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At least 1,063 records · Page 59

Sensor Systems for Space Life Sciences

Sensors 2000! (S2K!) is a NASA Ames Research Center engineering initiative designed to provide biosensor and bio-instrumentation systems technology expertise to NASA's life sciences spaceflight programs. S2K! covers the full spectrum of sensor technology applications, ranging from spaceflight hardware design and fabrication to advanced technology development, transfer and commercialization. S2K! is currently developing sensor systems for space biomedical applications on BION (a Russian biosatellite focused on Rhesus Monkey physiology) and NEUROLAB (a Space Shuttle flight devoted to neuroscience). It's Advanced Technology Development-Biosensors (ATD-B) project focuses efforts in five principle areas: biotelemetry Systems, chemical and biological sensors, physiological sensors, advanced instrumentation architectures, and data and information management. Technologies already developed and tested included, application-specific sensors, preamplifier hybrids, modular programmable signal conditioners, power conditioning and distribution systems, and a fully implantable dual channel biotelemeter. Systems currently under development include a portable receiver system compatible with an off-the-shelf analog biotelemeter, a 4 channel digital biotelemetry system which monitors pH, a multichannel, g-processor based PCM biotelemetry system, and hand-held personal monitoring systems. S2K! technology easily lends itself to telescience and telemedicine applications as a front-end measurement and data acquisition device, suitable for obtaining and configuring physiological information, and processing that information under control from a remote location.

Somps, Chris J.↗

Telemetric Sensors for the Space Life Sciences

Telemetric sensors for monitoring physiological changes in animal models in space are being developed by NASA's Sensors 2000! program. The sensors measure a variety of physiological measurands, including temperature, biopotentials, pressure, flow, acceleration, and chemical levels, and transmit these signals from the animals to a remote receiver via a wireless link. Thus physiologic information can be obtained continuously and automatically without animal handling, tethers, or percutaneous leads. We report here on NASA's development and testing of advanced wireless sensor systems for space life sciences research.

Hines, John W.↗

Research on the Effects of Fatigue within the Corporate/Business Aircraft Environment

In 1980, responding to a Congressional request, NASA Ames Research Center created a program to examine whether 'there is a safety problem of uncertain magnitude, due to transmeridian flying and a potential problem due to fatigue in association with various factors found in air transport operations.' The NASA Ames Fatigue/Jet Lag Program was created to collect systematic, scientific information on fatigue, sleep, circadian rhythms, and performance in flight operations. Three Program goals were established and continue to guide research efforts to: (1) determine the extent of fatigue, sleep loss, and circadian disruption in flight operations; (2) determine the impact of these factors on flight crew performance; (3) develop and evaluate countermeasures to mitigate the adverse effects of these factors and maximize flight crew performance and alertness. Since 1980, studies have been conducted in a variety of aviation environments, in controlled laboratory environments, as well as in a full-mission flight simulation. Early studies included investigations of short-haul, long-haul, and overnight cargo flight crews. In 1991, the name of the program was changed to the Fatigue Countermeasures Program to provide a greater emphasis on the development and evaluation of countermeasures. More recent work has examined the effects of planned cockpit rest as an operational countermeasure and provided analyses of the pertinent sleep/duty factors preceding an aviation accident at Guantanamo Bay, Cuba. The Short-Haul study examined the extent of sleep loss, circadian disruption, and fatigue engendered by flying commercial short-haul air transport operations (flight legs less than eight hours). This was one of the first field studies conducted by the NASA program and provided unique insight into the physiological and subjective effects of flying commercial short-haul operations. It demonstrated that a range of measures could be obtained in an operational environment without disturbing the regular performance of duties. The Long-Haul study examined how long-haul flight crews organized their sleep during a variety of international trip patterns and examined how duty requirements, local time, and the circadian system affected the timing, duration, and quality of sleep. Duty requirements and local time can be viewed as external/environmental constraints on time available for sleep, while the internal circadian system is a major physiological modulator of sleep duration and quality. The Overnight Cargo study documented the psychophysiological effects of flying overnight cargo operations. The data collected clearly demonstrated that overnight cargo operations, like other night work, involve physiological disruption not found in comparable daytime operations.

