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Intramuscular pressures beneath elastic and inelastic leggings

Leg compression devices have been used extensively by patients to combat chronic venous insufficiency and by astronauts to counteract orthostatic intolerance following spaceflight. However, the effects of elastic and inelastic leggings on the calf muscle pump have not been compared. The purpose of this study was to compare in normal subjects the effects of elastic and inelastic compression on leg intramuscular pressure (IMP), an objective index of calf muscle pump function. IMP in soleus and tibialis anterior muscles was measured with transducer-tipped catheters. Surface compression between each legging and the skin was recorded with an air bladder. Subjects were studied under three conditions: (1) control (no legging), (2) elastic legging, and (3) inelastic legging. Pressure data were recorded for each condition during recumbency, sitting, standing, walking, and running. Elastic leggings applied significantly greater surface compression during recumbency (20 +/- 1 mm Hg, mean +/- SE) than inelastic leggings (13 +/- 2 mm Hg). During recumbency, elastic leggings produced significantly higher soleus IMP of 25 +/- 1 mm Hg and tibialis anterior IMP of 28 +/- 1 mm Hg compared to 17 +/- 1 mm Hg and 20 +/- 2 mm Hg, respectively, generated by inelastic leggings and 8 +/- 1 mm Hg and 11 +/- 1 mm Hg, respectively, without leggings. During sitting, walking, and running, however, peak IMPs generated in the muscular compartments by elastic and inelastic leggings were similar. Our results suggest that elastic leg compression applied over a long period in the recumbent posture may impede microcirculation and jeopardize tissue viability.(ABSTRACT TRUNCATED AT 250 WORDS).

Clinical Trial↗

Airline chair-rest deconditioning: induction of immobilisation thromboemboli?

Air passenger miles will likely double by year 2020. The altered and restrictive environment in an airliner cabin can influence haematological homeostasis in passengers and crew. Flight-related deep venous thromboemboli (DVT) have been associated with at least 577 deaths on 42 of 120 airlines from 1977 to 1984 (25 deaths/million departures), whereas many such cases go unreported. However, there are four major factors that could influence formation of possible flight-induced DVT: sleeping accommodations (via sitting immobilisation); travellers' medical history (via tissue injury); cabin environmental factors (via lower partial pressure of oxygen and lower relative humidity); and the more encompassing chair-rest deconditioning (C-RD) syndrome. There is ample evidence that recent injury and surgery (especially in deconditioned hospitalised patients) facilitate thrombophlebitis and formation of DVT that may be exacerbated by the immobilisation of prolonged air travel.In the healthy flying population, immobilisation factors associated with prolonged (>5 hours) C-RD such as total body dehydration, hypovolaemia and increased blood viscosity, and reduced venous blood flow (pooling) in the legs may facilitate formation of DVT. However, data from at least four case-controlled epidemiological studies did not confirm a direct causative relationship between air travel and DVT, but factors such as a history of vascular thromboemboli, venous insufficiency, chronic heart failure, obesity, immobile standing position, more than three pregnancies, infectious disease, long-distance travel, muscular trauma and violent physical effort were significantly more frequent in DVT patients than in controls. Thus, there is no clear, direct evidence yet that prolonged sitting in airliner seats, or prolonged experimental chair-rest or bed-rest deconditioning treatments cause DVT in healthy people.

