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Double high-pressure chamber for chronic exposure of small animals whose design facilitates nutritional needs and waste products exchange without decompressing animals
Chronic hypoxia exposure effect on development and maintenance of renal hypertension in rats
The effects of chronic centrifugation on body composition and growth of rats, mice, monkeys, and man are studied. The benefits of exercise and restraint during acceleration are investigated. Physiological regulation and energy balance are also discussed.
In studies to determine the neurochemical mechanisms underlying adaptation to altered gravity we have investigated changes in neuropeptide levels in brainstem, cerebellum, hypothalamus, striatum, hippocampus, and cerebral cortex by radioimmunoassay. Fourteen days of hypergravity (hyperG) exposure resulted in significant increases in thyrotropin-releasing hormone (TRH) content of brainstem and cerebellum, but no changes in levels of other neuropeptides (beta-endorphin, cholecystokinin, met-enkephalin, somatostatin, and substance P) examined in these areas were found, nor were TRH levels significantly changed in any other brain regions investigated. The increase in TRH in brainstem and cerebellum was not seen in animals exposed only to the rotational component of centrifugation, suggesting that this increase was elicited by the alteration in the gravitational environment. The only other neuropeptide affected by chronic hyperG exposure was met-enkephalin, which was significantly decreased in the cerebral cortex. However, this alteration in met-enkephalin was found in both hyperG and rotation control animals and thus may be due to the rotational rather than the hyperG component of centrifugation. Thus it does not appear as if there is a generalized neuropeptide response to chronic hyperG following 2 weeks of exposure. Rather, there is an increase only of TRH and that occurs only in areas of the brain known to be heavily involved with vestibular inputs and motor control (both voluntary and autonomic). These results suggest that TRH may play a role in adaptation to altered gravity as it does in adaptation to altered vestibular input following labyrinthectomy, and in cerebellar and vestibular control of locomotion, as seen in studies of ataxia.
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A honey bee colony (Apis mellifera L.) was exposed 28 days to 2.45 GHz continuous wave microwaves at a power density (1 mW/sq cm) expected to be associated with rectennae in the solar power satellite power transmission system. Differences found between the control and microwave-treated colonies were not large, and were in the range of normal variation among similar colonies. Thus, there is an indication that microwave treatment had little, if any, effect on (1) flight and pollen foraging activity, (2) maintenance of internal colony temperature, (3) brood rearing activity, (4) food collection and storage, (5) colony weight, and (6) adult populations. Additional experiments are necessary before firm conclusions can be made.
Spacecraft and space stations, similar to other habitable confined spaces such as submarines, need to provide a breathable atmosphere for their inhabitants. The inevitable production of CO2 during respiration necessitates life support systems that "scrub" the atmosphere and lower CO2 levels. Due to operational limitations associated with space flight (limited mass, volume, power, and consumables) CO2 is not scrubbed down to its terrestrial equivalent of 0.03% CO2 (ppCO2 of 0.23 mmHg), but is kept below 0.7% (ppCO2 of 5.3 mmHg), a level established in NASA s 180-day mission Spacecraft Maximum Allowable Concentration (SMAC) to be safe and unlikely to cause symptoms. Reports of space flight crewmembers becoming symptomatic with headaches, fatigue, and malaise at levels below those known to cause such symptoms terrestrially has prompted studies measuring the levels of CO2 on both the space shuttle and the space station. Data from cabin atmosphere sampling were collected on space shuttle missions STS-113, STS-122, STS-123, and International Space Station Expeditions 12-15 and 17, and the measured CO2 levels were then correlated to symptoms reported by the crew. The results indicate that a correlation exists between CO2 levels and symptomatology, however causality cannot be established at this time. While the short-term effects of elevated CO2 exposure are well known terrestrially, less is known regarding potential long-term effects of prolonged exposure to a CO2-rich environment or how the physiological changes caused by microgravity may interact with such exposures. Other challenges include limitations in the CO2 monitors used, lack of convection in the microgravity environment, and formation of localized CO2 pockets. As it is unclear if the unique environment of space increases sensitivity to CO2 or if other confounding factors are present, further research is planned to elucidate these points. At the same time, efforts are underway to update the SMAC to a lower level
Radioactive contamination of the environment occurred in the early fifties as a result of the releases from the Mayak plutonium production complex (Southern Urals, Russia). The releases of liquid wastes into the Techa river resulted in chronic exposure of 30,000 residents of the riverside communities. Since 1951 90Sr body burdens have been measured for over half of this cohort. This paper presents the analysis of data on 90Sr in humans and describes the reconstruction of internal doses for these people.
