A study of physiological mechanisms and inter-relations between systemic and regional blood volume, blood flow and electrolyte balance interim progress report
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Abelman, W. H.↗
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A study of physiological mechanisms and inter-relations between systemic and regional blood volume, blood flow and electrolyte balance Interim progress report
Regulation of sodium excretion in healthy, obese volunteers, and circulatory response to orthostatic stress in man
Abelmann, W. H.↗
Quantitation of serum proteins on whole blood-electroimmunodiffusion technique applicable to capillary blood.
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Daniels, J. C.↗
Extra-corporeal blood access, sensing, and radiation methods and apparatuses
The described invention is related to extra-corporeal blood access and radiation methods and apparatuses and, in particular, to subjecting flowing blood to energy in variety of forms, including radiation, electromagnetic force fields or atomic particles. It is directed to methods and apparatuses for accessing flowing blood and for subjecting the blood to electrical conductive, electrostatic or electromagnetic fields or for radiating the blood with some type of radiation, e.g., radio waves, ultrasonic or audio waves, microwaves, IR rays, visible light, UV radiation, x-rays, alpha, beta or gamma rays. An apparatus is employed which includes one or more access ports or windows for radiating blood and/or for sensing/analyzing blood. This invention is useful for killing viruses and bacteria in blood, monitoring blood for medical purposes, genetic modification of blood, and analyzing and/or treating blood components.
Castle, Kent D.↗
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.↗
Hyperpolarized (129)Xe T (1) in oxygenated and deoxygenated blood
The viability of the new technique of hyperpolarized (129)Xe MRI (HypX-MRI) for imaging organs other than the lungs depends on whether the spin-lattice relaxation time, T(1), of (129)Xe is sufficiently long in the blood. In previous experiments by the authors, the T(1) was found to be strongly dependent upon the oxygenation of the blood, with T(1) increasing from about 3 s in deoxygenated samples to about 10 s in oxygenated samples. Contrarily, Tseng et al. (J. Magn. Reson. 1997; 126: 79-86) reported extremely long T(1) values deduced from an indirect experiment in which hyperpolarized (129)Xe was used to create a 'blood-foam'. They found that oxygenation decreased T(1). Pivotal to their experiment is the continual and rapid exchange of hyperpolarized (129)Xe between the gas phase (within blood-foam bubbles) and the dissolved phase (in the skin of the bubbles); this necessitated a complicated analysis to extract the T(1) of (129)Xe in blood. In the present study, the experimental design minimizes gas exchange after the initial bolus of hyperpolarized (129)Xe has been bubbled through the sample. This study confirms that oxygenation increases the T(1) of (129)Xe in blood, from about 4 s in freshly drawn venous blood, to about 13 s in blood oxygenated to arterial levels, and also shifts the red blood cell resonance to higher frequency. Copyright 2000 John Wiley & Sons, Ltd. Abbreviations used BOLD blood oxygen level dependent NOE nuclear overhouses effect PO(2) oxygen partial pressure RBC red blood cells RF radio frequency SNR signal-to-noise ratio.
NASA Discipline Life Support Systems↗
Whole Blood Activation Results in Altered T Cell and Monocyte Cytokine Production Profiles by Flow Cytometry
An excellent monitor of the immune balance of peripheral circulating cells is to determine their cytokine production patterns in response to stimuli. Using flow cytometry, a positive identification of cytokine producing cells in a mixed culture may be achieved. Recently, the ability to assess cytokine production following a whole-blood activation culture has been described. In this study, whole blood activation was compared to traditional PBMC activation and the individual cytokine secretion patterns for both T cells, T cell subsets and monocytes was determined by flow cytometry. RESULTS: For T cell cytokine assessment (IFNg/IL-10 and IL-21/L-4) following PMA +ionomycin activation: (1) a Significantly greater percentages of T cells producing IFNgamma and IL-2 were observed following whole-blood culture and (2) altered T cell cytokine production kinetics were observed by varying whole blood culture times. Four-color analysiS was used to allow assessment of cytokine production by specific T cell subsets. It was found that IFNgamma production was significantly elevated in the CD3+/CD8+ T cell population as compared to the CD3+/CD8- population following five hours of whole blood activation. Conversely, IL-2 and IL-10 production were Significantly elevated in the CD3+/CD8- T cell population as compared to the CD3+/CD8+ population. Monocyte cytokine production was assessed in both culture systems following LPS activation for 24 hours. A three-color flow cytometric was used to assess two cytokines (IL-1a/IL-12 and TNFa/IL-10) in conjunction with CD14. Nearly all monocytes were stimulated to produce IL-1a, IL-12 and TNFa. equally well in both culture systems, however monocyte production of IL-10 was significantly elevated in whole blood culture as compared to PBMC culture. IL-12 producing monocytes appeared to be a distinct subpopulation of the IL-1a producing set, whereas IL-10 and TNFa producing monocytes were largely mutually exclusive. IL-10 and TNFa producing monocytes may represent distinct monocyte subsets with unique functions. CONCLUSIONS: Whole blood culture eliminates the need to purify cell populations prior to culture and may have Significant utility for the routine monitoring of the cytokine balances of the peripheral blood T cell and monocyte populations. In addition, there are distinct advantages to performing whole-blood (WB) activation as compared to PBMC activation. These advantages would include retaining all various cell-cell interactions as well as any soluble factors present in serum that influence cell activation. In this study, alterations in cytokine production are demonstrated between whole blood and PBMC activation. It is likely that whole blood activation more accurately represents the in-vivo immune balance than PBMC activation.