Review, Tutorial↗

Surveillance of Ocular Parameters and Visual Function in Bed Rest Subjects

Recent visual changes in astronauts have raised concern about ocular health during long duration spaceflight. Seven cases have been documented in astronauts who spent 6 months aboard the International Space Station. These astronauts were male ranging in age from 45 to 55 years old. All astronauts exhibited pre- to post flight refractive changes. Decreased intraocular pressure (IOP) post flight was observed in 3 cases. Fundoscopic exams revealed post flight findings of choroidal folds in 4 cases, optic disc edema in 5 cases and the presence of cotton wool spots in 3 cases. Optical coherence tomography (OCT) confirmed findings of choroidal folds and disc edema, and also documented retinal nerve fiber layer thickening (5 cases). Findings from MRI examinations showed posterior globe flattening (5 cases), optic nerve sheath distention (6 cases) and torturous optic nerves (2 cases). Of the 7 cases, intracranial pressure was measured on 4 astronauts. These 4 showed elevated ICP post-flight that remained elevated for as long as 19 months in one case. While the etiology remains unknown, hypotheses speculate that venous insufficiency or hypertension in the brain caused by cephalad fluid shifts during spaceflight are possible mechanisms for ocular changes seen in astronauts. Head-down tilt bed rest is a spaceflight analog that induces cephalad fluid shifts. This study is designed to provide ocular monitoring of bed rest subjects and determine whether clinically relevant changes are found. Ocular Changes

Cromwell, Ronita L.↗

Risk of Microgravity-Induced Visual Impairment and Elevated Intracranial Pressure (VIIP)

Eight cases identified, represent 23.5% of the 34 crewmembers flown on the ISS, with inflight visual changes and pre-to-postflight refractive changes. In some cases, the changes were transient while in others they are persistent with varying degrees of visual impairment. (1) Decreased intraocular pressure (IOP) postflight was observed in 3 cases. (2) Fundoscopic exams revealed postflight findings of choroidal folds in 4 cases, optic disc edema in 5 cases and presence of cotton wool spots in 3 cases. (3) Optical coherence tomography (OCT) confirmed findings of choroidal folds and disc edema and documented retinal nerve fiber layer thickening (4 cases). (4) Findings from MRI examinations showed posterior globe flattening (5 cases) and optic nerve sheath distension (6 cases). (5) Opening cerebrospinal fluid (CSF) pressure was elevated in 4 cases postflight reflecting raised intracranial pressure. While the etiology remains unknown, hypotheses speculate that venous insufficiency or hypertension in the brain caused by cephalad fluid shifts during spaceflight are possible mechanisms for ocular changes in astronauts.

Otto, Christian↗

Latest advances in edema

Basic concepts in the physiopathology of edema are reviewed. The mechanisms of fluid exchange across the capillary endothelium are explained. Interstitial flow and lymph formation are examined. Clinical disorders of tissue and lymphatic transport, microcirculatory derangements in venous disorders, protein disorders, and lymphatic system disorders are explored. Techniques for investigational imaging of the lymphatic system are explained.

Review, Tutorial↗

Mechanism for negative water balance during weightlessness An hypothesis

The mechanism for the apparent decrease in body fluid volume in astronauts during spaceflight remains obscure. The widespread postulate that the hypohydration is the result of the Henry-Gauer reflex, a diuresis caused by inhibition of vasopressin secretion resulting from increased left and perhaps right atrial (central) venous pressure, has not been established with direct measurements on astronauts. An hypothesis is proposed to account for fluid-electrolyte shifts during weightlessness. A moderate but transient increase in central venous pressure occurs when orbit is entered that is insufficient to activate the Henry-Gauer reflex but sufficient to stimulate the release of atrial natriuretic peptides. Increased sodium excretion would facilitate some increased urinary water loss. The resulting relatively dilute plasma and interstitial fluids would cause fluid to shift into the cellular space, resulting in edema in the head and trunk and inhibition of thirst and drinking. Thus, the negative water balance in astronauts would be caused by a gradual natriuresis and diuresis coupled with reduced fluid intake.