Neri, David F.↗

Space Biosensor Systems: Implications for Technology Transfer

To meet the need for continuous, automated monitoring of animal subjects, including; humans, during space flight, NASA is developing advanced physiologic sensor and biotelemetry system technologies. The ability to continuously track basic physiological parameters, such as heart rate, blood pH, and body temperature, in untethered subjects in space is a challenging task. At NASA's Ames Research Center, where a key focus is gravitational biology research, engineers have teamed with life scientists to develop wireless sensor systems for automated physiologic monitoring of animal models as small as the rat. This technology is also being adapted, in collaboration with medical professionals, to meet human clinical monitoring needs both in space and on the ground. Thus, these advanced monitoring technologies have important dual-use functions; they meet space flight data collection requirements and constraints, while concurrently addressing a number of monitoring and data acquisition challenges on the ground in areas of clinical monitoring and biomedical research. Additional applications for these and related technologies are being sought and additional partnerships established that enhance development efforts, reduce costs and facilitate technology infusion between the public and private sectors. This paper describes technology transfer and co-development projects that have evolved out of NASA's miniaturized, implantable chemical sensor development efforts.

Hines, J. W.↗

Crew Factors in Flight Operations X: Alertness Management in Flight Operations

In response to a 1980 congressional request, NASA Ames Research Center initiated a Fatigue/Jet Lag Program to examine fatigue, sleep loss, and circadian disruption in aviation. Research has examined fatigue in a variety of flight environments using a range of measures (from self-report to performance to physiological). In 1991, the program evolved into the Fatigue Countermeasures Program, emphasizing the development and evaluation of strategies to maintain alertness and performance in operational settings. Over the years, the Federal Aviation Administration (FAA) has become a collaborative partner in support of fatigue research and other Program activities. From the inception of the Program, a principal goal was to return the information learned from research and other Program activities to the operational community. The objectives of this Education and Training Module are to explain what has been learned about the physiological mechanisms that underlie fatigue, demonstrate the application of this information in flight operations, and offer some specific fatigue countermeasure recommendations. It is intended for all segments of the aeronautics industry, including pilots, flight attendants, managers, schedulers, safety and policy personnel, maintenance crews, and others involved in an operational environment that challenges human physiological capabilities because of fatigue, sleep loss, and circadian disruption.

Rosekind, Mark R.↗

The Efficacy of Using Synthetic Vision Terrain-Textured Images to Improve Pilot Situation Awareness

The General Aviation Element of the Aviation Safety Program's Synthetic Vision Systems (SVS) Project is developing technology to eliminate low visibility induced General Aviation (GA) accidents. SVS displays present computer generated 3-dimensional imagery of the surrounding terrain on the Primary Flight Display (PFD) to greatly enhance pilot's situation awareness (SA), reducing or eliminating Controlled Flight into Terrain, as well as Low-Visibility Loss of Control accidents. SVS-conducted research is facilitating development of display concepts that provide the pilot with an unobstructed view of the outside terrain, regardless of weather conditions and time of day. A critical component of SVS displays is the appropriate presentation of terrain to the pilot. An experimental study is being conducted at NASA Langley Research Center (LaRC) to explore and quantify the relationship between the realism of the terrain presentation and resulting enhancements of pilot SA and performance. Composed of complementary simulation and flight test efforts, Terrain Portrayal for Head-Down Displays (TP-HDD) experiments will help researchers evaluate critical terrain portrayal concepts. The experimental effort is to provide data to enable design trades that optimize SVS applications, as well as develop requirements and recommendations to facilitate the certification process. In this part of the experiment a fixed based flight simulator was equipped with various types of Head Down flight displays, ranging from conventional round dials (typical of most GA aircraft) to glass cockpit style PFD's. The variations of the PFD included an assortment of texturing and Digital Elevation Model (DEM) resolution combinations. A test matrix of 10 terrain display configurations (in addition to the baseline displays) were evaluated by 27 pilots of various backgrounds and experience levels. Qualitative (questionnaires) and quantitative (pilot performance and physiological) data were collected during the experimental runs. This paper focuses on the experimental set-up and final physiological results of the TP-HDD simulation experiment. The physiological measures of skin temperature, heart rate, and muscle response, show a decreased engagement (while using the synthetic vision displays as compared to the baseline conventional display) of the sympathetic and somatic nervous system responses which, in turn, indicates a reduced level of mental workload. This decreased level of workload is expected to enable improvement in the pilot's situation and terrain awareness.