Crucian, Brian E.↗
Cerebral blood velocity and other cardiovascular responses to 2 days of head-down tilt
Spaceflight induces a cephalad redistribution of fluid volume and blood flow within the human body, and space motion sickness, which is a problem during the first few days of space flight, could be related to these changes in fluid status and in blood flow of the cerebrum and vestibular system. To evaluate possible changes in cerebral blood flow during simulated weightlessness, we measured blood velocity in the middle cerebral artery (MCA) along with retinal vascular diameters, intraocular pressure, impedance cardiography, and sphygmomanometry on nine men (26.2 +/- 6.6 yr) morning and evening for 2 days during continuous 10 deg head-down tilt (HDT). When subjects went from seated to head-down bed rest, their heart rate and retinal diameters decreased, and intraocular pressures increased. After 48 h of HDT, blood flow velocity in the MCA was decreased and thoracic impedance was increased, indicating less fluid in the thorax. Percent changes in blood flow velocities in the MCA after 48 h of HDT were inversely correlated with percent changes in retinal vascular diameters. Blood flow velocities in the MCA were inversely correlated (intersubject) with arterial pressures and retinal vascular diameters. Heart rate, stroke volume, cardiac output, systolic arterial pressure, and at times pulse pressure and blood flow velocities in the MCA were greater in the evening. Total peripheral resistance was higher in the morning. Although cerebral blood velocity is reduced after subjects are head down for 2 days, the inverse relationship with retinal vessel diameters, which have control analogous to that of cerebral vessels, indicates cerebral blood flow is not reduced.
Frey, Mary A. B.↗
Destruction of newly released red blood cells in space flight
Space flight results in a rapid change in total blood volume, plasma volume, and red blood cell mass because the space to contain blood is decreased. The plasma volume and total blood volume decreases during the first hours in space and remain at a decreased level for the remainder of the flight. During the first several hours following return to earth, plasma volume and total blood volume increase to preflight levels. During the first few days in space recently produced red blood cells disappear from the blood resulting in a decrease in red blood cell mass of 10-15%. Red cells 12 d old or older survive normally and production of new cells continues at near preflight levels. After the first few days in space, the red cell mass is stable at the decreased level. Following return to earth the hemoglobin and red blood cell mass concentrations decrease reflecting the increase in plasma volume. The erythropoietin levels increase responding to "postflight anemia"; red cell production increases, and the red cell mass is restored to preflight levels after several weeks.
STS-58 Shuttle Project↗
Method for Reducing Pumping Damage to Blood
Methods are provided for minimizing damage to blood in a blood pump wherein the blood pump comprises a plurality of pump components that may affect blood damage such as clearance between pump blades and housing, number of impeller blades, rounded or flat blade edges, variations in entrance angles of blades, impeller length, and the like. The process comprises selecting a plurality of pump components believed to affect blood damage such as those listed herein before. Construction variations for each of the plurality of pump components are then selected. The pump components and variations are preferably listed in a matrix for easy visual comparison of test results. Blood is circulated through a pump configuration to test each variation of each pump component. After each test, total blood damage is determined for the blood pump. Preferably each pump component variation is tested at least three times to provide statistical results and check consistency of results. The least hemolytic variation for each pump component is preferably selected as an optimized component. If no statistical difference as to blood damage is produced for a variation of a pump component, then the variation that provides preferred hydrodynamic performance is selected. To compare the variation of pump components such as impeller and stator blade geometries, the preferred embodiment of the invention uses a stereolithography technique for realizing complex shapes within a short time period.
