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Pharmacology in space: pharmacokinetics.

The possible pharmacokinetic mechanisms affected by microgravity are listed in Table 5. In studies of pharmacokinetics in humans, one has generally only access to drug concentrations in plasma and urine which are the results of several concurrent mechanisms. During weightlessness, different changes may occur in each step of the drug disposition process. The most important changes need to be identified and then predicted for the main drugs used in space. The use of a drug as a probe (Table 6) will permit to estimate the changes in specific pharmacokinetic parameters during spaceflight. However, this type of studies is technically difficult to carry out in space, but simulation studies on the ground are easier to perform. Two studies of hepatic blood flow showed no changes in this parameter during bedrest, but a more recent study showed changes in lidocaine disposition during a four-day head-down-tilt. Due to the large differences between individuals, pharmacokinetic changes must be fairly large (> 10-20%) to be observed in studies with probes. To detect a small change in weightlessness will require a number of subjects far higher than can be achieved in spaceflight. In summary, spaceflight is known to change many physiological parameters. The pharmacokinetics of drug disposition is determined by the combination of several complex phenomena. Each step of this process may be influenced by physiopathological changes occurring in spaceflight. This review shows how from a theoretical point of view absorption, distribution and elimination of drugs may be affected by weightlessness. The physiological changes most frequently involved in these modifications are the changes in blood flow due to the fluid shift.

Biological Availability↗

[Activity of the sympathetico-adrenal system in humans during modeling of weightlessness].

The state of the sympathico-adrenal system (SAS) before and during three days of suited immersion was investigated in six male subjects on the basis of renal excretion of adrenaline (A), noradrenaline (NA), dopamine (DA) and DOPA according to Vasilyev. Computer-aided analysis of the experimental data by the method of principal components showed that the SAS was functionally stressed in all subjects. Suited immersion that simulated hemodynamic, metabolic and vestibulo-motor effects of microgravity helped to distinguish between men with sustained and lowered capabilities of the SAS which are largely determined by the A-, NA-, and mixed type of its function. Clinical manifestations of A-crises in all subjects pointed to central genesis of SAS reactions to simulated microgravity. A correlation between the decline of SAS reserve capabilities and the level of the vestibulo-autonomic syndrome during suited immersion as well as drastic decrease of physical work capacity after immersion was established. It is emphasized that correction of unstable states of the SAS functional activity acquires special importance.

Adrenal Glands↗

A tactile display for international space station (ISS) extravehicular activity (EVA).

BACKGROUND: A tactile display to increase an astronaut's situational awareness during an extravehicular activity (EVA) has been developed and ground tested. The Tactor Locator System (TLS) is a non-intrusive, intuitive display capable of conveying position and velocity information via a vibrotactile stimulus applied to the subject's neck and torso. In the Earth's 1 G environment, perception of position and velocity is determined by the body's individual sensory systems. Under normal sensory conditions, redundant information from these sensory systems provides humans with an accurate sense of their position and motion. However, altered environments, including exposure to weightlessness, can lead to conflicting visual and vestibular cues, resulting in decreased situational awareness. The TLS was designed to provide somatosensory cues to complement the visual system during EVA operations. METHODS: An EVA task was simulated on a computer graphics workstation with a display of the International Space Station (ISS) and a target astronaut at an unknown location. Subjects were required to move about the ISS and acquire the target astronaut using either an auditory cue at the outset, or the TLS. Subjects used a 6 degree of freedom input device to command translational and rotational motion. The TLS was configured to act as a position aid, providing target direction information to the subject through a localized stimulus. RESULTS: Results show that the TLS decreases reaction time (p = 0.001) and movement time (p = 0.001) for simulated subject (astronaut) motion around the ISS. CONCLUSION: The TLS is a useful aid in increasing an astronaut's situational awareness, and warrants further testing to explore other uses, tasks and configurations.

Aerospace Medicine↗

Ethological experiments on human orientation behavior within a three-dimensional space--in microgravity.

In weightlessness situation the subject has to realize domestic and professional tasks comparable to those performed under normal gravity, whereas the "body tool" available to him has been placed in new conditions which require significant behavioral changes. The loss of weight, the disappearance or modification of some ideothetic and allothetic cues, notably the absence of gravity for the body's referential verticality have the most obvious effect of diversifying the astronaut's orientations. The vertical position is thus no longer the only one possible. This means that in order to efficiently accomplish his tasks, the subject has to invent new motor strategies which transform the quality of displacements and manipulations on the basis of the new orientation possibilities in a three-dimensional space. The previous ethological studies have dealt, in a global way, with the astronaut's motor behavior in microgravity, revealed according to an exhaustive quantitative description of the behavioral manifestions as a whole in terms of movement, posture and orientation. We now propose focusing more specifically on his spatial behavior in a three-dimensional space in microgravity. Such a situation is an exceptional experimental paradigm since at every moment, the relationships of the body referential to the surrounding space are infinitely variable: a man in space has to extract, process or use spatial information between the referentials of his moving body in all directions of the three-dimensional space and the fixed referentials of the physical environment of the space habitat. Furthermore, in the temporal dynamics, the previous ethological results showed that the behavioral events change according to the duration of the space mission, passing through different adaptative stages from a large behavioral diversity to complete behavioral reorganization. On the first day of his space mission the astronaut has however acquired experience of microgravity through his training, simulated on the ground and realized in parabolic flights. Some immediate adaptative processes are already present. As a result, the subject's experience of such a situation has to be emphasized from the initial moments of adaptation to microgravity. We thus postulate that the subject, through his orientation behavior in a three-dimensional space, according to his experience and over time, would elaborate a new representation of the space, as part of the whole adaptative process to this new environment. In order to verify such hypotheses, the present study will propose three levels of observation, i.e. three experiments in conditions of orbital flight, parabolic flight, visual simulation.