Uenking, Michael D.↗

Helping Video Games Rewire "Our Minds"

Biofeedback-modulated video games are games that respond to physiological signals as well as mouse, joystick or game controller input; they embody the concept of improving physiological functioning by rewarding specific healthy body signals with success at playing a video game. The NASA patented biofeedback-modulated game method blends biofeedback into popular off-the- shelf video games in such a way that the games do not lose their entertainment value. This method uses physiological signals (e.g., electroencephalogram frequency band ratio) not simply to drive a biofeedback display directly, or periodically modify a task as in other systems, but to continuously modulate parameters (e.g., game character speed and mobility) of a game task in real time while the game task is being performed by other means (e.g., a game controller). Biofeedback-modulated video games represent a new generation of computer and video game environments that train valuable mental skills beyond eye-hand coordination. These psychophysiological training technologies are poised to exploit the revolution in interactive multimedia home entertainment for the personal improvement, not just the diversion, of the user.

Pope, Alan T.↗

Effects of diet and exposure to hindlimb suspension on estrous cycling in Sprague-Dawley rats

Various factors can disrupt the female reproductive cycle resulting in subfertility. The primary objective of this study was to determine whether physiological changes associated with exposure to hypogravity disrupt reproductive cycles. The hindlimb suspension (HLS) model was used to simulate the major physiological effects of hypogravity in female Sprague-Dawley rats. Also, to determine whether diet may influence reproductive results, rats were fed purified American Institute of Nutrition (AIN)-93G or chow diet. Rats (n = 9-11/group) subjected to HLS had lengthened estrous cycles due to prolonged diestrus, indicating hypoestrogenism. Interestingly, HLS rats fed AIN-93G but not chow diet had significantly reduced time spent in estrus and decreased plasma estradiol. Attenuation of hypoestrogenism in the chow-fed rats suggested that diet provided an exogenous source of estrogen. The mechanism involved in the disruption of estrous cycling remains to be determined. HLS increased urinary corticosterone (CORT) levels during the initial 4 days of HLS, suggesting that physiological responses to acute stress may be a potential mechanism in the disruption of estrous cycles. Higher basal urinary CORT was observed in rats fed chow vs. AIN-93G diet. HLS resulted in increased urinary CORT. However, two-way ANOVA indicated a significant HLS effect (P < 0.001) but no effect of HLS x diet effect on urinary CORT levels, suggesting that estrogenic activity associated with the chow diet did not enhance the stress response. The results of this study indicate that HLS, diet, and the combination of HLS and diet influence estrous cycling. This has important implications for future reproductive success in the hypogravity environment of space.

Estrous Cycle/physiology↗

An in silico assessment of gene function and organization of the phenylpropanoid pathway metabolic networks in Arabidopsis thaliana and limitations thereof

The Arabidopsis genome sequencing in 2000 gave to science the first blueprint of a vascular plant. Its successful completion also prompted the US National Science Foundation to launch the Arabidopsis 2010 initiative, the goal of which is to identify the function of each gene by 2010. In this study, an exhaustive analysis of The Institute for Genomic Research (TIGR) and The Arabidopsis Information Resource (TAIR) databases, together with all currently compiled EST sequence data, was carried out in order to determine to what extent the various metabolic networks from phenylalanine ammonia lyase (PAL) to the monolignols were organized and/or could be predicted. In these databases, there are some 65 genes which have been annotated as encoding putative enzymatic steps in monolignol biosynthesis, although many of them have only very low homology to monolignol pathway genes of known function in other plant systems. Our detailed analysis revealed that presently only 13 genes (two PALs, a cinnamate-4-hydroxylase, a p-coumarate-3-hydroxylase, a ferulate-5-hydroxylase, three 4-coumarate-CoA ligases, a cinnamic acid O-methyl transferase, two cinnamoyl-CoA reductases) and two cinnamyl alcohol dehydrogenases can be classified as having a bona fide (definitive) function; the remaining 52 genes currently have undetermined physiological roles. The EST database entries for this particular set of genes also provided little new insight into how the monolignol pathway was organized in the different tissues and organs, this being perhaps a consequence of both limitations in how tissue samples were collected and in the incomplete nature of the EST collections. This analysis thus underscores the fact that even with genomic sequencing, presumed to provide the entire suite of putative genes in the monolignol-forming pathway, a very large effort needs to be conducted to establish actual catalytic roles (including enzyme versatility), as well as the physiological function(s) for each member of the (multi)gene families present and the metabolic networks that are operative. Additionally, one key to identifying physiological functions for many of these (and other) unknown genes, and their corresponding metabolic networks, awaits the development of technologies to comprehensively study molecular processes at the single cell level in particular tissues and organs, in order to establish the actual metabolic context.

