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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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197 records · Page 11
All sourcesNASA NTRSDOE OSTI
NASA NTRS1987

A new technique to determine the correlation between the QT interval and heart-rate for control and SIDS babies

The ability of the autonomic nervous system to alter the QT interval in response to heart rate changes is essential to cardiovascular control. An accurate way to determine the relation between QT intervals and their corresponding RR intervals is described. A computer algorithm measures the RR intervals using digital filtering and cross-correlating the QRS sections of consecutive waveforms. The QT intervals is calculated by choosing a section of, the ECG that includes the T wave and cross-correlating it with all the consecutive T waves. At least 4000 pairs of QT-RR intervals are computed for each subject and a best fit correlation function determines the relations between the QT and RR intervals. This technique enables to establish a precise correlation between RR and QT in order to distinguish between control and SIDS babies.

Non-NASA Center↗
NASA NTRS2001

Familial orthostatic tachycardia due to norepinephrine transporter deficiency

Orthostatic intolerance (OI) or postural tachycardia syndrome (POTS) is a syndrome primarily affecting young females, and is characterized by lightheadedness, palpitations, fatigue, altered mentation, and syncope primarily occurring with upright posture and being relieved by lying down. There is typically tachycardia and raised plasma norepinephrine levels on upright posture, but little or no orthostatic hypotension. The pathophysiology of OI is believed to be very heterogeneous. Most studies of the syndrome have focused on abnormalities in norepinephrine release. Here the hypothesis that abnormal norepinephrine transporter (NET) function might contribute to the pathophysiology in some patients with OI was tested. In a proband with significant orthostatic symptoms and tachycardia, disproportionately elevated plasma norepinephrine with standing, impaired systemic, and local clearance of infused tritiated norepinephrine, impaired tyramine responsiveness, and a dissociation between stimulated plasma norepinephrine and DHPG elevation were found. Studies of NET gene structure in the proband revealed a coding mutation that converts a highly conserved transmembrane domain Ala residue to Pro. Analysis of the protein produced by the mutant cDNA in transfected cells demonstrated greater than 98% reduction in activity relative to normal. NE, DHPG/NE, and heart rate correlated with the mutant allele in this family. CONCLUSION: These results represent the first identification of a specific genetic defect in OI and the first disease linked to a coding alteration in a Na+/Cl(-)-dependent neurotransmitter transporter. Identification of this mechanism may facilitate our understanding of genetic causes of OI and lead to the development of more effective therapeutic modalities.

Review, Tutorial↗
NASA NTRS2019

Integrated Research Plan to Assess the Combined Effects of Space Radiation, Altered Gravity, and Isolation and Confinement on Crew Health and Performance: Problem Statement

