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Alterations in left ventricular volumes induced by Valsalva manoeuvre

Five patients were studied with left ventriculography during different phases of the Valsalva manoeuvre. Small doses of contrast medium allowed adequate repetitive visualization of the left ventricle for volume calculation. During strain phase, the volume of the left ventricle decreased by nearly 50 per cent in each case, and stroke volume and cardiac output also dropped strikingly. Release of straining was attended by a sharp rebound of left ventricular volume to control levels, with a transient surge of increased cardiac output 42 per cent above that of the resting state.

Brooker, J. Z.↗

Pulmonary diffusing capacity, capillary blood volume, and cardiac output during sustained microgravity

We measured pulmonary diffusing capacity (DL), diffusing capacity per unit lung volume, pulmonary capillary blood volume (Vc), membrane diffusing capacity (Dm), pulmonary capillary blood flow or cardiac output (Qc), and cardiac stroke volume (SV) in four subjects exposed to nine days of microgravity. DL in microgravity was elevated compared with preflight standing values and was higher than preflight supine because of the elevation of both Vc and Dm. The elevation in Vc was comparable to that measured supine in 1 G, but the increase in Dm was in sharp contrast to the supine value. We postulate that, in 0 G, pulmonary capillary blood is evenly distributed throughout the lung, providing for uniform capillary filling, leading to an increase in the surface area available for diffusion. By contrast, in the supine 1-G state, the capillaries are less evenly filled, and although a similar increase in blood volume is observed, the corresponding increase in surface area does not occur. DL and its subdivisions showed no adaptive changes from the first measurement 24 h after the start of 0 G to eight days later. Similarly, there were no trends in the postflight data, suggesting that the principal mechanism of these changes was gravitational. The increase in Dm suggests that subclinical pulmonary edema did not result from exposure to 0 G. Qc was modestly increased inflight and decreased postflight compared with preflight standing. Compared with preflight standing, SV was increased 46 percent inflight and decreased 14 percent in the 1st week postflight. There were temporal changes in Qc and SV during 0 G, with the highest values recorded at the first measurement, 24 h into the flight. The lowest values of Qc and SV occurred on the day of return.

Prisk, G. K.↗

Mechanism of thirst attenuation during head-out water immersion in men

The purpose was to determine whether extracellular volume or osmolality was the major contributing factor for reduction of thirst in air and head-out water immersion in hypohydrated subjects. Eight males (19-25 yr) were subjected to thermoneutral immersion and thermoneutral air under two hydration conditions without further drinking: euhydration in water (Eu-H2O) and euhydration in air, and hypohydration in water (Hypo-H2O) and hypohydration in air (3.7% wt loss after exercise in heat). The increased thirst sensation with Hypo-H2O decreased (P < 0.05) within 10 min of immersion and continued thereafter. Mean plasma osmolality (288 +/- 1 mosmol/kgH2O) and sodium (140 +/- 1 meq/l) remained elevated, and plasma volume increased by 4.2 +/- 1.0% (P < 0.05) throughout Hypo-H2O. A sustained increase (P < 0.05) in stroke volume accompanied the prompt and sustained decrease in plasma renin activity and sustained increase (P < 0.05) in plasma atrial natriuretic peptide during Eu-H2O and Hypo-H2O. Plasma vasopressin decreased from 5.3 +/- 0.7 to 2.9 +/- 0.5 pg/ml (P < 0.05) during Hypo-H2O but was unchanged in Eu-H2O. These findings suggest a sustained stimulation of the atrial baroreceptors and reduction of a dipsogenic stimulus without major alterations of extracellular osmolality in Hypo-H2O. Thus it appears that vascular volume-induced stimuli of cardiopulmonary baroreceptors play a more important role than extracellular osmolality in reducing thirst sensations during immersion in hypohydrated subjects.

