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Macias, B.

Publications and source records attributed to Macias, B..

Use of Otoacousticemission Phase Change to Evaluate Countermeasures for Spaceflight-Associated Neuro-Ocular Syndrome

Spaceflight-associated neuro-ocular syndrome (SANS) is a human spaceflight risk recognized by NASA. Elevated intracranial pressure (ICP) has been implicated as a root cause of many SANS signs and symptoms, yet there is no reliable noninvasive means of monitoring ICP. We have developed a noninvasive method of monitoring ICP change that exploits ear canal acoustic and otoacoustic emission (OAE) measurements. Changed ICP alters pressure in the inner ear, leading to changes in the tension and position of middle ear (ME) components; tension of these components determines the phase of the stimulus in the ear canal and the OAE response sound transmission back through the ME. The OAE method has been validated in several studies, including our own experiments as part of the NASA Fluid Shifts study. Systematic OAE phase changes demonstrating increased ME tension (an ICP indicator) are observed as posture is changed from seated to supine to head-down tilt (HDT). This effect can be substantially mitigated by lower body negative pressure (LBNP). The OAE technique has also been used on International Space Station (ISS) crewmembers, providing evidence that ICP in microgravity is similar to that seen on the ground in the supine position. The OAE method is also a rapid and noninvasive means of assessing the effectiveness of SANS countermeasures. Here we report results from two studies which used OAEs. In the most recent study (Venous Congestion Countermeasures - VCCM), three promising countermeasures [LBNP, an impedance threshold device (ITD), and veno-occlusive thigh cuffs (VTC)] were applied individually and in combination. In our previous ITD-only study, ITD was investigated for its ability to reduce ICP and cephalic venous congestion in supine and various HDT postures. Internal jugular vein (IJV) ultrasound showed a clear decongestive effect at all postures, however OAE data showed that ITD only caused a phase decrease (tension decrease) in HDT postures. In supine, ITD appeared to INCREASE tension. This paradox leads us to hypothesize that the OAE method is not accurately representing ICP changes with countermeasures (CM), which can alter ME tension through other means, such as ME pressure (MEP) changes. More generally, the exact mechanism for observed OAE response and stimulus phase shifts are not clearly understood, specifically with regard to the effects of MEP. The VCCM study examined the effects of externally-applied MEP on OAE recordings to document the relationship between these parameters. Analysis of these data provide new insights to these OAE mechanisms, in addition to results on CM effectiveness.

Kemp, D.

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.

Evaluation of an Impedance Threshold Device as a VIIP Countermeasure

Visual Impairment/Intracranial Pressure (VIIP) is a top human spaceflight risk for which NASA does not currently have a proven mitigation strategy. Thigh cuffs (Braslets) and lower body negative pressure (LBNP; Chibis) devices have been or are currently being evaluated as a means to reduce VIIP signs and symptoms, but these methods alone may not provide sufficient relief of cephalic venous congestion and VIIP symptoms. Additionally, current LBNP devices are too large and cumbersome for their systematic use as a countermeasure. Therefore, a novel approach is needed that is easy to implement and provides specific relief of symptoms. This investigation will evaluate an impedance threshold device (ITD) as a VIIP countermeasure.

Ebert, D.

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.

