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Medical considerations for extending human presence in space.

The prospects for extending the length of time that humans can safely remain in space depend partly on resolution of a number of medical issues. Physiologic effects of weightlessness that may affect health during flight include loss of body fluid, functional alterations in the cardiovascular system, loss of red blood cells and bone mineral, compromised immune system function, and neurosensory disturbances. Some of the physiologic adaptations to weightlessness contribute to difficulties with readaptation to Earth's gravity. These include cardiovascular deconditioning and loss of body fluids and electrolytes; red blood cell mass; muscle mass, strength, and endurance; and bone mineral. Potentially harmful factors in space flight that are not related to weightlessness include radiation, altered circadian rhythms and rest/work cycles, and the closed, isolated environment of the spacecraft. There is no evidence that space flight has long-term effects on humans, except that bone mass lost during flight may not be replaced, and radiation damage is cumulative. However, the number of people who have spent several months or longer in space is still small. Only carefully-planned experiments in space preceded by thorough ground-based studies can provide the information needed to increase the amount of time humans can safely spend in space.

Adaptation, Physiological↗

Mathematical modeling of acute and chronic cardiovascular changes during Extended Duration Orbiter (EDO) flights.

The Extended Duration Orbiter (EDO) program aims to extend the capability of the Shuttle orbiter beyond its current 7-10 day limit on mission duration. This goal is to be accomplished in steps, partly due to our limited knowledge of the physiological changes resulting from long-term exposure to weightlessness and their likely influence on critical mission operations involved in EDO flights. Answers to questions related to physiologic adaptation to weightlessness are being actively sought at the present time to help implement the EDO program. In the cardiovascular area, the loss of orthostatic tolerance is a medical concern because of its potential adverse effects on crew performance and safety during reentry and following return to earth. Flight and ground-based physiologic studies are being planned to understand the mechanism and time course of spaceflight-induced orthostatic intolerance and to develop effective countermeasures for improving post-flight cardiovascular performance. Where feasible, these studies are aided by theoretical analyses using mathematical modeling and computer simulation of physiological systems. This paper is concerned with the application of proven models of circulatory and cardiovascular systems in the analysis of chronic cardiovascular changes under weightless conditions.

Cardiovascular Deconditioning↗

Metabolism and biochemistry in hypogravity.

The headward shift of body fluid and increase in stress-related hormones that occur in hypogravity bring about a number of changes in metabolism and biochemistry of the human body. Such alterations may have important effects on health during flight and during a recovery period after return to Earth. Body fluid and electrolytes are lost, and blood levels of several hormones that control metabolism are altered during space flight. Increased serum calcium may lead to an increased risk of renal stone formation during flight, and altered drug metabolism could influence the efficacy of therapeutic agents. Orthostatic intolerance and an increased risk of fracturing weakened bones are concerns at landing. It is important to understand biochemistry and metabolism in hypogravity so that clinically important developments can be anticipated and prevented or ameliorated.

Bed Rest↗

The physiology of spacecraft and space suit atmosphere selection.

The majority of the environmental factors which comprise the spacecraft and space suit environments can be controlled at "Earth normal" values, at optimum values, or at other values decided upon by spacecraft designers. Factors which are considered in arriving at control values and control ranges of these parameters include physiological, engineering, operational cost, and safety considerations. Several of the physiological considerations, including hypoxia and hyperoxia, hypercapnia, temperature regulation, and decompression sickness are identified and their impact on spacecraft and space suit atmosphere selection are considered. The past experience in controlling these parameters in U.S. and Soviet spacecraft and space suits and the associated physiological responses are reviewed. Current areas of physiological investigation relating to environmental factors in spacecraft are discussed, particularly decompression sickness which can occur as a result of change in pressure from Earth to spacecraft or spacecraft to space suit. Physiological considerations for long-term lunar or Martian missions will have different impacts on atmosphere selection and may result in the selection of atmospheres different than those currently in use.

Atmospheric Pressure↗

Cardiovascular function in space flight.