Bozeman, Richard J., Jr.↗
Effect of Hindlimb Unweighting on Tissue Blood Flow in the Rat
The purpose of this study was to characterize the distribution of blood flow in the rat during hindlimb unweighting (HU) and post-HU standing and exercise and examine whether the previously reported elevation in anaerobic metabolism observed with contractile activity in the atrophied soleus muscle was caused by a reduced hindlimb blood flow. After either 15 days of HU or cage control, blood flow was measured with radioactive microspheres during unweighting, normal standing, and running on a treadmill (15 m/min). In another group of control and experimental animals, blood flow was measured during preexercise (PE) treadmill standing and treadmill running (15 m/min). Soleus muscle blood flow was not different between groups during unweighting, PE standing, and running at 15 m/min. Chronic unweighting resulted in the tendency for greater blood flow to muscles composed of predominantly fast-twitch glycolytic fibers. With exercise, blood flow to visceral organs was reduced compared with PE values in the control rats, whereas flow to visceral organs in 15-day HU animals was unaltered by exercise. These higher flows to the viscera and to muscles composed of predominantly fast-twitch glycolytic fibers suggest an apparent reduction in the ability of the sympathetic nervous system to distribute cardiac output after chronic HU. In conclusion, because 15 days of HU did not affect blood flow to the soleus during exercise, the increased dependence of the atrophied soleus on anerobic energy production during contractile activity cannot be explained by a reduced muscle blood flow.
McDonald, K. S.↗
The Effects of Blood Glucose Levels on Cognitive Performance: A Review of the Literature
The purpose of this review paper is to discuss the research literature on the effects of blood glucose levels on executive and non-executive functions in humans. The review begins with a brief description of blood glucose, how it has been studied, previous syntheses of prior studies, and basic results regarding the role of blood glucose on cognitive functioning. The following sections describe work that investigated the effect of blood glucose on both non-executive and executive functions (e.g., sensory processing, psychomotor functioning, attention, vigilance, memory, language and communication, judgement and decision-making, and complex task performance). Within each section, summaries of the findings and challenges to the literature are included. Measurement conversions of blood glucose levels, blood glucose values, and associated symptoms are depicted. References to the types of tests used to investigate blood glucose and cognitive performance are provided. For more detailed descriptions of references within (and in addition to) this paper, an annotated bibliography is also provided. Several moderator variables including individual differences and contextual variables related to the effects of blood glucose levels on performance (e.g., age, gender, time of day, familiarity with the task and symptom awareness, expectancy effects, dose dependent effects, time dependent effects, task specific effects, rising and falling blood glucose levels, and speed and/or accuracy trade-offs) are addressed later in the paper. Some suggestions for future experimental methodologies are also made.
Feldman, Jolene↗
Whole Blood Activation Results in Enhanced Detection of T Cell and Monocyte Cytokine Production by Flow Cytometry
An excellent monitor of the immune balance of peripheral circulating cells is to determine their cytokine production patterns in response to stimuli. Using flow cytometry a positive identification of cytokine producing cells in a mixed culture may be achieved. Recently, the ability to assess cytokine production following a wholeblood activation culture has been described. We compared whole blood culture to standard PBMC culture and determined the individual cytokine secretion patterns for both T cells and monocytes via flow cytometry. For T cells cytokine assessment following PMA +ionomycin activation: (1) a significantly greater percentages of T cells producing IFNgamma and IL-2 were observed following whole-blood culture; (2) altered T cell cytokine production kinetics were observed by varying whole blood culture times. In addition, a four-color cytometric analysis was used to allow accurate phenotyping and quantitation of cytokine producing lymphocyte populations. Using this technique we found IFNgamma production to be significantly elevated in the CD3+/CD8+ T cell population as compared to the CD3+/CD8- population following five hours of whole blood activation. Conversely, IL-2 and IL-10 production were significantly elevated in the CD3+/CD8- T cell population as compared to the CD3+/CD8+ population. Monocyte cytokine production was assessed in both culture systems following LPS activation for 24 hours. A three-color flow cytometric was used to assess two cytokines in conjunction with CD 14. The cytokine pairs used for analysis were IL-1a/IL-12, and IL-10ITNFa. Nearly all monocytes were stimulated to produce IL-1a, IL-12 and TNFalpha equally well in both culture systems. Monocyte production of IL-10 was significantly elevated following whole blood culture as compared to PBMC culture. IL-12 producing monocytes appeared to be a distinct subpopulation of the IL-1a producing set, whereas IL-10 and TNFa producing monocytes were largely mutually exclusive. IL-10 and TNFa producing monocytes may represent functionally different monocyte subsets with distinct functions. Whole blood culture eliminates the need to purify cell populations prior to culture and may have significant utility for the routine monitoring of the cytokine balances of the peripheral blood T cell and monocyte populations. In addition, there are distinct advantages to performing whole-blood (WB) activation as compared to PBMC activation. These advantages would include retaining all various cell-cell interactions as well as any soluble factors present in serum that influence cell activation. It is likely that the altered cytokine production observed following whole blood culture more accurately represents the in-vivo immune balance.
