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Cardiovascular responses to hypogravic environments

The cardiovascular deconditioning observed during and after space flight is characterized in a review of human space and simulation studies and animal simulations. The various simulation techniques (horizontal bed rest, head-down tilt, and water immersion in man, and immobilization of animals) are examined, and sample results are presented in graphs. Countermeasures such as exercise regimens, fluid replacement, drugs, venous pooling, G-suits, oscillating beds, electrostimulation of muscles, lower-body negative pressure, body-surface cooling, and hypoxia are reviewed and found to be generally ineffective or unreliable. The need for future space experimentation in both humans and animals is indicated.

Sandler, H.↗

A laboratory for life sciences research in space

Biological studies hardware for Spacelab flights are described. The research animal holding facility has modular construction and is installed on a single ESA rack. A biotelemetry system will provide body temperature and EKG/heart rate data from a radio transmitter surgically implanted in the animals' stomachs. A plant growth unit (PGU) will be used to study micro-g plant lignin growth. The PGU is automated and can carry as many as 96 plants. A general purpose work station (GPWS) biohazard cabinet will be flown on Spacelab 4 to control liquid and chemical vapors released during experimentation. Spacelab 4 will be the premier flight of actual animal studies comprising measurements of hematology, muscle biochemistry, blood circulation, fluids and electrolytes, vestibular adaptation, etc., using rats and squirrel monkeys as subjects.

Williams, B. A.↗

Gravity, Body Mass and Composition, and Metabolic Rate

Metabolic rate and body composition as a function of sex and age were defined in 5 species of common laboratory mammals, the mouse, hamster, rat, guinea pig and rabbit. Oxygen consumption and carbon dioxide production rates were measured individually in 6 male and 6 female animals for each of 8 age cohorts ranging from 1 month to 2 years, and for each of the species. From the results it is evident that among these small mammals there is no indication of scaling of muscularity to body size, despite the 100-fold difference in body mass represented by the skeletal musculature seems to reach a pronounced peak value at age 2 to 3 months and then declines, the fraction of the fat-free body represented by other body components in older animals must increase complementarily. Under normal gravity conditions muscularity in small laboratory mammals displays large, systematic variation as a function both of species and age. This variation must be considered when such animals are subjects of experiments to study the effects of altered gravitational loading on the skeletal musculature of the mammal.

Nello Pace↗

Gravitational Effects on Reproduction, Growth, and Development of Mammals

The broad objective of this research program is to determine the role which gravity plays in the growth and development of mammalian animals. Current studies are focused on the effects of graded hypergravitatinal field intensities on mice, rats and other small sized laboratory animals using the chronic centrifugation technique. They include studies on reproduction and prenatal and postnatel growth and development. Among the important questions addressed are: (1) what stage or stages in animal development are affected by hypergravity and what are the effects? (2) is there a minimum or critical body size for hypergravity to produce a significant effect on growth and development? (3) are there field intensity thresholds for the preceding questions? From analysis of the body masses at birth of rats conceived and allowed to undergo gestation under 2.1G and under normal gravity (1G), it was found that there was no significant difference between the two groups. Futhermore, their growth rates postnatally were the same until they reached a body mass of approximately 50 grams when the 2.1G group showed a significantly slower rate. Results from these studies support the conclusion that prenatal as well as the early postnatal stages of growth and development of the rat are refractory to hyper-G.

Oyama, J.↗

Increase of plasma renin activity in male and female rabbits subjected to dysbaric conditions

The renin-angiotensin-aldosterone system may be implicated in hemodynamic alterations occurring in dysbaric disorders. This report concerns changes in plasma renin activity (PRA) induced by exposure of rabbits to a compression-decompression schedule that does not normally produce clinical manifestations of decompression sickness. The results revealed a significant increase in PRA in 19 of 23 animals following dysbaric exposure. Mean PRA rose from 1.18 ng ang I/ml hr (preexposure) to 2.40 ng ang I/ml hr (postexposure). The increase was particularly pronounced in female animals (217 percent). Asymptomatic intravascular gas bubbles (silent bubbles) were detected by gross or microscopic examination in the majority of the animals. Renin elaboration and secretion in asymptomatic dysbaric exposures may be mediated by bradykinin and/or prostaglandins released or activated in a chain reaction triggered by silent gas bubbles. This hypothesis is also applicable to increased PRA in altitude decompression. Alternatively elevation of PRA may result from decreased renal perfusion when dysbaric disorders are complicated by significant hypovolemia.