When inadequately protected humans are exposed to acute cold, excessive body heat is lost to the environment and unless heat production is increased and heat loss attenuated, body temperature will decrease. The primary physiological responses to counter the reduction in body temperature include marked cutaneous vasoconstriction and increased metabolism. These responses, and the hazards associated with such exposure, are mediated by a number of factors which contribute to heat production and loss. These include the severity and duration of the cold stimulus; exercise intensity; the magnitude of the metabolic response; and individual characteristics such as body composition, age, and gender. Chronic exposure to a cold environment, both natural and artificial, results in physiological alterations leading to adaptation. Three quite different, but not necessarily exclusive, patterns of human cold adaptation have been reported: metabolic, hypothermic, and insulative. Cold adaptation has also been associated with an habituation response, in which there is a desensitization, or damping, of the normal response to a cold stress. This review provides a comprehensive analysis of the human physiological and pathological responses to cold exposure. Particular attention is directed to the factors contributing to heat production and heat loss during acute cold stress, and the ability of humans to adapt to cold environments.
The effects of simulated microgravity (via the use of a slowly rotating clinostat), altered orientation (via alterations in the vector of a 1-g force), and hypergravity (via centrifugation) on the circadian rhythm of conidiation in Neurospora crassa were investigated. It was found that the clinostat, while capable of producing some of the microgravity effects seen in space (Sulzman, 1984), did not produce major repeatable results. Similarly, alterations of the vector of a 1-g gravity load were not adequate simulations of space flight on the conidiation rhythm. The results on the acute and chronic exposures to hypergravity demonstrated that chronic exposure of Neurospora to a 3-g force had no damping effect. On the other hand, an acute 10-min exposure to this hypergravity (the lift-off conditions) was found to cause significant damping on the circadian rhythm of conidiation. This effect was eliminated by a brief light pulse given 36 hrs after the exposure to 3 g.
Chronic centrifugation of 85- to 92-day-old Beagles at 2.0 x g and 2.6 x g for 26 weeks during the time of active skeletal growth caused skeletal abnormalities in the radius and the ulna of ten of 11 dogs. The pattern of change mimicked that found in naturally occurring and experimentally induced premature distal ulnar physeal closure or delayed growth at this physis. Minimal changes in bone density were detected by sensitive photon absorptiometric techniques. Skeletal abnormalities also were found in five of the six cage-control dogs, although the run-control dogs were radiographically normal.
The study examines intestinal transport of sugars (D-glucose and D-galactose) in vitro and assesses organ maintenance in chronically heat-exposed rats. The results suggest that the response of intestinal absorption to heat exposure in the rat involves changes in intestinal weight and in glucose utilization. Despite the reduction in total intestinal weight, the ability of intestinal tissue to transport hexose per unit weight remains stable. Differences in intestinal weight and glucose utilization between pair-fed and heat-exposed animals suggest that the intestinal response to chronic heat exposure is not solely a function of the amount of food consumed. Alterations of hexose transport appear to be related to altered glucose metabolism and not altered transport capacity.
As a ground-based model for weightlessness, the response of the chair-trained squirrel monkey to lower body positive pressure (LBPP) was evaluated in a length of study similar to a typical Space Shuttle mission (7 days). Results were compared to time control experiments that included chair-sitting without exposure to LBPP. Chronic exposure to LBPP results in an acute diuretic and natriuretic response independent of changes in plasma aldosterone concentrations and produces a chronic reduction in fluid volume lasting the duration in the stimulus.
Rhode Island Red female chicks at 2 weeks posthatch were subjected, for 7 d, to either earth gravity of 1 G or a 2-G hypergravity environment by chronic whole-body centrifugation. Animals were sacrificed at 3 weeks posthatch and the eyes were enucleated, fixed in 10% BNF, doubly embedded, sectioned at 7-8 microns and routinely processed with H & E for histological examination. Compared to normogravity controls, animal exposure for 1 week to the chronic effects of 2-G resulted in a significantly decreased mean width of the photoreceptor, inner nuclear, and inner plexiform retinal layers. The outer nuclear, outer plexiform, and ganglion cell layers of the retina appeared minimally affected by the hypergravity state since the mean width of these layers showed no noticeable differences from earth gravity control animals. The present anatomic findings suggest a reduction in the detection of motion or rapid changes in illumination by the avian retina when the animal is exposed at a 2-G environment.
