Table 3 Characteristics of included studies.
Study author Study acronym | Participating centres Study time-period (TP) Study duration (D) | Study objective | Study design | Study population | Study outcomes/ measures Analysis issues | Summary of venous ultrasound findings |
|---|---|---|---|---|---|---|
Arbeille et al.28 “Antarès” Spaceflight | On board MIR station Faculté de Médecine – Tours- France Institute of Biomedical Problems – Moscow-Russia TP: NR D: 89 days (pre-flight 60 days, in-flight 14 days and post-flight 15 days) | At rest: cardiovascular adaptation to 0 g at the level of the heart, the deep and superficial vessels. During LBNP (−25, −35, −45mmHg of 10 min): orthostatic tolerance by monitoring the cerebral and femoral response | Interventional Prospective study Repeated measurements - pre-flight (Days −60, −30, −10), in-flight (Days +5, +9, +12, and with the LBNP on day +11) - post-flight (at landing day +1, +3, +7, +15) | 1 astronaut | IJV and femoral vein CSA, IJV distensibility, IJV and hepatic vein indices Blood pressure and CVP Calf volume changes measured by plethysmography. Analysis limited to a single astronaut | IJV CSA increased from D1 in-flight, and femoral vein after D9. LBNP: Disadapted response for the femoral vascular resistance |
Arbeille et al.14 | Unité de médecine et de Physiologie Spatiales Tours - France Institute of Biomedical Problems, Moscow-Russia TP: NR D: until 6 months | To identify the major cardiovascular changes to real or simulated 0 g with a minimum of countermeasures Summary of multiple studies performed by the author. | Interventional Prospective studies Repeated measurements (Spaceflights: 6, 14, 21, 25 days and 6 months. HDT: 10 h, 4, 5, 7, 30 and 42 days) | NR Review and update regarding multiple studies by the author | IJV and femoral vein CSA Wilcoxon matched pair test Sample size not provided | IJV CSA significantly enlarged during the flight and HDT (+40%). Femoral vein significantly enlarged during spaceflight after 1 week (+15% to +35%), significantly decreased after 4–5 days of HDT (−20% to −35%) |
Arbeille et al.15 The Vessel Imaging study | ISS (NASA, ESA, CNES) TP: 2009–2013 D: 6 months | To investigate during a 6-month spaceflight the changes in the major central and peripheral vein properties, to quantify venous blood flow redistribution during the early and late phases of exposure to microgravity | Interventional Prospective cohort Repeated measurements -pre-flight (supine, seated) -in-flight (Day 15, 115, 135 and 15 days before return to earth) -post-flight (4 days after return) | 10 astronauts Age: 47 ± 5 Gender: M/F 7/3 Mass: 69 ± 12 kg Height: 1.72 ± 8 m | CSA of the IJV, portal, femoral, gastrocnemius and tibial veins Volume of the IJV and the portal vein Ratio of IJV to portal vein volumes 2/10 excluded from inflight analysis for missing data | Increased IJV and portal vein volumes, increased femoral vein area, and reduced calf vein area. Significant venous blood pooling that persists throughout the duration of the spaceflight |
Arbeille et al.16 | ISS (NASA, UCSD) TP: NR D: 210 ± 76 days | To investigate microgravity-associated increase in IJV volume, portal vein CSA, and intracranial venous blood velocity and determine if LBNP would return variables toward pre-flight levels | Interventional Prospective cohort Repeated measurements with and without LBNP: -pre-flight (supine, seated, 15° HDT) -in-flight (Day 45, 150) -post-flight (40 and 180 days after return to earth) | 14 astronauts Age: 47 ± 6 Gender: M/F 11/3 BMI: 26.4 ± 3 | IJV volume Portal vein area Middle cerebral vein velocity LBNP −25 mmHg Some measurements not available at various time points (due to poor ultrasound image quality, inability to find the middle cerebral vein, inadequate images of the portal vein). | Increased IJV volume and portal vein area Increased middle cerebral vein velocity. Sustained cephalad fluid shift (head and splanchnic regions) and impact on cerebral venous circulation. LBNP −25 mmHg restored variables at least back to pre-flight supine levels. |
Aunon et al.1 | ISS TP: NR D: NR | Case report | Descriptive | 1 patient | 1/ Reporting a case of a left IJV thrombosis in spaceflight detected during a vascular research study in an asymptomatic patient | 1/ Asymptomatic patient while the thrombus occlusive |
2/ US guided in real time and interpreted by two radiologists | 2/ US performed by astronaut | |||||