NASA Center ARC↗

Three-dimensional ballistocardiography and respiratory motion in sustained microgravity

BACKGROUND: We measured the three-dimensional ballistocardiogram (BCG) in a free-floating subject in sustained microgravity during spaceflight to test the usefulness of such measurements for future non-invasive monitoring of cardiac function, and to examine the effects of respiratory movement on the BCG in three axes. METHODS: Acceleration was measured using a three-axis accelerometer fastened to the lumbar region of the subject while simultaneous recordings of ECG, and respiratory motion via impedance plethysmography were also made. Data were recorded during a 146-s period of inactivity on the part of the subject during which time there was no contact with the spacecraft. RESULTS: Total body motion due to respiratory activity was consistent with that calculated from the known action of the diaphragm and conservation of momentum. The accelerations due to cardiac activity, ensemble averaged over the R-R interval, were greatest along the head-to-foot axis. Maximum amplitude of the HIJK complex of the BCG generated by ventricular ejection was greatest in the head to foot axis (approximately 70 x 10(-3) m x s(-2)), but there were also substantial accelerations along the dorsoventral axis of up to 43 10(-3) m x s(-2), that are not measured interrestrial two-dimensional studies. The amplitude of the BCG was strongly affected by lung volume, with accelerations being reduced 50 to 70% between end-inspiration and end-expiration. CONCLUSIONS: These data suggest a greatly reduced transmission of the cardiac motion to the body at end-expiration (FRC) than at higher lung volumes. The BCG might be further developed as a non-invasive means of monitoring parameters such as stroke volume in microgravity.

Flight Experiment↗

Mechanism of Thirst Attenuation During Head-Out Water Immersion in Men

The purpose was to determine whether extracellular volume or osmolality was the major contributing factor for reduction of thirst in air and head-out water immersion in hypohydrated subjects. Eight males (19 - 25 yr) were subjected to thermoneutral immersion and thermoneutral air under two hydration conditions without further drinking: euhydration in water (Eu-H2O) and euhydration in air, and hypohydration in water (Hypo-H2O) and hypohydration in air (3.7% wt loss after exercise in heat). The increased thirst sensation with Hypo-H2O decreased (P less than 0.05) within 10 min of immersion and continued thereafter. Mean plasma osmolality (288 +/- 1 mosmol/kg H2O) and sodium (140 +/- 1 meq/1) remained elevated, and plasma volume increased by 4.2 +/- 1.0% (P less than 0.05) throughout Hypo-H2O. A sustained increase (P less than 0.05) in stroke volume accompanied the prompt and sustained decrease in plasma renin activity and sustained increase (P less than 0.05) in plasma atrial natriuretic peptide during Eu-H2O and Hypo-H2O. Plasma vasopressin decreased from 5.3 +/- 0.7 to 2.9 +/- 0.5 pg/ml (P less than 0.05) during Hypo-H2O but was unchanged in Eu-H2O. These findings suggest a sustained stimulation of the atrial baroreceptors and reduction of a dipsogenic stimulus without major alterations of extracellular osmolality in Hypo-H2O. Thus it appears that vascular volume induced stimuli of cardiopulmonary baroreceptors play a more important role than extracellular osmolality in reducing thirst sensations during immersion in hypohydrated subjects. Thus the purpose for this study was to determine the relative importance of volume and osmotic stimuli, and associated hormonal interaction, for attenuation of thirst during immersion.

Wada, F.↗

Echocardiograms during six hours of bedrest at head-down and head-up tilt and during space flight

Left ventricular end-diastolic volume increased after 4 1/2 to 6 hours of space flight, but was significantly decreased after 5 to 6 days of space flight. To determine the role of acute gravitational effects in this phenomenon, responses to a 6-hour bedrest model of 0 gravity (G; 5 degrees head-down tilt) were compared with those of fractional gravity loads of 1/6 G, 1/3 G, and 2/3 G by using head-up tilts of 10 degrees, 20 degrees, and 42 degrees, respectively. On 4 different days, six healthy male subjects were tilted at one of the four angles for 6 hours. Cardiac dimensions and volumes were determined from two-dimensional and M-mode echocardiograms in the left lateral decubitus position at control (0), 2, 4, and 6 hours. Stroke volume decreased with time (P < .05) for all tilt angles when compared with control. Ejection fraction (EF) at -5 degrees was greater than at +20 degrees and +42 degrees (not significant); EF at +10 degrees was greater than at +42 degrees (not significant). For the tilt angles of -5 degrees, +10 degrees, and +20 degrees, mean heart rate decreased during the first 2 hours, and returned to control or was slightly elevated above control (+20 degrees) by 6 hours (not significant). At the +42 degrees angle of tilt, heart rate was increased above control at hours 2, 4, and 6. There were no significant differences in cardiac output at any time point for any tilt angle.(ABSTRACT TRUNCATED AT 250 WORDS).