On the Space Shuttle the mean CO2 levels have been 0.3% which is ten times normal air, while there have been extended periods with mean levels of 0.7% and peak concentrations of 2%. On the Space Station the projected mean concentration of CO2 is 0.7% and not to exceed 1.0%. To ensure that high level of CO2 does not compromise the integrity of the science on the Space Station, the effects of chronic exposure to high levels of CO2 were investigated. Following 7 days of cage adaptation animals exposed to 2% CO2 for 30 days were compared to control (ambient air) animals and the effects on the well-being, growth and renal function analyzed. Ten male rats per group were placed in individual metabolic cages which allowed monitoring of daily food and water consumption, as well as feces and urine to be collected. Cages were placed in a plexiglass chamber with internal environment controlled by a computer in conjunction with gas sensors. The elevated CO2 was held constant at 2.0 +/- 0.03% and the O2 at 20.9 +/- 0.15%. Body weight and food and water intake were measured daily for the first ten days of exposure and then every three to four days for the remaining three weeks. Urine was measured for pH, CO2 (as an indicator for bicarbonate) and ammonia (as an indicator for ammonium). During 2% CO2 exposure, animal growth, weight, food and water consumption were within normal ranges suggesting that their well-being was not affected. Urine pH decreased from 7.12 to 6.77 over the first 6 days of exposure and increased the following 24 days returning to pre-exposure levels. Urine NH4+ increased 68% the first 6 days then dropped to and remained at 29% higher than pre-exposure level. Urine bicarbonate concentration did not change the first 6 days, but significantly increased by day 30. These results of chronic exposure to 2% C02 are consistent with renal compensation for respiratory acidosis which may impact science conducted on the Space Shuttle or the Space Station if CO2 levels reach 2%.
The overarching objective of this project was to identify changes in neural and biochemical systems of the central and peripheral nervous systems (the CNS and PNS) that are related to disruptions of functional motor responses, or motor control. The identification of neural and biochemical changes that are related to sensory-motor adaptation elicited as animals react to changes in the gravitational field was of particular interest. Thus, the major objective of this work was to study disruptions of motor responses that arise after (sic. due to) chronic exposure to altered gravity (G). To do this, parallel studies investigating changes in neural, sensory, and neuromuscular systems were conducted after animals (rats) experienced chronic exposure to conditions of altered-G. Conditions of altered-G included hyper-G produced by centrifugation, micro-G produced by orbital flight, and simulated micro-G produced by hind limb suspension. A second major interest was to examine the contribution of putative changes in sensory systems to disruptions of motor responses. To do this, motor responses and reflexes of rats were studied following chronic treatment with streptomycin sulfate (STP, an ototoxic chemical) to damage the vestibular hair cells.
Arterial regions exposed to oscillatory shear (OS) in branched arteries are lesion-prone sites of atherosclerosis, whereas those of laminar shear (LS) are relatively well protected. Here, we examined the hypothesis that OS and LS differentially regulate production of O2- from the endothelial NAD(P)H oxidase, which, in turn, is responsible for their opposite effects on a critical atherogenic event, monocyte adhesion. We used aortic endothelial cells obtained from C57BL/6 (MAE-C57) and p47phox-/- (MAE-p47-/-) mice, which lack a component of NAD(P)H oxidase. O2- production was determined by dihydroethidium staining and an electron spin resonance using an electron spin trap methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine. Chronic exposure (18 h) to an arterial level of OS (+/- 5 dynes/cm2) increased O2- (2-fold) and monocyte adhesion (3-fold) in MAE-C57 cells, whereas chronic LS (15 dynes/cm2, 18 h) significantly decreased both monocyte adhesion and O2- compared with static conditions. In contrast, neither LS nor OS were able to induce O2- production and monocyte adhesion to MAE-p47-/-. Treating MAE-C57 with a cell-permeable superoxide dismutase compound, polyethylene glycol-superoxide dismutase, also inhibited OS-induced monocyte adhesion. In addition, over-expressing p47phox in MAE-p47-/- restored OS-induced O2- production and monocyte adhesion. These results suggest that chronic exposure of endothelial cells to OS stimulates O2- and/or its derivatives produced from p47phox-dependent NAD(P)H oxidase, which, in turn, leads to monocyte adhesion, an early and critical atherogenic event.
Spaceflight induces changes in human renal function, suggesting similar changes may occur in rats. Since rats continue to be the prime mammalian model for study in space, the effects of chronic microgravity on rat renal function should be clarified. Acute studies in rats using the ground-based microgravity simulation model, head-down tilt (HDT), have shown increases in glomerular filtration rate (GFR), electrolyte excretion, and a diuresis. However, long term effects of HDT have not been studied extensively. This study was performed to elucidate rat renal function following long-term simulated microgravity. Chronic exposure to HDT will cause an increase in GFR and electrolyte excretion in rats, similar to acute exposures, and lead to a decrease in the fractional excretion of filtered electrolytes. Experimental animals (HDT, n=10) were tail-suspended for 37 days and renal function compared to ambulatory controls (AMB, n=10). On day 37 of HDT, GFR, osmolal clearance, and electrolyte excretion were decreased, while plasma osmolality and free water clearance were increased. Urine output remained similar between groups. The fractional excretion of the filtered electrolytes was unchanged except for a decrease in the percentage of filtered calcium excreted. Chronic exposure to HDT results in decreased GFR and electrolyte excretion, but the fractional excretion of filtered electrolytes remained primarily unaffected.