3/ Image of subacute (?) venous thrombosis reported | 3/ Image compatible with a stagnant flow. No obvious direct image of the thrombus although a L12 MHz probe was used at 1 to 2 cm distance from skin. | |||||
4/ US surveillance at 7-to-21-day intervalsshowed progressive organisation and volume reduction of the thrombus. | 4/ Thrombus consistency pattern may depend on US compression test. The estimation of volume reduction may depend on probe positioning. No diameter or volume measurement was performed. | |||||
5/ No spontaneous flow. Flow through the affected IJV segment was first noted on treatment day 47, but only on augmentation by Müller manoeuvre. | 5/Flow on augmentation by Müller manoeuvre was detected through the affected IJV segment means this was a stagnant flow | |||||
6/ The absence of spontaneous flow persisted after 90 days of anticoagulation but on landing (4 days after anticoagulation was stopped), a point-of-care US examination revealed spontaneous flow. | 6/ How to explain the recovery of a spontaneous flow on landing (whereas it was absent during more than 90 days in space) other than by the abolition of stasis-related microgravity on landing. | |||||
David et al.17 | NASA Gagarin Cosmonaut Training Centre TP : NR D : NR | To assess the effects of the long-used Russian (known as the Russian pre-launch) tilt-table training protocol on IJV CSA in microgravity | A case study | A single healthy male volunteer astronaut | Multiple measurements of the CSA at −15°, −30°, and +50°, along with 0° (pre-tilt) and 0° (post-tilt). The average CSA was computed for each angle and compared to the in-flight average using Student’s t-test. | Right IJV-CSA were significantly different between in-flight values and several angles of the Russian tilt-table protocol (higher with negative angles), except for the 0° measurement (post-tilt 0°). |
Fomina et al.18 | Flights of Russian and Russian-French crews on board Mir orbital station TP: 1994–1999 D: (438-day astronaut-doctor mission, 15–17, 22–23, 25–27 of the main expedition) | To analyse changes in human venous haemodynamic during prolonged exposure (6 months) to weightlessness | Interventional Prospective cohort Repeated measurements | 7 astronauts for the US exam (six men) 33 to 52 years old | B-mode and doppler US - IJV CSA measurements before, during and after SF at rest and during a dosed Valsalva test (exhalation into a special mouthpiece connected to a manometer until a pressure of 50 mmHg was reached), - Femoral CSA measurements taken only at rest before, during and after SF. - Large abdominal veins (hepatic, portal and spleen veins) Occlusion plethysmography Analysis issues comparison of means (only 7 astronautrs for the US exam) | IJV CSA: significant increase by 28 ± 4.3% throughout the long-term SF, but no increasing trend in changes from month 1 to month 6. Wall distensibility did not increase (“increased IJV area most likely solely due to venous stasis”) Femoral area: significant increase by 31.3 ± 5.0% in the 1st month of SF; significant difference in femoral area between months 1 and 5–6 of SF (decrease in venous blood flow rate i.e. venous return) Abdominal veins (hepatic, portal and spleen veins) enlarged. |
Fomina et al.19 | Mir orbital space station (OSS) TP: NR D: 126 to 183 days (a physician cosmonaut on board for a 438-day mission) | To assess the effect of long-term use of prophylactic device (PD) Braslet on haemodynamic changes in a spaceflight lasting between 126 and 438 days | Interventional Prospective cohort Repeat measurements on the same day, after 5 h of Braslet use. Braslet during the flight in the daytime; Braslet-free period 10–12 h. Three investigations over 6 months in 6 men (a 38-year-old woman actively used PD Braslet only during the initial period of adaptation to weightlessness, and then only on the study day of the ECHO-Braslet experiment programme throughout the flight) | 7 cosmonauts (six men) aged 33 to 52 years old | Changes in haemodynamic were assessed as a percentage of the pre-mission background and relative to the control without PD Braslet on the day of the study. Mean values were calculated for the group of cosmonauts who regularly used PD Braslet (six), and the mean error of the mean values (M ± t). “Difference in the mean in small samples, odds ratio (p), Student’s Distribution (t)” | Braslet-free: Reduced SV −17%, CO −22%, renal artery resistance without significant changes in blood pressure and heart rate, cephalic congestion (blood rush), IJV and femoral vein dilation, tendency for average cerebral blood flow rate to decrease slightly Braslet: SV and CO: No change at months 1 and 3, higher at month 5. Reduction of cephalic congestion and IJV CSA, no noticeable effect on cerebral blood flow, femoral vein CSA higher |
