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At least 253 records · Page 14

Endogenous circulating sympatholytic factor in orthostatic intolerance

Sympathotonic orthostatic hypotension (SOH) is an idiopathic syndrome characterized by tachycardia, hypotension, elevated plasma norepinephrine, and symptoms of orthostatic intolerance provoked by assumption of an upright posture. We studied a woman with severe progressive SOH with blood pressure unresponsive to the pressor effects of alpha(1)-adrenergic receptor (AR) agonists. We tested the hypothesis that a circulating factor in this patient interferes with vascular adrenergic neurotransmission. Preincubation of porcine pulmonary artery vessel rings with patient plasma produced a dose-dependent inhibition of vasoconstriction to phenylephrine in vitro, abolished vasoconstriction to direct electrical stimulation, and had no effect on nonadrenergic vasoconstrictive stimuli (endothelin-1), PGF-2alpha (or KCl). Preincubation of vessels with control plasma was devoid of these effects. SOH plasma inhibited the binding of an alpha(1)-selective antagonist radioligand ([(125)I]HEAT) to membrane fractions derived from porcine pulmonary artery vessel rings, rat liver, and cell lines selectively overexpressing human ARs of the alpha(1B) subtype but not other AR subtypes (alpha(1A) and alpha(1D)). We conclude that a factor in SOH plasma can selectively and irreversibly inhibit adrenergic ligand binding to alpha(1B) ARs. We propose that this factor contributes to a novel pathogenesis for SOH in this patient. This patient's syndrome represents a new disease entity, and her plasma may provide a unique tool for probing the selective functions of alpha(1)-ARs.

Case Reports↗

Plasma volume and electrolyte shifts with heavy exercise in sitting and supine positions

An experimental study was carried out to compare fluid and electrolyte shifts after heavy exercise performed by four voluntary male subjects (26-45 yr) in sitting and supine positions. Plasma volume and electrolyte shifts were measured during the 6-min control period and for 60 min after a continuous peak oxygen uptake test. The results indicate that the most likely driving force for the restitution of plasma volume after peak exercise is provided by a change in hydrostatic and/or systemic blood pressures when exercise ceases.

Greenleaf, J. E.↗

Increased gluconeogenesis in hyper-G stressed rats

The role of gluconeogenesis in the altered carbohydrate metabolism in rats exposed to hyper-G stress is investigated. The blood levels of the substrates and hormones involved in gluconeogenesis were determined in rats exposed to 3.1 G for various time periods (0.25 to 24 hr). It is found that hyper-G stressed rats showed an immediate increase in plasma glucose at the onset of centrifugation which persisted throughout all the exposure periods. A substantial part of the initial rise in blood glucose is attributed to an increased rate of gluconeogenesis. An increase in liver glycogen deposition was observed in centrifuged rats as early as 0.50 hr exposure time, with progressively larger amounts accumulated as the exposure time was extended to 24 hr. It is concluded that the increase in gluconeogenic activity of hyper-G stressed rats is due to an increase in the mobilization of gluconeogenic substrates from perpheral tissues to the liver as a result of increases in circulating catecholamines and glucagon.

Daligcon, B. C.↗

Comparison of saline and fludrocortisone as fluid-loading countermeasures following exposure to simulated microgravity

Saline loading (SL) within hours of reentry is currently used as a countermeasure against postflight orthostatic hypotension in astronauts. However, its effects on blood volume expansion is not quantified and its effectiveness has proved marginal at best. The purposes of the present study were: (1) to quantify the effects of SL on plasma volume and orthostatic tolerance following exposure to simulated microgravity and (2) to compare these effects with the use of a pharacological fluid expander, fludrcortisone (F). Method: Eleven men (30-45 yr.) underwent a 15-minute stand test before and immediately after 7 days of head-down bedrest (BR). Five subjects ingested SL (8 g salt tablets with 1 liter of water) 2 hours before standing at the end of BR while the other 6 subjects received 0.2 mg oral doses of F at 0800 and 2200 hours the day before and 0800 hours the day the subjects got out of bed (i.e., 2 hours before standing). Plasma volume (PV) was measured before BR on day 7 of BR and after the final SL and F treatments just before the post-BR stand test. Blood pressure and heart rate were measured continuously during the stand tests. Results: BR decreased PV from 40.7 plus or minus 1.9 mml/kg to 35.9 plus or minus 1.1 ml/kg (minus 11.8 percent P less than 0.05). Following SL, PV remained at 36.4 plus or minus 1.5 ml/kg while F returned PV to 39.1 plus or minus 1.8 ml/kg. The post BR stand test was completed without syncopal symptoms by 5 of 6 F subjects but only 2 of 5 SL subjects. Conclusions: SL may be ineffective in restoring PV to preflight levels and may provide inadequate protection against postflight orthostatic hypotension. In contrast, F may provide a promising countermeasure since it restored PV and reduced the incidence of syncope following exposure to simulated microgravity in the present study.