Validation of a Cephalad Fluid Shift Countermeasure

INTRODUCTION: This project will provide critical data required to objectively determine how an optimized thigh cuff could be incorporated into the NASA integrated physiological countermeasure suite. This project will determine if thigh cuffs used during simulated spaceflight impact intracranial pressure (ICP), ocular structure and function, and intraocular pressure (IOP) using state of-the-art techniques. Additionally, some of the same methods, hardware, and protocols will be employed in the present investigation to enable direct comparisons to the International Space Station (ISS) "Fluid Shifts" experiment with Chibis-Lower Body Negative Pressure (LBNP). This study will determine the temporal physiological responses of thigh cuff application and removal on ocular and cerebral variables (including invasive ICP) in a microgravity analog. Furthermore, this proposed study will determine tissue pressure distribution applied by thigh cuffs in order to improve comfort, mobility, and efficacy of the countermeasure. Our specific aim is to determine the efficacy of a novel thigh cuff device to mitigate cephalad fluid shifts. We hypothesize that a thigh cuff countermeasure employed in a microgravity analog will temporarily reverse or attenuate ocular and cerebral-volume-pressure variables, approaching normal Earth-based seated posture, the most frequent posture assumed in daily life. In addition, we hypothesize that the magnitude of fluid and pressure redistribution using a thigh cuff countermeasure may require a longer exposure time than that of Chibis-LBNP (using ground-based data from our "Fluid Shifts" project). This project directly addresses Critical Path Roadmap Risks and Questions regarding "Risk of Spaceflight-Induced Intracranial Hypertension/Vision Alterations," and IRP Gap VIIP13: We need to identify preventative and treatment countermeasures to mitigate changes in ocular structure and function and intracranial pressure during spaceflight. METHODS: Noninvasive measures and tissue pressure distributions beneath thigh cuffs The objectives of this study are to: 1) determine the distribution of skin surface pressures beneath the advanced thigh cuff in ten subjects, 2) calibrate the built-in pressure measurement system of the advanced thigh cuff using an industry standard device, and 3) collect subjective feedback and data on the new cuff design to allow for further adjustments prior to invasive studies. A Tekscan Industrial Sensing (I-Scan) system will measure the pressure distribution of the advanced thigh cuff against the skin. In addition, we will measure blood pooling in the thigh and record the circumference of the thigh using Hokanson strain gauge plethysmography. The advanced thigh cuff will be adjusted to obtain a skin contact pressure of 30-50 mmHg as visualized on the Tekscan system. The built-in advanced thigh cuff pressure monitor will be recorded simultaneously to allow direct comparison to the Tekscan measurements. The volunteer will then remove the thigh cuff and remain at rest for five minutes with no legging applied. The thigh cuff will be donned again and pressure measurements will be taken in the same manner for up to 10 repetitions to show reproducibility of pressure after donning. At the conclusion of the study, subjects will be asked to flex their knee, stand, walk, and sit with the thigh cuff activated. During each of these maneuvers the subject will rate their pain/comfort using a modified Borg scale. Effect of thigh cuffs on ICP during simulated microgravity Ommaya reservoir patients will be recruited from the John Wayne Cancer Institute. Ommaya reservoirs provide safe and direct access for the measurement of ICP. Subjects will be instrumented for continuous blood pressure, ECG, and invasive ICP measures. The subjects will be positioned in the upright sitting posture for a 10-minute stabilization period. After the 10-minute stabilization period, imaging measures [ICP, Optical Coherence Tomography, IOP, ocular and vascular ultrasound] will be performed. Following baseline seated measures, the subject will be positioned randomly in the supine, 15deg head-down-tilt, and 15deg head-down-tilt with thigh cuffs and measures repeated. DISCUSSION: Tests to down-select thigh cuff designs will occur in early 2016. Invasive ICP and noninvasive eye imaging tests will begin in spring 2016. Supported by NSBRI through NCC 9-58.

Macias, B.

