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At least 37 records · Page 2

Mechanisms for vasopressin effects on intraocular pressure in anesthetized rats

Continuous intracameral infusions of a balanced salt solution (0.175 microliter min-1) have been reported to raise intraocular pressure (IOP) in anesthetized rats. Palm et al. (1995) previously reported that this effect was attenuated significantly by inclusion of arginine-vasopressin (AVP, 10 ng 0.175 microliter-1) in the infusate. This study used experimental and computer simulation methods to investigate factors underlying these changes in IOP. First, constant intracameral infusions of artificial cerebrospinal fluid (aCSF) at different fixed rates (0.049-0.35 microliter min-1) were used to estimate the outflow resistance. Secondly, IOP responses were measured during an 2 hr intracameral infusion of either aCSF or AVP that was the sum of a small constant component (0.05 microliter min-1) and a larger periodic component (0.25 microliter min-1, cycling for 4 min on, then 4 min off); the mean infusion rate was 0.175 microliter min-1. As shown previously for 0.175 microliter min-1 constant infusions, the periodic aCSF infusion induced a significant rise in IOP that was attenuated by AVP administration. Complex demodulation analysis and the estimated gain parameter of a second order transfer function fit to the periodic responses indicated that outflow resistance increased significantly during the infusions in both aCSF and AVP groups, but that the indices of resistance did not differ significantly between aCSF and AVP infused eyes. This finding implies that changes in outflow resistance do not explain the difference in IOP responses to intracameral aCSF and AVP. The two responses differed significantly, though, in damping factors, such that the aCSF responses were considerably more underdamped than the AVP responses. It is hypothesized that aCSF-induced increase in IOP reflects both (1) a small component reflecting increased outflow resistance and (2) a larger non-resistive component. Since the non-resistive component is insensitive to pretreatment with acetazolamide, it is suggested that the aCSF-induced elevation in IOP reflects primarily vascular perfusion changes that are reduced by local vasoconstrictor actions of AVP. The latter mechanism likely maintains vascular perfusion of the globe when intraocular hypertension develops.

NASA Discipline Cardiopulmonary↗

Inactivation of human interferon by body fluids

Description of the effects of human feces, bile, saliva, serum, and cerebrospinal fluid on interferon activity. It is shown that crude interferon is inactivated by at least 50% more than with the control medium used, when incubated for 4 hr in vitro in the presence of serum, saliva, or cerebrospinal liquid, and by close to 100% when incubated with stool extract or bile.

Cesario, T. C.↗

Mitigating Headward Fluid Shifts With Veno-Constrictive Thigh Cuffs During Spaceflight

Astronauts experience a chronic headward fluid shift in weightlessness as evidenced by increased cardiac output, decreased leg volume, a redistribution of venous fluid, and venous congestion in the upper body. Alterations in cerebrospinal fluid hydrodynamics and changes in cerebral venous pressure secondary to the headward fluid shift may contribute to ocular changes associated with spaceflight-associated neuro-ocular syndrome (SANS). Veno-constrictive thigh cuffs (VTC; Braslets) provided to Soyuz crewmembers alleviate symptoms of the headward fluid shift during the first week of spaceflight and have been documented to reduce internal jugular vein (IJV) distension during weightlessness. Application of VTCs designed collaboratively by NASA Johnson Space Center Cardiovascular and Vision Laboratory (CVL) and Clemson Textile Laboratory at Clemson University to improve fit and comfort was documented to mitigate changes in choroid thickness, intraocular pressure, and IJV area during posture-induced headward fluid shifts. VTC are demonstrated to reduce headward fluid shifts in both ground-based and spaceflight studies, and thus, may be a countermeasure against development of SANS. In addition, VTC are a simple mechanical countermeasure currently at a high technical readiness level (TRL) and are compact and lightweight, making them compatible with the spaceflight operations environment

Connor R. Ferguson↗

Microgravity-Induced Physiological Fluid Redistribution: Computational Analysis to Assess Influence of Physiological Parameters