Adult↗

Inhalation risk in low-gravity spacecraft.

Inhalation risks on long-duration manned spaced flight include gasses chronically released by outgassing of materials, gasses released during spills, thermodegradation events (including fires) with their attendant particulates, and fire extinguishment. As an example, an event in which electronic insulation consisting of polytetrafluoroethylene undergoes thermodegradation on the Space Station Freedom was modeled experimentally and theoretically from the initial chemistry and convective transport through pulmonary deposition in humans. The low-gravity environment was found to impact various stages of event simulation. Critical unknowns were identified, and these include the extent of production of ultrafine particles and polymeric products at the source in low gravity, the transport of ultrafine particles in the spacecraft air quality control system, and the biological response of the lung, including alveolar macrophages, to this inhalation risk in low gravity.

Aerosols↗

Human motion planning based on recursive dynamics and optimal control techniques.

This paper presents an efficient optimal control and recursive dynamics-based computer animation system for simulating and controlling the motion of articulated figures. A quasi-Newton nonlinear programming technique (super-linear convergence) is implemented to solve minimum torque-based human motion-planning problems. The explicit analytical gradients needed in the dynamics are derived using a matrix exponential formulation and Lie algebra. Cubic spline functions are used to make the search space for an optimal solution finite. Based on our formulations, our method is well conditioned and robust, in addition to being computationally efficient. To better illustrate the efficiency of our method, we present results of natural looking and physically correct human motions for a variety of human motion tasks involving open and closed loop kinematic chains.

Algorithms↗

Numerical simulation and experimental validation of the dynamics of multiple bubble merger during pool boiling under microgravity conditions.

Numerical simulation and experimental validation of the growth and departure of multiple merging bubbles and associated heat transfer on a horizontal heated surface during pool boiling under variable gravity conditions have been performed. A finite difference scheme is used to solve the equations governing mass, momentum, and energy in the vapor liquid phases. The vapor-liquid interface is captured by a level set method that is modified to include the influence of phase change at the liquid-vapor interface. Water is used as test liquid. The effects of reduced gravity condition and orientation of the bubbles on the bubble diameter, interfacial structure, bubble merger time, and departure time, as well as local heat fluxes, are studied. In the experiments, multiple vapor bubbles are produced on artificial cavities in the 2-10 micrometer diameter range, microfabricated on the polished silicon wafer with given spacing. The wafer was heated electrically from the back with miniature strain gage type heating elements in order to control the nucleation superheat. The experiments conducted in normal Earth gravity and in the low gravity environment of KC-135 aircraft are used to validate the numerical simulations.

Earth, Planet↗

An optimal control strategy for crop growth in advanced life support systems.

A feedback control method for regulating crop growth in advanced life support systems is presented. Two models for crop growth are considered, one developed by the agricultural industry and used by the Ames Research Center, and a mechanistic model, termed the Energy Cascade model. Proportional and pointwise-optimal control laws are applied to both models using wheat as the crop and light intensity as the control input. The control is particularly sensitive to errors in measurement of crop dry mass. However, it is shown that the proposed approach is a potentially viable way of controlling crop growth as it compensates for model errors and problems associated with applying the desired control input due to environmental disturbances. Grant numbers: NGT5-50229.

Biomass↗

[Continuous target of China's manned space project and research direction of space medico-engineering].

The subject of space medico-engineering which takes manned space flight as its own task, played an important role in China's manned space project, and developed rapidly. According to China's next three manned space objectives: 1) to develop the technology of extra-vehicle activity (EVA) and test the astronauts' performance ability of EVA; 2) to develop the technology of docking with other object spacecraft in space; 3) to found a relatively large space lab, the research directions and key technology of space medico-engineering have been given, including astronaut's selection and training; requirements and evaluation of medicine and ergonomics of the space lab design; the researches of fields in astronauts' medical monitoring and space medicine; technology of environmental control and life support system in space module; technology of EVA or docking; and technology of simulation of astronaut's training.

Aerospace Medicine↗

[Effects of simulated microgravity on preimplantation embryonic development of Kunming mouse in vitro].