Sams, Clarence F.↗
Beat-to-Beat Blood Pressure Monitor
This device provides non-invasive beat-to-beat blood pressure measurements and can be worn over the upper arm for prolonged durations. Phase and waveform analyses are performed on filtered proximal and distal photoplethysmographic (PPG) waveforms obtained from the brachial artery. The phase analysis is used primarily for the computation of the mean arterial pressure, while the waveform analysis is used primarily to obtain the pulse pressure. Real-time compliance estimate is used to refine both the mean arterial and pulse pressures to provide the beat-to-beat blood pressure measurement. This wearable physiological monitor can be used to continuously observe the beat-to-beat blood pressure (B3P). It can be used to monitor the effect of prolonged exposures to reduced gravitational environments and the effectiveness of various countermeasures. A number of researchers have used pulse wave velocity (PWV) of blood in the arteries to infer the beat-to-beat blood pressure. There has been documentation of relative success, but a device that is able to provide the required accuracy and repeatability has not yet been developed. It has been demonstrated that an accurate and repeatable blood pressure measurement can be obtained by measuring the phase change (e.g., phase velocity), amplitude change, and distortion of the PPG waveforms along the brachial artery. The approach is based on comparing the full PPG waveform between two points along the artery rather than measuring the time-of-flight. Minimizing the measurement separation and confining the measurement area to a single, well-defined artery allows the waveform to retain the general shape between the two measurement points. This allows signal processing of waveforms to determine the phase and amplitude changes. Photoplethysmography, which measures changes in arterial blood volume, is commonly used to obtain heart rate and blood oxygen saturation. The digitized PPG signals are used as inputs into the beat-to-beat blood pressure measurement algorithm.
Lee, Yong Jin↗
A large blood pressure-raising effect of nitric oxide synthase inhibition in humans
In experimental animals, systemic administration of nitric oxide synthase (NOS) inhibitors causes large increases in blood pressure that are in part sympathetically mediated. The aim of this study was to determine the extent to which these conclusions can be extrapolated to humans. In healthy normotensive humans, we measured blood pressure in response to two NOS inhibitors, NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME), the latter of which recently became available for use in humans. The major new findings are 3-fold. First, L-NAME produced robust increases in blood pressure that were more than 2 times larger than those previously reported in humans with L-NMMA and approximated those seen in experimental animals. L-NAME (4 mg/kg) raised mean arterial pressure by 24+/-2 mm Hg (n=27, P<0.001), whereas in subjects who received both inhibitors, a 12-fold higher dose of L-NMMA (50 mg/kg) raised mean arterial pressure by 15+/-2 mm Hg (n=4, P<0.05 vs L-NAME). Second, the L-NAME-induced increases in blood pressure were caused specifically by NOS inhibition because they were reversed by L-arginine (200 mg/kg, n=12) but not D-arginine (200 mg/kg, n=6) and because NG-nitro-D-arginine methyl ester (4 mg/kg, n=5) had no effect on blood pressure. Third, in humans, there is an important sympathetic component to the blood pressure-raising effect of NOS inhibition. alpha-Adrenergic blockade with phentolamine (0.2 mg/kg, n=9) attenuated the L-NAME-induced increase in blood pressure by 40% (P<0.05). From these data, we conclude that pharmacological inhibition of NOS causes large increases in blood pressure that are in part sympathetically mediated in humans as well as experimental animals.