Evaluation of an Impedance Threshold Device as a VIIP Countermeasure

Visual Impairment /Intracranial Pressure (VIIP) is a top human spaceflight risk for which NASA does not currently have a proven mitigation strategy. Thigh cuffs (Braslets) and lower body negative pressure (LBNP; Chibis) devices have been or are currently being evaluated as a means to reduce VIIP signs and symptoms, but these methods alone may not provide sufficient relief of cephalic venous congestion and VIIP symptoms. Additionally, current LBNP devices are too large and cumbersome for their systematic use as a countermeasure. Therefore, a novel approach is needed that is easy to implement and provides specific relief of symptoms. This investigation will evaluate an impedance threshold device (ITD) as a VIIP countermeasure. The ITD works by providing up to 7 cm H2O (approximately 5 mmHg) resistance to inspiratory air flow, effectively turning the thorax into a vacuum pump upon each inhalation which lowers the intrathoracic pressure (ITP) and facilitates venous return to the heart. The ITD is FDA-approved and was developed to augment venous return to the central circulation and increase cardiac output during cardiopulmonary resuscitation (CPR) and in patients with hypotension. While the effect of ITD on CPR survival outcomes is controversial, the ITD's ability to lower ITP with a concomitant decrease in intracranial pressure (ICP) is well documented. A similar concept that creates negative ITP during exhalation (intrathoracic pressure regulator; ITPR) decreased ICP in 16 of 20 patients with elevated ICP in a hospital pilot study. ITP and central venous pressure (CVP) have been shown to decrease in microgravity however ITP drops more than CVP, indicating an increased transmural CVP. This could explain the paradoxical distention of jugular veins (JV) in microgravity despite lower absolute CVP and also suggests that JV transmural pressure is not dramatically elevated. Use of an ITD may lower JV pressure enough to remove or relieve cephalic venous congestion. During spaceflight experiments with Braslet thigh cuffs and modified (open-glottis) Mueller maneuvers, Braslets alone reduced cardiac preload but only reduced the internal JV (IJV) cross sectional area by 23%. The addition of Mueller maneuvers resulted in an IJV area reduction of 48%. This project will test if ITD essentially applies a Mueller maneuver with added negative ITP in every respiratory cycle, acting to: 1) reduce venous congestion in the neck and 2) potentially lower ICP. The expected mechanism of action is that in microgravity (or an analog) blood is relocated toward the heart from vasculature in the head and neck. Once validated, the ITD would be an exceptionally easy countermeasure to deploy and test on the ISS. Dosage could be altered though 1) duration of application and 2) inspiratory resistance set point. Effects could be additionally enhanced through co-application with other countermeasures such as thigh cuffs or LBNP.

Ebert, D.

Fluid Shifts

INTRODUCTION: Mechanisms responsible for the ocular structural and functional changes that characterize the visual impairment and intracranial pressure (ICP) syndrome (VIIP) are unclear, but hypothesized to be secondary to the cephalad fluid shift experienced in spaceflight. This study will relate the fluid distribution and compartmentalization associated with long-duration spaceflight with VIIP symptoms. We also seek to determine whether the magnitude of fluid shifts during spaceflight, as well as the VIIP-related effects of those shifts, can be predicted preflight with acute hemodynamic manipulations, and also if lower body negative pressure (LBNP) can reverse the VIIP effects. METHODS: Physiologic variables will be examined pre-, in- and post-flight in 10 International Space Station crewmembers including: fluid compartmentalization (D2O and NaBr dilution); interstitial tissue thickness (ultrasound); vascular dimensions and dynamics (ultrasound and MRI (including cerebrospinal fluid pulsatility)); ocular measures (optical coherence tomography, intraocular pressure, ultrasound); and ICP measures (tympanic membrane displacement, otoacoustic emissions). Pre- and post-flight measures will be assessed while upright, supine and during 15 deg head-down tilt (HDT). In-flight measures will occur early and late during 6 or 12 month missions. LBNP will be evaluated as a countermeasure during HDT and during spaceflight. RESULTS: The first two crewmembers are in the preflight testing phase. Preliminary results characterize the acute fluid shifts experienced from upright, to supine and HDT postures (increased stroke volume, jugular dimensions and measures of ICP) which are reversed with 25 millimeters Hg LBNP. DISCUSSION: Initial results indicate that acute cephalad fluid shifts may be related to VIIP symptoms, but also may be reversible by LBNP. The effect of a chronic fluid shift has yet to be evaluated. Learning Objectives: Current spaceflight VIIP research is described, including novel hardware and countermeasures.

Stenger, M. B.

