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Research during the period 1 Oct. 1971 to 1 Oct. 1972 is reported. Studies discussed include: development of techniques for instrumentation of dogs and other animals, effects of temporary application of lower body negative pressure, and effect of infusing selected drugs on ventricular performance.
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Zippered tubing and rotating wheel dispense food pellets reliably without contamination.
A completely enclosed module was constructed for continuously maintaining an unanesthetized adult 10-12 kg monkey in a physiologically stable state of comfortable restraint for periods of at least 10 days, either on the ground or in an orbiting spacecraft. Energy balance determinations made during three different tests using a giant rhesus (malaca nemestrina) are presented in charts and graphs.
Instrumentation and life support systems are described for an experiment to determine the physiological effects of long term space flight on unrestrained, minimally instrumented rhesus macaques flown in orbit for periods up to six months or one year. On return from orbit, vestibular, cardiovascular, and skeletal muscle function will be tested. Blood chemistry and hematological studies will be conducted as well as tests of the immunological competence of selected animals. Nasal, rectal, and throat swabs will be used for bacterial and viral studies, and histopathological and histochemical investigations will be be made of all organs using light and electron microscopy. The experiment is being considered as a payload for the biomedical experiment scientific satellite.
The validity of biomedical research using animal subjects is highly dependent on the use of 'normal' and healthy animals. The current costs of research programs dictate that a minimum number of animals and test replicates be used to obtain the desired data. The use of healthy and standardized animals increases the probability of obtaining valid data while also permitting greater economy by reducing the between-individual variation, thus allowing the use of fewer animals. Areas of concern when planning animal payloads include constraints of the flight on candidate species selection, screening for physiological and psychological normalcy, procedures for routine care and quarantine of new animals and those returning from space, ground-based studies to determine experimental protocol, selection of instrumentation, stress during transportation for flight operations, housing and care facilities at launch and recovery sites, and the overall veterinary program.
It is a well-documented fact that cycles of light and dark (LD) are the major entraining agent or 'zeitgeber' for circadian rhythms and that cycles of eating and fasting (EF) are capable of synchronizing a few circadian rhythms in the squirrel monkey. In this paper, by contrasting how these rhythms are timed by LD and EF cycles, the differential coupling to the oscillating system within adult male squirrel monkeys is examined. The variables measured are the rhythms of drinking, colonic temperature, and urinary potassium and water excretion. Attention is given to a comparison of the reproducibility of the averaged waveforms of the rhythms, the stability of the timing of a phase reference point, and the rate of resynchronization of these rhythms following an abrupt 8-hr phase delay in the zeitgeber. It is shown that the colonic temperature rhythm is more tightly controlled by LD than EF cycles, and that the drinking and urinary rhythms are more tightly coupled to EF than LD cycles.
A 14 day ground based hypokinesia study with rhesus monkeys was conducted to determine if a spaceflight of similar duration might affect bone remodeling and calcium homeostatis. The monkeys were placed in total body casts and sacrificed either immediately upon decasting or 14 days after decasting. Changes in vertebral strength were noted and further deterioration of bone strength continued during the recovery phase. Resorption in the vertebrae increased dramatically while formation decreased. Cortical bone formation was impaired in the long bones. The immobilized animals showed a progressive decrease in total serum calcium which rebounded upon remobilization. Most mandibular parameters remained unchanged during casting except for retardation of osteon birth or maturation rate and density distribution of matrix and mineral moieties.
The renal and hemodynamic responses of squirrel monkeys to central vascular volume expansion induced by lower body positive pressure (LBPP) during the day and night are investigated. Twelve unanesthetized animals trained to sit in a metabolism chair in which they were restrained only at the waist by a partition separating upper and lower body chambers were subjected to 4 h of continuous LBPP during the day and night, and hemodynamic, urinary and drinking data were monitored. LBPP during day and night is found to induce similar increases in central venous pressure, rises in heart rate and elevations in mean arterial blood pressure. However, although daytime LBPP induced a significant increase in urine flow and sodium excretion, a marked nocturnal inhibition of the renal response to LBPP is observed. Analysis of the time course and circadian regulation patterns of the urinary responses suggests that several separate efferent control pathways are involved.
Central vascular expansion maintained for four days in conscious squirrel monkeys reconciles the apparently conflicting short-term fluid and electrolyte responses to water immersion and atrial balloon distension, with those described for prolonged weightlessness during space flight. The monkeys are subjected to an increased lower body positive air pressure (LBPP) of 20 torr which produces a 3 cm water increase in the central venous pressure. Results show a marked increase in the urinary excretion of sodium, potassium, and water during the firxt six hours of LBPP, and the diuresis is maintained throughout the period of LBPP, although the levels of sodium and potassium excretion decline after 24 hours of exposure. Plasma aldosterone transiently drops within the first three hours of LBPP, and then regains normal levels within 24 hours, after which time these levels are maintained despite the continued LBPP stimulus. It is suggested that the normal plasma aldosterone levels observed in the experiments, as well as during space flight, might, epresent a relative hyposecretion in terms of volume homeostasis and a relative hypersecretion with respect to plasma potassium regulation. Thus, kaliuresis and marked natriuresis is confined primarly to the first 24 hours of central volume expansion, a period for which comparable data from space flights are lacking.