Greenleaf, J. E.↗

Hemodynamic and autonomic nervous system responses to mixed meal ingestion in healthy young and old subjects and dysautonomic patients with postprandial hypotension

BACKGROUND. Although postprandial hypotension is a common cause of falls and syncope in elderly persons and in patients with autonomic insufficiency, the pathophysiology of this disorder remains unknown. METHODS AND RESULTS. We examined the hemodynamic, splanchnic blood pool, plasma norepinephrine (NE), and heart rate (HR) power spectra responses to a standardized 400-kcal mixed meal in 11 healthy young (age, 26 +/- 5 years) and nine healthy elderly (age, 80 +/- 5 years) subjects and 10 dysautonomic patients with symptomatic postprandial hypotension (age, 65 +/- 16 years). Cardiac and splanchnic blood pools were determined noninvasively by radionuclide scans, and forearm vascular resistance was determined using venous occlusion plethysmography. In healthy young and old subjects, splanchnic blood volume increased, but supine blood pressure remained unchanged after the meal. In both groups, HR increased and systemic vascular resistance remained stable. Forearm vascular resistance and cardiac index increased after the meal in elderly subjects, whereas these responses were highly variable and of smaller magnitude in the young. Young subjects demonstrated postprandial increases in low-frequency HR spectral power, representing cardiac sympatho-excitation, but plasma NE remained unchanged. In elderly subjects, plasma NE increased after the meal but without changes in the HR power spectrum. Patients with dysautonomia had a large postprandial decline in blood pressure associated with no change in forearm vascular resistance, a fall in systemic vascular resistance, and reduction in left ventricular end diastolic volume index. HR increased in these patients but without changes in plasma NE or the HR power spectrum. CONCLUSIONS. 1) In healthy elderly subjects, the maintenance of blood pressure homeostasis after food ingestion is associated with an increase in HR, forearm vascular resistance, cardiac index, and plasma NE. In both young and old, systemic vascular resistance is maintained. 2) Dysautonomic patients with postprandial hypotension fail to maintain systemic vascular resistance after a meal. This impairment in vascular response to meal ingestion may underlie the development of postprandial hypotension. 3) The measurement of mean HR or plasma NE does not adequately characterize autonomic cardiac control. Power spectral analysis suggests an impairment in the postprandial autonomic modulation of HR in healthy elderly and dysautonomic subjects, possibly predisposing to hypotension when vascular compensation is inadequate.

Non-NASA Center↗

Decompression sickness and venous gas emboli at 8.3 psia

This study sought to determine the bends risk on decompression from sea level to 8.3 psia. On the basis of several prior studies by NASA and the Air Force, this differential was expected to result in a minimal (about 5 percent) incidence of mild decompression sickness, and may be the pressure of choice for the next-generation NASA extravehicular activity (EVA) pressure suit. Thirty-one volunteer subjects, performing light work characteristic of EVA, were exposed to 8.3 psia pressure altitude for six hours. Limb bends incidence was 3.2 percent, and 25.8 percent of the subjects demonstrated significant intravascular bubbling. Those who bubbled were significantly older than the bubble-free group, but differed in no other aspect. An 8.3 psia advanced pressure suit design was considered insufficient to totally preclude the risk of decompression sickness.

Smead, Kenneth W.↗

Gender and Decompression Sickness: A Critical Review and Analysis

The author addressed the following questions: are women at greater risk of decompression sickness and venous gas emboli at certain times in their reproductive cycle, is risk modified by the use of birth control pills (BCP), and is there a difference in overall risk between men and women under the same decompression dose? The summary considers information from the few abstracts and reports that were available. Except for the observation of more Type II DCS in women, particularly in women who fly after diving, there was no compelling evidence of a difference in DCS risk between men and women SCUBA divers. Many women that presented with DCS symptoms seemed to be in or near menses, with statistically fewer cases reported as time increased from menses. There was no compelling evidence that the use of BCP in SCUBA divers increases the risk of DCS. There were insufficient data about VGE from SCUBA diving to make any conclusion about the incidence of VGE and gender. In contrast, there were ample data about VGE from research in altitude chambers. Women produced less VGE and less Grade IV VGE compared to men under the same decompression dose, certainly when resting oxygen prebreathe (PB) was performed prior to ascent to altitude. Dual-cycle ergometry exercise during PB tends to reduce the differences in VGE between men and women. There was no compelling evidence that the risk of altitude DCS was different between men and women. However, a large number of DCS cases were associated with menses, and the use of BCP did seem to put women at a slightly greater risk than those that did not use BCP. There were substantial observations that women comprised a larger number of difficult cases that required complicated medical management.