NASA Program Fundamental Space Biology↗

Evidence for vestibular regulation of autonomic functions in a mouse genetic model

Physiological responses to changes in the gravitational field and body position, as well as symptoms of patients with anxiety-related disorders, have indicated an interrelationship between vestibular function and stress responses. However, the relative significance of cochlear and vestibular information in autonomic regulation remains unresolved because of the difficulties in distinguishing the relative contributions of other proprioceptive and interoceptive inputs, including vagal and somatic information. To investigate the role of cochlear and vestibular function in central and physiological responses, we have examined the effects of increased gravity in wild-type mice and mice lacking the POU homeodomain transcription factor Brn-3.1 (Brn-3bPou4f3). The only known phenotype of the Brn-3.1(-/-) mouse is related to hearing and balance functions, owing to the failure of cochlear and vestibular hair cells to differentiate properly. Here, we show that normal physiological responses to increased gravity (2G exposure), such as a dramatic drop in body temperature and concomitant circadian adjustment, were completely absent in Brn-3.1(-/-) mice. In line with the lack of autonomic responses, the massive increase in neuronal activity after 2G exposure normally detected in wild-type mice was virtually abolished in Brn-3.1(-/-) mice. Our results suggest that cochlear and vestibular hair cells are the primary regulators of autonomic responses to altered gravity and provide genetic evidence that these cells are sufficient to alter neural activity in regions involved in autonomic and neuroendocrine control.

Non-NASA Center↗

Neuroimmunologic aspects of sleep and sleep loss

The complex and intimate interactions between the sleep and immune systems have been the focus of study for several years. Immune factors, particularly the interleukins, regulate sleep and in turn are altered by sleep and sleep deprivation. The sleep-wake cycle likewise regulates normal functioning of the immune system. Although a large number of studies have focused on the relationship between the immune system and sleep, relatively few studies have examined the effects of sleep deprivation on immune parameters. Studies of sleep deprivation's effects are important for several reasons. First, in the 21st century, various societal pressures require humans to work longer and sleep less. Sleep deprivation is becoming an occupational hazard in many industries. Second, to garner a greater understanding of the regulatory effects of sleep on the immune system, one must understand the consequences of sleep deprivation on the immune system. Significant detrimental effects on immune functioning can be seen after a few days of total sleep deprivation or even several days of partial sleep deprivation. Interestingly, not all of the changes in immune physiology that occur as a result of sleep deprivation appear to be negative. Numerous medical disorders involving the immune system are associated with changes in the sleep-wake physiology--either being caused by sleep dysfunction or being exacerbated by sleep disruption. These disorders include infectious diseases, fibromyalgia, cancers, and major depressive disorder. In this article, we will describe the relationships between sleep physiology and the immune system, in states of health and disease. Interspersed will be proposals for future research that may illuminate the clinical relevance of the relationships between sleeping, sleep loss and immune function in humans. Copyright 2001 by W.B. Saunders Company.