Space flight impacts human physiology in many ways, the most immediate being the marked cephalad (headward) shift of fluid upon introduction into the microgravity environment. This physiological response to microgravity points to the redistribution of blood and interstitial fluid as a major factor in the loss of venous tone and reduction in heart muscle efficiency which impact astronaut performance. In addition, researchers have hypothesized that a reduction in astronaut visual acuity, part of the Visual Impairment and Intracranial Pressure (VIIP) syndrome, is associated with this redistribution of fluid. VIIP arises within several months of beginning space flight and includes a variety of ophthalmic changes including posterior globe flattening, distension of the optic nerve sheath, and kinking of the optic nerve. We utilize a suite of lumped parameter models to simulate microgravity-induced fluid redistribution in the cardiovascular, central nervous and ocular systems to provide initial and boundary data to a 3D finite element simulation of ocular biomechanics in VIIP. Specifically, the lumped parameter cardiovascular model acts as the primary means of establishing how microgravity, and the associated lack of hydrostatic gradient, impacts fluid redistribution. The cardiovascular model consists of 16 compartments, including three cerebrospinal fluid (CSF) compartments, three cranial blood compartments, and 10 thoracic and lower limb blood compartments. To assess the models capability to address variations in physiological parameters, we completed a formal uncertainty and sensitivity analysis that evaluated the relative importance of 42 input parameters required in the model on relative compartment flows and compartment pressures. Utilizing the model in a pulsatile flow configuration, the sensitivity analysis identified the ten parameters that most influenced each compartment pressure. Generally, each compartment responded appropriately to parameter variations associated with itself and adjacent compartments. However, several unexpected interactions between components, such as between the choroid plexus and the lower capillaries, were found, and are due to simplifications in the formulation of the model. The analysis illustrates that highly influential parameters and those that have unique influences within the model formulation must be tightly controlled for successful model application.

gravitational physiology↗

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.↗

Quantitative Magnetic Resonance Image Assessment of the Optic Nerve and Surrounding Sheath after Spaceflight

A subset of long-duration spaceflight astronauts have experienced ophthalmic abnormalities, collectively termed spaceflight-associated neuro-ocular syndrome (SANS). Little is understood about the pathophysiology of SANS; however, microgravity-induced alterations in intracranial pressure (ICP) due to headward fluid shifts is the primary hypothesized contributor. In particular, potential changes in optic nerve (ON) tortuosity and ON sheath (ONS) distension may indicate altered cerebrospinal fluid dynamics during weightlessness. The present longitudinal study aims to provide a quantitative analysis of ON and ONS cross-sectional areas, and ON deviation, an indication of tortuosity, before and after spaceflight. Ten astronauts undergoing ~6-month missions on the International Space Station (ISS) underwent high-resolution magnetic resonance imaging (MRI) preflight and at five recovery timepoints extending to 1 year after return from the ISS. The mean changes in ON deviation, ON cross-sectional area, and ONS cross-sectional area immediately post flight were−0.14 mm (95% CI:−0.36 to 0.08, Bonferroni-adjusted P=1.00), 0.13 mm2(95% CI−0.66 to 0.91, Bonferroni-adjusted P=1.00), and−0.22 mm2(95% CI:−1.78 to 1.34, Bonferroni-adjusted P=1.00), respectively, and remained consistent during the recovery period. Terrestrially, ONS distension is associated with increased ICP; therefore, these results suggest that, on average, ICP was not pathologically elevated immediately after spaceflight. However, a subject diagnosed with optic disc edema (Frisen Grade 1, right eye) displayed increased ONS area post flight, although this increase is relatively small compared to clinical populations with increased ICP. Advanced quantitative MRI-based assessment of the ON and ONS could help our understanding of SANS and the role of ICP.

Jesse Rohr↗

An Integrated Biomechanical Model for Microgravity-Induced Visual Impairment

When gravitational unloading occurs upon entry to space, astronauts experience a major shift in the distribution of their bodily fluids, with a net headward movement. Measurements have shown that intraocular pressure spikes, and there is a strong suspicion that intracranial pressure also rises. Some astronauts in both short- and long-duration spaceflight develop visual acuity changes, which may or may not reverse upon return to earth gravity. To date, of the 36 U.S. astronauts who have participated in long-duration space missions on the International Space Station, 15 crew members have developed minor to severe visual decrements and anatomical changes. These ophthalmic changes include hyperopic shift, optic nerve distension, optic disc edema, globe flattening, choroidal folds, and elevated cerebrospinal fluid pressure. In order to understand the physical mechanisms behind these phenomena, NASA is developing an integrated model that appropriately captures whole-body fluids transport through lumped-parameter models for the cerebrospinal and cardiovascular systems. This data feeds into a finite element model for the ocular globe and retrobulbar subarachnoid space through time-dependent boundary conditions. Although tissue models and finite element representations of the corneo-scleral shell, retina, choroid and optic nerve head have been integrated to study pathological conditions such as glaucoma, the retrobulbar subarachnoid space behind the eye has received much less attention. This presentation will describe the development and scientific foundation of our holistic model.