Future crewed exploration missions to Mars could last up to three years and will expose astronauts to unprecedented environmental challenges. Challenges to the nervous system during these missions will include factors of: space radiation that can damage sensitive neurons in the central nervous system (CNS); isolation and confinement can affect cognition and behavior; and altered gravity that will change the astronauts’ perception of their environment and their spatial orientation, and will affect their coordination, balance, and locomotion. In the past, effects of spaceflight stressors have been characterized individually. However, long-term, simultaneous exposure to multiple stressors will produce a range of interrelated behavioral and biological effects that have the potential to adversely affect operationally relevant crew performance. These complex environmental challenges might interact synergistically and increase the overall risk to the health and performance of the astronaut. Therefore, NASA’s Human Research Program (HRP) has directed an integrated approach to characterize and mitigate the risk to the CNS from simultaneous exposure to these multiple spaceflight factors. The proposed research strategy focuses on systematically evaluating the relationships among three existing research risks associated with spaceflight: Risk of Acute (In-flight) and Late Central Nervous System Effects from Radiation (CNS), Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders (BMed), and Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Spaceflight (SM). NASA’s HRP approach is intended to identify the magnitude and types of interactions as they affect behavior, especially as it relates to operationally relevant performance (e.g., performance that depends on reaction time, procedural memory, etc.). In order to appropriately characterize this risk of multiple spaceflight environmental stressors, there is a recognition of the need to leverage research approaches using appropriate animal models and behavioral constructs. Very little has been documented on the combined effects of altered gravity, space radiation, and other psychological and cognitive stressors on the CNS. Preliminary evidence from rodents suggest that a combination of a minimum of exposures to even two of three stressors of: simulated space radiation, simulated microgravity, and simulated isolation and confinement, have produced different and more pronounced biological and performance effects than exposure to these same stressors individually. Structural and functional changes to the CNS of rodents exposed to transdisciplinary combined stressors indicate that important processes related to information processing are likely altered including impairment of exploratory and risk taking behaviors, as well as executive function including learning, memory, and cognitive flexibility — all of which may be linked to changes in related operational relevant performance. The fully integrated research plan outlines approaches to evaluate how combined, potentially synergistic, impacts of simultaneous exposures to spaceflight hazards will affect an astronaut’s CNS and their operationally relevant performance during future exploration missions, including missions to the Moon and Mars. The ultimate goals are to derive risk estimates for the combined, potentially synergistic, effects of the three major spaceflight hazards that will establish acceptable maximum decrement or change in a physiological or behavioral parameters during or after spaceflight, the acceptable limit of exposure to a spaceflight factor, and to evaluate strategies to mitigate any associated decrements in operationally relevant performance.

Steinberg, Susan L.↗
NASA NTRS1999

Characterization of ionic currents of cells of the subfornical organ that project to the supraoptic nuclei

The subfornical organ (SFO) is a forebrain structure that converts peripheral blood-borne signals reflecting the hydrational state of the body to neural signals and then through efferent fibers conveys this information to several central nervous system structures. One of the forebrain areas receiving input from the SFO is the supraoptic nucleus (SON), a source of vasopressin synthesis and control of release from the posterior pituitary. Little is known of the transduction and transmission processes by which this conversion of systemic information to brain input occurs. As a step in elucidating these mechanisms, the present study characterized the ionic currents of dissociated cells of the SFO that were identified as neurons that send efferents to the SON. A retrograde tracer was injected into the SON area in eleven-day-old rats. After three days for retrograde transport of the label, the SFOs of these animals were dissociated and plated for tissue culture. The retrograde tracer was used to identify the soma of SFO cells projecting to the SON so that voltage-dependent ionic currents using whole-cell voltage clamp methods could be studied. The three types of currents in labeled SFO neurons were characterized as a 1) rapid, transient inward current that can be blocked by tetrodotoxin (TTX) characteristic of a sodium current; 2) slow-onset sustained outward current that can be blocked by tetraethylammonium (TEA) characteristic of a delayed rectifier potassium current; and 3) remaining outward current that has a rapid-onset and transient characteristic of a potassium A-type current. Copyright 1999 Elsevier Science B.V.

Non-NASA Center↗
NASA NTRS1999

Hemodynamic actions of systemically injected pituitary adenylate cyclase activating polypeptide-27 in the rat

The aims of this study were (1) to characterize the hemodynamic mechanisms underlying the hypotensive effects of pituitary adenylate cyclase activating polypeptide-27 (PACAP-27 0.1-2.0 nmol/kg, i.v.) in pentobarbital-anesthetized rats, and (2) to determine the roles of the autonomic nervous system, adrenal catecholamines and endothelium-derived nitric oxide (NO) in the expression of PACAP-27-mediated effects on hemodynamic function. PACAP-27 produced dose-dependent decreases in mean arterial blood pressure and hindquarter and mesenteric vascular resistances in saline-treated rats. PACAP-27 also produced pronounced falls in mean arterial blood pressure in rats treated with the ganglion blocker, chlorisondamine (5 mg/kg, i.v.). The hypotensive and vasodilator actions of PACAP-27 were not attenuated by the beta-adrenoceptor antagonist, propranolol (1 mg/kg, i.v.), or the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME 50 micromol/kg, i.v.). PACAP-27 produced dose-dependent increases in heart rate whereas the hypotensive response produced by the nitrovasodilator, sodium nitroprusside (10 microg/kg, i.v.), was associated with a minimal tachycardia. The PACAP-27-induced tachycardia was unaffected by chlorisondamine, but was virtually abolished by propranolol. These results suggest that the vasodilator effects of PACAP-27 are due to actions in the microcirculation rather than to the release of adrenal catecholamines and that this vasodilation may not involve the release of endothelium-derived NO. These results also suggest that PACAP-27 produces tachycardia by directly releasing norepinephrine from cardiac sympathetic nerve terminals rather than by direct or baroreceptor reflex-mediated increases in sympathetic nerve activity.

