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At least 127 records · Page 7

Development of lower body negative pressure as a countermeasure for orthostatic intolerance

Exposure to prolonged (1-4 hr) lower body negative pressure (LBNP) is a countermeasure against postflight orthostatic intolerance which is used in the Soviet space program and planned for use in the American space program. LBNP in combination with fluid-loading is believed to act by promoting a transient positive fluid balance resulting in an increase in vascular, as well as extravascular fluid. Inflight LBNP also may provide beneficial orthostatic effects by restoring baroreceptor reflex functions and/or lower body venous compliance. Current research efforts at the Johnson Space Center are directed toward increasing the effectiveness and efficiency of the LBNP and saline countermeasure. A promising avenue may involve combining pharmacologic agents, such as inhaled anti-diuretic hormone, or mineralocorticoids, with mechanical stimuli such as LBNP.

Fortney, Suzanne M.↗

Luminal surface fabrication for cardiovascular prostheses

A method is provided for forming a mold surface with microscopic upstanding pillars for molding the inside surface of a vascular prostheses (synthetic blood vessel). The mold article is formed from a quantity of Teflon (polytetrafluoroethylene) which has a polished, flat surface on which a gold film has been sputter deposited. A photoresist layer, which cannot adhere directly to Teflon, adheres to the gold. The photoresist is exposed and developed leaving a sputter resistant mask defining the desired pillar locations, and the resulting workpiece is ion etched to form the pillars in the Teflon. A synthetic blood vessel material is cast against the Teflon mold to form blind recesses on the inside of the synthetic blood vessel, with the recesses being of predetermined uniform cross section and present in a predetermined uniform pattern.

Deininger, William D.↗

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↗

The Effects of CDKN1a/p21 on Oxidative Stress and Mitochondrial Function During Long Duration Spaceflight

Spaceflight factors, such as microgravity and space radiation, are known to put astronauts at risk for negative effects to their tissue regeneration and degenerative conditions. On our previous spaceflight research, we found that long duration spaceflight produced increased oxidative stress and activation of the inflammatory response as a major contributor to physiological changes, including alterations to the cardiovascular and musculoskeletal systems, metabolism, and the liver. Proliferation, apoptosis, and ion-channel remodeling of vascular smooth muscle cells, as well as endothelial inflammation, and nitric oxide synthase-nitric oxide system regulation have been shown by spaceflight and simulated spaceflight projects. CDKN1ap21 is a regulatory gene for tissue regeneration and also plays an important role in upregulating oxidative stress caused by radiation. In further research, we have also determined CDKN1ap21 to be overexpressed during spaceflight. When knocked out in mice, however, it protects against unloading-induced changes to the morphology and physiology of carotid arteries. In this proposal, we seek to test a potential dietary countermeasure to down-regulate CDKN1ap21 in the mice and protect against oxidative stress in the rodents. Specifically, we will expose both Wildtype and CDKN1ap21-null mice to hydrogen peroxide to induce oxidative stress and observe the molecular mechanisms in which a dietary supplement protects vascular smooth muscle cells against the consequences of the apoptotic environment within Wildtype mice versus the, hypothetically, sound physiology of CDKN1ap21-null mice. The successful completion of this experiment will conclusively determine accuracy of a dietary supplement as a CDKN1ap21 suppressor. This will provide a new perspective on the problem of increased oxidative stress developing into cardiovascular disease as a result of long-term space flight. This research will address the Human Research Plan Roadmaps Risk of Cardiac Rhythm Problems including CV-8, the Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure including Degen-6 and Degen-7, and the Risk of Adverse Health Event from Radiation Exposure including IM-8. Additionally, this research will address Space Biology Research Plans questions SBP CMB-1, SBP CMB-3, and SB AN-2.

