Engineering topics
Hargens, A.
Publications and source records attributed to Hargens, A..
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.
Fluid Shifts: Otoacoustical Emission Changes in Response to Posture and Lower Body Negative Pressure
INTRODUCTION: The purpose of the NASA Fluid Shifts 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 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 spaceflight-induced cephalad fluid shifts, but this hypothesis has not been tested. Due to the invasive nature of direct measures of ICP, a noninvasive technique of monitoring ICP is desired for use during spaceflight. The phase angle and amplitude of otoacoustic emissions (OAEs) have been shown to be sensitive to posture change and ICP (1, 2), therefore use of OAEs is an attractive option. OAEs are low-level sounds produced by the sensory cells of the cochlea in response to auditory stimulation. These sounds travel peripherally from the cochlea, through the oval window, to the ear canal where they can be recorded. OAE transmission is sensitive to changes in the stiffness of the oval window, occurring as a result of changes in cochlear pressure. Increased stiffness of the oval window largely affects the transmission of sound from the cochlea at frequencies between 800 Hz and 1600 Hz. OAEs can be self-recorded in the laboratory or on the ISS using a handheld device. Our primary objectives regarding OAE measures in this experiment were to 1) validate this method during preflight testing of each crewmember (while sitting, supine and in head-down tilt position), and 2) determine if OAE measures (and presumably ICP) are responsive to lower body negative pressure and to spaceflight. METHODS: Distortion-product otoacoustic emissions (DPOAEs) and transient evoked otoacoustic emissions (TEOAEs) were recorded preflight using the Otoport Advance OAE system (Otodynamics Ltd., Hatfield, UK). Data were collected in four conditions (seated, supine, 15 degrees head down tilt (HDT), and 15 degrees HDT with lower body negative pressure (LBNP)) to produce a range of ICP in each subject and test the susceptibility of OAEs to LBNP. LBNP was induced using the Russian Chibis suit to produce the same fit and pressures that would be experienced inflight during Chibis LBNP trials. Similar trials have occurred inflight on the ISS. A comparative analysis of preflight and inflight phase measurements and magnitudes was completed in both broad and narrow band frequency ranges. RESULTS: TEOAE data demonstrated notable phase shifts from 859-1640 Hz when the seated baseline condition is compared to supine, HDT, and HDT plus Chibis conditions. Changes were particularly pronounced at low frequencies and were consistent with the expected ICP changes. Preflight DPOAE magnitude data revealed changes consistent with increased ICP in two conditions at 1414 Hz, where a magnitude change (relative to the seated condition) was seen in the HDT position and in HDT plus Chibis. DISCUSSION: OAEs revealed systematic changes in phase and magnitude throughout all test conditions (including use of Chibis LBNP) that were consistent with ICP changes. Results indicate that OAEs may provide a rapid noninvasive means of monitoring ICP changes. The first two subjects are projected to complete inflight testing on the ISS in early 2016, with the full complement of 10 subjects scheduled to be complete in 2018.
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.
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.
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.
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.
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.
Contribution of the vertebral artery to cerebral circulation in the rat snake Elaphe obsoleta
Blood supplying the brain in vertebrates is carried primarily by the carotid vasculature. In most mammals, cerebral blood flow is supplemented by the vertebral arteries, which anastomose with the carotids at the base of the brain. In other tetrapods, cerebral blood is generally believed to be supplied exclusively by the carotid vasculature, and the vertebral arteries are usually described as disappearing into the dorsal musculature between the heart and head. There have been several reports of a vertebral artery connection with the cephalic vasculature in snakes. We measured regional blood flows using fluorescently labeled microspheres and demonstrated that the vertebral artery contributes a small but significant fraction of cerebral blood flow (approximately 13% of total) in the rat snake Elaphe obsoleta. Vascular casts of the anterior vessels revealed that the vertebral artery connection is indirect, through multiple anastomoses with the inferior spinal artery, which connects with the carotid vasculature near the base of the skull. Using digital subtraction angiography, fluoroscopy, and direct observations of flow in isolated vessels, we confirmed that blood in the inferior spinal artery flows craniad from a point anterior to the vertebral artery connections. Such collateral blood supply could potentially contribute to the maintenance of cerebral circulation during circumstances when craniad blood flow is compromised, e.g., during the gravitational stress of climbing.
Effects of static fingertip loading on carpal tunnel pressure
The purpose of this study was to explore the relationship between carpal tunnel pressure and fingertip force during a simple pressing task. Carpal tunnel pressure was measured in 15 healthy volunteers by means of a saline-filled catheter inserted percutaneously into the carpal tunnel of the nondominant hand. The subjects pressed on a load cell with the tip of the index finger and with 0, 6, 9, and 12 N of force. The task was repeated in 10 wrist postures: neutral; 10 and 20 degrees of ulnar deviation; 10 degrees of radial deviation; and 15, 30, and 45 degrees of both flexion and extension. Fingertip loading significantly increased carpal tunnel pressure for all wrist angles (p = 0.0001). Post hoc analyses identified significant increase (p < 0.05) in carpal tunnel pressure between unloaded (0 N) and all loaded conditions, as well as between the 6 and 12 N load conditions. This study demonstrates that the process whereby fingertip loading elevates carpal tunnel pressure is independent of wrist posture and that relatively small fingertip loads have a large effect on carpal tunnel pressure. It also reveals the response characteristics of carpal tunnel pressure to fingertip loading, which is one step in understanding the relationship between sustained grip and pinch activities and the aggravation or development of median neuropathy at the wrist.
Physiological adaptations and countermeasures associated with long-duration spaceflights
Since 1961, there have been more than 165 flights involving several hundred individuals who have remained in a space environment from 15 min to more than a year. In addition, plans exist for humans to explore, colonize, and remain in microgravity for 1000 d or more. This symposium will address the current state of knowledge in select aspects associated with the cardiovascular, fluid and electrolytes, musculoskeletal, and the neuroendocrine and immune systems. The authors will focus on responses, mechanisms, and the appropriate countermeasures to minimize or prevent the physiological and biochemical consequences of a microgravity environment. Since exercise is frequently cited as a generic countermeasure, this topic will be covered in greater detail. Models for simulated microgravity conditions will be discussed in subsequent manuscripts, as will future directions for ground-based research.
Experiment K-6-03. Gravity and skeletal growth, part 1. Part 2: Morphology and histochemistry of bone cells and vasculature of the tibia; Part 3: Nuclear volume analysis of osteoblast histogenesis in periodontal ligament cells; Part 4: Intervertebral disc swelling pressure associated with microgravity
Bone area, bone electrophysiology, bone vascularity, osteoblast morphology, and osteoblast histogenesis were studied in rats associated with Cosmos 1887. The results suggest that the synchronous animals were the only group with a significantly larger bone area than the basal group, that the bone electrical potential was more negative in flight than in the synchronous rats, that the endosteal osteoblasts from flight rats had greater numbers of transitional Golgi vesicles but no difference in the large Golgi saccules or the alkaline phosphatase activity, that the perioteal vasculature in the shaft of flight rats often showed very dense intraluminal deposits with adjacent degenerating osteocytes as well as lipid accumulations within the lumen of the vessels and sometimes degeneration of the vascular wall (this change was not present in the metaphyseal region of flight animals), and that the progenitor cells decreased in flight rats while the preosteoblasts increased compared to controls. Many of the results suggest that the animals were beginning to recover from the effects of spaceflight during the two day interval between landing and euthanasia; flight effects, such as the vascular changes, did not appear to recover.