Biological systems ranging from the most simple to the most complex generally survive exposure to microgravity. Changes in many characteristics of biological systems are well documented as a consequence of space flight. Attempts to devise countermeasures to microgravity may have direct pragmatic consequences for crew protection and may provide additional insights into the nature of microgravity influences on biological systems. Some of the most well documented changes occur in humans who have experienced space flight. Changes appear to be transient. Space adaption syndrome occurs relatively briefly whereas bone deterioration may require months of postflight time for restoration. It seems critical to recognize that these changes and others may derive from rather passive, active or even reactive changes in the biological systems that are hosts to them. For example, hydrostatic fluid redistributions may be quite passive occurrences that are realized through extensive fluid channels. Changes occur in cell metabolism because of fluid, nutrient and gas redistributions. Equally important are the misconstrued messages likely to be carried by fluid redistributions. These reactive events can trigger, for example, loss of fluids and electrolytes through altered kidney function. Each of these considerations must be evaluated in regard to the biological site affected. Countermeasures to the vast range of biological changes and sites are difficult to envision. The most obvious countermeasure is the restoration of gravity-like influences. Some options are discussed. Recent work has focussed on the use of magnetic fields. Pulsed electromagnetic fields (PEMF) are shown to alleviate bone deterioration produced in rodents exposed to tail suspension. Methods of PEMF exposure are consistent with human use in space. Related methods may provide muscular and neural benefits

Luttges, Marvin W.

English

NASA Technical Reports Server

N90-13957
COUNTERMEASURES TO MICROGRAV1TY
Marvin W. Luttges
Aerospace Engineering Sciences
Bioserve Space Technologies
University of Colorado
Boulder, CO 80309
and
Many physiological systems sustain easily documented changes as a
consequence of exposure to the space environment. Most often recorded in
studies of astronauts, these changes are believed to be largely the effects of
microgravity. Areas of physiological interest are summarized in Table 1. The
problems may have rapid onset as common to the neurovestibular effects that
cause space adaptation syndrome. Entry and exit to the microgravity
environment are often highlighted by vertigo and gastric disturbances. Or,
the problems may be protracted as in the case of bone deterioration that
develops somewhat more slowly and that recovers slowly upon return to
normal gravity. Unfortunately, the direct causes of these and the other
alterations are poorly understood. Thus, direct countermeasures may be
especially difficult to implement. Accordingly, I have attempted to provide a
conceptual set of considerations for obviating the effects of micrgravity. The
exercise may be whimsical but the thought it is meant to provoke may change
the way we approach some microgravity problems.
Based upon observations of biological systems exposed to the space
environment, it seems helpful to provide a structure within which to
categorize classes of effects. Simply, some effects may be quite passive
consequences of microgravity related to fluid redistributions or losses of
mechanical loading. Others may signal an active cellular or tissue response to
the altered environment in which they are immersed. Finally, some effects
are reactive in that cells and tissues respond actively but inappropriately to
the environment created by microgravity. Examples of such effects are
provided later. However, it is crucial to recognize that such effects may have
intraccllul_r, membrane, immediateextracellular, tissue, rg.Lg._ or organism
sites of action.
The passive consequences of microgravity translate into a variety of
hydrostatic, mechanical and electrical effects. For example, fluid
compartments change, loads on cells and tissues change and even a variety of
piezoelectric changes may occur. Other alterations occur, as well. At the
organism level, the consequences of fluid columns existing in the absence of
loading and pressure changes promote passive, active and reactive effects, for
example, in the cardiovascular and lymphatic systems. At the tissue level,
these effects are reflected in cardiac, vascular and, perhaps, immune system
changes. Mechanical and piezoelectric effects may be linked in regard to
bone changes. But, it is critical to recognize that some of the known effects of
microgravity on bone could result from passive microgravity influences on
bone circulation or from the extracellular dynamics of bone formation and
deterioration. Reactive changes are most evident in fluid shifts to the upper
body that result in hormone messages that signal increased kidney function.
Or, unweighted gravity sensors of the inner ear may produce spurious signals
that produce disorientation in the central nervous system as well as altered
neuromuscular-cerebellar communication to the peripheral nervous system.
