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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2001

Animal models for osteoporosis

Animal models will continue to be important tools in the quest to understand the contribution of specific genes to establishment of peak bone mass and optimal bone architecture, as well as the genetic basis for a predisposition toward accelerated bone loss in the presence of co-morbidity factors such as estrogen deficiency. Existing animal models will continue to be useful for modeling changes in bone metabolism and architecture induced by well-defined local and systemic factors. However, there is a critical unfulfilled need to develop and validate better animal models to allow fruitful investigation of the interaction of the multitude of factors which precipitate senile osteoporosis. Well characterized and validated animal models that can be recommended for investigation of the etiology, prevention and treatment of several forms of osteoporosis have been listed in Table 1. Also listed are models which are provisionally recommended. These latter models have potential but are inadequately characterized, deviate significantly from the human response, require careful choice of strain or age, or are not practical for most investigators to adopt. It cannot be stressed strongly enough that the enormous potential of laboratory animals as models for osteoporosis can only be realized if great care is taken in the choice of an appropriate species, age, experimental design, and measurements. Poor choices will results in misinterpretation of results which ultimately can bring harm to patients who suffer from osteoporosis by delaying advancement of knowledge.

NASA Discipline Regulatory Physiology↗
NASA NTRS1992

System identification of perilymphatic fistula in an animal model

An acute animal model has been developed in the chinchilla for the study of perilymphatic fistulas. Micropunctures were made in three sites to simulate bony, round window, and oval window fistulas. The eye movements in response to pressure applied to the external auditory canal were recorded after micropuncture induction and in preoperative controls. The main pressure stimulus was a pseudorandom binary sequence (PRBS) that rapidly changed between plus and minus 200 mm of water. The PRBS stimulus, with its wide frequency bandwidth, produced responses clearly above the preoperative baseline in 78 percent of the runs. The response was better between 0.5 and 3.3 Hz than it was below 0.5 Hz. The direction of horizontal eye movement was toward the side of the fistula with positive pressure applied in 92 percent of the runs. Vertical eye movements were also observed. The ratio of vertical eye displacement to horizontal eye displacement depended upon the site of the micropuncture induction. Thus, such a ratio measurement may be clinically useful in the noninvasive localization of perilymphatic fistulas in humans.

Non-NASA Center↗
NASA NTRS2005

Use of animal models for space flight physiology studies, with special focus on the immune system

Animal models have been used to study the effects of space flight on physiological systems. The animal models have been used because of the limited availability of human subjects for studies to be carried out in space as well as because of the need to carry out experiments requiring samples and experimental conditions that cannot be performed using humans. Experiments have been carried out in space using a variety of species, and included developmental biology studies. These species included rats, mice, non-human primates, fish, invertebrates, amphibians and insects. The species were chosen because they best fit the experimental conditions required for the experiments. Experiments with animals have also been carried out utilizing ground-based models that simulate some of the effects of exposure to space flight conditions. Most of the animal studies have generated results that parallel the effects of space flight on human physiological systems. Systems studied have included the neurovestibular system, the musculoskeletal system, the immune system, the neurological system, the hematological system, and the cardiovascular system. Hindlimb unloading, a ground-based model of some of the effects of space flight on the immune system, has been used to study the effects of space flight conditions on physiological parameters. For the immune system, exposure to hindlimb unloading has been shown to results in alterations of the immune system similar to those observed after space flight. This has permitted the development of experiments that demonstrated compromised resistance to infection in rodents maintained in the hindlimb unloading model as well as the beginning of studies to develop countermeasures to ameliorate or prevent such occurrences. Although there are limitations to the use of animal models for the effects of space flight on physiological systems, the animal models should prove very valuable in designing countermeasures for exploration class missions of the future.

Review↗
NASA NTRS1990

Animal models in motion sickness research

Practical information on candidate animal models for motion sickness research and on methods used to elicit and detect motion sickness in these models is provided. Four good potential models for use in motion sickness experiments include the dog, cat, squirrel monkey, and rat. It is concluded that the appropriate use of the animal models, combined with exploitation of state-of-the-art biomedical techniques, should generate a great step forward in the understanding of motion sickness mechanisms and in the development of efficient and effective approaches to its prevention and treatment in humans.

