Significant Achievements in Space Bioscience 1958-1964 Part 14

Metabolic Effects of Weightlessness

Without metabolic information, accurate planning of environmental systems for long flights is difficult. Importance is also attached to early evaluation of weightlessness effects on body-fluid equilibria. The results of Earth orbital flights and of terrestrial water-immersion experiments suggest the occurrence of undesirable changes, although no effects leading to operational incapacity have yet arisen.

In both rec.u.mbency and immersion, a similar redistribution of body fluids occurs. It has been suggested that rec.u.mbency may affect an extracellular fluid-volume receptor mechanism which by decreasing aldosterone secretion by the adrenal gland, would decrease sodium reabsorption by the renal tubules. Aldosterone excretion decreases during rec.u.mbency and during standing in water, but increases while standing in air. There is also evidence for cardiac atrial volume receptor mechanisms which respond to increased filling of the left atrium with reflex inhibition of release of pituitary antidiuretic hormone (ADH), resulting in diuresis (Henry-Gauer reflex).

Altered fluid equilibrium in buoyant states is accompanied by shifts in intracellular and extracellular electrolyte distribution, especially sodium and pota.s.sium. Evidence from rec.u.mbency studies indicates a strong correlation between loss of erect posture or weight bearing and excretion of calcium stores in bone.

A bone X-ray densitometry method has been developed by Mack, at Texas Woman's University, for accurately determining the loss of bone mineral (2 percent accuracy) in humans and animals. The heel bone and spine are X-rayed using a calibrated aluminum wedge as a standard. This technique will be used for preflight and postflight a.n.a.lysis of the primate being flown in the 30-day biosatellite. Comparative appraisal of bone mineral behavior in astronauts partic.i.p.ating in the Gemini and Apollo programs will be invaluable for future flight missions.

Bed rest and immobilization studies by Mack have shown loss of skeletal mineral and increased calcium in the urine and excreta. Four bed-rest studies, each extending for 2 weeks, compared different levels of calcium intake. Four men were used in each study and served as their own controls during extended ambulatory periods. During 2-week periods, up to 10 percent of calcium mineral was lost from the heel bone. Calcium was also determined in the urine and feces. In other studies, isometric exercises reduced loss of bone mineral during bed rest.

Excretion of calcium in the urine is accompanied by risk of its deposition as calculi or "kidney stones" in the urinary tract.

Currently, changes in calcium metabolism resulting from weightlessness over periods up to 2 weeks is not considered a hazard requiring precautionary measures.

Flights in excess of 2 weeks, however, const.i.tute a problem serious enough to warrant study on the 11-day orbital flights and the 30-day biosatellite primate mission. Therapeutic immobilization, post-poliomyelitis immobility, and experimental restraint in normal subjects lead to a negative calcium balance, with hypercalciuria.

Central Nervous System Functions in Weightlessness

The wide range of individual tolerances to the disturbing effects of vestibular stimulation has emphasized the importance of this factor in astronaut selection. At the same time, vestibular functions must be considered jointly with visual task performance, since both have special significance for such maneuvers as vehicle docking. Vestibular function in the weightless state remains almost completely unknown. Limited evidence from animal and manned s.p.a.ce flights suggests that head turning, resulting from vestibular stimulation, may seriously interfere with visuomotor performance, but that susceptibility to these disturbances is significantly different between individuals and that partial adaptation occurs relatively quickly.

NASA is currently collecting extensive baseline electroencephalogram data under controlled conditions in a form suitable for mathematical a.n.a.lysis. Data are being taken from about 200 subjects in major national and overseas centers. It is intended that this study will a.s.sist in astronaut selection and monitoring in s.p.a.ce.

Studies on many effects of weightlessness on nervous functions require monitoring of the autonomic nervous system, including such autonomic effects as gastrointestinal activity, secretion, lacrimation, salivation, sweating, and the central control of respiration. Urinary estimations of catecholamines and 5-hydroxyindoleacetic acid would provide important data on autonomic system activity if collected in flight and compared with preflight and postflight controls.

Major areas have been outlined in which prolonged weightlessness may be expected to interfere with performance, judgment, and, ultimately, chances of survival. These include cardiovascular, metabolic, central nervous, psychophysiological, and biorhythmic effects. They have been dealt with separately and in sequence, but have not been intended to be viewed as hierarchic. The relative scarcity of data necessarily precludes such an evaluation.

