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Direct measures of central venous pressure (CVP) while supine or supine with the legs elevated to simulate the prelaunch position on the Space Shuttle and during head-down tilt (HDT), parabolic flight (0 g), or spaceflight (0 g). Data are redrawn from previously published results by Buckey et al. (1996), Foldager et al. (1996), Norsk et al. (1987), and Videbaek and Norsk (1997). Data are represented as mean AE standard deviation, except for individual results shown by subject in astronauts and during one subject in head-down tilt Foldager et al. (1996).
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One hypothesized contributor to vision changes experienced by >75% of International Space Station astronauts is elevated intracranial pressure (ICP). While no definitive data yet exist, elevated ICP might be secondary to the microgravity-induced cephalad fluid shift, resulting in venous congestion (overfilling and distension) and inhibition of cere...
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... observation ( Arbeille et al. 1999Arbeille et al. , 2001Arbeille et al. , 2015. Head-down tilt, one analog of space- flight, produces distension of the jugular veins that likely results from a combination of a reversal of the hydrostatic gradient relative to the upright posture and an elevated CVP ( Gaffney et al. 1985;Foldager et al. 1996) (Fig. 4). In our experience, jugular vein distension is coupled with an incrementally increasing IJVP as the head-down tilt angle increases ( Martin et al. 2015). Specifically, we observed that IJVP measured using compression sonogra- phy, using the same techniques as described here, increased by ~50% when moving from supine to 10° head-down ...
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Background
Adverse effects of spaceflight on sensorimotor function have been linked to altered somatosensory and vestibular inputs in the microgravity environment. Whether these spaceflight sequelae have a central nervous system component is unknown. However, experimental studies have shown spaceflight-induced brain structural changes in rodents’ s...
Citations
... Based on our search criterion through electronic databases (Supplementary Tables 2-5): 165 records were obtained in PubMed, 66 in MEDLINE, 96 in Embase and 2 in Cochrane and EBM reviews yielding a total of 329 records Many records were duplicates (n = 138), were not eligible (n = 174) with all three eligibility criteria being unmet (n = 94), two of them unmet (n = 25), or only one unmet (n = 49) and other reasons (n = 6) such as records published in forms of abstract (n = 1), review (n = 2), reply/ comments (n = 1) and multiple records (n = 2). Thus, finally, 17 full text records were sought for retrieval and assessed for eligibility of which two were excluded (one a method description about remote echography 12 and the other a review paper 13 ), but 15 were retained 1,2,[14][15][16][17][18][19][20][21][22][23][24][25][26] . ...
... Included studies were published between 1994 and 2022. Two reported on acute exposure to microgravity and hypogravity during parabolic flight campaigns 23,24 , one on short-term 28 and ten on longterm (≥6 months) chronic exposure 2, [14][15][16]18,19,21,22,25,26 ; In three other studies the class of exposure duration was not reported 1,17,20 . Only three studies involved DVT detection 1,2,25 of which one reported exclusively on DVT 1 (Table 3). ...
... The purpose was to identify changes induced by microgravity in the upper body venous system to account for when carrying out explorations in spaceflight. Of the 16 spaceflight studies included, 13 focused solely on microgravity-related changes [14][15][16][17][18][19][20][21][22][23][24]26,28 , one exclusively on DVT detection 1 , and two studies on both microgravityrelated changes and DVT detection 2,25 . Most studies reported inflight V-US changes in contrast with terrestrial findings (pre-flight mainly) at the level of the IJVs, rarely the femoral veins. ...
The validity of venous ultrasound (V-US) for the diagnosis of deep vein thrombosis (DVT) during spaceflight is unknown and difficult to establish in diagnostic accuracy and diagnostic management studies in this context. We performed a systematic review of the use of V-US in the upper-body venous system in spaceflight to identify microgravity-related changes and the effect of venous interventions to reverse them, and to assess appropriateness of spaceflight V-US with terrestrial standards. An appropriateness tool was developed following expert panel discussions and review of terrestrial diagnostic studies, including criteria relevant to crew experience, in-flight equipment, assessment sites, ultrasound modalities, and DVT diagnosis. Microgravity-related findings reported as an increase in internal jugular vein (IJV) cross-sectional area and pressure were associated with reduced, stagnant, and retrograde flow. Changes were on average responsive to venous interventions using lower body negative pressure, Bracelets, Valsalva and Mueller manoeuvres, and contralateral IJV compression. In comparison with terrestrial standards, spaceflight V-US did not meet all appropriateness criteria. In DVT studies ( n = 3), a single thrombosis was reported and only ultrasound modality criterion met the standards. In the other studies ( n = 15), all the criteria were appropriate except crew experience criterion, which was appropriate in only four studies. Future practice and research should account for microgravity-related changes, evaluate individual effect of venous interventions, and adopt Earth-based V-US standards.