Flight Experiment↗

The effects of hindlimb unweighting on the capacitance of rat small mesenteric veins

Microgravity is associated with an impaired cardiac output response to orthostatic stress. Mesenteric veins are critical in modulating cardiac filling through venoconstriction. The purpose of this study was to determine the effects of simulated microgravity on the capacitance of rat mesenteric small veins. We constructed pressure-diameter relationships from vessels of 21-day hindlimb-unweighted (HLU) rats and control rats by changing the internal pressure and measuring the external diameter. Pressure-diameter relationships were obtained both before and after stimulation with norepinephrine (NE). The pressure-diameter curves of HLU vessels were shifted to larger diameters than control vessels. NE (10(-4) M) constricted veins from control animals such that the pressure-diameter relationship was significantly shifted downward (i.e., to smaller diameters at equal pressure). NE had no effect on vessels from HLU animals. These results indicate that, after HLU, unstressed vascular volume may be increased and can no longer decrease in response to sympathetic stimulation. This may partially underlie the mechanism leading to the exaggerated fall in cardiac output and stroke volume seen in astronauts during an orthostatic stress after exposure to microgravity.

Non-NASA Center↗

Influence of Gravity on Blood Volume and Flow Distribution

In our previous experiments during NASA Shuttle flights SLS 1 and 2 (9-15 days) and EUROMIR flights (30-90 days) we observed that pulmonary blood flow (cardiac output) was elevated initially, and surprisingly remained elevated for the duration of the flights. Stroke volume increased initially and then decreased, but was still above 1 Gz values. As venous return was constant, the changes in SV were secondary to modulation of heart rate. Mean blood pressure was at or slightly below 1 Gz levels in space, indicating a decrease in total peripheral resistance. It has been suggested that plasma volume is reduced in space, however cardiac output/venous return do not return to 1 Gz levels over the duration of flight. In spite of the increased cardiac output, central venous pressure was not elevated in space. These data suggest that there is a change in the basic relationship between cardiac output and central venous pressure, a persistent "hyperperfusion" and a re-distribution of blood flow and volume during space flight. Increased pulmonary blood flow has been reported to increase diffusing capacity in space, presumably due to the improved homogeneity of ventilation and perfusion. Other studies have suggested that ventilation may be independent of gravity, and perfusion may not be gravity- dependent. No data for the distribution of pulmonary blood volume were available for flight or simulated microgravity. Recent studies have suggested that the pulmonary vascular tree is influenced by sympathetic tone in a manner similar to that of the systemic system. This implies that the pulmonary circulation is dilated during microgravity and that the distribution of blood flow and volume may be influenced more by vascular control than by gravity. The cerebral circulation is influenced by sympathetic tone similarly to that of the systemic and pulmonary circulations; however its effects are modulated by cerebral autoregulation. Thus it is difficult to predict if cerebral perfusion is increased and if there is edema in space. Anecdotal evidence suggests there may be cerebral edema early in flight. Cerebral artery velocity has been shown to be elevated in simulated microgravity. The elevated cerebral artery velocity during simulated microgravity may reflect vasoconstriction of the arteries and not increased cerebral blood flow. The purpose of our investigations was to evaluate the effects of alterations in simulated gravity (+/-), resulting in changes in cardiac output (+/-), and on the blood flow and volume distribution in the lung and brain of human subjects. The first hypothesis of these studies was that blood flow and volume would be affected by gravity, but their distribution in the lung would be independent of gravity and due to vasoactivity changing vascular resistance in lung vessels. The vasodilitation of the lung vasculature (lower resistance) along with increased "compliance" of the heart could account for the absence of increased central venous pressure in microgravity. Secondly, we postulate that cerebral blood velocity is increased in microgravity due to large artery vasoconstriction, but that cerebral blood flow would be reduced due to autoregulation.