Vernikos, J.↗

Effects of pentobarbital on plasma glucose and free fatty acids in the rat.

Hyperglycemia and hypolipemia were observed in rats after the injection of sodium pentobarbital. The observed changes were independent of whether the blood was collected by decapitation or by needle puncture of the aorta. The hyperglycemic response was caused by two factors including the stress of the injection per se and the pharmacological action of the drug. Hyperlipemia was observed at 5 min postinjection. However, pentobarbital decreased plasma free fatty acids by 15 min postinjection. Both the hyperglycemia and hypolipemia responses were dose dependent.

Furner, R. L.↗

Clinical Aspects of the Control of Plasma Volume at Microgravity and During Return to One Gravity

Plasma volume is reduced by 10%-20% within 24 to 48 h of exposure to simulated or actual microgravity. The clinical importance of microgravity-induced hypovolemia is manifested by its relationship with orthostatic intolerance and reduced VO2max after return to one gravity (1G). Since there is no evidence to suggest plasma volume reduction during microgravity is associated with thirst or renal dysfunctions, a diuresis induced by an immediate blood volume shift to the central circulation appears responsible for microgravity-induced hypovolemia. Since most astronauts choose to restrict their fluid intake before a space mission, absence of increased urine output during actual spaceflight may be explained by low central venous pressure (CVP) which accompanies dehydration. Compelling evidence suggests that prolonged reduction in CVP during exposure to microgravity reflects a 'resetting' to a lower operating point which acts to limit plasma volume expansion during attempts to increase fluid intake. In groudbase and spaceflight experiments, successful restoration and maintenance of plasma volume prior to returning to an upright posture may depend upon development of treatments that can return CVP to its baseline 10 operating point. Fluid-loading and LBNP have not proved completely effective in restoring plasma volume, suggesting that they may not provide the stimulus to elevate the CVP operating point. On the other, exercise, which can chronically increase CVP, has been effective in expanding plasma volume when combined with adequate dietary intake of fluid and electrolytes. The success of designing experiments to understand the physiological mechanisms of and development of effective countermeasures for the control of plasma volume in microgravity and during return to one gravity will depend upon testing that can be conducted under standardized controlled baseline condi

Convertino, Victor A.↗

Altered baroreflex control of forearm vascular resistance during simulated microgravity

Reflex peripheral vasoconstriction induced by activation of cardiopulmonary baroreceptors in response to reduced central venous pressure (CVP) is a basic mechanism for elevating systemic vascular resistance and defending arterial blood pressure during orthostatically-induced reductions in cardiac filling and output. The sensitivity of the cardiopulmonary baroreflex response [defined as the slope of the relationship between changes in forearm vascular resistance (FVR) and CVP] and the resultant vasoconstriction are closely and inversely associated with the amount of circulating blood volume. Thus, a high-gain FVR response will be elicited by a hypovolemic state. Exposure to microgravity during spaceflight results in reduced plasma volume. It is therefore reasonable to expect that the FVR response to cardiopulmonary baroreceptor unloading would be accentuated following adaptation to microgravity. Such data could provide better insight about the physiological mechanisms underlying alterations in blood pressure control following spaceflight. We therefore exposed eleven men to 6 degrees head-down bedrest for 7 days and measured specific hemodynamic responses to low levels of the lower body negative pressure to determine if there are alterations in cardiopulmonary baroreceptor stimulus-FVR reflex response relationship during prolonged exposure to an analog of microgravity.