Hamilton et al.20 | ISS (NASA Telescience Centre in Houston, TX, and the Mission Control Centre in Korolyov, Moscow region, Russia) TP: NR D: NR | To examine the responses to modified Valsalva and Mueller manoeuvres measured by cardiac and vascular ultrasound (ECHO) in a baseline steady state and under the influence of thigh occlusion cuffs as a countermeasure device (Braslet cuffs) | Interventional Prospective cohort Repeated measurements during modified Valsalva and Mueller manoeuvres with and without thigh occlusion cuffs | 9 astronauts Age: NR Gender: NR | Effect of acute application of Braslet on cardiac parameters, and IJV and Femoral vein CSA Comparison of Valsalva, Mueller, and baseline manoeuvres with and without Braslet High quality study and reporting | Braslet reduces the effective circulating volume by sequestering fluid in the lower extremities (increased femoral vein area) Braslet reduces preload indexes measured by echocardiography. Braslet reduces IJV distention, increases sensitivity of IJV area to thoracic manoeuvres. |
Herault et al.21 | MIR station (French and Russian): three 6-month spaceflights TP: NR D: 3 long-term 6-month spaceflights | To study the effects of thigh cuffs (braslets) on cardiovascular adaptation (cardiac, arterial, and venous changes) and deconditioning in 0 g. | Interventional Prospective cohort At rest: Repeated measurements (pre-flight D-30, inflight 1 month/3 months/5 months, postflight D1 and D7): before thigh cuffs, after 5 h with the thigh cuffs. LBNP −45 mmHg (without the cuffs) 1 day after each resting measurement session | 6 astronauts | Cardiac parameters (LVEDV, SV, CO, ejection fraction) Arterial resistance: middle cerebral artery, carotid artery and renal artery resistance, femoral artery IJV and femoral vein CSA Calf volume | Inflight without cuffs Lower LVEDV and SV (vs preflight) CSA: IJV + 23% to +30%, Femoral vein: +33% to +70% Resistance: renal artery: −15% to −16%, Femoral artery −5% to −11% Inflights “with versus without” cuffs CSA: IJV −12% to −20%, Femoral vein +9% to +20% Increased resistance LBNP inflight/postflight versus pre-flight Less increase of femoral resistance and cerebral/femoral blood flow ratio Less increase in calf circumference |
Jasien et al.22 | ISS Multiple institutions and international partners and space agencies NASA, Houston Texas, Russian Federation State Research Centre Institute of Biomedical problems TP: NR D: 215 ± 72-day mission | To use multiple non-invasive methods (including IJV pressure) to assess intracranial pressure (ICP) before, during and after long-duration spaceflight, and to determine if use of LBNP could reduce ICP during spaceflight | Interventional Prospective cohort Repeated measurements -Pre-flight and post-flight postures: seated, supine, and 15° HDT -Inflight: D45 (FD45) and 150 (FD150) with and without LBNP -Postflight: R + 10, R + 30, R + 180 | 13 crewmembers (2 females, 11 males. Age (mean ± SD): 46 ± 6.6 Weight (mean ± SD): 81.5 ± 9.5 kg | Inflight versus pre-flight measurements of: - Cerebral and cochlear fluid pressure (CCFP) - Otoacoustic emissions (OAE) - Ultrasound measures of optic nerve sheath diameter (ONSD) - Ultrasound-based IJV pressure (IJVp) using VeinPress device Comparison of observed effects with modelled means (95% confidence intervals) | IJVP without LBNP Mean difference (95% CI) mmHg: - FD45 vs pre-flight supine: −2.6 (−6.6, 1.5) - FD45 vs pre-flight seated: 14.3 (10.1, 18.5) - FD45 versus 15° HDT: −4.1 (−0.1, −8.2) - FD45 vs FD150: −2.2 (−6.4, 2) IJVP with LBNP not measured |
Lee et al.23 | Lyndon B. Johnson Space Centre, NASA, Houston, TX, USA KBR, Houston, TX, USA Memorial Sloan Kettering Cancer Centre, NY, USA School of Kinesiology, University of Michigan, Ann Arbor, MI, USA Novespace, Bordeaux-Mérignac, F TP : 2018 D : 3 days | To characterise the relationships between gravitational level (Gz-level) and acute vascular changes | Interventional Prospective cohort Repeated measurements IJV CSA (and flow patterns), inferior vena cava (IVC) diameter, and common carotid artery (CCA) flow were measured using ultrasound in subjects while seated when exposed to 1.00-Gz, 0.75-Gz, 0.50-Gz, and 0.25-Gz during parabolic flight and while supine before flight (0-G analogue). | 9 subjects (5 F, 4 M) Age: 39 ± 6 years old (mean ± SD; range: 34–50 