Pendergast, D.↗

Association Between Cardiovascular and Intraocular Pressure Changes in a 14-Day 6 deg Head Down Tilt (HDT) Bed Rest Study: Possible Implications in Retinal Anatomy

Visual symptoms and intracranial pressure increase reported in astronauts returning from long duration missions in low Earth-orbit are thought to be related to fluid shifts within the body due to microgravity exposure. Because of this possible relation to fluid shifts, studies conducted in head-down tilt (HDT) bed rest are being monitored for potential changes in ocular health. These measures will also serve to determine whether HDT is a suitable ground-based analog to model subclinical cardiovascular and ocular changes that could shed light on the etiology of the VIIP syndrome observed in spaceflight. Sixteen healthy normotensive (12M, 4F, age range 29-54 years), non-smoker and normal weight subjects, volunteered to participate in a 14 day 6 deg head HDT study conducted at the NASA Flight Analogs Research Unit (FARU). This facility provides standard bed rest conditions (diet, wake/sleep time, time allowed in sunlight) during the time that the subjects stay at the FARU. Cardiovascular parameters were obtained in supine posture at BR-5, BR+0, and BR+3 and ocular monitoring was performed weekly. Intraocular pressure (IOP) increased from pre-bed rest BR-3) to the third day into bed rest (BR+3). Values reached a plateau towards the end of the bed rest phase (BR10) and decreased within the first three days of recovery (BR+2) returning to levels comparable to baseline at BR-3. As expected, most cardiovascular parameters were affected by 14 days of HDT bed rest. Plasma volume decreased as a result of bed rest but recovered to baseline levels by BR+3. Indications of cardiovascular deconditioning included increase in both systolic and diastolic blood pressure and heart rate, and a decrease in stroke volume and cardiac output between BR-5 and BR+3. Due to the experimental design of this study, we were not able to test the hypothesis that fluid shifts might be involved in the IOP increase during the bed rest phase, since cardiovascular measures were not available for those time points. There was no correlation between the largest change in IOP (BR-3 versus BR3) and cardiovascular measure changes between baseline (BR-5) and post bed rest (BR+2). While no clinically relevant visual changes were observed during the study, measurement of various retinal parameters was performed with optical coherence tomography (OCT). A decrease in central subfield retinal thickness was observed between BR+2 and baseline at BR-10, but no association was observed with IOP changes. This work investigates the time course of changes in IOP during 14-day HDT bed rest in an attempt to characterize HDT bed rest as a model of the VIIP syndrome and delve into its etiology.

Cromwell, Ronita↗

Effect of a central redistribution of fluid volume on response to lower-body negative pressure

Cardiovascular responses to lower-body negative pressure (LBNP) were studied following 1 hour of 6-deg head-down tilt to determine whether a redistribution of blood volume toward the central circulation modifies the subsequent response to orthostatic stress. Responses of 12 men, ages 30-39 years, were evaluated by electrocardiography, impedance cardiography, sphygmomanometry, and measurement of calf circumference. During the LBNP that followed head-down tilt, as compared with control LBNP (no preceding head-down tilt) subjects, had smaller stroke volume and cardiac output, greater total peripheral resistance, and less calf enlargement. These differences reflect differences in the variables immediately preceding LBNP. Magnitudes of the responses from pre-LBNP to each pressure stage of the LBNP procedure did not differ between protocols. Mean and diastolic arterial pressures were slightly elevated after LBNP-control, but they fell slightly during LBNP post-tilt.

Tomaselli, Clare M.↗

Sympathetic discharge and vascular resistance after bed rest

The effect of -6 degrees head-down-tilt bed rest (HDBR) for 14 days on supine sympathetic discharge and cardiovascular hemodynamics at rest was assessed. Mean arterial pressure, heart rate (n = 25), muscle sympathetic nerve activity (MSNA; n = 16) burst frequency, and forearm blood flow (n = 14) were measured, and forearm vascular resistance (FVR) was calculated. Stroke distance, our index of stroke volume, was derived from measurements of aortic mean blood velocity (Doppler) and R-R interval (n = 7). With these data, an index of total peripheral resistance was determined. Heart rate at rest was greater in the post (71 +/- 2 beats/min)- compared with the pre-HDBR test (66 +/- 2 beats/min; P < 0.003), but mean arterial pressure was unchanged. Aortic stroke distance during post-HDBR (15.5 +/- 1.1 cm/beat) was reduced from pre-HDBR levels (20.0 +/- 1.5 cm/beat) (P < 0.03). Also, MSNA burst frequency was reduced in the post (16.7 +/- 2.8 beats/min)- compared with the pre (25.2 +/- 2.6 beats/min)-HDBR condition (P < 0.01). Bed rest did not alter forearm blood flow, FVR, or total peripheral resistance. Thus reductions in MSNA with HDBR were not associated with a decrease in FVR.