Source record↗

Lumped Parameter Models of the Central Nervous System for VIIP Research

INTRODUCTION: Current long-duration missions to the International Space Station and future exploration-class missions beyond low-Earth orbit, such as to Mars and asteroids, expose astronauts to increased risk of Visual Impairment and Intracranial Pressure (VIIP) syndrome [1]. It has been hypothesized that the headward shift of cerebral spinal fluid (CSF) and blood in microgravity may cause significant elevation of intracranial pressure (ICP), which in turn induces VIIP syndrome through biomechanical pathways [1, 2]. However, there is insufficient evidence to confirm this hypothesis. In this light, we are developing lumped-parameter models of fluid transport in the central nervous system (CNS) as a means to simulate the influence of microgravity on ICP. The CNS models will also be used in concert with the lumped parameter and finite element models of the eye described in the realted IWS abstracts submitted by Nelson et al., Feola et al. and Ethier et al. METHODS: We have developed a nine compartment CNS model (Figure 1) capable of both time-dependent and steady state fluid transport simulations, based on the works of Stevens et al. [3]. The breakdown of compartments within the model includes: vascular (3), CSF (2), brain (1) and extracranial (3). The boundary pressure in the Central Arteries [A] node is prescribed using an oscillating pressure function PA(t) simulating the carotid pulsatile pressure wave as developed by Linninger et al. [4]. For each time step, pressures are integrated through time using an adaptive-timestep 4th and 5th order Runga-Kutta solver. Once pressures are found, constitutive equations are used to solve for flowrates (Q) between each compartment. In addition to fluid flow between the different compartments, compliance (C) interactions between neighboring compartments are represented. We are also developing a second CNS model based on the works of Linninger et al. [4] which takes a more granular approach to represent the interactions of the intracranial and spinal compartments with the inclusion of arteries, arterioles, capillaries, venules, veins, venous sinus, and ventricles. The flow through the arteries, veins and CSF compartments are governed by continuity, momentum and distensibility balance equations. Furthermore, unlike the Stevens et al. approach, the Monro-Kellie doctrine of constant cranial volume and the bi-phasic nature of the brain parenchyma are implemented. These features appear to be more consistent with the physiologic and anatomical behavior of the CNS, and follow a modeling philosophy similar to the lumped parameter eye model that is intended to be integrated with the CNS model. However, Linninger’s approach has never been implemented to include hydrostatic gradient and microgravity simulation capabilities. Therefore, we aim at implement this modeling approach for spaceflight simulations and assess its overall applicability to VIIP research. OBJECTIVES: We will present verification and validation test results for both models, as well as head-to-head comparison to explore their strengths and limitations with respect to mathematical implementation and physiological significance for VIIP research. In doing so, we hope to provide some guidance to the HRP research community on how to appropriately leverage lumped parameter models for space biomedical research.