In the former, the system simply behaves in a normal way, ignorant of the
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microgravity. In the latter case, the system may be adapting to a point of
accepting "noise" as a signal. In any event, candidates for microgravity
influences are both numerous and complicated. As stated above, poor
understanding of causal mechanism leads to limited and , perhaps, ineffective
countermeasures; or worse, contra-indicated countermeasures.
The list in Table 1 summarizes physiological "problem areas" in regard to a
few microgravity effects. Within each area effects are not well understood at
any physiological level, and it is difficult to determine whether the effects
arise from passive, active or reactive consequences of microgravity exposure.
A sample of candidate causal factors is listed in Table 2. Taken together, the
problems and their causes constitute an almost complete biomedical sciences
research agenda, with or without the complications of the space environment
exposure that may involved even more than microgravity and radiation
exposures. However, Table 2 highlights several microgravity influences that
have escaped serious research commitments. Direct mechanical effects on
cells, tissues, organs and organisms have not received systematic attention
except at high levels of exposure meant to simulate various traumatic insult
circumstances. Direct tissue elasticity influences of mechanical loading have
only recently received enhanced levels of research attention and, then, the
attention is limited to cardiovascular studies. Yet, it is readily apparent that
biological systems do function in the presence of nominal gravity and that
such functioning may include a variety of dependencies on the presence of
gravity-induced influences on the physiological environment. The problem
may be that the gravity influences are so ubiquitous that they have escaped
serious consideration. The space environment may make use rethink our
present complacency regarding the importance of gravity in living
organisms. The survival and function of biological systems in space may be a
simple reflection of robustness and inadvertently produced protection
protocols.
It is against this backdrop that we have begun to study ways to alleviate
microgravity effects on biological systems And, it is from the above outlined
"view" of the microgravity effects that we make some guarded
recommendations. In several instances we have proposed remedies that
appear facetious. This has been done to encourage a rather open-minded view
of both the nature of the problems and possible countermeasures. It may be
necessary to originate new methods or treatments. Modifications of existing
treatments for use in space may be inadequate. And overall, we may need to
institute some broad, novel concepts of space physiology.
Candidate Solutions
The items in Table 3 suggest several strategies for handling the
microgravity problems. Such strategies, of course, are not particularly novel.
The strategies range from replacement of nominal levels of gravity to broad
pharmacological treatments. Again, we are reminded that we are speculating
on therapies without much knowledge of the nature of a the problems. In
some sense, replacements are the most innocuous treatments to attempt. We
start there,
Perhaps the most common solution to microgravity problems is the simple
replacement of what's missing -- gravity. A variety of rotating space habitats
have been suggested including the now classic rotating torus concept circa
1950's. Realistically, we have very little data that focuses directly on the
214
consequencesof using centripetal forces as a substitute for gravity. Studies
done with a variety of centrifugal methodologies have interpretation
difficulties due to mixed centripetal-gravitational vectors, centripetal
gradients and Coriolis effects. Thus, the simple replacementof a gravity
vector may be much more difficult than expected. At this time, it would be
difficult to envision relevant physiological studies unless they were actually
conducted in the space environment.
Associated with the above biological interpretation difficulties are the
implementation difficulties of creating a man-rated rotating space habitat.
Structural problems would, at this time, be difficult to anticipate and center of
mass asymmetriescould contribute to much precessionand wobble. These
problems are additive to the problems of spin-up or spin-down and the
problems of egress or safety.
It seemsto follow from the above commentsthat evaluations in the 1.8
meter centrifuge planned for Space Station Freedom will provide the
biological rationale either for undertaking or dismissing the possibilities for a
rotating habitat. Even this capability will leave questionsunanswered. So, a
strong rationale for a rotating habitat may be quite far away.
The present approach to reduction of microgravity effects, of course,
centerson exercise. The value of this approachand the limitations are already
reasonably well documentedin what might be considered preliminary
demonstrations. The difficulty here is that exercisesdone in space have
neither been done consistently nor done in a highly controlled fashion.