NASA Discipline Space Human Factors↗

Cardiac atrophy after bed rest and spaceflight

Cardiac muscle adapts well to changes in loading conditions. For example, left ventricular (LV) hypertrophy may be induced physiologically (via exercise training) or pathologically (via hypertension or valvular heart disease). If hypertension is treated, LV hypertrophy regresses, suggesting a sensitivity to LV work. However, whether physical inactivity in nonathletic populations causes adaptive changes in LV mass or even frank atrophy is not clear. We exposed previously sedentary men to 6 (n = 5) and 12 (n = 3) wk of horizontal bed rest. LV and right ventricular (RV) mass and end-diastolic volume were measured using cine magnetic resonance imaging (MRI) at 2, 6, and 12 wk of bed rest; five healthy men were also studied before and after at least 6 wk of routine daily activities as controls. In addition, four astronauts were exposed to the complete elimination of hydrostatic gradients during a spaceflight of 10 days. During bed rest, LV mass decreased by 8.0 +/- 2.2% (P = 0.005) after 6 wk with an additional atrophy of 7.6 +/- 2.3% in the subjects who remained in bed for 12 wk; there was no change in LV mass for the control subjects (153.0 +/- 12.2 vs. 153.4 +/- 12.1 g, P = 0.81). Mean wall thickness decreased (4 +/- 2.5%, P = 0.01) after 6 wk of bed rest associated with the decrease in LV mass, suggesting a physiological remodeling with respect to altered load. LV end-diastolic volume decreased by 14 +/- 1.7% (P = 0.002) after 2 wk of bed rest and changed minimally thereafter. After 6 wk of bed rest, RV free wall mass decreased by 10 +/- 2.7% (P = 0.06) and RV end-diastolic volume by 16 +/- 7.9% (P = 0.06). After spaceflight, LV mass decreased by 12 +/- 6.9% (P = 0.07). In conclusion, cardiac atrophy occurs during prolonged (6 wk) horizontal bed rest and may also occur after short-term spaceflight. We suggest that cardiac atrophy is due to a physiological adaptation to reduced myocardial load and work in real or simulated microgravity and demonstrates the plasticity of cardiac muscle under different loading conditions.

Flight Experiment↗

Selected contribution: a three-dimensional model for assessment of in vitro toxicity in balaena mysticetus renal tissue

This study established two- and three-dimensional renal proximal tubular cell cultures of the endangered species bowhead whale (Balaena mysticetus), developed SV40-transfected cultures, and cloned the 61-amino acid open reading frame for the metallothionein protein, the primary binding site for heavy metal contamination in mammals. Microgravity research, modulations in mechanical culture conditions (modeled microgravity), and shear stress have spawned innovative approaches to understanding the dynamics of cellular interactions, gene expression, and differentiation in several cellular systems. These investigations have led to the creation of ex vivo tissue models capable of serving as physiological research analogs for three-dimensional cellular interactions. These models are enabling studies in immune function, tissue modeling for basic research, and neoplasia. Three-dimensional cellular models emulate aspects of in vivo cellular architecture and physiology and may facilitate environmental toxicological studies aimed at elucidating biological functions and responses at the cellular level. Marine mammals occupy a significant ecological niche (72% of the Earth's surface is water) in terms of the potential for information on bioaccumulation and transport of terrestrial and marine environmental toxins in high-order vertebrates. Few ex vivo models of marine mammal physiology exist in vitro to accomplish the aforementioned studies. Techniques developed in this investigation, based on previous tissue modeling successes, may serve to facilitate similar research in other marine mammals.

Whales/genetics/physiology↗

Autogenic-feedback training exercise is superior to promethazine for control of motion sickness symptoms

Motion sickness symptoms affect approximately 50% of the crew during space travel and are commonly treated with intramuscular injections of promethazine. The purpose of this paper is to compare the effectiveness of three treatments for motion sickness: intramuscular injections (i.m.) of promethazine, a physiological training method (autogenic-feedback training exercise [AFTE]), and a no-treatment control. An earlier study tested the effects of promethazine on cognitive and psychomotor performance and motion sickness tolerance in a rotating chair. For the present paper, motion sickness tolerance, symptom reports, and physiological responses of these subjects were compared to matched subjects selected from an existing database who received either AFTE or no treatment. Three groups of 11 men, between the ages of 33 and 40 years, were matched on the number of rotations tolerated during their initial rotating-chair motion sickness test. The motion sickness test procedures and the 7-day interval between tests were the same for all subjects. The drug group was tested under four treatment conditions: baseline (no injections), a 25 mg dose of promethazine, a 50 mg dose of promethazine, and a placebo of sterile saline. AFTE subjects were given four 30-minute AFTE sessions before their second, third, and fourth motion sickness tests (6 hours total). The no-treatment control subjects were only given the four rotating-chair tests. Motion sickness tolerance was significantly increased after 4 hours of AFTE when compared to either 25 mg (p < 0.00003) or 50 mg (p < 0.00001) of promethazine. The control and promethazine groups did not differ. AFTE subjects reported fewer or no symptoms at higher rotational velocities than subjects in the control or promethazine groups. The primary physiological effect of promethazine was an inhibition of skin conductance level. The AFTE group showed significantly less heart rate and skin conductance variability during motion sickness tests administered after training.