Changes in orthostatic heart rate have been noted universally in Soviet and U.S. crewmembers post space flight. The magnitude of these changes appears to be influenced by mission duration, with increasing orthostatic intolerance for the first 7-10 days of flight and then a partial recovery in the orthostatic heart rate response. Fluid loading has been used as a countermeasure to this postflight orthostatic intolerance. Previous reports have documented the effectiveness of this technique, but it has also been noted that the effectiveness of volume expansion diminishes as flight duration exceeds one week. The response of carotid baroreceptor function was investigated utilizing a commercially available neck collar which could apply positive and negative pressure to effect receptor stimulation. Bedrest studies had validated the usefulness and validity of the device. In these studies it was shown that carotid baroreceptor function curves demonstrated less responsiveness to orthostatic stimulation than control individuals. Twelve Space Shuttle crewmembers were examined pre- and postflight from flights lasting from 4-5 days. Plots of baroreceptor function were constructed and plotted as change in R-R interval vs. carotid distending pressure (an orthostatic stimulus). Typical sigmoidal curves were obtained. Postflight the resting heart rate was higher (smaller R-R interval) and the range of R-R value and the slope of the carotid sigmoidal response were both depressed. These changes were not significant immediately postflight (L + O), but did become significant by the second day postflight (L + 2), and remained suppressed for several days thereafter. It is hypothesized that the early adaptation to space flight involves a central fluid shift during the initial days of flight, but subsequent alterations in neural controlling mechanisms (such as carotid baroreceptor function) contribute to orthostatic intolerance.

Adaptation, Physiological↗

Countermeasures against space flight related bone loss.

This paper reviews human data concerning bone loss and attempted countermeasures during spaceflight and bed rest, a commonly employed technique to simulate the effects of weightlessness on the musculoskeletal system.

Bed Rest↗

Does bed rest produce changes in orthostatic function comparable to those induced by space flight?

Use of bed rest to simulate microgravity exposure is not well validated. We compared heart rate (HR) and blood pressure (BP) responses to standing in bed-rest (BR) subjects (n=11) to those of two astronaut groups. One astronaut group (n=28) fluid loaded (FL) before landing by consuming a water and salt tablet mixture, the second astronaut group (n=8) did not (NL). Bed-rest or microgravity exposure lasted approximately 7.0 days. Preexposure, the responses to standing did not differ between groups. Postexposure, all groups demonstrated an increased HR response (p<0.01), a decreased SBP response (p<0.05), no change in DBP response, and a reduced PP response (p<0.05) compared to preexposure. Change in HR response was lowest for the FL group, presumably due to increased plasma volume induced by fluid consumption. These findings generally support bed rest as a valid simulator of microgravity.

Adult↗

Cardiovascular responses to KC-135 hyper-gravity.

The present study was designed with two intentions; Are the effects of angular velocity detectable in the cardiovascular responses during the hyper-G? Another is object to examine how the otolith signal could modify the cardiovascular responses provoked by the exposure to the hyper-G. NASA/KC-135 hyper-gravity flight was used to generate high gravito-inertial forces to exclude a possible effect of angular velocity. Six healthy subjects was indicated to make dorsal flexion of the neck to reduce the otolith input. An exposure to +l.8Gz stress resulted in a remarkable increase of systolic and diastolic blood pressure, thereby pulse pressure became a little bit narrower. R-R interval revealed a tachycardia during the hyper-G except one subject. The present experiment bore the similar cardiovascular responses as those observed in the previous studies with a short rotating radius, suggesting that almost no effect of angular velocity acts on their responses. A weaker otolith input could possibly work on them. However a systematical observation can not recognize among the subjects for the vestibular effect on the cardiovascular responses. This fact of vestibular qualification leads us to speculate that it would depend on the subjects or other factors.

Adult↗

Spatial orientation during locomotion [correction of locomation] following space flight.

To investigate changes in spatial orientation ability and walking performance following space flight, 7 astronaut subjects were asked pre- and post-flight to perform a goal directed locomotion paradigm which consisted of walking a triangular path with and without vision. This new paradigm, involving inputs from different sensory systems, allows quantification of several critical parameters, like orientation performance, walking velocities and postural stability, in a natural walking task. The paper presented here mainly focuses on spatial orientation performance quantified by the errors in walking the previously seen path without vision. Errors in length and reaching the corners did not change significantly from pre- to post-flight, while absolute angular errors slightly increased post-flight. The significant decrease in walking velocity and a change in head-trunk coordination while walking around the corners of the path observed post-flight may suggest that during re-adaptation to gravity the mechanisms which are necessary to perform the task have to be re-accomplished.