Daunton, Nancy G.↗
NASA NTRS1986

Selection of an appropriate animal model for study of bone loss in weightlessness

Prolonged weightlessness in space flight results in a slow progressive demineralization of bone accompanied by an increased calcium output in the urine resulting in negative calcium balances. This possibly irreversible bone loss may constitute a serious limiting factor to long duration manned space flight. A number of preventative measures have been suggested, i.e., exercise during flight, dietary calcium supplements, use of specific prophylactic drugs. In order to facilitate research in these areas it is necessary to develop appropriate ground-based animal models that simulate the human condition of osteoporsis. An appropriate animal model would permit bone density studies, calcium balance studies, biochemical analyses, ground-based simulation models of weightlessness (bed rest, restraint, immobilization) and the planning of inflight experiments. Several animal models have been proposed in the biomedical research literature, but have inherent deficiencies. The purpose of this project was to evaluate models in the literature and determine which of these most closely simulates the phenomenon of bone loss in humans with regard to growth, bone remodeling, structural, chemical and mineralization similarities to human. This was accomplished by a comprehensive computer assisted literature search and report. Three animal models were examined closely for their relative suitability: the albino rat, monkey, and Beagle.

Wolinsky, I.↗
NASA NTRS1986

Cataractogenic potential of ionizing radiations in animal models that simulate man

Aspects of experiments on radiation-induced lenticular opacification during the life spans of two animal models, the New Zealand white rabbit and the rhesus monkey, are compared and contrasted with published results from a life-span study of another animal model, the beagle dog, and the most recent data from the ongoing study of the survivors from radiation exposure at Hiroshima and Nagasaki. An important connection among the three animal studies is that all the measurements of cataract indices were made by one of the authors (Lee), so variation from personal subjectivity was reduced to a minimum. The primary objective of the rabbit experiments (radiations involved: Fe-56, Ar-40, and Ne-20 ions and Co-60 gamma photons) is an evaluation of hazards to astronauts from Galactic particulate radiations. An analogous evaluation of hazards from solar flares during space flight is being made with monkeys exposed to 32, 55, 138 and 400-MeV protons. Conclusions are drawn about the proper use of animal models to simulate radiation responses in man and the levels of radiation-induced lenticular opacification that pose risks to man in space.

Lett, J. T.↗
NASA NTRS1987

Life sciences research in space: The requirement for animal models

Use of animals in NASA space programs is reviewed. Animals are needed because life science experimentation frequently requires long-term controlled exposure to environments, statistical validation, invasive instrumentation or biological tissue sampling, tissue destruction, exposure to dangerous or unknown agents, or sacrifice of the subject. The availability and use of human subjects inflight is complicated by the multiple needs and demands upon crew time. Because only living organisms can sense, integrate and respond to the environment around them, the sole use of tissue culture and computer models is insufficient for understanding the influence of the space environment on intact organisms. Equipment for spaceborne experiments with animals is described.

Fuller, C. A.↗
NASA NTRS0992

Current status: Animal models of nausea

The advantages, and possible benefits of a valid, reliable animal model for nausea are discussed, and difficulties inherent to the development of a model are considered. A principle problem for developing models arises because nausea is a subjective sensation that can be identified only in humans. Several putative measures of nausea in animals are considered, with more detailed consideration directed to variation in cardiac rate, levels of vasopressin, and conditioned taste aversion. Demonstration that putative measures are associated with reported nausea in humans is proposed as a requirement for validating measures to be used in animal models. The necessity for a 'real-time' measure of nausea is proposed as an important factor for future research; and the need for improved understanding of the neuroanatomy underlying the emetic syndrome is discussed.

Robert A Fox↗
NASA NTRS2001

Animal model of neuropathic tachycardia syndrome

Clinically relevant autonomic dysfunction can result from either complete or partial loss of sympathetic outflow to effector organs. Reported animal models of autonomic neuropathy have aimed to achieve complete lesions of sympathetic nerves, but incomplete lesions might be more relevant to certain clinical entities. We hypothesized that loss of sympathetic innervation would result in a predicted decrease in arterial pressure and a compensatory increase in heart rate. Increased heart rate due to loss of sympathetic innervation is seemingly paradoxical, but it provides a mechanistic explanation for clinical autonomic syndromes such as neuropathic postural tachycardia syndrome. Partially dysautonomic animals were generated by selectively lesioning postganglionic sympathetic neurons with 150 mg/kg 6-hydroxydopamine hydrobromide in male Sprague-Dawley rats. Blood pressure and heart rate were monitored using radiotelemetry. Systolic blood pressure decreased within hours postlesion (Delta>20 mm Hg). Within 4 days postlesion, heart rate rose and remained elevated above control levels. The severity of the lesion was determined functionally and pharmacologically by spectral analysis and responsiveness to tyramine. Low-frequency spectral power of systolic blood pressure was reduced postlesion and correlated with the diminished tyramine responsiveness (r=0.9572, P=0.0053). The tachycardia was abolished by treatment with the beta-antagonist propranolol, demonstrating that it was mediated by catecholamines acting on cardiac beta-receptors. Partial lesions of the autonomic nervous system have been hypothesized to underlie many disorders, including neuropathic postural tachycardia syndrome. This animal model may help us better understand the pathophysiology of autonomic dysfunction and lead to development of therapeutic interventions.