Non-NASA Center↗
NASA NTRS2002

Cardiovascular and sympathetic neural responses to handgrip and cold pressor stimuli in humans before, during and after spaceflight

Astronauts returning to Earth have reduced orthostatic tolerance and exercise capacity. Alterations in autonomic nervous system and neuromuscular function after spaceflight might contribute to this problem. In this study, we tested the hypothesis that exposure to microgravity impairs autonomic neural control of sympathetic outflow in response to peripheral afferent stimulation produced by handgrip and a cold pressor test in humans. We studied five astronauts approximately 72 and 23 days before, and on landing day after the 16 day Neurolab (STS-90) space shuttle mission, and four of the astronauts during flight (day 12 or 13). Heart rate, arterial pressure and peroneal muscle sympathetic nerve activity (MSNA) were recorded before and during static handgrip sustained to fatigue at 40 % of maximum voluntary contraction, followed by 2 min of circulatory arrest pre-, in- and post-flight. The cold pressor test was applied only before (five astronauts) and during flight (day 12 or 13, four astronauts). Mean (+/- S.E.M.) baseline heart rates and arterial pressures were similar among pre-, in- and post-flight measurements. At the same relative fatiguing force, the peak systolic pressure and mean arterial pressure during static handgrip were not different before, during and after spaceflight. The peak diastolic pressure tended to be higher post- than pre-flight (112 +/- 6 vs. 99 +/- 5 mmHg, P = 0.088). Contraction-induced rises in heart rate were similar pre-, in- and post-flight. MSNA was higher post-flight in all subjects before static handgrip (26 +/- 4 post- vs. 15 +/- 4 bursts min(-1) pre-flight, P = 0.017). Contraction-evoked peak MSNA responses were not different before, during, and after spaceflight (41 +/- 4, 38 +/- 5 and 46 +/- 6 bursts min(-1), all P > 0.05). MSNA during post-handgrip circulatory arrest was higher post- than pre- or in-flight (41 +/- 1 vs. 33 +/- 3 and 30 +/- 5 bursts min(-1), P = 0.038 and 0.036). Similarly, responses of MSNA and blood pressure to the cold pressor test were well maintained in-flight. We conclude that modulation of muscle sympathetic neural outflow by muscle metaboreceptors and skin nociceptors is preserved during short duration spaceflight.

NASA Discipline Neuroscience↗
NASA NTRS1996

A dual-input nonlinear system analysis of autonomic modulation of heart rate

Linear analyses of fluctuations in heart rate and other hemodynamic variables have been used to elucidate cardiovascular regulatory mechanisms. The role of nonlinear contributions to fluctuations in hemodynamic variables has not been fully explored. This paper presents a nonlinear system analysis of the effect of fluctuations in instantaneous lung volume (ILV) and arterial blood pressure (ABP) on heart rate (HR) fluctuations. To successfully employ a nonlinear analysis based on the Laguerre expansion technique (LET), we introduce an efficient procedure for broadening the spectral content of the ILV and ABP inputs to the model by adding white noise. Results from computer simulations demonstrate the effectiveness of broadening the spectral band of input signals to obtain consistent and stable kernel estimates with the use of the LET. Without broadening the band of the ILV and ABP inputs, the LET did not provide stable kernel estimates. Moreover, we extend the LET to the case of multiple inputs in order to accommodate the analysis of the combined effect of ILV and ABP effect on heart rate. Analyzes of data based on the second-order Volterra-Wiener model reveal an important contribution of the second-order kernels to the description of the effect of lung volume and arterial blood pressure on heart rate. Furthermore, physiological effects of the autonomic blocking agents propranolol and atropine on changes in the first- and second-order kernels are also discussed.