Nelson, Emily S.↗

Hormonal regulation of fluid and electrolyte metabolism during periods of headward fluid shifts

In the broadest sense, this project evaluates how spaceflight induced shifts of blood and interstitial fluids into the thorax affect regulation by the central nervous system (CNS) of fluid-electrolyte hormone secretion. Specifically, it focuses on the role of hormones related to salt/water balance and their potential function in the control of intracranial pressure and cerebrospinal fluid (CSF) composition. Fluid-electrolyte status during spaceflight gradually equilibrates, with a reduction in all body fluid compartments. Related to this is the cardiovascular deconditioning of spaceflight which is manifested upon return to earth as orthostatic intolerance.

Keil, Lanny C.↗

Computational Modeling of Cephalad Fluid Shift for Application to Microgravity-Induced Visual Impairment

An improved understanding of spaceflight-induced ocular pathology, including the loss of visual acuity, globe flattening, optic disk edema and distension of the optic nerve and optic nerve sheath, is of keen interest to space medicine. Cephalad fluid shift causes a profoundly altered distribution of fluid within the compartments of the head and body, and may indirectly generate phenomena that are biomechanically relevant to visual function, such as choroidal engorgement, compromised drainage of blood and cerebrospinal fluid (CSF), and altered translaminar pressure gradient posterior to the eye. The experimental body of evidence with respect to the consequences of fluid shift has not yet been able to provide a definitive picture of the sequence of events. On earth, elevated intracranial pressure (ICP) is associated with idiopathic intracranial hypertension (IIH), which can produce ocular pathologies that look similar to those seen in some astronauts returning from long-duration flight. However, the clinically observable features of the Visual Impairment and Intracranial Pressure (VIIP) syndrome in space and IIH on earth are not entirely consistent. Moreover, there are at present no experimental measurements of ICP in microgravity. By its very nature, physiological measurements in spaceflight are sparse, and the space environment does not lend itself to well-controlled experiments. In the absence of such data, numerical modeling can play a role in the investigation of biomechanical causal pathways that are suspected of involvement in VIIP. In this work, we describe the conceptual framework for modeling the altered compartmental fluid distribution that represents an equilibrium fluid distribution resulting from the loss of hydrostatic pressure gradient.

Nelson, Emily S.↗

CO2 Effects in Space: Relationship to Intracranial Hypertension

This slide presentation reviews the effects of enhanced exposure to CO2 on Earth and in space. The effects of enhanced exposure to CO2 are experienced in almost all bodily systems. In space some of the effects are heightened due to the fluid shifts to the thorax and head. This fluid shift results in increased intracranial pressure, congested cerebral circulation, increased Cerebral Blood Flow (CBF) and Intravenous dilatation. The mechanism of the effect of CO2 on CBF is diagrammed, as is the Cerebrospinal Fluid (CSF) production. A listing of Neuroendocrine targets is included.

Alexander, David J.↗

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.↗

Melatonin concentrations in the sudden infant death syndrome

The melatonin levels in various body fluids of the sudden infant death syndrome (SIDS) infants are compared with those of infants of comparable age who died of other causes to examine a possible relationship between pineal function and SIDS. After adjusting for age differences, cerebrospinal fluid melatonin levels are found to be significantly lower in the SIDS infants. It is suggested that diminished melatonin production may be characteristic of SIDS and could represent an impairment in the maturation of physiologic circadian organization.

