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All sourcesNASA NTRSDOE OSTI
NASA NTRS1994

Cerebral versus systemic hemodynamics during graded orthostatic stress in humans

BACKGROUND: Orthostatic syncope is usually attributed to cerebral hypoperfusion secondary to systemic hemodynamic collapse. Recent research in patients with neurocardiogenic syncope has suggested that cerebral vasoconstriction may occur during orthostatic hypotension, compromising cerebral autoregulation and possibly contributing to the loss of consciousness. However, the regulation of cerebral blood flow (CBF) in such patients may be quite different from that of healthy individuals, particularly when assessed during the rapidly changing hemodynamic conditions associated with neurocardiogenic syncope. To be able to interpret the pathophysiological significance of these observations, a clear understanding of the normal responses of the cerebral circulation to orthostatic stress must be obtained, particularly in the context of the known changes in systemic and regional distributions of blood flow and vascular resistance during orthostasis. Therefore, the specific aim of this study was to examine the changes that occur in the cerebral circulation during graded reductions in central blood volume in the absence of systemic hypotension in healthy humans. We hypothesized that cerebral vasoconstriction would occur and CBF would decrease due to activation of the sympathetic nervous system. We further hypothesized, however, that the magnitude of this change would be small compared with changes in systemic or skeletal muscle vascular resistance in healthy subjects with intact autoregulation and would be unlikely to cause syncope without concomitant hypotension. METHODS AND RESULTS: To test this hypothesis, we studied 13 healthy men (age, 27 +/- 7 years) during progressive lower body negative pressure (LBNP). We measured systemic flow (Qc is cardiac output; C2H2 rebreathing), regional forearm flow (FBF; venous occlusion plethysmography), and blood pressure (BP; Finapres) and calculated systemic (SVR) and forearm (FVR) vascular resistances. Changes in brain blood flow were estimated from changes in the blood flow velocity in the middle cerebral artery (VMCA) using transcranial Doppler. Pulsatility (systolic minus diastolic/mean velocity) normalized for systemic arterial pressure pulsatility was used as an index of distal cerebral vascular resistance. End-tidal PACO2 was closely monitored during LBNP. From rest to maximal LBNP before the onset of symptoms or systemic hypotension, Qc and FBF decreased by 29.9% and 34.4%, respectively. VMCA decreased less, by 15.5% consistent with a smaller decrease in CBF. Similarly, SVR and FVR increased by 62.8% and 69.8%, respectively, whereas pulsatility increased by 17.2%, suggestive of a mild degree of small-vessel cerebral vasoconstriction. Seven of 13 subjects had presyncope during LBNP, all associated with a sudden drop in BP (29 +/- 9%). By comparison, hyperventilation alone caused greater changes in VMCA (42 +/- 2%) and pulsatility but never caused presyncope. In a separate group of 3 subjects, superimposition of hyperventilation during highlevel LBNP caused a further decrease in VMCA (31 +/- 7%) but no change in BP or level of consciousness. CONCLUSIONS: We conclude that cerebral vasoconstriction occurs in healthy humans during graded reductions in central blood volume caused by LBNP. However, the magnitude of this response is small compared with changes in SVR or FVR during LBNP or other stimuli known to induce cerebral vasoconstriction (hypocapnia). We speculate that this degree of cerebral vasoconstriction is not by itself sufficient to cause syncope during orthostatic stress. However, it may exacerbate the decrease in CBF associated with hypotension if hemodynamic instability develops.