Soviet experience with zero gravity and weightlessness has increased their emphasis on this s.p.a.ce-flight factor and was an important topic at the May 1964 COSPAR meeting. Discussion of the postflight medical status of Bykovsky (5-day flight) and Tereshkova (3-day flight) revealed a concern for the significance of prolonged weightlessness and the presence of postflight physical debility and fatigue following Vostok flights 3 through 6. These changes persisted for several days. Among the physiological conditions singled out for mention were-

(1) _Body fluids_- Cosmonauts have shown a postflight weight loss of 1.9 to 2.4 kg apparently resulting from a redistribution of body fluid in response to elimination of the hydrostatic pressure gradients caused by Earth gravity. There is the suggestion that this redistribution is complete within the first 24 hours of flight. t.i.tov is reported to have been dehydrated alter his flight with early hemoconcentration. These findings directly support predictions made from ground-based research.

(2) _Cardiovascular_- Postflight orthostatic tachycardia is reported for t.i.tov as long as 23 hours after landing; at 48 hours there was significant residual intolerance to the upright posture.

Cosmonauts have demonstrated a 20- to 35-percent increase in oxygen consumption during the standard postflight exercise test.

In both of these areas there was a return to normal within the postflight period of study. The Soviets have continued their biological experiments in s.p.a.ce with the Vostok/Voshkod series. Fixing of histologic specimens in flight by Bykovsky demonstrated a critical role for man and made possible an expanded experimental program. Biopackages have become more complex with each succeeding flight.

With the exception of postflight orthostatic intolerance after the third and fourth Mercury flights, changes as a result of exposure to a zero-gravity environment have not been noted by U.S. investigations in s.p.a.ce. Ground-based research proceeds here at an advanced pace and is supported in large measure by both the USAF and NASA. A study of the relationships among renal and systemic hemodynamics, neurohumoral cardiovascular regulation, and renal excretory function in differently positioned subjects is underway, as are studies of acceleration tolerance.

DEPRESSED METABOLISM

In antic.i.p.ation of prolonged manned s.p.a.ce flights, NASA has sponsored research related to metabolism depression. The daily food requirements, for example, of astronauts during a voyage of several months can const.i.tute a major portion of the weight and storage capacity of the s.p.a.cecraft. A somewhat promising and fundamental approach to this problem is the reduction of the astronauts' daily metabolic requirements. It has been suggested that astronauts on prolonged s.p.a.ce missions be put in a state of suspended animation until their destination is reached. Though this sounds fantastic, 10 years ago no cell had been frozen to cryogenic temperatures and survived. Today it is commonplace for tissues to be frozen, stored at low temperatures, and thawed and then to maintain their viability and function.

Animal metabolism may be depressed by reducing body temperature, as in hibernation and hypothermia. Other means by which metabolism can be lowered include drugs and electronarcosis. Hibernation is a nonstressful state and results in a great decrease in metabolism. However, human beings are not hibernators, and much research is needed before the mechanism of hibernation is understood, and the possibility of inducing it in humans evaluated. Hypothermia is the direct cooling of the body to temperatures where metabolism is substantially depressed. Extracorporeal circulation systems combined with cooling are in routine use in most medical centers throughout the world. Hypothermia is not an ideal solution, however, since general body hypothermia is a stressful condition. Pharmacologic induction of hypothermia can be accomplished by such drugs as chlorpromazine and harbamil. Other drugs can be used to depress metabolism, but all have some disadvantage.

In recent years there has been a growing interest in electronarcosis, the induction of sleep by an electric current. Although potentially valuable, this method is far from routine application.

Outstanding advances have been made in metabolism suppression. Recent progress in the biochemistry and physiology of hibernation and hypothermia have shown that the oxygen requirements of individual mammals, organs, and tissues can be reduced. When the chemical composition of the blood and the cardiac output are sufficient to meet cellular requirements, regulatory mechanisms remain effective and animal survival is a.s.sured. In contrast, when oxygen transport is interrupted, a reduction in cellular activity occurs and regulation is impaired. In induced hypothermia, the low temperature slows the rates of all processes and modifies the action of metabolites and other substances.

This in itself is not harmful, as shown by the true hibernating animal (e.g., ground squirrel), but will become disastrous as soon as anoxia and chemical imbalance begin to develop.

The phenomenon of natural hibernation is being investigated in the laboratory in the hope that the unusual tolerance of hibernating animals to reduced metabolism and low body temperature may some day be produced artificially in ordinary laboratory animals and man. Experiments with the ground squirrel, a typical hibernator, show that the artificially cooled ground squirrel does not tolerate such long periods of low body temperature as does a naturally hibernating animal.

Other studies of the brown adipose tissue (fat), which is present in most hibernating mammals, show it to be essential to hibernation.

Indications that brown fat has a thermogenic role in rats exposed to low temperatures suggest that this may be the case in true hibernators ([ref.199]). Arousal of the hibernating animal by cold is triggered by sympathetically activated thermogenesis in areas of brown fat so located, relative to the vasculature, that the heat is transferred to areas of the body concerned with normal metabolic and nervous activity.