NASA Discipline Regulatory Physiology↗
NASA NTRS2015

Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Space flight

Control of vehicles and other complex systems is a high-level integrative function of the central nervous system (CNS). It requires well-functioning subsystem performance, including good visual acuity, eye-hand coordination, spatial and geographic orientation perception, and cognitive function. Evidence from space flight research demonstrates that the function of each of these subsystems is altered by removing gravity, a fundamental orientation reference, which is sensed by vestibular, proprioceptive, and haptic receptors and used by the CNS for spatial orientation, posture, navigation, and coordination of movements. The available evidence also shows that the degree of alteration of each subsystem depends on a number of crew- and mission-related factors. There is only limited operational evidence that these alterations cause functional impacts on mission-critical vehicle (or complex system) control capabilities. Furthermore, while much of the operational performance data collected during space flight has not been available for independent analysis, those that have been reviewed are somewhat equivocal owing to uncontrolled (and/or unmeasured) environmental and/or engineering factors. Whether this can be improved by further analysis of previously inaccessible operational data or by development of new operational research protocols remains to be seen. The true operational risks will be estimable only after we have filled the knowledge gaps and when we can accurately assess integrated performance in off-nominal operational settings (Paloski et al. 2008). Thus, our current understanding of the Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Space flight is limited primarily to extrapolation of scientific research findings, and, since there are limited ground-based analogs of the sensorimotor and vestibular changes associated with space flight, observation of their functional impacts is limited to studies performed in the space flight environment. Fortunately, many sensorimotor and vestibular experiments have been performed during and/or after space flight missions since 1959 (Reschke et al. 2007). While not all of these experiments were directly relevant to the question of vehicle/complex system control, most provide insight into changes in aspects of sensorimotor control that might bear on the physiological subsystems underlying this high-level integrated function.

Bloomberg, Jacob J.↗
NASA NTRS2001

The catecholamine response to spaceflight: role of diet and gender

Compared with men, women appear to have a decreased sympathetic nervous system (SNS) response to stress. The two manifestations where the sexual dimorphism has been the most pronounced involve the response of the SNS to fluid shifts and fuel metabolism during exercise. The objectives of this study were to investigate whether a similar sexual dimorphism was found in the response to spaceflight. To do so, we compared catecholamine excretion by male and female astronauts from two similar shuttle missions, Spacelab Life Sciences 1 (SLS1, 1991) and 2 (SLS2, 1993) for evidence of sexual dimorphism. To evaluate the variability of the catecholamine response in men, we compared catecholamine excretion from the two SLS missions against the 1996 Life and Microgravity Sciences Mission (LMS) and the 1973 Skylab missions. RESULTS: No gender- or mission-dependent changes were found with epinephrine. Separating out the SLS1/2 data by gender shows that norepinephrine excretion was essentially unchanged with spaceflight in women (98 +/- 10%; n = 3) and substantially decreased with the men (41 +/- 9%; n = 4, P < 0.05). Data are a percentage of mean preflight value +/- SE. Comparisons among males demonstrated significant mission effects on norepinephrine excretion. After flight, there was a transient increase in norepinephrine but no evidence of any gender-specific effects. We conclude that norepinephrine excretion during spaceflight is both mission and gender dependent. Men show the greater response, with at least three factors being involved, a response to microgravity, energy balance, and the ratio of carbohydrate to fat in the diet.