... Central venous pressure (CVP) is a key haemodynamic parameter relevant to the assessment of venous compliance, cephalad fluid shift and change in cardiac filling pressure, and it has a strong linear relationship with intracranial pressure (Buckey et al., 1996;Hansen et al., 2021;Lawley et al., 2017;Mader et al., 2011;Martin et al., 2016). ...
... Therefore, the internal jugular vein is often used as a non-invasive surrogate for venous pressure due to its role in cerebral venous drainage and direct connection to the central venous circulation. Compression sonography has been proposed as a novel method for non-invasive measurement of venous pressures during spaceflight (Marshall-Goebel et al., 2019;Martin et al., 2016). In this technique, a fluid-filled bladder and manometer is fitted to an ultrasound probe to quantify hold-down pressure while imaging a vein. ...
... during spaceflight (Martin et al., 2016), and data supporting the accuracy of compression sonography on larger, deeper veins in the neck are limited. A single study comparing compression ultrasound of the jugular veins to invasive measurements of CVP showed a poor correlation in the range of 0-10 mmHg (Tomoeda et al., 2020). ...
Compression sonography has been proposed as a method for non‐invasive measurement of venous pressures during spaceflight, but initial reports of venous pressure measured by compression ultrasound conflict with prior reports of invasively measured central venous pressure (CVP). The aim of this study is to determine the agreement of compression sonography of the internal jugular vein (IJVP) with invasive measures of CVP over a range of pressures relevant to microgravity exposure. Ten healthy volunteers (18–55 years, five female) completed two 3‐day sessions of supine bed rest to simulate microgravity. IJVP and CVP were measured in the seated position, and in the supine position throughout 3 days of bed rest. The range of CVP recorded was in line with previous reports of CVP during changes in posture on Earth and in microgravity. The correlation between IJVP and CVP was poor when measured during spontaneous breathing (r = 0.29; R² = 0.09; P = 0.0002; standard error of the estimate (SEE) = 3.0 mmHg) or end‐expiration CVP (CVPEE; r = 0.19; R² = 0.04; P = 0.121; SEE = 3.0 mmHg). There was a modest correlation between the change in CVP and the change in IJVP for both spontaneous ΔCVP (r = 0.49; R² = 0.24; P < 0.0001) and ΔCVPEE (r = 0.58; R² = 0.34; P < 0.0001). Bland–Altman analysis of IJVP revealed a large positive bias compared to spontaneous breathing CVP (3.6 mmHg; SD = 4.0; CV = 85%; P < 0.0001) and CVPEE (3.6 mmHg; SD = 4.2; CV = 84%; P < 0.0001). Assessment of absolute IJVP via compression sonography correlated poorly with direct measurements of CVP by invasive catheterization over a range of venous pressures that are physiologically relevant to spaceflight. However, compression sonography showed modest utility for tracking changes in venous pressure over time.
... This lack of specificity due to higher pressures needed to compress, and thus collapse a vein may potentially be alleviated by simply using an adjacent artery as a visual 'pressure gauge'. For instance, by increasing the pressure applied at the ultrasound probe to that required to almost close the adjacent artery, the visualised vein segment should be completely compressed 37 . ...
The recent incidental discovery of an asymptomatic venous thrombosis (VT) in the internal jugular vein of an astronaut on the International Space Station prompted a necessary, immediate response from the space medicine community. The European Space Agency formed a topical team to review the pathophysiology, risk and clinical presentation of venous thrombosis and the evaluation of its prevention, diagnosis, mitigation, and management strategies in spaceflight. In this article, we discuss the findings of the ESA VT Topical Team over its 2-year term, report the key gaps as we see them in the above areas which are hindering understanding VT in space. We provide research recommendations in a stepwise manner that build upon existing resources, and highlight the initial steps required to enable further evaluation of this newly identified pertinent medical risk.
... Measurements of IJVP with the VeinPress are likely slightly elevated compared with the true venous pressure, because of compression of the tissue surrounding the IJV. Changes in fluid compartmentalization (79)(80)(81), including fluid shift to extravascular spaces as well as potential changes in the neck tissue due to chronic muscular deconditioning over long-duration spaceflight, may result in both a reduced venous pressure as well as an underestimation of that measurement (82). Third, there are fundamental differences in the vascular response to tilt compared with true microgravity. ...