Vera, J.↗

Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

BACKGROUND: Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. Astronauts participating in long-duration missions may be at an increased risk of oxidative stress and inflammatory damage due to radiation, psychological stress, altered physical activity, nutritional insufficiency, and hyperoxia during extravehicular activity. By studying one identical twin during his 1-year ISS mission and his ground-based twin, this work extends a current NASA-funded investigation to determine whether these spaceflight factors contribute to an accelerated progression of atherosclerosis. This study of twins affords a unique opportunity to examine spaceflight-related atherosclerosis risk that is independent of the confounding factors associated with different genotypes. PURPOSE: The purpose of this investigation was to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and determine if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. These physiological and biochemical data will be extended by using an exploratory approach to investigate the relationship between intermediate phenotypes and risk factors for atherosclerosis and the metabolomic signature from plasma and urine samples. Since metabolites are often the indirect products of gene expression, we simultaneously assessed gene expression and DNA methylation in leukocytes. HYPOTHESIS: We predict that, compared to the ground-based twin, the space-flown twin will experience elevated biomarkers of oxidative stress and inflammatory damage, altered arterial structure and function, accelerated telomere shortening, dysregulation of genes associated with oxidative stress and inflammation, and a metabolic profile shift that is associated with elevated atherosclerosis risk factors. METHODS: In the space-flown twin, a panel of biomarkers of oxidative and inflammatory stress were measured in venous blood samples and in 24-h (in-flight) and 48-h (pre- and post-flight) urine pools collected twice before flight, six times during the mission (~FD15, 75, 180, 240, 300, 335), and early in the post-flight recovery phase (3-5 days after landing). We also measured metabolomic (targeted and untargeted approaches) and genomic markers (DNA methylation, mRNA gene expression, telomere length) in these samples. Arterial structure, assessed from measures of intima-media thickness, also were measured using standard clinical ultrasound at the same time points. Arterial function was assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and a sensitive predictor of atherosclerotic risk, only before and after spaceflight. All of the same measures were obtained in the ground-based twin, but less frequently. DISCUSSION: All data collection has been completed for both the space-flown twin and the ground-based twin. Vascular structure and function measures have been analyzed, blood and urine samples have been batch-processed. Results from these individuals will be compared to each other, to data from other Twin Study investigations, and to the larger complement of subjects participating in the companion study currently ongoing in ISS astronauts.

Lee, Stuart M. C.↗

Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

Background: Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. Astronauts participating in long-duration missions may be at an increased risk of oxidative stress and inflammatory damage due to radiation, psychological stress, altered physical activity, nutritional insufficiency, and hyperoxia during extravehicular activity. By studying one identical twin during his 1-year ISS mission and one ground-based twin, this work extends a current NASA-funded investigation to determine whether these spaceflight factors contribute to an accelerated progression of atherosclerosis. This study of twins affords a unique opportunity to examine the spaceflight-related atherosclerosis risk independent of the confounding factors associated with different genotypes. Purpose: The purpose of this investigation is to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and determine if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. These physiological and biochemical data will be extended by using an exploratory approach to investigate the relationship between intermediate phenotypes and risk factors for atherosclerosis and the metabolomic signature from plasma and urine samples. Since metabolites are often the indirect products of gene expression, we will simultaneously assess gene expression and DNA methylation in leukocytes. Hypothesis: We predict that the space-flown twin will experience elevated biomarkers of oxidative stress and inflammatory damage, altered arterial structure and function, accelerated telomere shortening, dysregulation of genes associated with oxidative stress and inflammation, and a metabolic profile shift that is associated with elevated atherosclerosis risk factors. Conversely, these will not be observed in the ground-based twin. Methods: We will measure blood and urine biomarkers of oxidative stress and inflammation as well as arterial structure and function (carotid intima-medial thickness and brachial artery flow-mediated dilation) in one twin astronaut before, during, and after long-duration spaceflight and in his twin serving as a ground-based control. Furthermore, we will measure metabolomics (targeted and untargeted approaches) and genomic markers (DNA methylation, mRNA gene expression, telomere length) to elucidate the molecular mechanisms involved. A panel of biomarkers of oxidative and inflammatory stress will be measured in venous blood samples and 24-hour (in-flight) and 48-hour (pre- and post-flight) urine pools twice before flight, early (flight days 15 and 60) and late (2 weeks before landing) during the mission, and early in the post-flight recovery phase (approximately 3-5 days after landing). Arterial structure, assessed from measures of intima-media thickness, will be measured at the same times. Arterial function will be assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and a sensitive predictor of atherosclerotic risk, only before and after spaceflight. Discussion: Pre- and in-flight data collection is in progress for the space-flown twin, and similar data have been obtained from the ground-based twin. Blood and urine samples will be batch processed when received from ISS after the conclusion of the 1-year mission. Results from these individual subjects will be compared to the larger complement of subjects participating in the companion study currently ongoing in ISS astronauts.

Lee, Stuart M. C.↗