Chryssanthou, C.↗

Core temperature of tailless rats exposed to centrifugation

The role of the tail in the altered thermoregulation of rats during acute exposure to hypergravity was investigated, using groups of rats of two ages: 55 days (young) and 138 days (old). Rectal and foot temperature changes were measured in intact and tailless rats subjected to 1 h centrifugation of 2.8 G, with preceding (1 h) and following (1-3 h) 1 G periods. At 22 C, the loss of body heat from the tail per se does not measurably contribute to the hypothermia induced by hypergravity. However, the heat loss from the feet was greater in the tailless rats than in the intact rats from the young group of animals, although there was no significant difference between the tailless and intact rats in the old animal group. It is concluded that the inhibition of heat production is a significant factor in the hypothermia of centrifuged tailless rats, as it has been previously shown to be in the intact animals.

Monson, C. B.↗

Effects of muscle atrophy on motor control

As a biological tissue, muscle adapts to the demands of usage. One traditional way of assessing the extent of this adaptation has been to examine the effects of an altered-activity protocol on the physiological properties of muscles. However, in order to accurately interpret the changes associated with an activity pattern, it is necessary to employ an appropriate control model. A substantial literature exists which reports altered-use effects by comparing experimental observations with those from animals raised in small laboratory cages. Some evidence suggests that small-cage-reared animals actually represent a model of reduced use. For example, laboratory animals subjected to limited physical activity have shown resistance to insulin-induced glucose uptake which can be altered by exercise training. This project concerned itself with the basic mechanisms underlying muscle atrophy. Specifically, the project addressed the issue of the appropriateness of rats raised in conventional-sized cages as experimental models to examine this phenomenon. The project hypothesis was that rats raised in small cages are inappropriate models for the study of muscle atrophy. The experimental protocol involved: 1) raising two populations of rats, one group in conventional (small)-sized cages and the other group in a much larger (133x) cage, from weanling age (21 days) through to young adulthood (125 days); 2) comparison of size- and force-related characteristics of selected test muscles in an acute terminal paradigm.

Stuart, D. G.↗

Skeletal mass change as a function of gravitational loading

The hypothesis that increased loading on an animal by chronic centrifugation results in an increase in skeletal mass was tested, using metabolically mature hamsters, rats, guinea pigs, Dutch rabbits and New Zealand rabbits representing a body mass range from 0.15 to 3.8 kg. Groups of 12 male animals of each species were subjeted to 2.0 g for 6 weeks on a 2.74 radius centrifuge with one degree of freedom. Subsequently, six of the animals were killed to measure whole body composition, while the rest comprised the control group, recovering for four weeks at 1.0 g prior to composition analysis. Results show a significant increase in bone mineral mass at 2.0 g. These centrifuge experiment results were then compared with the results of the USSR Cosmos Biosatellite experiment, whereby five rats experienced osteoporosis after 18.5 days of weightlessness. The opposing nature of effects that occurred at 0 g and 2.0 g is indicated schematically of particular interest is the fact that the bone mineral mass of the Cosmos 1129 flight rats was 17 pct less than that of the 1.0 g controls; whereas the bone mineral mass of the centrifuge rats was 18 pct greater than that of their 1.0 g controls. It is concluded that the bone mineral mass of the rat is directly proportional to gravitational loading over the range of 0 g to 2.0 g.

Pace, N.↗

Effect of macular ablation on frequency and latency of motion-induced emesis in the squirrel monkey

Three previously motion-emetic sensitive squirrel monkeys were rendered refractory to a standard motion-emetic regimen by a two-stage utriculosacculectomy procedure which preserved the cristae ampullares of semicircular canals. Three nonoperated control squirrel monkeys tested on the same motion-emetic regimen time schedule as the operated animals remained motion-emetic sensitive with regard to incidence, frequency, and latency of motion-induced emetic responses. Following a sham surgical procedure (stapedectomy) performed on two of the latter animals and one additional new animal, the emetic incidence decreased from 100 to 89 percent, but the frequency and latency were not altered significantly.