Soviet work comparing various depressed metabolic states and resistances to acceleration shows deep winter hibernation to be most effective, followed by deep hypothermia, and drug narcosis as the least effective.

Experimental evidence is being acc.u.mulated to show that hibernation and hypothermia somewhat protect animals against radiation. Clinical studies on irradiation of cancer patients indicate that lowering the body temperature reduces cellular metabolism and thus decreases tissue sensitivity to gamma radiation ([ref.200]).

The use of prolonged hypothermia, hibernation, drugs, and electronarcosis appears to hold some potential for reducing astronauts'

metabolic requirements. If one or mote of these methods become practical, human requirements for food and oxygen could be drastically reduced. Simultaneously, these methods may afford radiation protection and acceleration tolerance.

NUTRITION IN s.p.a.cE

Includes part of [ref.201]. See also [ref.202].

The human body can use food stores so that the nutritional requirements can be reduced for a short time. This will vary widely among individuals and each individual may exhibit characteristic patterns of nutritional behavior. During reduced food intake, muscular efficiency may not change significantly over a period of 4 to 6 days; unfortunately, however, mental activity begins to decline after 24 hours. Feeding requirements can be divided into two categories: short term (for missions of less than 21 days) and long term. Since dehydration can occur in a matter of hours under adverse conditions, water requirements must be considered as a special case.

Water Requirements

Water requirements are extremely critical and the amount supplied should not under any circ.u.mstances be kept to a minimum. Rather, a large margin of safety should be allowed.

Present data on water requirements show a very strong dependence upon suit inlet temperatures. In the absence of an accurately controlled suit temperature, water requirements can easily double. If this should occur, the mission would probably have to be aborted, since it is doubtful if electrolyte balance would be maintained at such high rates of water loss. Normal or even extreme conditions of the terrestrial environment usually include diurnal variation in temperature which may modify water needs. These conditions will not be obtained in the s.p.a.cecraft.

In addition to ground-based experiments, measurements of water intake should be made under actual flight conditions. Data from short-term flights should be used for extrapolation to longer missions.

Formula Diets

The tacit a.s.sumption which now prevails, "Astronauts even on short-term missions require a diet of great variety," is apparently not well supported. In many parts of the world, people live on a monotonous diet consisting of only a few types of food with no apparent ill effects, provided their nutritional requirements are satisfied. Experimental evidence from many sources (e.g., the Army Medical Research and Nutrition Laboratory) shows that individuals can be kept on a single disagreeable formula diet for as long as 60 to 90 days without harm.

Since highly motivated individuals are chosen for s.p.a.ce flights, it is unlikely that they would object to the monotony of a formula diet and would probably prefer its simplicity. Also, there are definite possibilities of developing a much more acceptable formula than present types. There is no reason to antic.i.p.ate adverse effects from the use of formula diets in short-term flights.

Formula diets would be extremely desirable for short-term flights. A formula diet (a rehydrated liquid formula could be used) would considerably reduce the number of manipulations and the time required for in-flight preparation, compared to a varied diet. These two improvements could contribute materially to the safety of a flight, since the astronauts would not be preoccupied with food preparation for so long a period, and the food could be dispensed without removing suit components, such as gloves. Storage requirements could be simplified with this type of diet. Weight, however, would not be lowered without the development of more refined formulas than those now available.

Formula diets could readily be adapted to the determined metabolic requirements of the individual astronaut. Packaging problems will be simplified by using formula diets, which can easily be given a variety of flavors and colors.

Waste

The problem of waste production is intimately related to nutrition and can be solved or simplified by dietary changes. Any diet should be adjusted for the minimum production of feces, before and during even short flights. Water will be sequestered by acc.u.mulation in the feces, and the net loss, under normal conditions, would be approximately 40 to 60 grams per man per day. Flatus can be a serious problem, since considerable concentrations of toxic gases may acc.u.mulate. The purification system for the recirculated atmosphere must be able to remove these, although the diet should be planned to minimize the problem. The collection of urine and its storage is of importance, particularly on short-term flights, and individual packaging and labeling of urine specimens will be necessary for the a.n.a.lyses.

Metabolism

An accurately measured intake of nutrients, calories, and water is necessary for determining metabolic demands imposed in any s.p.a.ce flight.

There is insufficient knowledge to predict total metabolic requirements under the numerous stresses which can be antic.i.p.ated. Simulator studies are of great importance even for short-duration flights.

The two most important variables to be considered in establishing the minimal diet are protein and energy requirements. NASA is supporting research at the University of California (Berkeley) to determine these requirements and to estimate individual variation in healthy young men.

The possibility of minimizing need through biological adaptation is being explored.