Oxidative Stress↗

Effect of hypokinesia on cardiac contractile function and nervous regulation of the heart

Longterm hypokinesia caused cardiac deadaptation in rabbits, which resulted in the diminishing of the left ventricular rate of contraction and relaxation, joined later by decreased vascular resistance. As a results, the ejection rate as well as stroke volume and cardiac output were normal. The decrease of the relaxation speed was more obvious at a high heart rate and results in shortening of the diastolic pause and diminishing of cardiac output. Hearts of the hypokinetic animals were characterized by normal maximal pressure developed by a unit of muccardial mass aorta clamping, decreased adrenoreactivity, and increased cholinoreactivity. This complex of changes is contrary to changes observed in adaptation to exercise, but is similar to changes observed in compensatory hypertrophy of the heart.

Meyerson, F. Z.↗

Proteomic Assessment of Fluid Shifts and Association with Visual Impairment and Intracranial Pressure in Twin Astronauts

BACKGROUND: Astronauts participating in long duration space missions are at an increased risk of physiological disruptions. The development of visual impairment and intracranial pressure (VIIP) syndrome is one of the leading health concerns for crew members on long-duration space missions; microgravity-induced fluid shifts and chronic elevated cabin CO2 may be contributing factors. By studying physiological and molecular changes in one identical twin during his 1-year ISS mission and his ground-based co-twin, this work extends a current NASA-funded investigation to assess space flight induced "Fluid Shifts" in association with the development of VIIP. This twin study uniquely integrates physiological and -omic signatures to further our understanding of the molecular mechanisms underlying space flight-induced VIIP. We are: (i) conducting longitudinal proteomic assessments of plasma to identify fluid regulation-related molecular pathways altered by long-term space flight; and (ii) integrating physiological and proteomic data with genomic data to understand the genomic mechanism by which these proteomic signatures are regulated. PURPOSE: We are exploring proteomic signatures and genomic mechanisms underlying space flight-induced VIIP symptoms with the future goal of developing early biomarkers to detect and monitor the progression of VIIP. This study is first to employ a male monozygous twin pair to systematically determine the impact of fluid distribution in microgravity, integrating a comprehensive set of structural and functional measures with proteomic, metabolomic and genomic data. This project has a broader impact on Earth-based clinical areas, such as traumatic brain injury-induced elevations of intracranial pressure, hydrocephalus, and glaucoma. HYPOTHESIS: We predict that the space-flown twin will experience a space flight-induced alteration in proteins and peptides related to fluid balance, fluid control and brain injury as compared to his pre-flight protein/peptide signatures. Conversely, the trajectory of these protein signatures will remain relatively constant in his ground based co-twin. METHODS: We are using proteomic and standard immunoelectrophoresis techniques to delineate the change in protein signatures throughout the course of a long duration space flight in relation to the development of VIIP. We are also applying a novel cell-based metaboloic organ system assay ("Organs on a Plate") to address how these circulating biomarkers affect physiological processes at the cellular and organ level which could result in VIIP symptoms. These molecular data will be correlated with physiological measures (eg. extra and intracellular fluid volume, vascular filling/flow patterns, MRI, and Optic Coherence Tomography. DISCUSSION: Pre- and in-flight data collection is in progress for the space-flown twin, and similar data have been obtained from the ground-based twin. Biosamples will be batch processed when received from ISS after the conclusion of the 1-year mission. Omic and Physiological measures from the twin astronauts will be compared to similar data being collected on twin subjects who participated in simulated microgravity study. bed rest study.

Rana, Brinda K.↗

Standing Without Gravity: the Use of Lower Body Negative Pressure for Research and Reconditioning in Spaceflight