Subject numbers have been small and subjects have varied considerably in a
number of important ways; age, health, conditioning level, sex etc. It is yet to
be determined whether or not we have identified and used the most effective
exercise protocols. Nevertheless,the critical drawbackof exercise is that (1) it
does not seemto be a panaceafor treatmentof all microgravity effects and (2)
it takes a significant toll on the length of time astronautsmight otherwise
have available for productive experiments, observations and maintenance. If
exercise is to be the mainstay treatment for microgravity effects it must be
made more effective and less time consuming. Ideally, it should be made
recreational, as well. Such constraints, together, lead to a difficult challenge
for medical practitioners and exercise physiologists.
For a number of tissues, it appearsthat somedegree of healing and/or
protection from deterioration might be afforded using either electrical or
magnetic fields. At Bioserve we have pursued these possibilities for a rodent
tail suspensionmodel using changesin bone as the focal point of our analyses.
Pulsed magnetic fields have prevented the bone deterioration usually seen in
tail-suspendedmice. Many variables, of course, are important. Field strength,
pulse characteristics, field orientation, animal age and duration of daily
treatment have been consideredexperimentally. Some of these results were
reportedat the annual ASGSB, 1988 meetings. Currently, effects of magnetic
field treatments are being done for nervous system and muscular system
tissuesas well as bone. All of the experimentsare promising but we are trying
to (1) learn the limits of these treatments,(2) look for any evidenceof side
effecs and (3) sculpture the protocols for tests in the microgravity
environment.
215
Our observations with these electromagneticeffects raised the possibility
that rather ubiquitous force gradients (in the above case, magnetic fields)
might substitute for some of the gravity forces experiencedby organisms. The
resulting "mixed gradients" could have desirable consequencesat the
organism, tissue and even cellular levels. We have begun to formalize this
kind of hypothesis. It may not be unreasonbleto assumethat other ubiquitous
variables could be found, as well. Again, however, the challengesand
problems are significant in understandingand using such approachesto
counteracting microgravity effects.
The next approach to devising countermeasuresis the use of passively-
induced gravity effects. This approachmakes several assumptionsabout the
causal factors, in microgravity deterioration or dysfunctions. Simply stated,
the assumptions relate to some unquantified and uncharacterizedneed of
organisms for gravity-promoted bulk fluid motions and mechanical force
gradients. The effects might relate to modestmixing within cellular milieus,
differential forces produced across a cell and/or cell membrane,organ
distortions with allied mechanical and fluid forces generated asymmetrically
within the organ, or to organism asymmetries,again, leading to a variety of
different forcing functions. The linking of such forces is evident, for
example, in the galloping horse that uses the various locomotive forces to aid
in respiration. Evidence for the importance of such effects is just now arising
from experimental literature. Nevertheless, some speculation on associated
countermeasures to microgravity-induced losses of such factors seems
warranted.
Assuming that fluidic mixing at a variety of tissue compartment levels is to
be accomplished and that mechanical forces are to be generated across such
tissue compartments, the replacement strategies appear quite clear. Direct
acceleration and deceleration forces can be applied to the organism in
microgravity. Or, direct mechanical forces can be applied. This treatment, I
suppose, is tantamount to suggesting that astronauts be made to "bounce off
the walls" in an almost literal sense. The resulting brief episodes and
differing vectors for acceleration -- deceleration forces may provide fluid
mixing and mechanical shear forces otherwise lost to the microgravity
environment. Following some hypothetical biological need for gravity, it
appears that a fair amount of direct mechanical stimulation should be
provided. This could range from slow, broad coverage stimulation nearing
whole body massage to rapid, narrowly directed stimulation such as focused
ultrasound. With appropriate selection of acoustical wavelengths and
intensities, it might be possible to effect virtually all tissue, organ and cellular
compartments regardless of size and distance from the body surface. The
beneficial effects might be reduced flow stagnation, reduced need for
metabolic pumping across the cells and tissues in lieu of mechanical gradients,
and enhanced tissue reactivity to stimuli like stretch stimuli used to maintain
skeletal muscle tonus or stretch stimuli needed to elicit rather autonmous
smooth muscle responses. Whether such approaches are likely to aid in the
search for countermeasures remains to be seen. However, it seems equally
important to evaluate the need of biological systems for such fluidic and
mechanical stimuli. It may be important to separate the gratuitous production
of these effects by exercise such that exercise can be supplanted, in duration,
by more passive mechanical and fluidic stimulation. This approach allows
more time for the simultaneous production of useful work in space by the
astronauts.