NASA Program Space Physiology and Countermeasures↗

Clinical aspects of the control of plasma volume at microgravity and during return to one gravity

Plasma volume is reduced by 10-20% within 24-48 h of exposure to simulated or actual microgravity. The clinical importance of microgravity induced hypovolemia is manifested by its relationship with orthostatic intolerance and reduced maximal oxygen uptake (VO2max) after return to one gravity (1G). Since there is no evidence to suggest that plasma volume reduction during microgravity is associated with thirst or renal dysfunctions, a diuresis induced by an immediate blood volume shift to the central circulation appears responsible for microgravity-induced hypovolemia. Since most astronauts choose to restrict their fluid intake before a space mission, absence of increased urine output during actual space flight may be explained by low central venous pressure (CVP) which accompanies dehydration. Compelling evidence suggests that prolonged reduction in CVP during exposure to microgravity reflects a "resetting" to a lower operating point, which acts to limit plasma volume expansion during attempts to increase fluid intake. In ground based and space flight experiments, successful restoration and maintenance of plasma volume prior to returning to an upright posture may depend upon development of treatments that can return CVP to its baseline IG operating point. Fluid-loading and lower body negative pressure (LBNP) have not proved completely effective in restoring plasma volume, suggesting that they may not provide the stimulus to elevate the CVP operating point. On the other hand, exercise, which can chronically increase CVP, has been effective in expanding plasma volume when combined with adequate dietary intake of fluid and electrolytes. The success of designing experiments to understand the physiological mechanisms of and development of effective counter measures for the control of plasma volume in microgravity and during return to IG will depend upon testing that can be conducted under standardized controlled baseline conditions during both ground-based and space flight investigations.

Review, Tutorial↗

Application of Acute Maximal Exercise to Enhance Mechanisms Underlying Blood Pressure Regulation and Orthostatic Tolerance After Exposure to Simulated Microgravity

Development of orthostatic hypotension and intolerance in astronauts who return to earth following a spaceflight mission represents a significant operational concern to NASA. Reduced plasma volume, vascular resistance, and baroreflex responsiveness following exposure to actual and ground-based analogs of microgravity have been associated with orthostatic instability, suggesting that these mechanisms may contribute alone or in combination to compromise of blood pressure regulation after spaceflight. It therefore seems reasonable that development of procedures designed to reverse or restore the effects of microgravity on regulatory mechanisms of blood volume, vascular resistance and cardiac function should provide some protection against postflight orthostatic intolerance. Several investigations have provided evidence that a single bout of exhaustive dynamic exercise enhances functions of mechanisms responsible for blood pressure stability. Therefore, the purpose of our research project was to conduct a series of experiments using ground-based analogs of reduced gravity (i.e., prolonged restriction to the upright standing posture) in human subjects to investigate the hypothesis that a single bout of dynamic maximal exercise would restore blood volume, vascular resistance and cardiac function and improve blood pressure stability.

Convertino, V. A.↗

The effects of horizontal body casting on blood volume, drug responsiveness, and +Gz tolerance in the rhesus monkey

To simulate the weightless condition, eight rhesus monkeys, instrumented with solid-state pressure transducers, were horizontally restrained in body casts for 28 days. Blood volume decreased an average of 13% after 14 days of restraint, due mainly to a drop in plasma volume. Aortic pressure and heart rate responses to norepinephrine and phenylephrine decreased after 14 days of restraint. The monkeys did not show a statistically significant decreased tolerance to a 90 deg sudden upright tilt after horizontal restraint. During the fifth week of casting, four animals were subjected to +Gz acceleration tests on a centrifuge. The acceleration tolerance of the casted monkeys was significantly reduced compared to four similarly instrumented control animals. These findings indicate that the cardiovascular deconditioning associated with simulated weightlessness results from an inability to maintain central blood volume during orthostatic stress.