Weightlessness during spaceflight causes cephalad redistribution of intravascular and extravascular fluid, provoking cardiovascular and autonomic nervous system adaptations. The resulting functional state is appropriate for weightlessness but can result in orthostatic hypotension and intolerance during and after return to a persistent acceleration or gravitational environment. Lower body negative pressure (LBNP) applies subambient air pressure to the legs and lower abdomen inside a volume sealed at the waist, and decompression by 40‐50 mmHg reverses the spaceflight‐induced cephalad shift. LBNP has been used both to test the state of cardiovascular system during spaceflight and as a countermeasure by all space‐faring nations. Two configurations have thus far been used in spaceflight since the first LBNP flew on the first Soviet Salyut station in 1971. The Soviet and Russian configuration, used in four Salyut stations, the Mir space station and the Russian segment of the International Space Station, has no saddle to support the body so during decompression the feet press against the bottom of the collapsible chamber which shortens and applies force against the feet proportional to the decompression level. Thus, activation of the skeletal musculature partially counteracts vascular and venous pooling in the enclosed body segments, stimulating the orthostatic compensatory mechanisms as they would be standing on Earth. In the American configuration, used aboard Skylab and the Space Shuttle, a saddle supported the astronaut so the feet did not contact the bottom of the chamber, and vascular engorgement was not countered by muscular contraction. This minimized skeletal muscle involvement, unmasked vascular compensatory mechanisms for research purposes, and allowed measurements of changes in leg volume and muscle sympathetic nerve activity. Both variants have demonstrated research and therapeutic value in appropriately designed protocols. LBNP continues to be used for research and countermeasures on ISS, and future versions may explore the value of exercise during LBNP as an integrated countermeasure. This paperwill review the history and development of LBNP for spaceflight research and therapeutic purposes.

Charles, John B.↗

Exploring Endothelial Function Risk Factors and Optic Disc Edema Changes During Strict 6º Head-Down Tilt Bed Rest

Approximately 20% of astronauts on International Space Station missions experience ophthalmic pathologies including optic disc edema, part of what is characterized as Spaceflight Associated Neuro-ocular Syndrome (SANS). While the cause of SANS is unknown, there are likely multiple contributing factors, including genetics, that may affect the response to spaceflight in affected individuals. B-vitamin status and the presence of specific one-carbon pathway single nucleotide polymorphism (SNP) alleles predicted the incidence of SANS pathologies in astronauts and in bed rest subjects. There are several hypotheses for how genetic variants could lead to SANS, specifically related to endothelial function. The biochemical pathway to which these genes are associated is intimately involved in maintaining endothelial function via nitric oxide synthase (eNOS) coupling and nitric oxide (NO) production. Furthermore, eNOS uncoupling can impair the functional status of the endothelial glycocalyx, which lines the entirety of the vascular lumen and affects endothelial function. Vascular distension, stasis and altered shear forces, which are associated with headward fluid shifts, may also contribute to glycocalyx dysfunction and shedding, resulting in endothelial dysfunction and increased vascular permeability and tissue edema, potentially contributing to optic nerve and optic disc edema in affected individuals. Given the findings relating genetics and the risk of optic disc edema in astronauts during flight and subjects during bed rest, further investigation is warranted. In this study, we will assess the same genetic variants in another bed rest study: AGBRESA. Some of the AGBRESA subjects developed optic disc edema, but their genetics have not been studied. Furthermore, we will test available urine samples from prior bed rest studies (VaPER and AGBRESA) for markers of glycocalyx degradation to expand our understanding of factors contributing to SANS.

S R Zwart↗

Early events in geotropism of seedling shoots

Developments during the first ten minutes of geotropic stimulation in plant seedling shoots are reviewed. Topics include induction and curvature; early processes; the relationship between auxin, electric field, calcium, and differential growth; gravity reception leading to Went-Cholodny transport; and comparison of root and shoot. Early processes reviewed are sedimentation of amyloplasts, release of ethylene, rise of electrical and auxin asymmetry, redistribution of calcium, asymmetric vascular transport, increase in tendency to deposit callose, and simulation of putative exocytotic voltage transients.