216
For a number of biological effects produced in microgravity, it is tempting
to employ directed pharmacological treatments. Thus, the microgravity
dysfunctions are treated like any of a large number of other medical maladies.
Many and more powerfu.l drugs are being developed. Some, like calcium loss
inhibitors for bone, are at the thresholdof FDA approval. Yet, at some point or
another, it seemsreasonableto question the use of drugs since already a major
segmentof American society is taking drugs to reducethe side effects of other
drugs or is at risk in taking drugs with one another that don't mix either
chemically or pharmacologically. The thing to be rememberedhere is that all
drugs are "poisons." Unless a ubiquitousdrug is found that is capableof
treating most microgravity effects in different tissues at about the. same time,
drugs made for the variety of known physiological dysfunctions of
microgravity would undoubtedly yield an unacceptably large number of side
effects. Where possible to elicit general systemic effects, the drug would have
to promote stasis or general anabolic biases--- this, of course, is a situation
being pursued by world class athletes and the side-effects of these treatments
are only too well known. As above, the implementationof pharmaceutical
countermeasuresto microgravity makes more assumptions about our
information and therapeuticswizardry than we could reasonably live up to for
several decades.
The other treatments mentioned as countermeasuressimply reflect some
current beliefs about nutrition and organism health. Even in the nominal
gravity conditions of Earth it is difficult to reconcile the role of nutrition in
health and diseasestates. The impact may be subtle and the required studies
for corroboration must be, by nature, longitudinal. Only now are we
beginning to grasp the significance of and the methodologies for longitudinal
studiesthat may extend for 3 or 4 decades.
From each of the somewhatwistful comments regarding protection from
microgravity effects in space, two things are abundantlyclear. (1) We really
don't know what the microgravity effects on biological organismsare! And,
(2) we are not especially accomplishedin instituting effective
countermeasuresfor any of a wide variety of known medical dysfunctions.
Yet, we are likely to have to control microgravity effects or minimize the
influences of such effects on astronautsif SpaceStation Freedom is to become
an effective reality. We must use this rather overwhelming challenge to learn
what we can regarding biological system dependenceon gravity, biological
dysfunctions without gravity and biological independencefrom gravity. Only
then, can long spacemissions becomea reality and can man's future as a
spacefarer be assured.
217
COUNTERMEASURES TO
MICROGRAVITY
PROBLEM AREAS
MUSCULOSKELETAL
CARDIOVASCULAR
MICROBIOLOGICAL
RADIATION
FLUID/ELECTROLYTES
IMMUNOLOGICAL
PULMONARY
PHARMACOLOGICAL
BEHAVIORAL
TOXICOLOGICAL
NEUROVESTIBULAR
Table 1
218
COUNTERMEASURES TO
MICROGRAVITY
CAUSAL FACTORS
WEIGHTLESSNESS
NO CONVECTION
Loss of shear stresses on
and tissues
Loss of some fluid motion
Fluid redistributions
Altered tissue elasticity-fluid
interactions
Reduced cell to cell
communication
cells
ALTERED INTERNAL MILIEU
Erroneous sensor function
Erroneous mechanical vectors
Altered hormonal states
Table 2
219
COUNTERMEASURES TO
MICROGRAVITY
CANDIDATE SOLUTIONS
ARTIFICIAL GRAVITY
EXERCISE-INDUCED
MECHANICAL EFFECTS
ELECTROMAGNETIC
EFFECTS
PASSIVELY-INDUCED
GRAVITY EFFECTS
DISABLED SENSORS
NUTRITION
ARTIFICIAL CHANGES
CHEMICAL MILIEU
IN
Table 3
220


Countermeasures to microgravity

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