NASA Discipline Cardiopulmonary↗
NASA NTRS1998

Age alters the cardiovascular response to direct passive heating

During direct passive heating in young men, a dramatic increase in skin blood flow is achieved by a rise in cardiac output (Qc) and redistribution of flow from the splanchnic and renal vascular beds. To examine the effect of age on these responses, seven young (Y; 23 +/- 1 yr) and seven older (O; 70 +/- 3 yr) men were passively heated with water-perfused suits to their individual limit of thermal tolerance. Measurements included heart rate (HR), Qc (by acetylene rebreathing), central venous pressure (via peripherally inserted central catheter), blood pressures (by brachial auscultation), skin blood flow (from increases in forearm blood flow by venous occlusion plethysmography), splanchnic blood flow (by indocyanine green clearance), renal blood flow (by p-aminohippurate clearance), and esophageal and mean skin temperatures. Qc was significantly lower in the older than in the young men (11.1 +/- 0.7 and 7.4 +/- 0.2 l/min in Y and O, respectively, at the limit of thermal tolerance; P < 0. 05), despite similar increases in esophageal and mean skin temperatures and time to reach the limit of thermal tolerance. A lower stroke volume (99 +/- 7 and 68 +/- 4 ml/beat in Y and O, respectively, P < 0.05), most likely due to an attenuated increase in inotropic function during heating, was the primary factor for the lower Qc observed in the older men. Increases in HR were similar in the young and older men; however, when expressed as a percentage of maximal HR, the older men relied on a greater proportion of their chronotropic reserve to obtain the same HR response (62 +/- 3 and 75 +/- 4% maximal HR in Y and O, respectively, P < 0.05). Furthermore, the older men redistributed less blood flow from the combined splanchnic and renal circulations at the limit of thermal tolerance (960 +/- 80 and 720 +/- 100 ml/min in Y and O, respectively, P < 0. 05). As a result of these combined attenuated responses, the older men had a significantly lower increase in total blood flow directed to the skin.

Clinical Trial↗
NASA NTRS1999

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.↗
NASA NTRS1972

Thyroid and adrenal cortical rhythmicity during bed rest.

The effects of prolonged bed rest on adrenocortical and thyroid function were assessed in eight healthy males, aged 20-40 years, who were submitted to bed rest for 56 days on a 14L:10D regimen (lights-on, 9:00 AM). Four of these subjects exercised three times daily throughout the experiment. Circulating cortisol, triiodothyronine, and thyroxine, concentrations were determined in blood samples drawn at four hourly intervals for 48-hr periods before, 10, 20, 30, 42, and 54 days during, and 10 days post-bed rest. Significant fluctuations in the circulating levels of all three hormones occurred with peaks at 7:30 AM. The suggestion is advanced that thyroid rhythms may be posture dependent.

Vernikos-Danellis, J.↗
NASA NTRS1987

Cardiovascular dynamics during the initial period of head-down tilt

The cardiovascular response to 1 h of 60-deg head-down tilt was studied in 12 male subjects, ages 30-39 years, to simulate the early effects of weightlessness. Fluid shifts, hemodynamic variables, and indices of myocardial contractility were evaluated by utilizing electrocardiography, systolic time intervals, impedance cardiography, sphygmomanometry, and measurement of calf circumference. Most cardiovascular variables remained stable throughout the initial 30 min of the protocol, even though translocation of fluid from the legs to the thorax commenced immediately with the onset of head-down tilt. In contrast, minutes 30-60 were characterized by reduced stroke volume, cardiac output, mean stroke ejection rate, and Heather index concomitant with an elevation in mean arterial pressure. Intrathoracic fluid volume continued to increase, while leg volume continued to decrease. This latter physiological response suggests intrathoracic sequestration of fluid volume; blood was apparently redistributed to the pulmonary circulation rather than being retained in the great veins.

Tomaselli, Clare Marie↗
NASA NTRS1989

Lack of effect of vasopressin replacement on renin hypersecretion in Brattleboro rats

The congenital vasopressin deficiency in homozygous Brattleboro rats with diabetes insipidus is associated with elevated plasma renin activity at rest and supernormal responses to stimuli that increase renin secretion. The mechanism underlying this phenomenon was investigated by infusing homozygous and heterozygous Brattleboro rats with a dose of arginine vasopressin that restored plasma vasopressin to normal in the homozygous animals. The resulting data indicate that increased renin secretion in homozygous rats results from increased sympathetic activity. Because circulating vasopressin does not cross the blood-brain barrier, it seems likely that the increased sympathetic activity is central in origin.