In order to investigate the development of Kunming mouse preimplantation embryos cultured in vitro under simulated microgravtiy, one-cell and 4-cell embryos of Kunming mouse (Fertilization In Situ) were cultured in CZB or KSOM media under simulated microgravity or normal gravity environment respectively. The results showed that under normal gravity, the percentage of passing 2-cell development block embryos was not different in CZB with in KSOM, but the percentage of blastocysts was lower in CZB than that in KSOM significantly. The percentages of passing 2-cell development block embryos and blastocysts in CZB or KSOM were lower under simulated microgravity than those under normal gravity. It is suggested that the frequency of early embryonic lethality is possibly increased by simulated microgravity.

Animals↗

[General patterns of bone atrophy in the absence of a weight load on the skeleton].

The rate of atrophic changes in spongy bones of the weightless man was estimated, using studies of human, dog and rat bones, as well as observations of neurological patients bed-stricken for a long time. Taking into consideration data on the literature on the bone status and mineral balance in real and simulated space flights, two models were built. The models make it possible to estimate osteoporosis of spongy bones of the axial skeleton in the absence of weight loading. One of the models--an intraspecies model for the human population--is based on the experimentally found rate of the physiological rearrangement of various spongy bones. The other--interspecies--model is built with reference to the parameters determining the rate, i. e. bone density and metabolism. The average monthly rates of axial bone losses calculated by means of the two independent methods are essentially identical. The data obtained allow prediction of the decrease of tolerance to head-to-feet impact acceleration as a function of flight duration.

Adult↗

[Role of dynamic factors of space flight in the pathogenesis of lymphoid organ involution (experimental morphologic study)].

The role of the dynamic factors in accidental involution of lymph organs has been investigated in a ground-based study simulating a 20-day space flight. It has been inferred from the study that lymph organ involution observed in rats exposed to prolonged space flights is caused by chronic and acute stresses. Chronic stress is associated with weightlessness and leads to hypoplasia of lymph organs; acute stress is connected with the transition from weightlessness to normal gravity (gravity stress), thus enhancing chronic stress induced lymph tissue hypoplasia. Spleens of both weightless and hypokinetic rats show inhibition of erythropoiesis and accumulation of hemosiderine due to accelerated erythrocyte degradation caused by diminished motor activity.

Acute Disease↗

Evolution of bioconvective patterns in variable gravity.

Measurements are reported of the evolution of bioconvective patterns in shallow, dense cultures of microorganisms subjected to varying gravity. Various statistical properties of this random, quasi-two-dimensional structure have been found: Aboav's law is obeyed, the average vertex angles follow predictions for regular polygons, and the area of a pattern varies linearly with its number of sides. As gravity varies between 1 g and 1.8g (g = 9.8 m s-1), these statistical properties continue to hold despite a tripling of the number of polygons and a reduced average polygon dimension by a third. This work compares with experiments on soap foams, Langmuir monolayer foams, metal grains, and simulations.

Animals↗

Pharmacology in space: pharmacotherapy.

This chapter summarized the information available on the pharmacological kits onboard spacecraft and on the use of drugs in space, while the next chapter is dedicated to the impacts of weightlessness on drug pharmacokinetics. The need of a selected group of drugs for the use of astronauts during short-term and long-term spaceflights has been discussed. Recommendations are made for a Space Pharmacopoeia as well as for the areas of research needed to adapt medication to the weightlessness of the space environment. Although the usefulness of these drugs has been clearly demonstrated, their use also raises several problems. Physiological changes due to weightlessness may induce changes in pharmacokinetic behavior of drugs and influence their dosage regimen. Inflight data obtained by salivary drug monitoring have shown changes in the distribution of scopolamine and a significant change in the disposition of the common pain-relief agent acetaminophen taken inflight, in both drug concentration and time course. The authors of this study emphasize, however, that their data are preliminary and as yet incomplete. Further simulation studies and, if possible, inflight experiments are required. In vitro studies of the antibacterial activity of antibiotics under space conditions have shown an increased resistance of Escherichia Coli to colistin and kanamycin, and a lowered resistance of Staphylococcus Aureus to oxacillin, chloramphenicol, and erythromycin. The possible consequences of these findings for the treatment of infections contracted by astronauts are yet to be elucidated. There is still a lack of pharmacological countermeasures, particularly for preventing the progressive bone demineralization occurring in weightlessness. The treatment of space motion sickness with drugs carries with it the problem of undesirable side-effects on psychomotor performance. In order to arrive at the most appropriate medical kit for a particular mission, the best trade-off of risk versus benefit for the individual and the mission must always be attempted for any pharmacological agent.

Aerospace Medicine↗

Computer systems analysis of the cardiovascular mechanisms of reentry orthostasis in astronauts.

Reentry orthostasis secondary to a prolonged exposure to microgravity is a common problem among astronauts. However, the physiologic mechanisms are poorly understood due to the many control systems involved. In this study an advanced computer model of cardiovascular functioning was employed in a systems analysis approach to clarify the relative importance of some of the adaptive physiologic processes engaged when humans return from space. After simulation of the conditions of zero gravity for one month, the model predicted that the change in capacitance of the lower extremity veins resulting from a loss of external fluid forces in the dehydrated extracellular compartment was the dominant mechanism associated with reentry orthostasis. This condition appears accentuated in women due to their inherent lower center of gravity and proportionately larger mass in the lower extremities.

Adaptation, Physiological↗

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