NASA Discipline Regulatory Physiology↗
NASA NTRS2000

Neck afferent involvement in cardiovascular control during movement

It is well established that labyrinth and neck afferent information contributes to the regulation of somatomotor function during movement and changes in posture. There is also convincing evidence that the vestibular system participates in the modulation of sympathetic outflow and cardiovascular function during changes in posture, presumably to prevent orthostatic hypotension. However, the labyrinth organs do not provide any signals concerning body movements with respect to the head. In contrast, the neck receptors, particularly muscle spindles, are well located and suited to provide information about changes in body position with respect to the head and vestibular signals. Studies in the cat suggest that neck afferent information may modulate the vestibulosympathetic reflex responses to head-neck movements. There is some evidence in the cat to suggest involvement of low threshold mechanoreceptors. However, human studies do not indicate that low threshold mechanoreceptors in the neck modulate cardiovascular responses. The human studies are consistent with the studies in the cat in that they demonstrate the importance of otolith activation in mediating cardiovascular and sympathetic responses to changes in posture. This paper briefly reviews the current experimental evidence concerning the involvement of neck afferent information in the modulation of cardiovascular control during movement and changes in posture.

Review↗
DOE OSTI2022

Selective posttranslational inhibition of Ca V β 1 -associated voltage-dependent calcium channels with a functionalized nanobody

Ca 2+ influx through high-voltage-activated calcium channels (HVACCs) controls diverse cellular functions. A critical feature enabling a singular signal, Ca 2+ influx, to mediate disparate functions is diversity of HVACC pore-forming α1 and auxiliary Ca V β 1 –Ca V β 4 subunits. Selective Ca V α 1 blockers have enabled deciphering their unique physiological roles. By contrast, the capacity to post-translationally inhibit HVACCs based on Ca V β isoform is non-existent. Conventional gene knockout/shRNA approaches do not adequately address this deficit owing to subunit reshuffling and partially overlapping functions of Ca V β isoforms. Here, we identify a nanobody (nb.E8) that selectively binds Ca V β 1 SH3 domain and inhibits Ca V β 1 -associated HVACCs by reducing channel surface density, decreasing open probability, and speeding inactivation. Functionalizing nb.E8 with Nedd4L HECT domain yielded Chisel-1 which eliminated current through Ca V β 1 -reconstituted Ca V 1/Ca V 2 and native Ca V 1.1 channels in skeletal muscle, strongly suppressed depolarization-evoked Ca 2+ influx and excitation-transcription coupling in hippocampal neurons, but was inert against Ca V β 2 -associated Ca V 1.2 in cardiomyocytes. The results introduce an original method for probing distinctive functions of ion channel auxiliary subunit isoforms, reveal additional dimensions of Ca V β 1 signaling in neurons, and describe a genetically-encoded HVACC inhibitor with unique properties.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1998

Role of the flocculus of the cerebellum in motor learning of the vestibulo-ocular reflex

Structure-function studies at the systems level are an effective method for understanding the relationship of the central nervous system to behavior. Motor learning or adaptation of the vestibulo-ocular reflex is a clear example wherein this approach has been productive. During a vestibulo-ocular reflex the brain converts a head velocity signal, transduced through the vestibular semicircular canals, into an eye movement command delivered to the extraocular muscles. If the viewed target remains on the fovea of the retina, the reflex is compensatory, and its gain, eye velocity/head velocity, is one. When the image of the viewed object slips across the retina, visual acuity decreases, and the gain of the reflex, which is no longer one, is plastically adapted or adjusted until retinal stability is restored. The anatomic substrate for this plasticity thus involves brain structures in which visual-vestibular interaction can potentially occur, as well as vestibular and visual sensory and oculomotor motor structures. Further, it has been known for many years that removal of the flocculus of the cerebellum permanently precludes further vestibulo-ocular reflex adaptation, demonstrating the involvement of the cerebellum in this behavior. Maekawa and Simpson (J Neurophysiol 1973;36: 649-66) discovered that one visual input to the flocculus involved the accessory optic system and the inferior olive. Ensuing work has demonstrated that the visual signals used to adapt the vestibulo-ocular reflex are transmitted by this accessory optic system to the flocculus and subsequently to brain stem structures involved in vestibulo-ocular reflex plasticity. Presently the inclusive list of anatomic sites involved in vestibulo-ocular reflex circuitry and its adaptive plasticity is small. Our laboratory continues to believe that this behavior should be caused by interactions within this small class of neurons. By studying each class of identified neuron and its interactions with others within the list, we hope to ultimately understand the mechanisms used by the brain in the expression of this behavior.