Clinical Trial↗

Salmonella infections in the absence of the major histocompatibility complex II

We examined the pathogenesis of the facultative intracellular bacterium, Salmonella typhimurium in MHCII-/-, C2D knock-out mice, and wild-type C57BL/6J mice. The MHCII knock-out shortened the kinetics of animal death and reduced the dose of S. typhimurium needed to kill mice. We measured the physiological and cytokine responses of both mouse strains after S. typhimurium injection. Animal weight loss, spleen weights, liver weights, thymus weights, and serum corticosterone concentrations were comparable after injection with several doses of bacteria. The only physiological differences observed between the two strains were observed 3 days after injection of the highest dose of bacteria tested. Serum concentrations of tumor necrosis factor alpha, interleukin-2, and interleukin-6 increased in a dose-dependent fashion irrespective of mouse MHCII expression. Therefore, even in the absence of MHCII, mice are able to mount relatively normal physiological and immunological responses. Consistent with these normal responses, an increased percentage of MHCII-/- mice, primed with a low dose of bacteria 13 days earlier, were able to survive a lethal challenge of Salmonella compared with unprimed controls. Lastly, C2D mice had significantly higher serum interleukin-10 concentrations than C57BL/6J mice 48 h after infection with all doses of S. typhimurium. C2D macrophages also secreted significantly more IL-10 and less NO and O2- after lipopolysaccharide or phorbol ester stimulation in vitro than wild-type macrophages.

Non-NASA Center↗

Functional Performance Evaluation

The Extended Duration Orbiter Medical Project (EDOMP) was established to address specific issues associated with optimizing the ability of crews to complete mission tasks deemed essential to entry, landing, and egress for spaceflights lasting up to 16 days. The main objectives of this functional performance evaluation were to investigate the physiological effects of long-duration spaceflight on skeletal muscle strength and endurance, as well as aerobic capacity and orthostatic function. Long-duration exposure to a microgravity environment may produce physiological alterations that affect crew ability to complete critical tasks such as extravehicular activity (EVA), intravehicular activity (IVA), and nominal or emergency egress. Ultimately, this information will be used to develop and verify countermeasures. The answers to three specific functional performance questions were sought: (1) What are the performance decrements resulting from missions of varying durations? (2) What are the physical requirements for successful entry, landing, and emergency egress from the Shuttle? and (3) What combination of preflight fitness training and in-flight countermeasures will minimize in-flight muscle performance decrements? To answer these questions, the Exercise Countermeasures Project looked at physiological changes associated with muscle degradation as well as orthostatic intolerance. A means of ensuring motor coordination was necessary to maintain proficiency in piloting skills, EVA, and IVA tasks. In addition, it was necessary to maintain musculoskeletal strength and function to meet the rigors associated with moderate altitude bailout and with nominal or emergency egress from the landed Orbiter. Eight investigations, referred to as Detailed Supplementary Objectives (DSOs) 475, 476, 477, 606, 608, 617, 618, and 624, were conducted to study muscle degradation and the effects of exercise on exercise capacity and orthostatic function (Table 3-1). This chapter is divided into three parts. Part 1 describes specific findings from studies of muscle strength, endurance, fiber size, and volume. Part 2 describes results from studies of how in-flight exercise affects postflight exercise capacity and orthostatic function. Part 3 focuses on the development of new noninvasive methods for assessing body composition in astronauts and how those methods can be used to correlate measures of exercise performance and changes in body composition.