NASA Discipline Regulatory Physiology↗
NASA NTRS2017

Advantage of Animal Models with Metabolic Flexibility for Space Research Beyond Low Earth Orbit

As the worlds space agencies and commercial entities continue to expand beyond Low Earth Orbit (LEO), novel approaches to carry out biomedical experiments with animals are required to address the challenge of adaptation to space flight and new planetary environments. The extended time and distance of space travel along with reduced involvement of Earth-based mission support increases the cumulative impact of the risks encountered in space. To respond to these challenges, it becomes increasingly important to develop the capability to manage an organisms self-regulatory control system, which would enable survival in extraterrestrial environments. To significantly reduce the risk to animals on future long duration space missions, we propose the use of metabolically flexible animal models as pathfinders, which are capable of tolerating the environmental extremes exhibited in spaceflight, including altered gravity, exposure to space radiation, chemically reactive planetary environments and temperature extremes.In this report we survey several of the pivotal metabolic flexibility studies and discuss the importance of utilizing animal models with metabolic flexibility with particular attention given to the ability to suppress the organism's metabolism in spaceflight experiments beyond LEO. The presented analysis demonstrates the adjuvant benefits of these factors to minimize damage caused by exposure to spaceflight and extreme planetary environments. Examples of microorganisms and animal models with dormancy capabilities suitable for space research are considered in the context of their survivability under hostile or deadly environments outside of Earth. Potential steps toward implementation of metabolic control technology in spaceflight architecture and its benefits for animal experiments and manned space exploration missions are discussed.

metabolic flexibility↗
NASA NTRS2017

Advantage of Animal Models with Metabolic Flexibility for Space Research Beyond Low Earth Orbit

As the world's space agencies and commercial entities continue to expand beyond Low Earth Orbit (LEO), novel approaches to carry out biomedical experiments with animals are required to address the challenge of adaptation to space flight and new planetary environments. The extended time and distance of space travel along with reduced involvement of Earth-based mission support increases the cumulative impact of the risks encountered in space. To respond to these challenges, it becomes increasingly important to develop the capability to manage an organism's self-regulatory control system, which would enable survival in extraterrestrial environments. To significantly reduce the risk to animals on future long duration space missions, we propose the use of metabolically flexible animal models as "pathfinders," which are capable of tolerating the environmental extremes exhibited in spaceflight, including altered gravity, exposure to space radiation, chemically reactive planetary environments and temperature extremes. In this report we survey several of the pivotal metabolic flexibility studies and discuss the importance of utilizing animal models with metabolic flexibility with particular attention given to the ability to suppress the organism's metabolism in spaceflight experiments beyond LEO. The presented analysis demonstrates the adjuvant benefits of these factors to minimize damage caused by exposure to spaceflight and extreme planetary environments. Examples of microorganisms and animal models with dormancy capabilities suitable for space research are considered in the context of their survivability under hostile or deadly environments outside of Earth. Potential steps toward implementation of metabolic control technology in spaceflight architecture and its benefits for animal experiments and manned space exploration missions are discussed.

metabilic flexibility↗
NASA NTRS2010

Animal Models and Bone Histomorphometry: Translational Research for the Human Research Program

This slide presentation reviews the use of animal models to research and inform bone morphology, in particular relating to human research in bone loss as a result of low gravity environments. Reasons for use of animal models as tools for human research programs include: time-efficient, cost-effective, invasive measures, and predictability as some model are predictive for drug effects.

Sibonga, Jean D.↗
NASA NTRS1995

[Quantification and monitoring of vascular resistance in the lower limbs by the Doppler method (animal model)]

The object of this study was to define and validate a non-invasive method of evaluation and monitoring of vascular resistances in the leg. Blood flow velocity was measured by Doppler ultrasound in an animal model (ewe) with similar blood flow characteristics in the lower limb as man and allowing access to the required invasive measurements for validation of the method (pressure and flow). Vascular resistances distal to the measuring point (femoral, for example) were assessed using the resistance index R = D/S, S being the peak systolic deflection and D that of diastolic reflux of the Doppler spectral analysis of flow in the femoral artery. The values and variations of this resistance index were compared with the vascular resistances calculated from measurements of pressure and flow at the point of Doppler sampling and expressed in mmHg/ml/min. Femoral flow was measured by Doppler ultrasound (Doppler-echo), and mean pressure by an arterial catheter introduced into the abdominal aorta. Compression of the lower limb veins induced a venous return resulting in a reduction of cardiac output and femoral flow. During compression, femoral flow decreased by an average of 29% (p < 0.001) although mean pressure and heart rate did not change significantly. The femoral resistance index (Rf) increased by an average of 37.5% (p < 0.01) and vascular resistances increased by 45.9% (p < 0.01). Injection of 1 mg adrenaline induced peripheral vasoconstriction with an increase in blood pressure and a decrease in heart rate and femoral flow.(ABSTRACT TRUNCATED AT 250 WORDS).