Sturner, W. Q.↗

Investigation of Tear Biomarkers as an Indicator of Human Health

Scientific literature suggests that tear biomarkers can be used as a guide towards clinical diagnosis of human health (Hagan et al., 2016). This study will investigate whether tear biomarkers represents a research and clinical opportunity to assess human health prior to, during, and after exposure to the spaceflight environment. The focus of this study is to compare biomarkers previously identified as potentially relevant to both ocular and brain health against unique physiological outcomes of exposure to the space flight environment. Study subjects suffering from terrestrial conditions thought to be similar to Spaceflight Associated Neuro-ocular Syndrome (SANS: formerly VIIP), e.g. patients with idiopathic intracranial hypertension (IIH) and optic neuritis may be relevant to conditions associated with spaceflight. This study will review methodologies, tear biomarkers related to state of ocular and brain health, the strengths and weakness of using tear fluid biomarkers versus other body fluid samples, and will survey current tear fluid biomarker knowledge in research and clinical practice. A strength of using tear biomarkers is that sampling is non-invasive and used as a guide in understanding pathologies, including ocular and systemic inflammatory conditions (Cocho et al., 2016)., Salvisberg et al., 2014). Moreover, tear biomarkers may reflect diseases affecting the central nervous system (CNS) (Salvisberg et al., 2014). For example, in multiple sclerosis (MS), the concordance rate between tear biomarkers versus cerebrospinal fluid (CSF) is approximately 83%, indicating that, in the majority of cases, tears are at least as effective as CSF in potentially identifying novel MS biomarkers (Devos et al., 2001).

Morton, Stephen↗

Hindlimb Suspension (HLS) in Rodents for the Study of Intracranial Pressure, Molecular and Histologic Changes in the Eye, and CSF Production Regulation and Resorption: A Status Report of Two Studies

This status report corresponds to two studies tied to an animal experiment being executed at the University of California Davis (Charles Fuller's laboratory). The animal protocol uses the well-documented rat hindlimb suspension (HLS) model, to examine the relationship between cephalic fluid shifts and the regulation of intracranial (ICP) and intraocular (IOP) pressures as well as visual system structure and function. Long Evans rats are subjected to HLS durations of 7, 14, 28 and 90 days. Subgroups of the 90-day animals are studied for recovery periods of 7, 14, 28 or 90 days. All HLS subjects have age-matched cage controls. Various animal cohorts are planned for this study: young males, young females and old males. In addition to the live measures (ICP by telemetry, IOP and retinal parameters by optical coherence tomography) which are shared with the Fuller study, the specific outcomes for this study include: -Gene expression analysis of the retina -Histologic analysis - Analysis of the microvasculature of retina flat mounts by NASA's VESsel GENeration Analysis (VESGEN) Software. To date, the young male and female cohorts are being completed. Due to the need to keep technical variation to a minimum, the histologic and genomic analyses have been delayed until all samples from each cohort are available and can be processed in a single batch per cohort. The samples received so far correspond to young males sacrificed at 7,14, 28 and 90 days of HLS and at 90 days of recovery; and from young females sacrificed at 7, 14 and 28 of HLS. A complementary study titled: "A gene expression and histologic approach to the study of cerebrospinal fluid (CSF) production and outflow in hindlimb suspended rats" seeks to study the molecular components of CSF production and outflow modulation as a result of HLS, bringing a molecular and histologic approach to investigate genome wide expression changes in the arachnoid villi and choroid plexus of HLS rats compared to rats in normal posture.

Theriot, C. A.↗

Digital simulation and experimental evaluation of the CO2-H(plus) control of pulmonary ventilation

Previous models of the CO2-H(+) control of ventilation have been concerned either with the response to CO2 inhalation, or the response to perfusion of the surface of the medulla with mock cerebrospinal fluid having a high P sub CO2. Simulation of both responses with the same model has not been attempted. The purpose of the present study was two fold; first to develop such a model and, second, to obtain experimental data from human subjects for both developing this model and for evaluating this and future models.

Milhorn, H. T., Jr.↗

Intrathoracic and venous pressure relationships during responses to changes in body position

Simultaneous end-expiratory pressures, referred to midthoracic level, in the superior and abdominal venae cavae, pericardial space, and right and left heart, were recorded without thoracotomy in three anesthetized dogs during sudden changes from supine to vertical head-up or head-down body positions. Intrathoracic and dependent great vein pressures referred to midchest level (sixth thoracic vertebra) decreased and showed simple hydrostatic gradients in either vertical position. However, a discontinuity in the large vein hydrostatic gradient occurred just distal to the superior margin of the thorax in either body position and was resumed again above this level. It is concluded that, just as the cerebrospinal fluid and intraperitoneal pressures minimize the effects of gravitational and inertial forces on the cerebral and visceral circulations, the pericardial and pleural pressures have a similar role for the heart proper.

Avasthey, P.↗