Golin, Raffaello M. A.↗
NASA NTRS2010

Introduction to Vector Field Visualization

Vector field visualization techniques are essential to help us understand the complex dynamics of flow fields. These can be found in a wide range of applications such as study of flows around an aircraft, the blood flow in our heart chambers, ocean circulation models, and severe weather predictions. The vector fields from these various applications can be visually depicted using a number of techniques such as particle traces and advecting textures. In this tutorial, we present several fundamental algorithms in flow visualization including particle integration, particle tracking in time-dependent flows, and seeding strategies. For flows near surfaces, a wide variety of synthetic texture-based algorithms have been developed to depict near-body flow features. The most common approach is based on the Line Integral Convolution (LIC) algorithm. There also exist extensions of LIC to support more flexible texture generations for 3D flow data. This tutorial reviews these algorithms. Tensor fields are found in several real-world applications and also require the aid of visualization to help users understand their data sets. Examples where one can find tensor fields include mechanics to see how material respond to external forces, civil engineering and geomechanics of roads and bridges, and the study of neural pathway via diffusion tensor imaging. This tutorial will provide an overview of the different tensor field visualization techniques, discuss basic tensor decompositions, and go into detail on glyph based methods, deformation based methods, and streamline based methods. Practical examples will be used when presenting the methods; and applications from some case studies will be used as part of the motivation.

Kao, David↗
NASA NTRSDate not supplied

Appetite and Food Intake During 11 Days of Mild Hypobaric Hypoxia

Introduction Reduced food consumption and loss of body mass and muscle mass have been observed during spaceflight. Hypoxic conditions that astronauts may encounter on exploration missions may further implicate satiety signals and dietary intake. Appetite, food intake, and satiety hormones were investigated under the conditions of mild hypoxia and high energy output during simulated extravehicular activity (EVA) to determine the adequacy of a mission relevant space food system to support energy balance and body composition. Methods Foods realistic to early Artemis missions was packed by meal for each subject for the 11-day test based on estimated energy requirements (EER) and estimated EVA caloric requirements. No hot water or food warmer was provided and only room temperature water was available to rehydrate food and beverages in-mission, mimicking plans for early Artemis missions. Measures included food records (pre-mission, in-mission); fasted body weight (pre-mission, in-mission); Dual-energy X-ray absorptiometry (DXA) (pre-mission, post-mission); subjective ratings and feedback of food acceptability, mealtime and meal preparation sufficiency, appetite, and nausea (in-mission); and circulating ghrelin and leptin concentration in fasted blood samples (pre-mission, in-mission: pre-post EVA). Results All subjects consumed fewer calories in-mission than predicted. On average, subjects consumed 341 calories less on EVA days compared to non-EVA days in-mission (p=0.0511). The total weight loss estimate from daily weight measurements (-1.1 kg, p=0.0028) is consistent with underconsumption and supported by DXA measurements (-1.3 kg total body mass, p=0.0123 and -1.6 kg fat mass, p=0.0016). In general, most foods that were consumed were given acceptable scores, but subject comments indicated that the most acceptable foods were those not intended to be heated. Comments also indicated that subjects found their favorite foods early in the mission and avoided the foods that they did not like throughout the mission. Habitability scores indicated that overall aspects of the food system were considered borderline or unacceptable over the length of this mission. Foods that caused gas were avoided pre-EVA to prevent discomfort during pressure changes. Average fruit and vegetable intake decreased during the mission, dropping from 4.8 servings/d pre-mission to 3.4 servings/d on non-EVA days in-mission (p=0.0872) and 2.3 servings on EVA days (p=0.0020). Fasting ghrelin concentrations tended to be lower pre-EVA and on non-EVA days when exposed to mild hypoxia compared to normoxic conditions pre-mission and post-EVA (p=0.0136). Fasting levels of leptin did not change. Discussion Food intake was reduced in-mission, resulting in a caloric deficit and weight loss for most subjects. Crew food and appetite ratings and comments indicated this was due to a combination of food choices, lack of preference, lack of preparation capability, lack of time for meal preparation, consumption, and cleanup, and physiological challenges with the changing pressure. The regulation of appetite stimulating hormone ghrelin, but not the appetite suppressor leptin, appeared to be sensitive to hypoxic conditions. Conclusions Food preparation capabilities and time for meals are important for promoting adequate food intake. Reduced appetite and food intake during missions may further be aggravated under hypoxic conditions through the suppression of ghrelin. Lack of time for meals on EVA days, and avoidance of potential gas-causing foods (e.g., health promoting fruits and vegetables) prior to EVAs, demonstrate the importance of scheduling ample recovery time between EVA days.

