types and quantities of contractile proteins present in skeletal muscle fibers determine muscle function. As shown in Figure 1, the pool of contractile proteins is determined by 4 important processes: i) transcription of sarcomeric genes; ii) translation of sarcomeric mRNA transcripts; iii) myofibrillar assembly; and iv) myofibrillar disassembly (i.e., protein degradation). Any factor(s) affecting one or more of these systems will ultimately impact skeletal muscle function. With respect to Figure 1, the objective of this paper is to provide a focused summary of the affects of short duration spaceflights on myosin composition of the soleus (SOL) muscle. This will be achieved by describing the affects of spaceflight upon: i) mechanical properties of skeletal muscle that are determined by the types and quantity of myosin; ii) myosin heavy chain (MHC) protein isoform composition; and ii) MHC mRNA isoform content. Data reported in this paper are from spaceflight missions having durations of 6 (PARE-02;2) and 14 days (SLS-2).

Animals↗

Functional and cellular adaptation to weightlessness in primates.

Considerable data has been collected on the response of hindlimb muscles to unloading due to both spaceflight and hindlimb suspension. One generalized response to a reduction in load is muscle fiber atrophy, although not all muscles respond the same. For example, predominantly slow extensor muscles like the Sol exhibit a large reduction in fiber size to unloading, while fast extensors like the plantaris and fast flexors like the tibialis anterior show little, if any, atrophy. Our understanding of how muscles respond to microgravity, however, has come primarily from the examination of hindlimb muscles in the unrestrained rat in space. The non-human primate spaceflight paradigm differs considerably from the rodent paradigm in that the monkeys are restrained, usually in a sitting position, while in space. Recently, we examined the effects of microgravity on muscles of the Rhesus monkey by taking biopsies of selected hindlimb muscles prior to and following spaceflights of 14 and 12 day durations (Cosmos 2044 and 2229). Our results revealed that the monkey's response to microgravity differs from that of the rat. The apparent differences in the atrophic response of the hindlimb muscles of the monkey and rat to spaceflight may be attributed to 1) a species difference, 2) a difference in the manner in which the animals were maintained during the flight (i.e., chair restraint or "free-floating"), and/or 3) an ability of the monkeys to counteract the effects of spaceflight with resistive exercise.

Animals↗

Estimations of changes in plasma volume during simulated weightlessness.

Results of previous investigations on the effects of simulated microgravity (thermoneutral (34.5 degrees C) head-out water immersion, WI) have indicated that plasma volume (PV) increases initially and thereafter decreases to attain values below the pre-immersion level. In these cases, changes in hematocrit (Hct) and hemoglobin concentration (Hgb) were used as indicators of relative changes in PV. In order to test whether changes in Hct and Hgb are accurate measures of changes in PV during simulated microgravity, direct measurements of PV were performed with a modified Evans blue dye dilution technique before, during, and after a 12 h WI experiment. Furthermore, PV was determined with the same technique before, during, and after acute 6 degrees head-down tilt (HDT). Changes in PV were then compared with changes calculated from changes in Hct and Hgb.

Dye Dilution Technique↗

Achieving maximum plant yield in a weightless, bioregenerative system for a space craft.

Limitations to maximum plant yield are photosynthesis, respiration, and harvest index (edible/total biomass). Our best results with wheat equal 97.5 g total biomass m-2 day-1. Theoretical maximums for our continuous 900 micromoles photons m-2 s-1 = 175 g carbohydrate, so our life-cycle efficiency is about 56%. Mineral nutrition has posed problems, but these are now nearly solved. CO2 levels are about 80 micromoles m-3 (1700 ppm; ambient = 330 ppm). We have grown wheat plants successfully under low-pressure sodium lamps. The main factor promising increased yields is canopy development. About half the life cycle is required to develop a canopy that uses light efficiently. At that point, we achieve 89% of maximum theoretical growth, suggesting that most parameters are nearly optimal. The next important frontier concerns application of these techniques to the microgravity environment of a space craft. There are engineering problems connected with circulation of nutrient solutions, for example. Plant responses to microgravity could decrease or increase yields. Leaves become epinastic, grass nodes elongate, and roots grow out of their medium. We are proposing space experiments to study these problems.

Biomass↗

Thymic involution in the suspended rat model for weightlessness: decreased glucocorticoid receptor concentration.

Hindlimb muscle atrophy, thymic involution and adrenal hypertrophy in rats during spaceflight can be simulated using suspension models. Skeletal muscle and thymus are sensitive to glucocorticoids (GC) and previous studies have demonstrated that muscle atrophy in suspended rats is associated with increased GC receptor concentration. The objectives were to confirm thymic involution during suspension, and determine if involution correlated with increased GC receptor concentration. Seven days of antiorthostatic (AO) suspension of rats produced a significant (P<0.001) reduction in thymic wet weight not associated with an alteration of % water content. GC receptor concentration (pmol/mg protein) decreased 20% (P<0.025) in thymus glands from 7 day AO suspended rats. Suspension, therefore, is associated with involution of the thymus but this is not dependent upon AO positioning. Thymus GC receptor concentrations were depressed in 7 day suspended rats, in contrast with previous observations on skeletal muscle, suggesting that different mechanisms may underlie these responses.