Greenisen, Michael C.↗

Recent bed rest results and countermeasure development at NASA

Bedrest studies of normal subjects provide opportunities to understand physiologic responses to supine posture and inactivity. Furthermore, head-down tilt has been a valuable procedure to investigate adaptation to microgravity and development of countermeasures to maintain the health and well-being of humans during space-flight. Recent bedrest experiments at NASA have ranged in duration from a few hours to 17 weeks. Acute studies of 6 degrees head-down tilt indicate that elevation of capillary blood pressure from 28 to 34 mm Hg and increased capillary perfusion in tissues of the head cause facial and intracranial edema. Intracranial pressure increases from 2 to 17 mm Hg going from upright posture to 6 degrees head-down tilt. Microvessels of the head have a low capacity to constrict and diminish local perfusion. Elevation of blood and tissue fluid pressures/flow in the head may also explain the higher headward bone density associated with long-term head-down tilt. These mechanistic studies of head-down tilt, along with a better understanding of the relative stresses involved with upright posture and lower body negative pressure, have facilitated development of suitable physiologic countermeasures to maintain astronaut health during microgravity. Presently no exercise hardware is available to provide a blood pressure gradient from head to feet in space. However, recent studies in our laboratory suggest that treadmill exercise using a graded lower-body compression suit and 100 mmHg lower body negative pressure provides equivalent or greater physiologic stress than similar upright exercise on Earth. Therefore, exercise within a lower body negative pressure chamber may provide a cost-effective and simple countermeasure to maintain the cardiovascular and neuro-musculoskeletal systems of astronauts during long-duration flight.

manned↗

Mechanisms of alpha 1-adrenergic vascular desensitization in conscious dogs

To investigate the mechanisms of alpha 1-adrenergic vascular desensitization, osmotic minipumps containing either saline (n = 9) or amidephrine mesylate (AMD) (n = 9), a selective alpha 1-adrenergic receptor agonist, were implanted subcutaneously in dogs with chronically implanted arterial and right atrial pressure catheters and aortic flow probes. After chronic alpha 1-adrenergic receptor stimulation, significant physiological desensitization to acute AMD challenges was observed, i.e., pressor and vasoconstrictor responses to the alpha 1-adrenergic agonist were significantly depressed (p < 0.01) compared with responses in the same dogs studied in the conscious state before pump implantation. However, physiological desensitization to acute challenges of the neurotransmitter norepinephrine (NE) (0.1 micrograms/kg per minute) in the presence of beta-adrenergic receptor blockade was not observed for either mean arterial pressure (MAP) (30 +/- 7 versus 28 +/- 5 mm Hg) or total peripheral resistance (TPR) (29.8 +/- 4.9 versus 28.9 +/- 7.3 mm Hg/l per minute). In the presence of beta-adrenergic receptor plus ganglionic blockade after AMD pump implantation, physiological desensitization to NE was unmasked since the control responses to NE (0.1 micrograms/kg per minute) before the AMD pumps were now greater (p < 0.01) than after chronic AMD administration for both MAP (66 +/- 5 versus 32 +/- 2 mm Hg) and TPR (42.6 +/- 10.3 versus 23.9 +/- 4.4 mm Hg/l per minute). In the presence of beta-adrenergic receptor, ganglionic, plus NE-uptake blockade after AMD pump implantation, desensitization was even more apparent, since NE (0.1 micrograms/kg per minute) induced even greater differences in MAP (33 +/- 5 versus 109 +/- 6 mm Hg) and TPR (28.1 +/- 1.8 versus 111.8 +/- 14.7 mm Hg/l per minute). The maximal force of contraction induced by NE in the presence or absence of endothelium was significantly decreased (p < 0.05) in vitro in mesenteric artery rings from AMD pump dogs compared with saline control dogs. Furthermore, alpha 1-adrenergic receptor density, as determined by [3H]prazosin binding in membrane preparations from vessels in the mesentery, was decreased (8.2 +/- 1.0 versus 18.4 +/- 1.4 fmol/mg protein, p < 0.001) without any change in Kd in the AMD pump dogs compared with the saline pump dogs.(ABSTRACT TRUNCATED AT 400 WORDS).

Non-NASA Center↗