NASA Discipline Musculoskeletal↗

Examining Individual Differences in Temporal Profiles of Cardiovascular Responses to the Head Down Tilt during Fluid Loading

Upon returning to Earth after an extended exposure to micro-gravity in space many astronauts have experienced symptoms of light headedness and fainting associated with post-flight orthostatic intolerance (low blood pressure). The main reason for this condition is the reduced fluid volume in the body while in space. A preventative treatment was proposed to prevent this condition by fluid loading to restore lost plasma volume by giving crew members salt tablets and water prior to re-entry. In order to simulate micro-gravity effects on earth test subjects are placed in a supine position with their head below the level of their heart (6 head down tilt-HDT). The purpose of the present study is to define individual differences in the time course of cardiac stroke volume responses to HDT (6 hours) and the effectiveness of fluid loading for mitigating orthostatic intolerance when standing . Echocardiography and impedance cardiography data will be collected on 8 men and 8 women to examine heart function to HDT. A second objective is to determine if the effects of fluid loading vary due to individual differences (e.g., age, gender, height, weight, physical fitness, etc.).

orthostatic intolerance↗

Validation of On-Orbit Methodology for the Assessment of Cardiac Function and Changes in the Circulating Volume Using Ultrasound and Braslet-M Occlusion Cuffs

The objective of this joint U.S. - Russian project was the development and validation of an in-flight methodology to assess a number of cardiac and vascular parameters associated with circulating volume and its manipulation in long-duration space flight. Responses to modified Valsalva and Mueller maneuvers were measured by cardiac and vascular ultrasound (US) before, during, and after temporary volume reduction by means of Braslet-M thigh occlusion cuffs (Russia). Materials and Methods: The study protocol was conducted in 14 sessions on 9 ISS crewmembers, with an average exposure to microgravity of 122 days. Baseline cardiovascular measurements were taken by echocardiography in multiple modes (including tissue Doppler of both ventricles) and femoral and jugular vein imaging on the International Space Station (ISS). The Braslet devices were then applied and measurements were repeated after >10 minutes. The cuffs were then released and the hemodynamic recovery process was monitored. Modified Valsalva and Mueller maneuvers were used throughout the protocol. All US data were acquired by the HDI-5000 ultrasound system aboard the ISS (ATL/Philips, USA) during remotely guided sessions. The study protocol, including the use of Braslet-M for this purpose, was approved by the ISS Human Research Multilateral Review Board (HRMRB). Results: The effects of fluid sequestration on a number of echocardiographic and vascular parameters were readily detectable by in-flight US, as were responses to respiratory maneuvers. The overall volume status assessment methodology appears to be valid and practical, with a decrease in left heart lateral E (tissue Doppler) as one of the most reliable measures. Increase in the femoral vein cross-sectional areas was consistently observed with Braslet application. Other significant differences and trends within the extensive cardiovascular data were also observed. (Decreased - RV and LV preload indices, Cardiac Output, LV E all maneuvers, LV Stroke Volume). Conclusions: This Study: 1) Addressed specific aspects of operational space medicine and space physiology, including assessment of circulating volume disturbances 2) Expanded the applications of diagnostic ultrasound imaging and Doppler techniques in microgravity. 3) Used respiratory maneuvers against the background of acute circulating volume manipulations which appear to enhance our ability to noninvasively detect volume-dependency in a number of cardiac and vascular parameters. 4) Determined that Tei index is not clinically changed therefore contractility not altered in the face of reduced preload. 5) Determined that increased Femoral Vein Area indicating blood being sequestered in lower extremities correlates with reduced preload and cardiac output. 6) That Braslet may be the only feasible means of acutely treating high pressure pulmonary edema in reduced gravity environments.