years), Height: 171 ± 11 cm (157–187 cm) Weight 65 ± 10 kg (50–85 kg). | Right IJV CSA Doppler flow patterns IJV pressure Right CCA CSA and flow No issues Descriptive and graphical summaries Linear regression Generalised estimating equations using an independence correlation structure (GEE-Ind) to account for repeated measurements within subject Paired t-test | IJV area progressively increased from 12 (95% CI: 9–16) mm2 during 1.00-Gz seated to 24 (13–35), 34 (21–46), 68 (40–97), and 103 (75–131) mm2 during 0.75-Gz, 0.50-Gz, and 0.25-Gz seated and 1.00-Gz supine, respectively. IJV flow patterns shifted from the continuous forward flow observed during 1.00-Gz and 0.75-Gz seated to pulsatile flow during 0.50-Gz seated, 0.25-Gz seated, and 1.00-Gz supine. IJV pressure: minimal difference from 1.00-Gz supine to 0.25-Gz seated for two subjects and an increased IJV pressure in one subject. IJV pressure at 0.50-Gz seated (9.5 ± 3.4 mmHg) was lower than 1.00-Gz supine (19.1 ± 7.6 mmHg) for all five subjects [difference: 9.6 (95% CI: 5.0–14.1), p = 0.003]. Unable to detect differences in IVC diameter measured during 1.00-G seated and any level of partial gravity or during 1.00-Gz supine. |
Marshall-Goebel et al.2 Multi-institution international fluid shifts study | KBR, Houston, TX. Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Russian Federation University Hospital Trousseau, Tours, F Applied Biostatistics Laboratory, School of Nursing, University of Michigan, Ann Arbor. Department of Surgery, Henry Ford Hospital, Detroit, Michigan. Department of Orthopaedic Surgery, UC San Diego Medical Centre, University of California, San Diego NASA, Johnson Space Centre, Houston, TX TP: not explicit to protect the identities of participants D: Spaceflight 180 days | To assess IJV area and pressure, as well as characterise the Doppler flow velocity profile during spaceflight compared with various postures on Earth and to investigate if lower body negative pressure (−25 mmHg) is associated with reversing the headward fluid shift experienced during spaceflight. | Interventional Prospective cohort Design: longitudinal, with astronauts providing data from each of 3 postures preflight and postflight (seated, supine, head-down tilt), and 2 in-flight conditions observed at 2 periods (spaceflight and spaceflight with LBNP at approximate flight days 50 and 150) Non-invasive IJVP (mmHg) measured by compression US using the VeinPress device. | 11 crew members Age (mean [SD]: 46.9 [6.3] years. Gender: 9 [82%] men. Body mass index (mean [SD] 26.4 [3]) | Longitudinal study with comparison of spaceflight (+/− LBNP) at different times with pre-flight and postflight postures for analysis of: - Mean IJV area - Mean IJV pressure Analysis of - Flow patterns - Thrombus formation No issues in analysis Mixed models | Mean IJV area: -Pre-flight seated position 9.8 (95% CI, −1.2 to 20.7) mm2 -Spaceflight: 70.3 (95%CI, 59.3–81.2) mm2 (P < 0.001). Mean IJV pressure: -Preflight seated position: 5.1 (95% CI, 2.5–7.8) mm Hg -Spaceflight: 21.1 (95%CI, 18.5–23.7) mm Hg (P < 0.001). Stagnant (n = 5) or reverse (n = 1) flow in the IJV on approximate flight day 50 in 6 crew members (55%) Occlusive IJV thrombus (with stagnant flow): 1 crew member (same case as in Aunon S.M. et al (2020) publication Potential partial IJV thrombus (with stagnant flow): 1 subject retrospectively. LBNP −25 mmHg during spaceflight reduced IJV area and improved blood flow in 10 of 17 sessions (59%) |
Martin et al.24 | KBRwyle Science, Technology & Engineering Group, Houston, Texas MEI Technologies, Houston, Texas Universities Space Research Association, Houston, Texas NASA Johnson Space Centre, Houston, Texas TP: NR D: Four flights (Each flight lasted approximately 2.5 h) | To measure IJV pressure (IJVP) during normo- and hypo-gravity as an index of venous congestion. To determine whether IJVP, as a potential contributor to elevated ICP, was increased from normal (1 G) to weightlessness (0 G). | IJVP was measured during normal gravity (1 G - supine) and weightlessness (0 G - seated) produced by parabolic flight - at rest (end-expiration) and during controlled breathing manoeuvres (10 mmHg, 20 mmHg). Each flight included 40 parabolas, providing about 20 sec of 0 G or partial gravity per parabola. Each reduced gravity parabola was preceded and followed by a hypergravity phase of up to 1.8 G lasting about 20 sec. IJVP also was measured in two subjects during parabolas approximating Lunar (1/6 G) and Martian gravity (1/3 