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 Before, During, and After Prolonged Space Flight and their Association with Intracranial Pressure and Visual Impairment

With the conclusion of the Space Shuttle program, 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 in Space Shuttle crewmembers after their short-duration missions were largely transient, but more than 30% of ISS astronauts experience more profound changes in vision, some with objective structural and functional findings such as papilledema and choroidal folds on ophthalmologic examination. Globe flattening, optic nerve sheath dilatation, optic nerve tortuosity, and other findings have been noted in imaging studies. This pattern is referred to as visual impairment and intracranial pressure (VIIP) syndrome. The VIIP signs and symptoms, as well as postflight lumbar puncture data, suggest that elevated intracranial pressure (ICP) is associated with the space flight-induced cephalad fluid shifts, but this hypothesis has not been systematically tested. The purpose of this study is to objectively characterize the fluid distribution and compartmentalization associated with long-duration space flight, and to correlate the 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, can be predicted by crewmember baseline data and responses to acute hemodynamic manipulations (such as head-down tilt tests) obtained before flight. Lastly, we will evaluate the patterns of fluid distribution in astronaut subjects on the ISS during the use of lower body negative pressure (LBNP) and respiratory maneuvers to characterize and explain general and individual responses during space flight.

Stenger, M.

Excercise Within LBNP as an Artificial Gravity Countermeasure

Previous exercise in space has lacked sufficient loads to maintain preflight cardiovascular and musculoskeletal mass and function. Lower body negative pressure (LBNP) produces a static force equivalent to one Earth body weight by each 52 mm Hg of LBNP during supine posture. LBNP also provides transmural blood pressures simulating upright exercise. Thus, this artificial-gravity concept may help maintain cardiovascular and musculoskeletal systems of crewmembers during prolonged exposure to microgravity. Currently available, bungee cord assisted, treadmill exercise is limited by harness discomfort, lower than normal loads, abnormal post-flight gait, and the absence of gravitational blood pressures within the vascular system. PURPOSE: This project evaluates a method to create artificial gravity using supine LBNP treadmill exercise to prevent loss of physiologic function in microgravity simulated by 30 days of bed rest. Identical twins were used as volunteers so that statistical power could be maximized. This countermeasure is being transitioned to space flight. CURRENT STATUS OF RESEARCH Methods: Six sets of identical twins (6 females and 14 males, 21-36 years) remained in 6 head-down tilt (HDT) bed rest for 30 days to simulate prolonged microgravity. Six subjects were randomly selected to exercise supine in an LBNP chamber for 40 minutes six days per week (EX group), while their twin brothers served as non-exercise controls (CON). Pressure within the exercise LBNP chamber was adjusted to increase load, hence increasing exercise intensity. During supine treadmill exercise, LBNP (52-63 mmHg) was applied to produce foot ward forces equivalent to those for upright running on Earth at 1.0-1.2 times body weight (BW) and subjects performed an interval exercise protocol (40-80% peak exercise capacity [VO2pk]). Five minutes of resting LBNP immediately followed each exercise session. Results: Orthostatic tolerance time decreased significantly after 30 days bed rest in the CON group, but was relatively maintained in the EX group. VO2pk was maintained in EX males, but not in CON males. Isokinetic knee strength (extension, peak torque) decreased significantly in CON males, but was preserved in EX males. The EX group had significantly higher spine muscle strength after bed rest than the CON group. The cross-sectional area of spinal muscle at L4/5 level decreased significantly in the CON group but not in the EX group. Urinary n-telopeptide excretion, an index of bone resorption, was increased during bed rest in CON, but not in EX subjects. This suggests protection by LBNP exercise against the increase in bone resorption typically seen in simulated and actual microgravity. Significant changes in bone mineral density (BMD) in the spine and ribs were observed in CON subjects, but not in EX subjects. Conclusions: Our treadmill exercise protocol within LBNP plus a short period of post-exercise LBNP maintains orthostatic responses, upright exercise capacity and other important physiologic parameters during bed rest. These results document the efficacy of our apparatus and exercise protocol for maintaining physiologic structure and function during long-duration microgravity as simulated by 30 days of HDT bed rest. FUTURE PLANS: More sets of female identical twins are needed to reach significance. The LBNP exercise chamber will be redesigned for flight.

Hargens, A. R.