Grace L Douglas↗
NASA NTRS2023

Appetite and Food Intake During 11 Days of Mild Hypobaric Hypoxia

Introduction Reduced food consumption and loss of body mass and muscle mass have been observed during spaceflight. Hypoxic conditions that astronauts may encounter on exploration missions may further implicate satiety signals and dietary intake. Appetite, food intake, and satiety hormones were investigated under the conditions of mild hypoxia and high energy output during simulated extravehicular activity (EVA) to determine the adequacy of a mission relevant space food system to support energy balance and body composition. Methods Foods realistic to early Artemis missions was packed by meal for each subject for the 11-day test based on estimated energy requirements (EER) and estimated EVA caloric requirements. No hot water or food warmer was provided and only room temperature water was available to rehydrate food and beverages in-mission, mimicking plans for early Artemis missions. Measures included food records (pre-mission, in-mission); fasted body weight (pre-mission, in-mission); Dual-energy X-ray absorptiometry (DXA) (pre-mission, post-mission); subjective ratings and feedback of food acceptability, mealtime and meal preparation sufficiency, appetite, and nausea (in-mission); and circulating ghrelin and leptin concentration in fasted blood samples (pre-mission, in-mission: pre-post EVA). Results All subjects consumed fewer calories in-mission than predicted. On average, subjects consumed 341 calories less on EVA days compared to non-EVA days in-mission (p=0.0511). The total weight loss estimate from daily weight measurements (-1.1 kg, p=0.0028) is consistent with underconsumption and supported by DXA measurements (-1.3 kg total body mass, p=0.0123 and -1.6 kg fat mass, p=0.0016). In general, most foods that were consumed were given acceptable scores, but subject comments indicated that the most acceptable foods were those not intended to be heated. Comments also indicated that subjects found their favorite foods early in the mission and avoided the foods that they did not like throughout the mission. Habitability scores indicated that overall aspects of the food system were considered borderline or unacceptable over the length of this mission. Foods that caused gas were avoided pre-EVA to prevent discomfort during pressure changes. Average fruit and vegetable intake decreased during the mission, dropping from 4.8 servings/d pre-mission to 3.4 servings/d on non-EVA days in-mission (p=0.0872) and 2.3 servings on EVA days (p=0.0020). Fasting ghrelin concentrations tended to be lower pre-EVA and on non-EVA days when exposed to mild hypoxia compared to normoxic conditions pre-mission and post-EVA (p=0.0136). Fasting levels of leptin did not change. Discussion Food intake was reduced in-mission, resulting in a caloric deficit and weight loss for most subjects. Crew food and appetite ratings and comments indicated this was due to a combination of food choices, lack of preference, lack of preparation capability, lack of time for meal preparation, consumption, and cleanup, and physiological challenges with the changing pressure. The regulation of appetite stimulating hormone ghrelin, but not the appetite suppressor leptin, appeared to be sensitive to hypoxic conditions. Conclusions Food preparation capabilities and time for meals are important for promoting adequate food intake. Reduced appetite and food intake during missions may further be aggravated under hypoxic conditions through the suppression of ghrelin. Lack of time for meals on EVA days, and avoidance of potential gas-causing foods (e.g., health promoting fruits and vegetables) prior to EVAs, demonstrate the importance of scheduling ample recovery time between EVA days.

Lichar Dillon↗
NASA NTRS1995

Simulated Microgravity Increases Cutaneous Blood Flow in the Head and Leg of Humans