Animals↗

Cardiovascular and hormonal (aldosterone) responses in a rat model which mimics responses to weightlessness.

Cardiovascular responses and fluid/electrolyte shifts seen during spaceflight have been attributed to cephalad redistribution of vascular fluid. The antiorthostatic (AO) rat (suspended, head-down tilt of 15-20 degrees) is used to model these responses. This study documents that elevated blood pressures in AO rats are sustained for periods of up to seven days, compared with presuspension values. Increased blood pressures in AO rats suggests a specific response to AO positioning, potentially relatable to a cephalad fluid shift. To assess a role for hormonal regulation of sodium excretion, serum aldosterone levels were measured. Circulating aldosterone concentrations were seen to increase approximately 100% during seven days of AO suspension concurrently with a pronounced natriuresis. These results suggest that aldosterone many not be involved in the long term regulation of increased Na+ excretion in AO animals. These studies continue to show the usefulness of models for the development of animal protocols for space flight.

Adaptation, Physiological↗

[Effects of simulated weightlessness and overweight on the growth of osteoblast cultured in vitro].

A special rotator designed for this experiment was used to simulate the gravitational conditions. 3 groups of osteoblast cells were cultured under simulated hypogravity, normal (1 g) or hypergravity acceleratively (3 g) for 7 d. Changes of cell shape and speed of cell division were observed. The results showed that cells cultured under simulated hypogravity became round and cells divided slowly as compared with 1g group. While cells cultured under 3 g divided more actively and many growth spots appeared in the culture bottle.

Biophysical Phenomena↗

[Ultrastructural changes of arterial wall from different body parts of rats during simulated weightlessness].

OBJECTIVE: To test the nature of remodeling of arteries in different body parts in adapting to local hemodynamic changes induced by tail-suspension. METHOD: Ultrastructural changes of hindlimb and cerebral arteries from 4-wk tail-suspended (SUS-4), 1-wk recovered (REC-1), and control (CON) rats were studied by transmission electron microscopy. RESULT: For the hindquarter arteries, like the femoral artery and anterior tibial artery, there were fewer smooth muscle layers, less myofilaments in the smooth muscle cell (SMC), and more intercellular substance in SUS-4 group than in CON group. After 1-wk recovery, the internal elastic lamina of the arteries thickened, the amount of myofilaments in SMC increased, the content of intercellular substance restored, and neoformative SMCs emerged under the endothelium. With respect to arteries in the neck region and the brain, like the common carotid artery and basilar artery, SMCs of contractile phenotype were converted to that of synthetic phenotype, and migration and hyperplasia of SMCs also happened. After 1-wk recovery all these alterations were somewhat restored. CONCLUSION: It provided further evidence that peripheral effector mechanism might play an important role in the genesis of postflight orthostatic intolerance.

Actin Cytoskeleton↗

Diminished plasma cGMP during weightlessness.

We performed an experiment within the project "RLF" (Russian long-term flight) on a cosmonaut onboard the space station MIR. For creating an analogue to orthostatic stress, we used lower body negative pressure (LBNP) as stimulus. Decrease in central and peripheral baroreceptor load by LBNP can be used as a cardiovascular countermeasure in cosmonauts or for inducing endocrine responses. Altered steady-state plasma concentration values of volume sensitive hormones have been observed inflight as well as postflight. Within this project we measured plasma ANP and cGMP as second messenger. Changes in plasma cGMP concentration are generally considered to be a good indicator of those in ANP activity. However, in our experiments depression of cGMP during space flight was more impressive than ANP decline. We are not aware of previous measurements of plasma cGMP under these conditions, and believe to be the first to report complete suppression of plasma cGMP during long-term stay in space.

Atrial Natriuretic Factor↗

Surgical instrument restraint in weightlessness.

BACKGROUND: Performing a surgical procedure during spaceflight will become more likely in the future as the duration of missions becomes longer. Only minimal surgical capability was available on previous missions since the definitive medical care time was short and the likelihood of a surgical event too low to justify carrying surgical hardware onboard. Early demonstrations of surgical procedures in the microgravity environment of parabolic flight indicated the need for careful logistical planning and restraint of surgical hardware. Human ergonomics also has more effect in microgravity than in the conventional 1-G environment. METHODS: Three methods of surgical instrument restraint--a Minor Surgical Kit (MSK), a Surgical Restraint Scrub Suit (SRSS), and a Surgical Tray (ST)--were evaluated in parabolic flight surgical procedures. RESULTS: The MSK was easily stored, easily deployed, and demonstrated the best ability to facilitate a surgical procedure in microgravity. CONCLUSION: Important factors in a surgical restraint system for microgravity include excellent organization of supplies, ability to maintain sterility, accessibility while providing secure restraint, ability to dispose of sharp items and biological trash, and ergonomic efficiency.

Aerospace Medicine↗