Hamilton, Douglas↗

A semi-automatic method for left ventricle volume estimate: an in vivo validation study

This study aims to the validation of the left ventricular (LV) volume estimates obtained by processing volumetric data utilizing a segmentation model based on level set technique. The validation has been performed by comparing real-time volumetric echo data (RT3DE) and magnetic resonance (MRI) data. A validation protocol has been defined. The validation protocol was applied to twenty-four estimates (range 61-467 ml) obtained from normal and pathologic subjects, which underwent both RT3DE and MRI. A statistical analysis was performed on each estimate and on clinical parameters as stroke volume (SV) and ejection fraction (EF). Assuming MRI estimates (x) as a reference, an excellent correlation was found with volume measured by utilizing the segmentation procedure (y) (y=0.89x + 13.78, r=0.98). The mean error on SV was 8 ml and the mean error on EF was 2%. This study demonstrated that the segmentation technique is reliably applicable on human hearts in clinical practice.

NASA Discipline Cardiopulmonary↗

Cardiovascular Deconditioning in Humans: Alteration in Cardiovascular Regulation and Function During Simulated Microgravity

Alterations in cardiovascular regulation and function that occur during and after space flight have been reported. These alterations are manifested, for example, by reduced orthostatic tolerance upon reentry to the earth's gravity from space. However, the precise physiologic mechanisms responsible for these alterations remain to be fully elucidated. Perhaps, as a result, effective countermeasures have yet to be developed. In this project we apply a powerful, new method - cardiovascular system identification (CSI) - for the study of the effects of space flight on the cardiovascular system so that effective countermeasures can be developed. CSI involves the mathematical analysis of second-to-second fluctuations in non-invasively measured heart rate, arterial blood pressure (ABP), and instantaneous lung volume (ILV - respiratory activity) in order to characterize quantitatively the physiologic mechanisms responsible for the couplings between these signals. Through the characterization of all the physiologic mechanisms coupling these signals, CSI provides a model of the closed-loop cardiovascular regulatory state in an individual subject. The model includes quantitative descriptions of the heart rate baroreflex, autonomic function, as well as other important physiologic mechanisms. We are in the process of incorporating beat-to-beat fluctuations of stroke volume into the CSI technique in order to quantify additional physiologic mechanisms such as those involved in control of peripheral vascular resistance and alterations in cardiac contractility. We apply CSI in conjunction with the two general protocols of the Human Studies Core project. The first protocol involves ground-based, human head down tilt bed rest to simulate microgravity and acute stressors - upright tilt, standing and bicycle exercise - to provide orthostatic and exercise challenges. The second protocol is intended to be the same as the first but with the addition of sleep deprivation to determine whether this contributes to cardiovascular alterations. In these studies, we focus on the basic physiologic mechanisms responsible for the alterations in cardiovascular regulation and function during the simulated microgravity in order to formulate hypotheses regarding what countermeasures are likely to be most effective. Compared to our original proposal, the protocol we are using has been slightly modified to lengthen the bed rest period to 16 days and streamline the data collection. These modifications provide us data on a longer bed rest period and have enabled us to increase our subject throughput. Based on review of our preliminary data we have decided to test a countermeasure which is applied the very end of the bed rest period. We will use the same bed rest protocol to test this countermeasure. We anticipate completing the baseline data collection in our first protocol plus testing of the countermeasure in an additional eight subjects, at which time we plan to initiate the second protocol which includes sleep deprivation. In future studies, we plan to apply CSI to test other potential countermeasures in conjunction with the same bed rest, sleep deprivation and acute stressor models. We also anticipate applying CSI for studying astronauts before and after space flight and ultimately, during space flight. The application of CSI is providing information relevant to the development and evaluation of effective countermeasures allowing humans to adapt appropriately upon re-exposure to a gravity field, and to live and work for longer periods of time in microgravity.