The cutaneous micro-circulation vasodilates during acute 6 deg. head-down tilt (HDT, simulated microgravity) relative to upright conditions, more in the lower body than in the upper body. We expected that relative magnitudes of and differences between upper and lower body cutaneous blood flow elevation would be sustained during initial acclimation to simulated microgravity. We measured cutaneous micro-vascular blood flow with laser-Doppler flowmetry at the leg (over the distal tibia) and cheek (over the zygomatic arch) of eight healthy men before, during, and after 24 h of HDT. Results were calculated as a percentage of baseline value (100% measured during pre-tilt upright sitting). Cutaneous blood flow in the cheek increased significantly to 165 +/- 37% (mean + SE, p less than 0.05) at 9-12 h HDT, then returned to near baseline values by 24 h HDT (114 +/- 29%, NSD), despite increased local arterial pressure. Microvascular flow in the leg remained significantly elevated above baseline throughout 24 h HDT (427 +/- 85% at 3 h HDT and 215 +/- 142% at 24 h HDT, p less than 0.05). During the 6-h upright sitting recovery period, cheek and leg blood flow levels returned to near pre-tilt baseline values. Because hydrostatic effects of HDT increase local arterial pressure at the carotid sinus, baroreflex-mediated withdrawal of sympathetic tone probably contributed to increased microvascular flows at the head and leg during HDT. In the leg, baroreflex effects combined with minimal stimulation of local veno-arteriolar and myogenic autoregulatory vasoconstriction to elicit relatively larger and more sustained increases in cutaneous flow during HDT. In the cheek, delayed myogenic vasoconstriction and/or humoral effects apparently compensated for flow elevation by 24 h of HDT. Therefore, localized vascular adaptations to gravity probably explain differences in acclimation of lower and upper body blood flow to HDT and actual microgravity.

Stout, M. Shannon↗
NASA NTRS1972

Coronary flow and left ventricular function during environmental stress.

A canine model was used to study the effects of different environmental stresses on the heart and coronary circulation. The heart was surgically instrumented to measure coronary blood flow, left ventricular pressure, and other cardiovascular variables. Coronary flow was recorded by telemetry. Physiologic data were processed and analyzed by analog and digital computers. By these methods the physiologic response to altitude hypoxia, carbon monoxide, hypercapnia, acceleration, exercise, and the interaction of altitude hypoxia and carbon monoxide were described. The effects of some of these stresses on the heart and coronary circulation are discussed.

Erickson, H. H.↗
NASA NTRS1975

Myocardial blood flow: Roentgen videodensitometry techniques

The current status of roentgen videodensitometric techniques that provide an objective assessment of blood flow at selected sites within the coronary circulation were described. Roentgen videodensitometry employs conventional radiopaque indicators, radiological equipment and coronary angiographic techniques. Roentgen videodensitometry techniques developed in the laboratory during the past nine years, and for the past three years were applied to analysis of angiograms in the clinical cardiac catheterization laboratory.

Smith, H. C.↗
NASA NTRS1997

Endothelial Cell Morphology and Migration are Altered by Changes in Gravitational Fields

Many of the physiological changes of the cardiovascular system during space flight may originate from the dysfunction of basic biological mechanisms caused by microgravity. The weightlessness affects the system when blood and other fluids move to the upper body causing the heart to enlarge to handle the increased blood flow to the upper extremities and decrease circulating volume. Increase arterial pressure triggers baroreceptors which signal the brain to adjust heart rate. Hemodynarnic studies indicate that the microgravity-induced headward fluid redistribution results in various cardiovascular changes such as; alteration of vascular permeability resulting in lipid accumulation in the lumen of the vasculature and degeneration of the the vascular wall, capillary alteration with extensive endothelial invagination. Achieving a true microgravity environment in ground based studies for prolonged periods is virtually impossible. The application of vector-averaged gravity to mammalian cells using horizontal clinostat produces alterations of cellular behavior similar to those observed in microgravity. Similarly, the low shear, horizontally rotating bioreactor (originally designed by NASA) also duplicates several properties of microgravity. Additionally, increasing gravity, i.e., hypcrgravity is easily achieved. Hypergravity has been found to increase the proliferation of several different cell lines (e.g., chick embryo fibroblasts) while decreasing cell motility and slowing liver regeneration following partial hepatectomy. The effect of altered gravity on cells maybe similar to those of other physical forces, i.e. shear stress. Previous studies examining laminar flow and shear stress on endothelial cells found that the cells elongate, orient with the direction of flow, and reorganize their F-actin structure, with concomitant increase in cell stiffness. These studies suggest that alterations in the gravity environment will change the behavior of most cells, including vascular cells. However, few studies have been directed at assessing the effect of altered gravitational field on vascular cell fiction and metabolism, Using image analysis we examined how bovine aortic endothelial cells altered their morphological characteristics and their response to a denudation injury when cells were subjected to simulated microgravity and hypergravity.