Review↗

Physiological water model development

The water of the human body can be categorized as existing in two main compartments: intracellular water and extracellular water. The intracellular water consists of all the water within the cells and constitutes over half of the total body water. Since red blood cells are surrounded by plasma, and all other cells are surrounded by interstitial fluid, the intracellular compartment has been subdivided to represent these two cell types. The extracellular water, which includes all of the fluid outside of the cells, can be further subdivided into compartments which represent the interstitial fluid, circulating blood plasma, lymph, and transcellular water. The interstitial fluid surrounds cells outside of the vascular system whereas plasma is contained within the blood vessels. Avascular tissues such as dense connective tissue and cartilage contain interstitial water which slowly equilibrates with tracers used to determine extracellular fluid volume. For this reason, additional compartments are sometimes used to represent these avascular tissues. The average size of each compartment, in terms of percent body weight, has been determined for adult males and females. These compartments and the forces which cause flow between them are presented. The kidneys, a main compartment, receive about 25 percent of the cardiac output and filters out a fluid similar to plasma. The composition of this filtered fluid changes as it flows through the kidney tubules since compounds are continually being secreted and reabsorbed. Through this mechanism, the kidneys eliminate wastes while conserving body water, electrolytes, and metabolites. Since sodium accounts for over 90 percent of the cations in the extracellular fluid, and the number of cations is balanced by the number of anions, considering the renal handling sodium and water only should sufficiently describe the relationship between the plasma compartment and kidneys. A kidney function model is presented which has been adapted from a previous model of normal renal function in man. To test the validity of the proposed kidney model, results predicted by the model will be compared to actual data involving injected or ingested fluids and subsequent urine flow rates. Comparison of the model simulation to actual data following the ingestion of 1 liter of water is shown. The model simulation is also shown with actual data following the intravenous infusion of hypertonic saline.

Doty, Susan↗

Body Fluids Monitor

Method and apparatus are described for determining volumes of body fluids in a subject using bioelectrical response spectroscopy. The human body is represented using an electrical circuit. Intra-cellular water is represented by a resistor in series with a capacitor; extra-cellular water is represented by a resistor in series with two parallel inductors. The parallel inductors represent the resistance due to vascular fluids. An alternating, low amperage, multifrequency signal is applied to determine a subject's impedance and resistance. From these data, statistical regression is used to determine a 1% impedance where the subject's impedance changes by no more than 1% over a 25 kHz interval. Circuit component, of the human body circuit are determined based on the 1% impedance. Equations for calculating total body water, extra-cellular water, total blood volume, and plasma volume are developed based on the circuit components.

Siconolfi, Steven F.↗

Blood Vessel Tension Tester

In the photo, a medical researcher is using a specially designed laboratory apparatus for measuring blood vessel tension. It was designed by Langley Research Center as a service to researchers of Norfolk General Hospital and Eastern Virginia Medical School, Norfolk, Virginia. The investigators are studying how vascular smooth muscle-muscle in the walls of blood vessels-reacts to various stimulants, such as coffee, tea, alcohol or drugs. They sought help from Langley Research Center in devising a method of measuring the tension in blood vessel segments subjected to various stimuli. The task was complicated by the extremely small size of the specimens to be tested, blood vessel "loops" resembling small rubber bands, some only half a millimeter in diameter. Langley's Instrumentation Development Section responded with a miniaturized system whose key components are a "micropositioner" for stretching a length of blood vessel and a strain gage for measuring the smooth muscle tension developed. The micropositioner is a two-pronged holder. The loop of Mood vessel is hooked over the prongs and it is stretched by increasing the distance between the prongs in minute increments, fractions of a millimeter. At each increase, the tension developed is carefully measured. In some experiments, the holder and specimen are lowered into the test tubes shown, which contain a saline solution simulating body fluid; the effect of the compound on developed tension is then measured. The device has functioned well and the investigators say it has saved several months research time.