A squirrel monkey feeder and automatic urine collection system were designed to fly on the Spacelab 4 Shuttle Mission presently scheduled for January 1986. Prototypes of the feeder and urine collection systems were fabricated and extensively tested on squirrel monkeys at the National Aeronautics and Space Administration's (NASA) Ames Research Center (ARC). The feeder design minimizes impact on the monkey's limited space in the cage and features improved reliability and biocompatibility over previous systems. The urine collection system is the first flight qualified, automatic urine collection device for squirrel monkeys. Flight systems are currently being fabricated.
In connection with studies regarding the hazards posed by ionizing radiations to man in space, the U.S. Air Force conducted an experiment about 20 years ago. In this experiment a large number of young rhesus monkeys was exposed to proton fluxes similar to those to be anticipated during solar flares. After irradiation, the animals were kept at the USAF School of Aerospace Medicine in Texas. The monkeys have been employed in investigations concerning aspects of late radiation damage. These investigations are discussed, taking into account the propagation of fibroblasts from irradiated monkeys. The results of the investigations are evaluated, giving attention also to experiments with white rabbits. It is found that, except in the case of major solar flares, when acute radiation damage could lead quickly to death, the hazards to astronauts from space radiations arise from such debilitating late effects as cataracts, damage to the central nervous system and benign tumors, and life-threatening neoplasia.
The effect of hyperdynamic field (12 d at 1.5 G and 35 d at 2.0 G phases, preceded and followed by 1.0 G phases of 15 and 18 days, respectively) on the circadian rhythm in the feeding and drinking of the squirrel monkey was studied. Two lighting regimens were employed: (1) the 24-hr light-dark cycle (LD 12:12) at all G phases and (2) constant light (LL) during the two 1.0 G phases and a 2.0 G phase. In the LD regimen, both feeding and drinking rhythms were entrained with the 24-hr periods at all G levels, but a phase delay occurred in high G environment. In the LL regimen, the rhythm persisted with a free-running period greater than 24 hours and an increase at 2.0 G, compared to the 1.0 G phases. Thus, although the circadian rhythm is functional at high G, some of its components appear to be regulated at different homeostatic levels.
Osteopenic changes in the tibial compact bone of fifteen adult male monkeys immobilized for up to 7 months are examined histologically. Osteonal formation in the proximal tibia is analyzed. The analysis reveals the loss of haversian bone in the proximal tibia, increased activation with excessive depth of penetration of osteoclastic activity, rapid bone loss, and resorption cavities of irregular size and orientation. Osteonal formation following reambulation is examined; the recovery of cortical is a repair and rejuvenation process characterized by refilling of resorption cavities and remodeling activities.
Serial high-contrast radiographs were obtained of both arms and the right leg of two flight and four control monkeys for the period L-60 to S+16. Longitudinal growth of the tibia, radius and ulna was linear over this period in the control monkeys. In the flight monkey for whom the feeder malfunctioned, there were significant decreases in growth of the long bones. There were also hypermineralized growth arrest lines produced in the distal radial and ulnar metaphyses following resumption of growth. In the other flight monkey, there was a suggestion of decreased long bone growth during flight and immediate postflight periods, but this recovered by the end of the postflight control experiment. There was also an increase in intracortical resorption, indicative of skeletal activation. No major changes in cortical thickness or other parameters were noted, but modification of the techniques to obtain very high quality radiographs in further studies should allow subtle changes in these processes to be quantified.
Although it is now well accepted that exposure to the hypogravic environment of space induces a shift of fluid from the lower extremities toward the upper body, the actual physiological responses to this central volume expansion have not been well characterized. Because it is likely that the fluid and electrolyte response to hypogravity plays a critical role in the development of Cardiovascular Deconditioning, elucidation of these mechanisms is of critical importance. The goal of flight experiment 223, scheduled to fly on SLS-2, is the definition of the basic renal, fluid and electrolyte response to spaceflight in four instrumented squirrel monkeys. The studies were those required to support the development of flight hardware and optimal inflight procedures, and to evaluate a ground-based model for weightlessness, lower body positive pressure (LBPP).
Experimental studies of the role of vestibular end organs in motion sickness experienced by squirrel monkeys are reviewed. The first experiments in motion-sickness-susceptible squirrel monkeys were performed under a free-moving condition with horizontal rotation and vertical oscillation. In the following experiments, the vestibular-visual conflict in the pitch plane was given to the chair-restrained (upright position) squirrel monkeys. Results of this study showed that the existence of otolith afferents, which continually signal the directional change of gravity and linear acceleration vectors, was necessary for the elicitation of emesis by the sensory conflict in pitch.