... Third, the data collected were limited to noninvasive measures, in particular for IJVP. The VeinPress device used in the study was chosen for its heritage of use in previous spaceflight and parabolic flight investigations (10,24,82), thus facilitating direct comparison between studies. It is acknowledged that invasive measures, such as venous catheterization, may provide more accurate measurements of IJVP. ...
Altered-gravity affects hemodynamics and blood flow in the neck. At least one incidence of jugular venous thrombosis has been reported in an astronaut on the International Space Station. This investigation explores the impact of changes in the direction of the gravitational vector on the characteristics of the neck arteries and veins. Twelve subjects underwent graded tilt from 45° head-up to 45° head-down in 15° increments in both supine and prone positions. At each angle, the cross-sectional area of the left and right common carotid arteries, A CCA , and internal jugular veins, A IJV , were measured using ultrasound. Internal jugular venous pressure, IJVP, was also measured using compression sonography. Gravitational dose-response curves were generated from experimental data. A CCA did not show any gravitational dependence. Conversely, both A IJV and IJVP increased in a non-linear fashion with head-down tilt. A IJV was significantly larger on the right side than the left side at all tilt angles. In addition, IJVP was significantly elevated in the prone position compared to the supine position, most likely due to raised intrathoracic pressure whilst prone. Dose-response curves were compared with existing experimental data from parabolic flight and spaceflight studies, showing good agreement on an acute timescale. The quantification of jugular hemodynamics as a function of changes in the gravitational vector presented herein provides a terrestrial model to reference spaceflight-induced changes, contributes to the assessment of the pathogenesis of spaceflight venous thromboembolism events, and informs the development of countermeasures.
... There have been attempts to estimate central venous pressure noninvasively, but no suitable methods have been established (Martin et al., 2016;Zamboni et al., 2020). ...
New findings:
What is the central question of this study? Facial skin blood flow (SBF) might increase during head-down tilt (HDT). However, the effect of HDT on facial SBF remains controversial. In addition, the changes in facial SBF in the cheek (cheek SBF) during a steeper angle of HDT (>-12° HDT) have not been investigated. What is the main finding and its importance? This study showed that cheek SBF decreased during -30° HDT, alongside increased vascular resistance. Furthermore, vascular impedance was suggested to be elevated, accompanied by an increased hydrostatic pressure gradient caused by HDT. Constriction of the facial skin vascular bed and congestion of venous return owing to the steep angle of HDT can decrease facial SBF.
Abstract:
Head-down tilt (HDT) has been used to simulate microgravity in ground-based studies and clinical procedures including the Trendelenburg position or in certain surgical operations. Facial skin blood flow (SBF) might be altered by HDT, but the effect of a steeper angle of HDT (>-12° HDT) on facial SBF remains unclear. We examined alterations in facial SBF in the cheek (cheek SBF) using two different angles (-10 and -30°) of HDT and lying horizontal (0°) in a supine position for 10 min, to test the hypothesis that cheek SBF would increase with a steeper angle of HDT. Cheek SBF was measured continuously by laser Doppler flowmetry. Cheek skin vascular resistance and the pulsatility index of cheek SBF were calculated to assess the circulatory effects on the facial skin vascular bed in the cheek. Cheek SBF decreased significantly during -30° HDT. In addition, the resistance in cheek SBF increased significantly during -30° HDT. The pulsatility index of cheek SBF increased during both -10 and -30° HDT. Contrary to our hypothesis, cheek SBF decreased during -30° HDT along with increased skin vascular resistance. Vascular impedance, estimated by the pulsatility index in the cheek SBF, was elevated during both -10 and -30° HDT, and elevated vascular impedance would be related to increased hydrostatic pressure induced by HDT. Skin vascular constriction and venous return congestion would be induced by -30° HDT, leading to deceased cheek SBF. The present study suggested that facial SBF in the cheek decreased during acute exposure to a steep angle of HDT (∼-30° HDT).
... Increased CSA occurs immediately upon assuming a head down position (Arbeille et al., 2001;Clenaghan et al., 2005;Schreiber et al., 2002) and has been observed to remain enlarged for up to 42 days of continuous HDT (Arbeille et al., 2001). Due to the highly compliant nature of veins, CSA expansion is indicative of increased venous pressure (Chua Chiaco et al., 2013;Dawson et al., 2004;Martin et al., 2016). Elevated IJV pressure in HDT contributes to the hydrostatic gradient that increases intracranial pressure (Petersen et al., 2016). ...