Melhado, Caroline↗
NASA NTRS1997

Changes in gravity inhibit lymphocyte locomotion through type I collagen

Immunity relies on the circulation of lymphocytes through many different tissues including blood vessels, lymphatic channels, and lymphoid organs. The ability of lymphocytes to traverse the interstitium in both nonlymphoid and lymphoid tissues can be determined in vitro by assaying their capacity to locomote through Type I collagen. In an attempt to characterize potential causes of microgravity-induced immunosuppression, we investigated the effects of simulated microgravity on human lymphocyte function in vitro using a specialized rotating-wall vessel culture system developed at the Johnson Space Center. This very low shear culture system randomizes gravitational vectors and provides an in vitro approximation of microgravity. In the randomized gravity of the rotating-wall vessel culture system, peripheral blood lymphocytes did not locomote through Type I collagen, whereas static cultures supported normal movement. Although cells remained viable during the entire culture period, peripheral blood lymphocytes transferred to unit gravity (static culture) after 6 h in the rotating-wall vessel culture system were slow to recover and locomote into collagen matrix. After 72 h in the rotating-wall vessel culture system and an additional 72 h in static culture, peripheral blood lymphocytes did not recover their ability to locomote. Loss of locomotory activity in rotating-wall vessel cultures appears to be related to changes in the activation state of the lymphocytes and the expression of adhesion molecules. Culture in the rotating-wall vessel system blunted the ability of peripheral blood lymphocytes to respond to polyclonal activation with phytohemagglutinin. Locomotory response remained intact when peripheral blood lymphocytes were activated by anti-CD3 antibody and interleukin-2 prior to introduction into the rotating-wall vessel culture system. Thus, in addition to the systemic stress factors that may affect immunity, isolated lymphocytes respond to gravitational changes by ceasing locomotion through model interstitium. These in vitro investigations suggest that microgravity induces non-stress-related changes in cell function that may be critical to immunity. Preliminary analysis of locomotion in true microgravity revealed a substantial inhibition of cellular movement in Type I collagen. Thus, the rotating-wall vessel culture system provides a model for analyzing the microgravity-induced inhibition of lymphocyte locomotion and the investigation of the mechanisms related to lymphocyte movement.

Weightlessness↗
NASA NTRS2009

Right Ventricular Tissue Doppler Assessment in Space During Circulating Volume Modification using the Braslet-M Device

This joint U.S. - Russian work aims to establish a methodology for assessing cardiac function in microgravity in association with manipulation of central circulating volume. Russian Braslet-M occlusion cuffs were used to temporarily increase the volume of blood in the lower extremities, which effectively reduces the volume returning to the heart in the central circulation. A novel methodology was tested on the International Space Station (ISS) to assess the volume status of crewmembers by evaluating the responses to application and release of the Braslet-on-occlusion cuffs, as well as to modified Valsalva and Mueller maneuvers. Baseline echocardiographic tissue Doppler imaging (TDI) of the right ventricular free wall with no Braslet applied shows early diastolic E' (16 cm/sec), late diastolic A' (14 cm/sec), and systolic (12 cm/sec) velocities compatible with normal subjects on Earth. TDI of the RV free wall with Braslet applied shows that early diastolic E' decreased by 50% (8 cm/sec), late diastolic A' increased by 45%, and systolic S' remains unchanged. TDI of the RV free wall approximately 8 beats after the Braslet was released shows early diastolic E' (8 cm/sec), late diastolic A' (12 cm/sec), and systolic S' (13 cm/sec) velocities. During this portion of the release, early diastolic E' did not recover to baseline values but late diastolic A' and systolic S' recovered to pre-Braslet values. The pre-systolic cross-sectional area of the internal jugular vein with Braslet off was 1.07 cm(sup 2) and 1.13 cm(sup 2) 10 min after the Braslet was applied. The presystolic cross-sectional area of the common femoral vein with Braslet off was 0.50 cm(sup 2), and was 0.54 cm(sup 2) 10 min after the Braslet was applied. The right ventricular myocardial performance Tei index also was calculated for comparison with typical values found in healthy subjects on Earth. Baseline and Braslet-on values for Tei index were 0.25 and 0.22 respectively. Braslet Tei indices are within normal ranges found in healthy subjects and temporarily become greater than 0.4 during the dynamic Braslet release portion of this study. Tissue Doppler imaging of the right ventricle revealed that the Braslet influenced cardiac preload and that fluid was sequestered in the lower-extremity interstitial and vascular space after only 10 minutes of application. This report demonstrates that Braslet application affects right ventricular physiology in long-duration space flight based on TDI and that this effect is in part due to venous hemodynamics.