Electronic Data Processing↗

Efficacy of Doppler ultrasound [correction of utrasound] for screening symptoms of decompression sickness during simulated extravehicular activities.

Doppler ultrasound is frequently used for monitoring circulating microbubbles during decompression to assess the symptoms of Decompression Sickness (DCS). This analysis was carried out to evaluate its effectiveness for screening symptoms of DCS during simulated extravehicular activities (EVA). The information from various hypobaric chamber studies carried out at the NASA Johnson Space Center, Houston, TX was used in this analysis (n=516). The circulating microbubbles were detected in the precordial area in 42% (218/516), and symptoms were reported in 16% (81/516) of these exposures. The accuracy of Doppler-detectable bubbles (Spencer grades) on all symptoms of DCS was examined by calculating measures of sensitivity and specificity. The efficacy of Doppler as a screening device was examined by calculating their positive predictive value (PPV) and negative predictive value (NPV). The results of these analyses indicated that the sensitivity of Doppler decreased, and the PPV increased with higher Spencer grades. However, the likelihood of detecting true negative cases (NPV) was consistently higher with all bubble grades. Due to the high false-positive rate and low prior probabilities of the risk of DCS, Doppler was found to be more useful to identify those who did not develop DCS, than to detect positive cases of DCS in the simulated EVA exposures.

Decompression Sickness↗

Energy utilization rates during shuttle extravehicular activities.

The work rates or energy utilization rates during EVA are major factors in sizing of life support systems. These rates also provide a measure of ease of EVA and its cost in crew fatigue. From the first Shuttle EVA on the STS-6 mission in 1983, we have conducted 59 man-EVA and 341 man-hours of EVA. Energy utilization rates have been measured on each of these EVA. Metabolic rate was measured during each EVA using oxygen utilization corrected for suit leakage. From 1981-1987, these data were available for average data over the EVA or over large segments of the EVA. Since 1987, EVA oxygen utilization data were available at 2-minute intervals. The average metabolic rate on Shuttle EVA (194 kcal/hr.) has been significantly lower than metabolic rates during Apollo and Skylab missions. Peak rates have been below design levels, infrequent, and of short duration. The data suggest that the energy cost of tasks may be inversely related to the degree of training for the task. The data provide insight on the safety margins provided by life support designs and on the energy cost of Station construction EVA.

Aerospace Medicine↗

On the correlation between individual biochemical parameters of human blood serum following space flight and their basal values.

The article presents data concerning the osmolality and concentration of electrolytes and hormones regulating their balance for blood serum of 223 cosmonauts and astronauts. The obtained results allow us to judge the constancy of physicochemical parameters for the blood serum of healthy individuals and how they react to extreme conditions of space flight. The parameters used for evaluation included not just absolute values for the examined indices, but also how they responded to space flight, the dependence on baseline values and the interrelationship between ions. These data are important to predict the effect of exposure to extreme conditions and point to what extent the effect depends on the characteristics of the individual.

Aerospace Medicine↗

A system for the accurate measurement of pointing responses.

We present an accurate, yet relatively inexpensive, system for measuring the direction of pointing responses. This system utilizes off-the-shelf business presentation components in a novel way to help detect and quantify the pointing measurements. The system configuration, measurement features, and procedures to enhance measurement accuracy are described.

Computer Terminals↗

Pharmacology in space. Part 1. Influence of adaptive changes on pharmacokinetics.

The topic of pharmacology in space, i.e. the administration of drugs during space flight and the subsequent pharmacokinetic handling of the pharmaceuticals, is a new field about which little is known. In a two-part series, Claire Lathers and colleagues highlight some of the current questions in this field. In this first article the physiological and biochemical changes associated with weightlessness in space are discussed. These changes induce adaptive alterations which may influence the pharmacokinetic properties of drugs. The cardiovascular system is of particular relevance here. Also discussed are the classes of pharmacological agent that are most likely to be used during space flight for medical problems and thus, by necessity, will become drugs to be examined in space to determine whether their pharmacokinetic and pharmacodynamic properties are altered. Therapy of the most common spaceflight ailment-motion sickness-will be considered next month in Part 2.