Brizzee, Kenneth R.↗

Protein turnover in adipose tissue from fasted or diabetic rats

Protein synthesis and degradation in vitro were compared in epididymal fat pads from animals deprived of food for 48 h or treated 6 or 12 days prior with streptozotocin to induce diabetes. Although both fasting and diabetes led to depressed (-24 to -57 percent) protein synthesis, the diminution in protein degradation (-63 to -72 percent) was even greater, so that net in vitro protein balance improved dramatically. Insulin failed to inhibit protein degradation in fat pads of these rats as it does for fed animals. Although insulin stimulated protein synthesis in fat pads of fasted and 12 day diabetic rats, the absolute change was much smaller than that seen in the fed state. The inhibition of protein degradation by leucine also seems to be less in fasted animals, probably because leucine catabolism is slower in fasting. These results show that fasting and diabetes may improve protein balance in adipose tissue but diminish the regulatory effects of insulin.

Tischler, Marc E.↗

Role of glucocorticoids in the response of rat leg muscles to reduced activity

Adrenalectomy did not prevent atrophy of rat soleus muscle during 6 days of tail cast suspension. Cortisol treatment enhanced the atrophy and caused atrophy of the weight-bearing soleus and both extensor digitorum longus (EDL) muscles. Unloading led to increased sarcoplasmic protein concentration in the soleus but cortisol administration increased the myhofibrillar (+stromal) protein concentration in both muscles. Suspension of hindlimbs of adrenalectomized animals led to faster protein degradation, slower sarcoplasmic protein degradation, and faster myofibrillar protein synthesis in the isolated soleus, whereas with cortisol-treated animals, the difference in synthesis of myofibrillar proteins was enhanced and that of sarcoplasmic proteins was abolished. Both soleus and EDL of suspended, cortisol-treated animals showed faster protein degradation. It is unlikely that any elevation in circulating glucocorticoids was solely responsible for atrophy of the soleus in this model, but catabolic amounts of glucocorticoids could alter the response of muscle to unloading.

Jaspers, Stephen R.↗

Need, utilization, and configuration of a large, multi-G centrifuge on the Space Station

A large, multi-g centrifuge is required on the Space Station (1) to provide valid 1-g controls for the study of zero-g effects on animals and plants and to study readaptation to 1 g; (2) to store animals at 1 g prior to short-term zero-g experimentation; (3) to permit g-level threshold studies of gravity effects. These requirements can be met by a 13-ft-diam., center-mounted centrifuge, on which up to 48 modular habitats with animals (squirrel monkey, rat, mouse) and plants are attached. The advantages of locating this centrifuge with the vivarium, a common environmental control and life support system, a general-purpose work station and storage of food, water, and supplies in an attached short module, are elaborated. Servicing and operation of the centrifuge, as well as minimizing its impact on other Space Station functions are also considered.

Bonting, Sjoerd L.↗

The Franco-American macaque experiment

The details of studies to be carried out jointly by French and American teams on two rhesus monkeys prepared for future experiments aboard the Space Shuttle are discussed together with the equipment involved. Seven science discipline teams were formed, which will study the effects of flight and/or weightlessness on the bone and calcium metabolism, the behavior, the cardiovascular system, the fluid balance and electrolytes, the muscle system, the neurovestibular interactions, and the sleep/biorhythm cycles. New behavioral training techniques were developed, in which the animals were trained to respond to behavioral tasks in order to measure the parameters involving eye/hand coordination, the response time to target tracking, visual discrimination, and muscle forces used by the animals. A large data set will be obtained from different animals on the two to three Space Shuttle flights; the hardware technologies developed for these experiments will be applied for primate experiments on the Space Station.