Non-contact coded hemodynamic imaging (CHI) is a novel wide-field near-infrared spectroscopy system which monitors blood volume by quantifying attenuation of light passing through the underlying vessels. This study tested the hypothesis that CHI-based jugular venous attenuation (JVA) would be larger in men, and change in JVA would be greater in men compared to women during two fluid shift challenges. The association of JVA with ultrasound-based cross-sectional area (CSA) was also tested. Ten men and 10 women completed three levels of head-down tilt (HDT) and four levels of lower body negative pressure (LBNP). Both JVA and CSA were increased by HDT and reduced by LBNP (all p < 0.001). Main effects of sex indicated that JVA was higher in men than women during both HDT (p = 0.003) and LBNP (p = 0.011). Interaction effects of sex and condition were observed for JVA during HDT (p = 0.005) and LBNP (p < 0.001). We observed moderate repeated-measures correlations (rrm ) between JVA and CSA in women during HDT (rrm = 0.57, p = 0.011) and in both men (rr m = 0.74, p < 0.001) and women (rrm = 0.66, p < 0.001) during LBNP. While median within-person correlation coefficients indicated an even stronger association between JVA and CSA, this association became unreliable for small changes in CSA. As hypothesized, JVA was greater and changed more in men compared to women during both HDT and LBNP. CHI provides a non-contact method of tracking large changes in internal jugular vein blood volume that occur with acute fluid shifts, but data should be interpreted in a sex-dependent manner.
... The µg environment occurs when the sum of all forces acting on the aircraft, apart from gravity, reaches values near zero [83]. Researchers can experiment on gravity levels between 1 × 10 −2 and 1 × 10 −3 G between 20 and 30 s [83][84][85][86][87]. This parabola is repeated consecutively to increase the timeframe of µg. ...
... During another parabolic flight, researchers tried to determine the behaviour of the internal jugular pressure and its possible causality on visual impairment and intracranial pressure observed in astronauts onboard the ISS [86]. The findings revealed that the internal jugular venous pressure increases considerably with fluid shifts induced by µg. ...
On Earth, humans are subjected to a gravitational force that has been an important determinant in human evolution and function. During spaceflight, astronauts are subjected to several hazards including a prolonged state of microgravity that induces a myriad of physiological adaptations leading to orthostatic intolerance. This review summarises all known cardiovascular diseases related to human spaceflight and focusses on the cardiovascular changes related to human spaceflight (in vivo) as well as cellular and molecular changes (in vitro). Upon entering microgravity, cephalad fluid shift occurs and increases the stroke volume (35–46%) and cardiac output (18–41%). Despite this increase, astronauts enter a state of hypovolemia (10–15% decrease in blood volume). The absence of orthostatic pressure and a decrease in arterial pressures reduces the workload of the heart and is believed to be the underlying mechanism for the development of cardiac atrophy in space. Cellular and molecular changes include altered cell shape and endothelial dysfunction through suppressed cellular proliferation as well as increased cell apoptosis and oxidative stress. Human spaceflight is associated with several cardiovascular risk factors. Through the use of microgravity platforms, multiple physiological changes can be studied and stimulate the development of appropriate tools and countermeasures for future human spaceflight missions in low Earth orbit and beyond.
... These changes may help explain alterations in vision and cognition observed in astronauts returning from space missions. [135][136][137] Altered gravitation forces and biophysical forces may have direct impacts on pericyte and interstitial fluid dynamics as well. Pericytes experience different magnitudes of perivascular hydrodynamic stresses as the transmural pressure difference decreases from arterioles to venules, and altered gradients in space may have profound impacts on fluid mechanisms and perivascular structural function. ...
The complex and dynamic system of fluid flow through the perivascular and interstitial spaces of the central nervous system has new-found implications for neurological diseases. Cerebrospinal fluid movement throughout the CNS parenchyma is more dynamic than could be explained via passive diffusion mechanisms alone. Indeed, a semi-structured glial-lymphatic (glymphatic) system of astrocyte-supported extracellular perivascular channels serves to directionally channel extracellular fluid, clearing metabolites and peptides to optimize neurologic function. Clinical studies of the glymphatic network has to date proven challenging, with most data gleaned from rodent models and post-mortem investigations. However, increasing evidence suggests that disordered glymphatic function contributes to the pathophysiology of CNS aging, neurodegenerative disease, and CNS injuries, as well as normal pressure hydrocephalus. Unlocking such pathophysiology could provide important avenues toward novel therapeutics. We here provide a multidisciplinary overview of glymphatics and critically review accumulating evidence regarding its structure, function, and hypothesized relevance to neurological disease. We highlight emerging technologies of relevance to the longitudinal evaluation of glymphatic function in health and disease. Finally, we discuss the translational opportunities and challenges of studying glymphatic science.