Humans↗

Pharmacology in space. Part 2. Controlling motion sickness.

In this second article in the two-part series on pharmacology in space, Claire Lathers and colleagues discuss the pharmacology of drugs used to control motion sickness in space and note that the pharmacology of the 'ideal' agent has yet to be worked out. That motion sickness may impair the pharmacological action of a drug by interfering with its absorption and distribution because of alteration of physiology is a problem unique to pharmacology in space. The authors comment on the problem of designing suitable ground-based studies to evaluate the pharmacological effect of drugs to be used in space and discuss the use of salivary samples collected during space flight to allow pharmacokinetic evaluations necessary for non-invasive clinical drug monitoring.

Humans↗

Microgravity induces prostaglandin E2 and interleukin-6 production in normal rat osteoblasts: role in bone demineralization.

It has been suggested that microgravity alters bone metabolism. Evidence for this phenomenon includes the negative calcium balance and decreased bone density in astronauts, as well as, inhibition of bone formation in rats flown for 2 to 3 weeks. However, the specific mechanisms that modulate these changes in microgravity are unknown. The purpose of this study was to clarify the mechanism of microgravity-induced bone demineralization using normal rat osteoblasts obtained from femur marrow cultures. The osteoblasts were cultured for 5 days during a Shuttle-Spacelab flight (STS-65). After collection of the culture medium, the cellular DNA and RNA were fixed on board. Enzyme-immunoassay of the culture medium for prostaglandin E2 (PGE2) indicated that microgravity induced a 4.5- to 136-fold increase in flight samples as compared to the ground control cultures. This increase of PGE2 production was consistent with a 3.3- to 9.5-fold elevation of inducible prostaglandin G/H synthase-2 (PGHS-2) mRNA, quantitated by reverse transcription-polymerase chain reaction (RT-PCR). The mRNA induction for the constitutive isozyme PGHS-1 was less than that for PGHS-2. The interleukin-6 (IL-6) mRNA was also increased (6.4- to 9.3-fold) in microgravity as compared to the ground controls. Since PGE2 and IL-6 are both known to play a role in osteoclast formation and bone resorption, these data provide molecular mechanisms that contribute to our understanding of microgravity-induced alterations in the bone resorption process.

Animals↗

Measurement of differential proton spectra onboard the Space Shuttle using a thermoluminescent dosimetry system.

An experimental technique that permits the extraction of orbit-averaged, differential energy spectra of trapped radiation belt protons using simple passive detectors is described. An inversion technique is used for the data analysis. The basic principle of the described system is measurement of the energy deposited in six thermoluminescent (TLD) detector assemblies behind various spherical absorbers. The technique has been applied to a detector assembly flown on four Shuttle flights. Although severe restraints were placed on the flight package, the differential energy spectra derived from these measurements are in good agreement with analytical results using a modified trapped proton environment model. The technique shows good promise for measuring the spectra in low inclination orbits where the flux of high energy galactic cosmic rays protons is small. Modifications to the detector assembly to improve the accuracy and to extend the range of the system to higher energies are suggested.

Cosmic Radiation↗

Parallel line analysis: multifunctional software for the biomedical sciences.

An easy to use, interactive FORTRAN program for analyzing the results of parallel line assays is described. The program is menu driven and consists of five major components: data entry, data editing, manual analysis, manual plotting, and automatic analysis and plotting. Data can be entered from the terminal or from previously created data files. The data editing portion of the program is used to inspect and modify data and to statistically identify outliers. The manual analysis component is used to test the assumptions necessary for parallel line assays using analysis of covariance techniques and to determine potency ratios with confidence limits. The manual plotting component provides a graphic display of the data on the terminal screen or on a standard line printer. The automatic portion runs through multiple analyses without operator input. Data may be saved in a special file to expedite input at a future time.

Data Interpretation, Statistical↗