Non-NASA Center↗
NASA NTRS1999

Abnormal norepinephrine clearance and adrenergic receptor sensitivity in idiopathic orthostatic intolerance

BACKGROUND: Chronic orthostatic intolerance (OI) is characterized by symptoms of inadequate cerebral perfusion with standing, in the absence of significant orthostatic hypotension. A heart rate increase of >/=30 bpm is typical. Possible underlying pathophysiologies include hypovolemia, partial dysautonomia, or a primary hyperadrenergic state. We tested the hypothesis that patients with OI have functional abnormalities in autonomic neurons regulating cardiovascular responses. METHODS AND RESULTS: Thirteen patients with chronic OI and 10 control subjects underwent a battery of autonomic tests. Systemic norepinephrine (NE) kinetics were determined with the patients supine and standing before and after tyramine administration. In addition, baroreflex sensitivity, hemodynamic responses to bolus injections of adrenergic agonists, and intrinsic heart rate were determined. Resting supine NE spillover and clearance were similar in both groups. With standing, patients had a greater decrease in NE clearance than control subjects (55+/-5% versus 30+/-7%, P<0.02). After tyramine, NE spillover did not change significantly in patients but increased 50+/-10% in control subjects (P<0.001). The dose of isoproterenol required to increase heart rate 25 bpm was lower in patients than in control subjects (0.5+/-0.05 versus 1.0+/-0.1 microg, P<0.005), and the dose of phenylephrine required to increase systolic blood pressure 25 mm Hg was lower in patients than control subjects (105+/-11 versus 210+/-12 microg, P<0.001). Baroreflex sensitivity was lower in patients (12+/-1 versus 18+/-2 ms/mm Hg, P<0.02), but the intrinsic heart rate was similar in both groups. CONCLUSIONS: The decreased NE clearance with standing, resistance to the NE-releasing effect of tyramine, and increased sensitivity to adrenergic agonists demonstrate dramatically disordered sympathetic cardiovascular regulation in patients with chronic OI.

Clinical Trial↗
NASA NTRS2024

Transfer of NASA Technology to the DoD: Mitigating Motion Sickness with Autogenic Feedback Training Exercise

Motion sickness poses a significant safety risk, particularly in the context of aviation. Given its prevalence among aviators and its detrimental impact on performance, researchers have attempted to identify effective mitigation strategies for motion sickness. Currently, many of the existing interventions are pharmacological, and while effective, they present a problem due to their associated adverse side effects. The primary goals of the current research were 1) demonstrate the value of the application of Autogenic-Feedback Training Exercise (AFTE), a physiological training program developed by NASA to mitigate the impact of operational stressors such as motion sickness and spatial disorientation on human physiology and performance and 2) evaluate a new enhanced version of AFTE training software and demonstrate the ability to apply it remotely and train other personnel to administer it. AFTE combines principles of autogenic therapy, and biofeedback in training individuals to control their physiological reactions through a series of relaxation and arousal exercises. This study included twenty-six participants, 17 men and 9 women. On day 1 participants were tested in a rotating chair (pre-test) to determine their motion sickness tolerance (measured as minutes of rotation); days 2-5 consisted of four AFTE training sessions, each 30-min. in duration for a total of 2 hours; and on day 6 the participants were re-tested in the rotating chair. Results revealed a significant increase in motion sickness tolerance with AFTE on the post-test when compared to pre-test, participants had significantly lower symptom diagnostic scores post-test, and there was no significant gender effect. In addressing the first goal it was concluded that the modified 2-hour version of AFTE significantly improved motion sickness tolerance with participants experiencing fewer symptoms. A second goal of this research was to refine and transfer a NASA technology, software and methods for applications within DOD by training other personnel to administer AFTE. A comparison of NASA and NAMRU-D trainers on AFTE outcome for improving participants’ motion sickness tolerance revealed no significant difference indicating the successful transfer of methods to DOD. In addition, remote AFTE training of military aviators at distant sites was feasible. A third goal was to identify individual patterns of interoceptive abilities and related autonomic metrics able to predict stress response and training outcome. These data included measures of personality traits obtained from questionnaires and specific autonomic measures (e.g., heart rate variability) collected by NAMRU-D investigators. These results will be reported in a separate paper.