Cohen, Richard↗

Fluid Shifts

NASA is focusing on long-duration missions on the International Space Station (ISS) and future exploration-class missions beyond low Earth orbit. Visual acuity changes observed after short-duration missions were largely transient, but more than 30% of ISS astronauts experience more profound, chronic changes with objective structural and functional findings such as papilledema and choroidal folds. Globe flattening, optic nerve sheath dilation, and optic nerve tortuosity also are apparent. This pattern is referred to as the visual impairment and intracranial pressure (VIIP) syndrome. VIIP signs and symptoms, as well as postflight lumbar puncture data, suggest that elevated intracranial pressure (ICP) may be associated with the space flight-induced cephalad fluid shifts, but this hypothesis has not been tested. The purpose of this study is to characterize fluid distribution and compartmentalization associated with long-duration space flight, and to correlate these findings with vision changes and other elements of the VIIP syndrome. We also seek to determine whether the magnitude of fluid shifts during space flight, as well as the VIIP-related effects of those shifts, is predicted by the crewmember's pre-flight condition and responses to acute hemodynamic manipulations (such as head-down tilt). Lastly, we will evaluate the patterns of fluid distribution in ISS astronauts during acute reversal of fluid shifts through application of lower body negative pressure (LBNP) interventions to characterize and explain general and individual responses. We will examine a variety of physiologic variables in 10 long-duration ISS crewmembers using the test conditions and timeline presented in the Figure below. Measures include: (1) fluid compartmentalization (total body water by D2O, extracellular fluid by NaBr, intracellular fluid by calculation, plasma volume by CO rebreathe, interstitial fluid by calculation); (2) forehead/eyelids, tibia, calcaneus tissue thickness (by ultrasound); (3) vascular dimensions by ultrasound (jugular veins, cerebral and carotid arteries, vertebral arteries and veins, portal vein); (4) vascular dynamics by MRI (head/neck blood flow, cerebrospinal fluid pulsatility); (5) ocular measures (optical coherence tomography, intraocular pressure, 2-dimensional ultrasound including optic nerve sheath diameter, globe flattening, and retina-choroid thickness, Doppler ultrasound of ophthalmic and retinal arteries, and veins); (6) cardiac variables by ultrasound (inferior vena cava, tricuspid flow and tissue Doppler, pulmonic valve, stroke volume, right heart dimensions and function, four-chamber views); and (7) ICP measures (tympanic membrane displacement, distortion-product otoacoustic emissions, and ICP calculated by MRI). On the ground, acute head-down tilt will induce cephalad fluid shifts, whereas LBNP will oppose these shifts. Controlled Mueller maneuvers will manipulate cardiovascular variables. Through interventions applied before, during, and after flight, we intend to fully evaluate the relationship between fluid shifts and the VIIP syndrome. This study has been selected for flight implementation and is one of the candidate investigations being considered for the one year mission.

Stenger, Michael↗

Fluid Shifts

NASA is focusing on long-duration missions on the International Space Station (ISS) and future exploration-class missions beyond low-Earth orbit. Visual acuity changes observed after short-duration missions were largely transient, but more than 50% of ISS astronauts experienced more profound, chronic changes with objective structural and functional findings such as papilledema and choroidal folds. Globe flattening, optic nerve sheath dilation, and optic nerve tortuosity also are apparent. This pattern is referred to as the visual impairment and intracranial pressure (VIIP) syndrome. VIIP signs and symptoms, as well as postflight lumbar puncture data, suggest that elevated intracranial pressure (ICP) may be associated with the spaceflight-induced cephalad fluid shifts, but this hypothesis has not been tested. The purpose of this study is to characterize fluid distribution and compartmentalization associated with long-duration spaceflight, and to correlate these findings with vision changes and other elements of the VIIP syndrome. We also seek to determine whether the magnitude of fluid shifts during spaceflight, as well as the VIIP-related effects of those shifts, is predicted by the crewmember's preflight conditions and responses to acute hemodynamic manipulations (such as head-down tilt). Lastly, we will evaluate the patterns of fluid distribution in ISS astronauts during acute reversal of fluid shifts through application of lower body negative pressure (LBNP) interventions to characterize and explain general and individual responses. METHODS: We will examine a variety of physiologic variables in 10 long-duration ISS crewmembers using the test conditions and timeline presented in the Figure below. Measures include: (1) fluid compartmentalization (total body water by D2O, extracellular fluid by NaBr, intracellular fluid by calculation, plasma volume by CO rebreathe, interstitial fluid by calculation); (2) forehead/eyelids, tibia, calcaneus tissue thickness (by ultrasound); (3) vascular dimensions by ultrasound (jugular veins, cerebral and carotid arteries, vertebral arteries and veins, portal vein); (4) vascular dynamics by MRI (head/neck blood flow, cerebrospinal fluid pulsatility); (5) ocular measures (optical coherence tomography, intraocular pressure, 2-dimensional ultrasound including optic nerve sheath diameter, globe flattening, and retina-choroid thickness, Doppler ultrasound of ophthalmic and retinal arteries, and veins); (6) cardiac variables by ultrasound (inferior vena cava, tricuspid flow and tissue Doppler, pulmonic valve, stroke volume, right heart dimensions and function, four-chamber views); and (7) ICP measures (tympanic membrane displacement, distortion-product otoacoustic emissions, and ICP calculated by MRI). On the ground, acute head-down tilt will induce cephalad fluid shifts, whereas LBNP will oppose these shifts. Controlled Mueller maneuvers will manipulate cardiovascular variables. Through interventions applied before, during, and after flight, we intend to fully evaluate the relationship between fluid shifts and the VIIP syndrome.