Non-NASA Center↗
A technique for extracting blood samples from mice in fire toxicity tests
The extraction of adequate blood samples from moribund and dead mice has been a problem because of the small quantity of blood in each animal and the short time available between the animals' death and coagulation of the blood. These difficulties are particularly critical in fire toxicity tests because removal of the test animals while observing proper safety precautions for personnel is time-consuming. Techniques for extracting blood samples from mice were evaluated, and a technique was developed to obtain up to 0.8 ml of blood from a single mouse after death. The technique involves rapid exposure and cutting of the posterior vena cava and accumulation of blood in the peritoneal space. Blood samples of 0.5 ml or more from individual mice have been consistently obtained as much as 16 minutes after apparent death. Results of carboxyhemoglobin analyses of blood appeared reproducible and consistent with carbon monoxide concentrations in the exposure chamber.
Bucci, T. J.↗
Effect of hindlimb unweighting on tissue blood flow in the rat
This study characterized distribution of blood flow in the rat during hindlimb unweighting (HU), and post-HU standing and exercise. The relationship between reduced hindlimb blood flow and the previously observed elevation in anaerobic metabolism observed with contractile activity in the atrophied soleus muscle was examined (Witzmann et al., 1992). Blood flow was measured during unweighting, normal standing, and running on a treadmill (15 m/min), after 15 days of HU or cage control. For another group blood flow was measured during preexercise treadmill standing and treadmill running. During unweighting, PE standing, and running no difference in soleus blood flow was observed between groups. Muscles composed mainly of fast twitch glycolytic fibers received greater blood flow during chronic unweighting. With exercise blood flow to visceral organs was reduced in control animals, a similar change was not seen in 15 day HU rats. These changes suggest a reduction in the ability of the sympathetic nervous system to distribute cardiac output after chronic HU. A reduction in blood flow to the soleus during exercise was not observed after HU and so does not explain the increased dependence of the atrophied soleus on anerobic energy production during contractile activity.
Mcdonald, K. S.↗
Bone Blood Flow During Simulated Microgravity: Physiological and Molecular Mechanisms
Blood flow to bone has been shown to affect bone mass and presumably bone strength. Preliminary data indicate that blood flow to the rat femur decreases after 14 days of simulated microgravity, using hindlimb suspension (HLS). If adult rats subjected to HLS are given dobutamine, a synthetic catecholamine which can cause peripheral vasodilation and increased blood flow, the loss of cortical bone area usually observed is prevented. Further, mechanisms exist at the molecular level to link changes in bone blood flow to changes in bone cell activity, particularly for vasoactive agents like nitric oxide (NO). The decreases in fluid shear stress created by fluid flow associated with the shifts of plasma volume during microgravity may result in alterations in expression of vasoactive agents such as NO, producing important functional effects on bone cells. The primary aim of this project is to characterize changes in 1) bone blood flow, 2) indices of bone mass, geometry, and strength, and 3) changes in gene expression for modulators of nitric oxide activity (e.g., nitric oxide synthase) and other candidate genes involved in signal transduction of mechanical loading after 3, 7, 14, 21, and 28 days of HLS in the adult rat. Using a rat of at least 5 months of age avoids inadvertently studying effects of simulated microgravity on growing, rather than adult, bone. Utilizing the results of these studies, we will then define how altered blood flow contributes to changes in bone with simulated microgravity by administering a vasodilatory agent (which increases blood flow to tissues) during hindlimb suspension. In all studies, responses in the unloaded hindlimb bones (tibial shaft, femoral neck) will be compared with those in the weightbearing humeral shaft and the non-weightbearing calvarium (skull) from the same animal. Bone volumetric mineral density and geometry will be quantified by peripheral quantitative CT; structural and material properties of the long bones will be determined by 3-point bending (tibia, humerus) or compression (femoral neck) testing to failure. A unique aspect of these studies will be defining the time course of changes in gene expression in bone cell populations with unloading, accomplished with Northern blots, in situ hybridization, and immunohistochemistry. These studies have high relevance for concurrent protocols being proposed by investigators on NSBRI Cardiovascular and Muscle teams, with blood flow data available on a number of tissues other than bone. Further, dobutamine and other Beta-agonists have been tested as countermeasures for altered muscle and cardiovascular function. Results of the intervention tested in our studies have potential relevance for a number of systemic changes seen with prolonged spaceflight.
Bloomfield, Susan A.↗