autonomic nervous system↗
NASA NTRS2000

Orthostatic stress is necessary to maintain the dynamic range of cardiovascular control in space

In the upright position, gravity fills the low-pressure systems of human circulation with blood and interstitial fluid in the sections below the diaphragm. Without gravity one pressure component in the vessels disappears and the relationship between hydrostatic pressure and oncotic pressure, which regulates fluid passage across the capillary endothelium in the terminal vascular bed, shifts constantly. The visible consequences of this are a puffy face and "bird" legs. The plasma volume shrinks in space and the range of cardiovascular control is reduced. When they stand up for the first time after landing, 30-50% of astronauts suffer from orthostatic intolerance. It remains unclear whether microgravity impairs cardiovascular reflexes, or whether it is the altered volume status that causes the cardiovascular instability following space flight. Lower body negative pressure was used in several space missions to stimulate the cardiovascular reflexes before, during and after a space flight. The results show that cardiovascular reflexes are maintained in microgravity. However, the astronauts' volume status changed in space, towards a volume-retracted state, as measurements of fluid-regulating hormones have shown. It can be hypothesized that the control of circulation and body fluid homeostasis in humans is adapted to their upright posture in the Earth's gravitational field. Autonomic control regulates fluid distribution to maintain the blood pressure in that posture, which most of us have to cope with for two-thirds of the day. A determined amount of interstitial volume is necessary to maintain the dynamic range of cardiovascular control in the upright posture; otherwise orthostatic intolerance may occur more often.

manned↗
NASA NTRS2001

Gender differences in autonomic cardiovascular regulation: spectral, hormonal, and hemodynamic indexes

The autonomic nervous system drives variability in heart rate, vascular tone, cardiac ejection, and arterial pressure, but gender differences in autonomic regulation of the latter three parameters are not well documented. In addition to mean values, we used spectral analysis to calculate variability in arterial pressure, heart rate (R-R interval, RRI), stroke volume, and total peripheral resistance (TPR) and measured circulating levels of catecholamines and pancreatic polypeptide in two groups of 25 +/- 1.2-yr-old, healthy men and healthy follicular-phase women (40 total subjects, 10 men and 10 women per group). Group 1 subjects were studied supine, before and after beta- and muscarinic autonomic blockades, administered singly and together on separate days of study. Group 2 subjects were studied supine and drug free with the additional measurement of skin perfusion. In the unblocked state, we found that circulating levels of epinephrine and total spectral power of stroke volume, TPR, and skin perfusion ranged from two to six times greater in men than in women. The difference (men > women) in spectral power of TPR was maintained after beta- and muscarinic blockades, suggesting that the greater oscillations of vascular resistance in men may be alpha-adrenergically mediated. Men exhibited muscarinic buffering of mean TPR whereas women exhibited beta-adrenergic buffering of mean TPR as well as TPR and heart rate oscillations. Women had a greater distribution of RRI power in the breathing frequency range and a less negative slope of ln RRI power vs. ln frequency, both indicators that parasympathetic stimuli were the dominant influence on women's heart rate variability. The results of our study suggest a predominance of sympathetic vascular regulation in men compared with a dominant parasympathetic influence on heart rate regulation in women.