Stenger, M.↗

Fluid Shifts

Introduction. NASA's Human Research Program is focused on addressing health risks associated with long-duration missions on the International Space Station (ISS) and future exploration-class missions beyond low Earth orbit. Visual acuity changes observed after short-duration missions were largely transient, but now more than 50 percent of ISS astronauts have experienced more profound, chronic changes with objective structural findings such as optic disc edema, globe flattening and choroidal folds. These structural and functional changes are referred to as the visual impairment and intracranial pressure (VIIP) syndrome. Development of VIIP symptoms may be related to elevated intracranial pressure (ICP) secondary to spaceflight-induced cephalad fluid shifts, but this hypothesis has not been tested. The purpose of this study is to characterize fluid distribution and compartmentalization associated with long-duration spaceflight and to determine if a relation exists with vision changes and other elements of the VIIP syndrome. We also seek to determine whether the magnitude of fluid shifts during spaceflight, as well as any VIIP-related effects of those shifts, are predicted by the crewmember's pre-flight status and responses to acute hemodynamic manipulations, specifically posture changes and lower body negative pressure. Methods. We will examine a variety of physiologic variables in 10 long-duration ISS crewmembers using the test conditions and timeline presented in the figure below. Measures include: (1) fluid compartmentalization (total body water by D2O, extracellular fluid by NaBr, intracellular fluid by calculation, plasma volume by CO rebreathe, interstitial fluid by calculation); (2) forehead/eyelids, tibia, and calcaneus tissue thickness (by ultrasound); (3) vascular dimensions by ultrasound (jugular veins, cerebral and carotid arteries, vertebral arteries and veins, portal vein); (4) vascular dynamics by MRI (head/neck blood flow, cerebrospinal fluid pulsatility); (5) ocular measures (optical coherence tomography; intraocular pressure; 2-dimensional ultrasound including optic nerve sheath diameter, globe flattening, and retina-choroid thickness; Doppler ultrasound of ophthalmic and retinal arteries and veins); (6) cardiac variables by ultrasound (inferior vena cava, tricuspid flow and tissue Doppler, pulmonic valve, stroke volume, right heart dimensions and function, four-chamber views); and (7) ICP measures (tympanic membrane displacement, otoacoustic emissions). Pre- and post-flight, acute head-down tilt will induce cephalad fluid shifts, whereas lower body negative pressure will oppose these shifts. Controlled Mueller maneuvers will manipulate cardiovascular variables. Through interventions applied before, during, and after flight, we intend to fully evaluate the relationship between fluid shifts and the VIIP syndrome. Discussion. Ten subjects have consented to participate in this experiment, including the recent One-Year Mission crewmembers, who have recently completed R plus180 testing; all other subjects have completed pre-flight testing. Preliminary results from the One-Year Mission crewmembers will be presented, including measures of ocular structure and function, vascular dimensions, fluid distribution, and non-invasive estimates of intracranial pressure.

Stenger, M. B.↗