G). Non-invasive IJVP (mmHg) measured by compression US using the VeinPress device. | 11 normal, healthy subjects (3 M, 8 F) Mean age: 39.5 years, range 27–60 yrs) Mean height: 168 cm, range: 157–196 cm; Mean weight: 66.6 kg, range: 50.5–109.9 kg) | Differences in IJVP between 1 G and 0 G tested using a paired T-test. No statistical issues A mixed-effects linear regression model to examine the effect of gravity and breathing manoeuvres on IJVP using dummy-coded grouping variables for gravity and pressure relative to 1 G seated. Bootstrap resampling performed to improve estimates of variance given the small sample size. Holm correction for multiple comparisons between baseline and each treatment condition. | IJVP was higher in 0 G than 1 G (23.9 ± 5.6 vs. 9.9 ± 5.1 mmHg, mean ± SD P < 0.001) in all subjects. IJVP increased as gravity levels decreased in two subjects. IJVP was greater in 0 G than 1 G at all expiration pressures (P < 0.01). IJVP is elevated during acute exposure to reduced gravity and may be elevated further by conditions that increase intrathoracic pressure. |
Pavela et al.25 | NASA, Houston, TX, USA. KBR, Houston, TX, USA. Department of Radiology, University of Texas MD Anderson Cancer Centre, Houston, TX, USA. Aegis Aerospace, Inc., Houston, TX, USA. TP: NR D: 2150 person-days spaceflight | To report the Doppler US findings of the bilateral IJV evaluations and discuss their relevance to a possible prothrombotic state | Interventional Prospective cohort Repeated measurements Duplex US of the bilateral IJV was conducted on all NASA astronauts terrestrially, and at three points during spaceflight. Respiratory manoeuvres were performed (normal-effort respiration, Valsalva, modified Mueller and manual compression of the contralateral IJV). | 11 NASA astronauts (six male, five female) | Images were analysed for thrombosis, CSA and certain hemodynamic characteristics, including peak velocity (PV) and degree of echogenicity. Evaluation by matching terrestrial and in-flight ultrasounds. Right and left IJV CSA and IJV-PV measurements were compared with the Wilcoxon test. Separate mixed effects generalised linear models. Univariable linear regression models Univariate proportional odds logistic regression models | No thrombosis detected. IJV-CSA: The left IJV significantly smaller than the right IJV at terrestrial baseline and first and second in-flight exams (p = 0.04, 0.02, 0.01, 0.2). Compared to terrestrial baseline, the in-flight right IJV-CSA was significantly increased on all exams, and the left IJV-CSA was significantly increased on the third exam. Echogenicity: Six of 11 astronauts had mild-moderate echogenicity in the left IJV during spaceflight, but none had more than mild echogenicity in the right IJV. Peak velocity: Compared to terrestrial US, in-flight peak velocity was reduced and lowest in the left IJV. Two astronauts developed retrograde blood flow in the left IJV Respiratory manoeuvres Flow response as expected |
Zamboni et al.26 | Vascular Diseases Centre and Department of Physics and Earth Sciences, University of Ferrara, Ferrara, Italy Italian Space Agency European Space Agency (ESA) NASA TP: NR D: 6 months | To provide proof of concept for the feasibility of measuring IJV pulse variations before, during and after the experiment in microgravity. IJV pulse extrapolated from an US video recording of the IJV synchronised with ECG that produces a CSA time trace (IJV pulse trace) | Feasibility study A series of cross-sectional scans of bilateral IJVs lasting approximately 30 s on each side Six experimental sessions (the third and the fourth performed in the ISS). | A 37-y-old female astronaut | Mean and standard deviation of the IJV pulse waves and the phase relationship between such waves and P and T waves on the ECG calculated from approximately 30 cardiac cycles. Verification that such parameters had the same accuracy on Earth as under microgravity. Values in terms of sensitivity, specificity & accuracy but reference standard not reported. Many study limitations in the design, conduct, analysis and reporting. | The sensitivity, specificity and accuracy in microgravity did not significantly differ from those on Earth. On board the ISS, the parameters increased approximately by 15% in the first session, whereas in the second session, they decreased by more than 50%. Authors conclusion: “The experiment indicated the feasibility of deriving a IJV pulse trace from a B-mode US examination self-performed by an astronaut in microgravity”. |