Non-NASA Center↗
NASA NTRS2023

Automated Fluidics Device for Extraction and Quantification of miRNA Biomarkers From Blood

Radiation Assessment DuRing Exposure And long-Duration Spaceflight (RADREADS) demonstrates space-compatible point-of-care technology for quantitative biological monitoring of blood miRNA biomarkers in response to long-term low dose radiation exposure. This individualized monitoring approach will inform targeted treatment strategies to maximize medical resource utilization by accounting for individual susceptibility to radiation-related illnesses. As human spaceflight progresses beyond Earth’s magnetic shielding, radiation exposure poses a significant risk to astronaut health and safety. Extended operation in this environment comes with an increased risk of radiation exposure, leading to higher risks of radiation sickness, cancer, central nervous system effects, and degenerative diseases. While conventional physical dosimetry techniques capture radiation dose, individualistic susceptibility to radiation damage is varied. Multiple characteristics, including age, body weight, sex, genetics, and immune status, have been found to influence radiosensitivity (Liu et al. 2011, and Bouffler 2016). This differential response necessitates individualized monitoring and targeted treatment strategies to maximize medical resource utilization; however, a practical diagnostic platform for quantifying long-term, low dose radiation-induced tissue damage does not currently exist. MicroRNAs (miRNAs) are a class of small, non-coding RNAs that regulate gene expression by mediating the degradation of messenger RNA. The levels of particular miRNAs are influenced by biological processes such as inflammation and serve as biomarkers for a variety of conditions including cancer (Singh et al. 2017). MicroRNAs are found in various bodily fluids and are amenable to collection via liquid biopsies, providing a minimally invasive and easily quantifiable readout for a variety of radiosensitive reporters. A preliminary signature of 15 spaceflight sensitive miRNA has been identified in rodent and human studies, including miR-21-5p, miR-24-3p, miR-92a-3p, miR-17-5p, miR-16a-3p, miR-34a-3p, and miR-223-3p. These targets generally increased expression with radiation dose and linear energy transfer, though variation between individuals is not yet described. Current gaps in the field include a lack of understanding of longitudinal biological responses to long-term, low dose radiation exposure and the absence of space-compatible point-of-care technology for quantitative biological monitoring. In this body of work, we aim to develop an automated bleed-to-read system to process whole blood for the detection of miRNA biomarkers in order to monitor individualistic responses to radiation exposure. This will be achieved via separating serum (or plasma) from whole blood, followed by extraction, amplification, and quantification of the miRNA using a RT-qPCR reaction. Previously, the WetLab-2 hardware enabled execution of a RT-qPCR reaction aboard ISS; however, it is a manual system that requires crew manipulation and bulky components (Parra et al. 2017). To address these issues, automated fluid handling hardware was developed for each stage of sample preparation. Extraction of total RNA is achieved by sequentially pumping reagents through an off-the-shelf nucleic acid binding column (miRNeasy Serum/Plasma Advanced Kit, Qiagen). This approach eliminates several manual pipetting and centrifuging steps and limits the use of toxic chemicals commonly found in other sample processing techniques. The resulting elution will then be automatically dispensed for RT-qPCR analysis using a compact rotary qPCR (Mic qPCR Cycler, Bio Molecular Systems) that will improve spaceflight compatibility by removing bubbles from the detection region, another challenge highlighted by WetLab-2 (Parra et al. 2017). Efforts are also being made to simplify the RT-qPCR reaction to a 1-step air-dryable mix to improve long-term reagent stability at room temperature and reduce system complexity. By automating the RT-qPCR processes via microfluidic manipulation, RADREADS will reduce crewmember hands-on time and enable the personalized detection of radiation-induced tissue damage during long duration missions. Minimally invasive, longitudinal monitoring of individual’s response to radiation exposure will inform how the physiological system responds to long-term low dose space radiation and enables development of targeted countermeasures by the medical team. Ultimately, this portable technology will require minimal technical expertise and can also be used to monitor miRNA biomarkers associated with other diseases.

Tristen Head↗