... Noninvasive pressure in the left and right IJV was measured using a Vivid Q ultrasound machine (General Electric) and the VeinPress compression sonography system (Meridian AG), as previously described (16). Briefly, the IJV was imaged through a pressure-sensing fluid-filled bladder connected to a 5-12 MHz linear array probe. ...
... These results are in line with other studies that implemented differing noninvasive and invasive measures of ICP during LBNP (9,22,23). In addition, central venous pressure has been shown to decrease by $2 mmHg per 10 mmHg LBNP (24), and when applied in the supine position at low levels (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), LBNP elicits the same physiological responses as the loss of $1 L of centrally available blood volume (25). As LBNP devices enclose the lower limbs and are normally sealed at the iliac crest (8), the lumbar spinal CSF space also may be influenced by LBNP, shifting CSF out of the cranial space and into the spinal subarachnoid space and thecal sac, thus lowering ICP at the level of the external auditory meatus. ...
Head-to-foot gravitationally-induced hydrostatic pressure gradients in the upright posture on Earth are absent in weightlessness. This results in a relative headward fluid shift in the vascular and cerebrospinal fluid compartments and may underlie multiple physiological consequences of spaceflight, including the Spaceflight Associated Neuro-ocular Syndrome. Here, we tested 3 mechanical countermeasures (lower body negative pressure [LBNP], veno-constrictive thigh cuffs [VTC] and impedance threshold device [ITD] resistive inspiratory breathing) individually and in combination to reduce a posture-induced headward fluid shift as a ground-based spaceflight analog. Ten healthy subjects (5 male) underwent baseline measures (seated and supine postures) followed by countermeasure exposure in the supine posture. Noninvasive measurements included ultrasound (internal jugular veins [IJV] cross-sectional area, cardiac stroke volume, optic nerve sheath diameter, noninvasive IJV pressure), transient evoked otoacoustic emissions (OAE; intracranial pressure index), intraocular pressure, choroidal thickness from optical coherence tomography imaging, and brachial blood pressure. Compared to the supine posture, IJV area decreased 48% with application of LBNP (mean ratio: 0.52, 95% CI: 0.44-0.60, P<0.001), 31% with VTC (mean ratio: 0.69, 95% CI: 0.55-0.87, P<0.001), and 56% with ITD (mean ratio: 0.44, 95% CI: 0.12-1.70, P=0.46), measured at end-inspiration. LBNP was the only individual countermeasure to decrease the OAE phase angle (Δ -12.9 degrees, 95% CI: -25 to -0.9, P=0.027), and use of combined countermeasures did not result in greater effects. Thus, LBNP, and to a lesser extent VTC and ITD, represent promising headward fluid shift countermeasures, but will require future testing in analog and spaceflight environments.
... Post-flight MRIs of astronauts have shown findings similar to those seen in terrestrial high ICP states such as idiopathic intracranial hypertension (IIH) including posterior globe flattening and concavity of the pituitary dome (31). Jugular venous distension (JVD) occurs in microgravity studies supporting a hypothesis of venous congestion in the microgravity environment impeding cerebrospinal fluid absorption (3,32,33). Furthermore, optic disc edema seen in SANS is a hallmark sign of terrestrial high ICP (3,34). Lastly, post-flight lumbar puncture readings in astronauts with optic disc edema showed an upper limit of high normal to slightly elevated post flight opening pressures (21-28.5 cm H 2 0), though these may not be representative as they were collected 12-57 days post flight (17). ...
Astronauts who undergo prolonged periods of spaceflight may develop a unique constellation of neuro-ocular findings termed Spaceflight Associated Neuro-Ocular Syndrome (SANS). SANS is a disorder that is unique to spaceflight and has no terrestrial equivalent. The prevalence of SANS increases with increasing spaceflight duration and although there have been residual, structural, ocular changes noted, no irreversible or permanent visual loss has occurred after SANS, with the longest spaceflight to date being 14 months. These microgravity-induced findings are being actively investigated by the United States' National Aeronautics Space Administration (NASA) and SANS is a potential obstacle to future longer duration, manned, deep space flight missions. The pathophysiology of SANS remains incompletely understood but continues to be a subject of intense study by NASA and others. The study of SANS is of course partially limited by the small sample size of humans undergoing spaceflight. Therefore, identifying a terrestrial experimental model of SANS is imperative to facilitate its study and for testing of preventative measures and treatments. Head-down tilt bed rest (HDTBR) on Earth has emerged as one promising possibility. In this paper, we review the HDTBR as an analog for SANS pathogenesis; the clinical and imaging overlap between SANS and HDTBR studies; and potential SANS countermeasures that have been or could be tested with HDTBR.