Non-NASA Center↗
NASA NTRSDate not supplied

NASA GeneLab Platform Utilized for Biological Response to Space Radiation in Animal Models

Ionizing radiation from Galactic Cosmic Rays (GCR) is one of the major risk factors that will impact the health of astronauts on extended missions outside the protective effects of Earth’s magnetic field. The NASA GeneLab project has detailed information on radiation exposure using animal models with curated dosimetry information for spaceflight experiments. We analyzed multiple GeneLab omics datasets associated with both ground-based and spaceflight radiation studies that included in vivo and in vitro approaches. A range of ions from protons to iron particles with doses from 0.1 Gy to 1.0 Gy for ground studies and samples flown in Low Earth Orbit (LEO) with total doses of 1.0 mGy to 30 mGy were utilized From this analysis we were able to identify distinct biological signatures associating specific ions with specific biological responses due to radiation exposure in space. For example, we discovered changes in mitochondrial function, ribosomal assembly, and immune pathways as a function of dose. We provided a summary of how the GeneLab’s rich database of omics experiments with animal models can be used to generate novel hypotheses to better understand human health risks from GCR exposures.

Afshin Beheshti↗
NASA NTRS1991

Man in space - The use of animal models

The use of animal surrogates as experimental subjects in order to provide essential missing information on the effects of long-term spaceflights, to validate countermeasures, and to test medical treatment techniques is discussed. Research needs also include the definition of biomedical adaptations to flight, and the developments of standards for safe space missions to assure human health and productivity during and following flight. NASA research plans in this area are outlined. Over the next 40 years, NASA plans to concentrate on the use of rodents and nonhuman primates as the models of choice for various physiological responses observed in humans during extended stays in space. This research will include flights on the Space Shuttle, unmanned biosatellites, and the Space Station Freedom.

Ballard, Rodney W.↗
NASA NTRS2002

Effects of perfluorohexane vapor on relative blood flow distribution in an animal model of surfactant-depleted lung injury

OBJECTIVE: To test the hypothesis that treatment with vaporized perfluorocarbon affects the relative pulmonary blood flow distribution in an animal model of surfactant-depleted acute lung injury. DESIGN: Prospective, randomized, controlled trial. SETTING: A university research laboratory. SUBJECTS: Fourteen New Zealand White rabbits (weighing 3.0-4.5 kg). INTERVENTIONS: The animals were ventilated with an FIO(2) of 1.0 before induction of acute lung injury. Acute lung injury was induced by repeated saline lung lavages. Eight rabbits were randomized to 60 mins of treatment with an inspiratory perfluorohexane vapor concentration of 0.2 in oxygen. To compensate for the reduced FIO(2) during perfluorohexane treatment, FIO(2) was reduced to 0.8 in control animals. Change in relative pulmonary blood flow distribution was assessed by using fluorescent-labeled microspheres. MEASUREMENTS AND MAIN RESULTS: Microsphere data showed a redistribution of relative pulmonary blood flow attributable to depletion of surfactant. Relative pulmonary blood flow shifted from areas that were initially high-flow to areas that were initially low-flow. During the study period, relative pulmonary blood flow of high-flow areas decreased further in the control group, whereas it increased in the treatment group. This difference was statistically significant between the groups (p =.02) as well as in the treatment group compared with the initial injury (p =.03). Shunt increased in both groups over time (control group, 30% +/- 10% to 63% +/- 20%; treatment group, 37% +/- 20% to 49% +/- 23%), but the changes compared with injury were significantly less in the treatment group (p =.03). CONCLUSION: Short treatment with perfluorohexane vapor partially reversed the shift of relative pulmonary blood flow from high-flow to low-flow areas attributable to surfactant depletion.

NASA Discipline Cardiopulmonary↗
NASA NTRS1987

Bone density in limb-immobilized beagles: An animal model for bone loss in weightlessness

Prolonged weightlessness is man in space flight results in a slow progressive demineralization of bone accompanied by an increased calcium output in the urine resulting in negative calcium balances. This possibly irreversible bone loss may constitute a serious limiting factor to long duration manned space flight. In order to seek and test preventative measures an appropriate ground based animal model simulating weightlessness is necessary. Use of the mature Beagle in limb immobilization has been documented as an excellent model for orthopedic research since this animal most closely simulates the phenomenom of bone loss with regards to growth, remodeling, structure, chemistry and mineralization. The purpose of this project is to develop a research protocol for the study of bone loss in Beagles during and after cast immobilization of a hindleg; research will then be initiated.

Wolinsky, Ira↗