Source record↗

Skin cooling maintains cerebral blood flow velocity and orthostatic tolerance during tilting in heated humans

Orthostatic tolerance is reduced in the heat-stressed human. The purpose of this project was to identify whether skin-surface cooling improves orthostatic tolerance. Nine subjects were exposed to 10 min of 60 degrees head-up tilting in each of four conditions: normothermia (NT-tilt), heat stress (HT-tilt), normothermia plus skin-surface cooling 1 min before and throughout tilting (NT-tilt(cool)), and heat stress plus skin-surface cooling 1 min before and throughout tilting (HT-tilt(cool)). Heating and cooling were accomplished by perfusing 46 and 15 degrees C water, respectively, though a tube-lined suit worn by each subject. During HT-tilt, four of nine subjects developed presyncopal symptoms resulting in the termination of the tilt test. In contrast, no subject experienced presyncopal symptoms during NT-tilt, NT-tilt(cool), or HT-tilt(cool). During the HT-tilt procedure, mean arterial blood pressure (MAP) and cerebral blood flow velocity (CBFV) decreased. However, during HT-tilt(cool), MAP, total peripheral resistance, and CBFV were significantly greater relative to HT-tilt (all P < 0.01). No differences were observed in calculated cerebral vascular resistance between the four conditions. These data suggest that skin-surface cooling prevents the fall in CBFV during upright tilting and improves orthostatic tolerance, presumably via maintenance of MAP. Hence, skin-surface cooling may be a potent countermeasure to protect against orthostatic intolerance observed in heat-stressed humans.

Clinical Trial↗

Mechanisms of Orthostatic Tolerance Improvement Following Artificial Gravity Exposure Differ Between Men and Women

We recently determined that a short exposure to artificial gravity (AG) improved the orthostatic tolerance limit (OTL) of cardiovascularly deconditioned subjects. We now seek to determine the mechanisms of that improvement in these hypovolemic men and women. Methods. We determined the orthostatic tolerance limit (OTL) of 9 men and 8 women following a 90 min exposure to AG compared to 90 min of head down bed rest (HDBR). In both cases (21 days apart), subjects were made hypovolemic (low salt diet plus 20 mg intravenous furosemide). Orthostatic tolerance was determined from a combination of head up tilt and increasing lower body negative pressure until presyncope. Mean values and correlations with OTL were determined for heart rate, blood pressure, stroke volume, cardiac output and peripheral resistance (Finometer), cerebral artery blood velocity (DWL), partial pressure of carbon dioxide (Novametrics) and body segmental impedance (UFI THRIM) were measured during supine baseline, during OTL to presyncope and during supine recovery Results. Orthostatic tolerance of these hypovolemic subjects was significantly greater on the day of AG exposure than on the HDBR day. Regression of OTL on these variables identified significant relationships on the HDBR day that were not evident on the AG day: resting TPR correlated positively while resting cerebral flow correlated negatively with OTL. On both days, women's resting stroke volume correlated positively with orthostatic tolerance. Higher group mean values of stroke volume and cerebral artery flow and lower values of blood pressure, peripheral vascular and cerebrovascular resistance both at control and during OTL testing were observed on the AG day. Even though regression of OTL on resting stroke volume was significant only in women, presyncopal stroke volume reached the same level on each day of study for both men and women while the OTL test lasted 30% longer in men and 22% longer in women. Cerebral artery flow appeared to follow stroke volume and absolute values of cerebral flow did not correlate with the development of presyncope. Women responded to AG exposure with elevated cerebral flow at resting control and throughout the OTL test, implying a loss of autoregulation in deconditioned (hypovolemic) women following AG exposure. Conclusions. Before countermeasures to space flight cardiovascular deconditioning are established, gender differences in cardiovascular responses to orthostatic stress, in general, and to orthostatic stress following exposure to artificial gravity, in particular, need to be determined. Since, in both men and women, a single, acute bout of AG exposure improved orthostatic tolerance, the feasibility of short exposures to AG during longer spaceflights or prior to entry into a gravity (Earth or Mars) environment, should be explored. Given the known beneficial effects of AG on other organ systems, the present study indicates that the positive effects of AG on cardiac stroke volume make AG a likely candidate for maintaining cardiovascular conditioning.