Hamilton, D. R.↗
NASA NTRS1986

Flow cytometry analysis of hormone receptors on human peripheral blood mononuclear cells to identify stress-induced neuroendocrine effects

Understanding the role of circulating peptide hormones in the pathogenesis of space-flight induced disorders would be greatly facilitated by a method which monitors chronic levels of hormones and their effects upon in vivo cell physiology. Single and simultaneous multiparameter flow cytometry analysis was employed to identify subpopulations of mononuclear cells bearing receptors for ACTH, Endorphin, and Somatomedin-C using monoclonal antibodies and monospecific antisera with indirect immunofluorescence. Blood samples were obtained from normal donors and subjects participating in decompression chamber studies (acute stress), medical student academic examination (chronic stress), and a drug study (Dexamethasone). Preliminary results indicate most ACTH and Endorphin receptor positive cells are monocytes and B-cells, exhibit little diurnal variation but the relative percentages of receptor positive cells are influenced by exposure to various stressors and ACTH inhibition. This study demonstrates the capability of flow cytometry analysis to study cell surface hormone receptor regulation which should allow insight into neuroendocrine modulation of the immune and other cellular systems during exposure to stress or microgravity.

Meehan, R. T.↗
NASA NTRS2001

Effects of spaceflight on human calf hemodynamics

Chronic microgravity may modify adaptations of the leg circulation to gravitational pressures. We measured resting calf compliance and blood flow with venous occlusion plethysmography, and arterial blood pressure with sphygmomanometry, in seven subjects before, during, and after spaceflight. Calf vascular resistance equaled mean arterial pressure divided by calf flow. Compliance equaled the slope of the calf volume change and venous occlusion pressure relationship for thigh cuff pressures of 20, 40, 60, and 80 mmHg held for 1, 2, 3, and 4 min, respectively, with 1-min breaks between occlusions. Calf blood flow decreased 41% in microgravity (to 1.15 +/- 0.16 ml x 100 ml(-1) x min(-1)) relative to 1-G supine conditions (1.94 +/- 0.19 ml x 100 ml(-1) x min(-1), P = 0.01), and arterial pressure tended to increase (P = 0.05), such that calf vascular resistance doubled in microgravity (preflight: 43 +/- 4 units; in-flight: 83 +/- 13 units; P < 0.001) yet returned to preflight levels after flight. Calf compliance remained unchanged in microgravity but tended to increase during the first week postflight (P > 0.2). Calf vasoconstriction in microgravity qualitatively agrees with the "upright set-point" hypothesis: the circulation seeks conditions approximating upright posture on Earth. No calf hemodynamic result exhibited obvious mechanistic implications for postflight orthostatic intolerance.

NASA Experiment Number 178294 2/2↗
NASA NTRS1999

Salivary Pharmacodynamics and Bioavailability of Promethazine in Human Subjects

The acute effects of exposure to microgravity include the development of space motion sickness which usually requires therapeutic intervention. The current drug of choice, promethazine (PMZ), has side effects which include nausea, drowsiness, dizziness, sedation and impaired psychomotor performance. In a ground-based study with commercial airline pilots and shuttle simulator trainers, we measured sleep and psychomotor performance variables, and physiological variables such as blood pressure and heart rate, as a function of circulating drug concentrations in the body. We evaluated a non-invasive sampling method (saliva) as a means of assessing pharmacodynamics following a single intramuscular (IM) dose of PMZ.

Putcha, Lakshmi↗