Cipriano, Leonard F.↗

Proceedings of a conference on Cardiovascular Bioinstrumentation

The Ames Research Center (ARC) has a long history in the development of cardiovascular (CV) instrumentation for human and animal research. The ARC Cardiovascular Research Lab under the Space Physiology Branch, Space Research Directorate, supports both ground-based and space-based animal and human research goals. The Cardiovascular Research Laboratory was established at ARC in the mid 1960's to conduct ground-based animal research and support development of advanced cardiovascular instrumentation applicable to spaceflight. The ARC Biomedical Research Program also conducts human studies with a CV instrumentation focus.

Ballard, Rodney W.↗

Using an instrumented manikin for Space Station Freedom analysis

One of the most intriguing and complex areas of current computer graphics research is animating human figures to behave in a realistic manner. Believable, accurate human models are desirable for many everyday uses including industrial and architectural design, medical applications, and human factors evaluations. For zero-gravity (0-g) spacecraft design and mission planning scenarios, they are particularly valuable since 0-g conditions are difficult to simulate in a one-gravity Earth environment. At NASA/JSC, an in-house human modeling package called PLAID is currently being used to produce animations for human factors evaluation of Space Station Freedom design issues. Presented here is an introductory background discussion of problems encountered in existing techniques for animating human models and how an instrumented manikin can help improve the realism of these models.

Orr, Linda↗

Software systems for modeling articulated figures

Research in computer animation and simulation of human task performance requires sophisticated geometric modeling and user interface tools. The software for a research environment should present the programmer with a powerful but flexible substrate of facilities for displaying and manipulating geometric objects, yet insure that future tools have a consistent and friendly user interface. Jack is a system which provides a flexible and extensible programmer and user interface for displaying and manipulating complex geometric figures, particularly human figures in a 3D working environment. It is a basic software framework for high-performance Silicon Graphics IRIS workstations for modeling and manipulating geometric objects in a general but powerful way. It provides a consistent and user-friendly interface across various applications in computer animation and simulation of human task performance. Currently, Jack provides input and control for applications including lighting specification and image rendering, anthropometric modeling, figure positioning, inverse kinematics, dynamic simulation, and keyframe animation.

Phillips, Cary B.↗

Experiment K-6-03. Gravity and skeletal growth, part 1. Part 2: Morphology and histochemistry of bone cells and vasculature of the tibia; Part 3: Nuclear volume analysis of osteoblast histogenesis in periodontal ligament cells; Part 4: Intervertebral disc swelling pressure associated with microgravity

Bone area, bone electrophysiology, bone vascularity, osteoblast morphology, and osteoblast histogenesis were studied in rats associated with Cosmos 1887. The results suggest that the synchronous animals were the only group with a significantly larger bone area than the basal group, that the bone electrical potential was more negative in flight than in the synchronous rats, that the endosteal osteoblasts from flight rats had greater numbers of transitional Golgi vesicles but no difference in the large Golgi saccules or the alkaline phosphatase activity, that the perioteal vasculature in the shaft of flight rats often showed very dense intraluminal deposits with adjacent degenerating osteocytes as well as lipid accumulations within the lumen of the vessels and sometimes degeneration of the vascular wall (this change was not present in the metaphyseal region of flight animals), and that the progenitor cells decreased in flight rats while the preosteoblasts increased compared to controls. Many of the results suggest that the animals were beginning to recover from the effects of spaceflight during the two day interval between landing and euthanasia; flight effects, such as the vascular changes, did not appear to recover.

Holton, E.↗

Atrophy of the soleus muscle by hindlimb unweighting

This paper reviews data derived from the animal hindlimb unweighting model. The review presents the following information about the unweighted soleus muscle: electromyogram activity, the amount and type of protein lost, capillarization, oxidative capacity, glycolytic enzyme activities, fiber cross section, contractile properties, glucose uptake, sensitivity to insulin, the rates of protein synthesis and degradation, the glucocorticoid receptor numbers, the responses of specific mRNAs, and changes in metabolic concentrations. Data of all these studies show that the stress response of the animal to hindlimb suspension is transient and minimal in magnitude (though somewhat variable) and that, after one week of unweighting, the animal exhibits no chronic signs of stress.

Thomason, Donald B.↗