Evans, J. M.↗

The heart works against gravity

The circulatory systems of vertebrate animals are closed, and blood leaves and returns to the heart at the same level. It is often concluded, therefore, that the heart works only against the viscous resistance of the system, not against gravity, even in vascular loops above the heart in which the siphon principle operates. However, we argue that the siphon principle does not assist blood flow in superior vascular loops if any of the descending vasculature is collapsible. If central arterial blood pressure is insufficient to support a blood column between the heart and the head, blood flow ceases because of vascular collapse. Furthermore, the siphon principle does not assist the heart even when a continuous stream of blood is flowing in a superior loop. The potential energy gained by blood as it is pumped to the head is lost to friction in partially collapsed descending vessels and thus is not regained. Application of the Poiseuille equation to flow in collapsible vessels is limited; resistance depends on flow rate in partially collapsed vessels with no transmural pressure difference, but flow rate is independent of resistance. Thus the pressure developed by the heart to establish a given flow rate is independent of the resistance occurring in the partially collapsed vessels. The pressure depends only on the height of the blood column and the resistance in the noncollapsed parts of the system. Simple laboratory models, involving water flow in collapsible tubing, dispel the idea that the siphon principle facilitates blood flow and suggest that previously published results may have been affected by experimental artifact.

Review, Tutorial↗

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

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

Cohen, Richard↗

Localization of the ANG II type 2 receptor in the microcirculation of skeletal muscle

Only functional studies have suggested the presence of the ANG II type 2 (AT2) receptor in the microcirculation. To determine the distribution of this receptor in the rat skeletal muscle microcirculation, a polyclonal rabbit anti-rat antiserum was developed and used for immunohistochemistry and Western blot analysis. The antiserum was prepared against a highly specific and antigenic AT2-receptor synthetic peptide and was validated by competition and sensitivity assays. Western blot analysis demonstrated a prominent, single band at approximately 40 kDa in cremaster and soleus muscle. Immunohistochemical analysis revealed a wide distribution of AT2 receptors throughout the skeletal muscle microcirculation in large and small microvessels. Microanatomic studies displayed an endothelial localization of the AT2 receptor, whereas dual labeling with smooth muscle alpha-actin also showed colocalization of the AT2 receptor with vascular smooth muscle cells. Other cells associated with the microvessels also stained positive for AT2 receptors. Briefly, this study confirms previous functional data and localizes the AT2 receptor to the microcirculation. These studies demonstrate that the AT2 receptor is present on a variety of vascular cell types and that it is situated in a fashion that would allow it to directly oppose ANG II type 1 receptor actions.

NASA Discipline Cardiopulmonary↗

Arctic Tundra Vegetation Functional Types Based on Photosynthetic Physiology and Optical Properties

Climate change in tundra regions may alter vegetation species composition and ecosystem carbon balance. Remote sensing provides critical tools for monitoring these changes as optical signals provide a way to scale from plot measurements to regional patterns. Gas exchange measurements of pure patches of key vegetation functional types (lichens, mosses, and vascular plants) in sedge tundra at Barrow AK, show three significantly different values of light use efficiency (LUE) with values of 0.013+/-0.001, 0.0018+/-0.0002, and 0.0012 0.0001 mol C/mol absorbed quanta for vascular plants, mosses and lichens, respectively. Further, discriminant analysis of patch reflectance identifies five spectral bands that can separate each vegetation functional type as well as nongreen material (bare soil, standing water, and dead leaves). These results were tested along a 100 m transect where midsummer spectral reflectance and vegetation coverage were measured at one meter intervals. Area-averaged canopy LUE estimated from coverage fractions of the three functional types varied widely, even over short distances. Patch-level statistical discriminant functions applied to in situ hyperspectral reflectance successfully unmixed cover fractions of the vegetation functional types. These functions, developed from the tram data, were applied to 30 m spatial resolution Earth Observing-1 Hyperion imaging spectrometer data to examine regional variability in distribution of the vegetation functional types and from those distributions, the variability of LUE. Across the landscape, there was a fivefold variation in tundra LUE that was correlated to a spectral vegetation index developed to detect vegetation chlorophyll content.

Huemmrich, Karl F.↗