Dickey, D. T.↗

Renal and cardiovascular responses to water immersion in trained runners and swimmers

The purpose of this study was to determine if fluid-electrolyte, renal, hormonal, and cardiovascular responses during and after multi-hour water immersion were associated with aerobic training. Additionally, we compared these responses in those who trained in a hypogravic versus a 1-g environment. Seventeen men comprised three similarly aged groups: six long-distance runners, five competitive swimmers, and six untrained control subjects. Each subject underwent 5 h of immersion in water [mean (SE)] 36.0 (0.5) degrees C to the neck. Immediately before and at each hour of immersion, blood and urine samples were collected and analyzed for sodium (Na), potassium, osmolality, and creatinine (Cr). Plasma antidiuretic hormone and aldosterone were also measured. Hematocrits were used to calculate relative changes in plasma volume (% delta Vpl). Heart rate response to submaximal cycle ergometer exercise (35% peak oxygen uptake) was measured before and after water immersion. Water immersion induced significant increases in urine flow, Na clearance (CNa), and a 3-5% decrease in Vpl. Urine flow during immersion was greater (P < 0.05) in runners [2.4 (0.4) ml.min-1] compared to controls [1.3 (0.1) ml.min-1]. However, % delta Vpl, CCr, CNa and CH2O during immersion were not different (P > 0.05) between runners, swimmers, and controls. After 5 h of immersion, there was an increase (P < 0.05) in submaximal exercise heart rate of 9 (3) and 10 (3) beats.min-1 in both runners and controls, respectively, but no change (P > 0.05) was observed in swimmers.(ABSTRACT TRUNCATED AT 250 WORDS).

Running/physiology↗

Effect of head-down-tilt bed rest and hypovolemia on dynamic regulation of heart rate and blood pressure

Adaptation to head-down-tilt bed rest leads to an apparent abnormality of baroreflex regulation of cardiac period. We hypothesized that this "deconditioning response" could primarily be a result of hypovolemia, rather than a unique adaptation of the autonomic nervous system to bed rest. To test this hypothesis, nine healthy subjects underwent 2 wk of -6 degrees head-down bed rest. One year later, five of these same subjects underwent acute hypovolemia with furosemide to produce the same reductions in plasma volume observed after bed rest. We took advantage of power spectral and transfer function analysis to examine the dynamic relationship between blood pressure (BP) and R-R interval. We found that 1) there were no significant differences between these two interventions with respect to changes in numerous cardiovascular indices, including cardiac filling pressures, arterial pressure, cardiac output, or stroke volume; 2) normalized high-frequency (0.15-0.25 Hz) power of R-R interval variability decreased significantly after both conditions, consistent with similar degrees of vagal withdrawal; 3) transfer function gain (BP to R-R interval), used as an index of arterial-cardiac baroreflex sensitivity, decreased significantly to a similar extent after both conditions in the high-frequency range; the gain also decreased similarly when expressed as BP to heart rate x stroke volume, which provides an index of the ability of the baroreflex to alter BP by modifying systemic flow; and 4) however, the low-frequency (0.05-0.15 Hz) power of systolic BP variability decreased after bed rest (-22%) compared with an increase (+155%) after acute hypovolemia, suggesting a differential response for the regulation of vascular resistance (interaction, P < 0.05). The similarity of changes in the reflex control of the circulation under both conditions is consistent with the hypothesis that reductions in plasma volume may be largely responsible for the observed changes in cardiac baroreflex control after bed rest. However, changes in vasomotor function associated with these two conditions may be different and may suggest a cardiovascular remodeling after bed rest.

Non-NASA Center↗

405 nm violet-blue light inactivates hepatitis C cell culture virus (HCVcc) in ex vivo human platelet concentrates and plasma

Abstract Added safety measures coupled with the development and use of pathogen reduction technologies (PRT) significantly reduces the risk of transfusion-transmitted infections (TTIs) from blood products. Current approved PRTs utilize chemical and/or UV-light based inactivation methods. While the effectiveness of these PRTs in reducing pathogens are well documented, these can cause tolerable yet unintended consequences on the quality and efficacy of the transfusion products. As an alternative to UV-based approaches, we have previously demonstrated that 405 nm violet-blue light exposure successfully inactivates a variety of pathogens, including bacteria, parasites, and viruses, in both platelet concentrates (PCs) and plasma. Herein, we show that 405 nm light treatment effectively inactivates hepatitis C cell culture virus (HCVcc) by up to ~ 3.8 log10 in small volumes of a variety of matrices, such as cell culture media, PBS, plasma, and PCs with 27 J/cm 2 of light exposure, and total inactivation of HCVcc after 162 J/cm 2 light exposure. Furthermore, we demonstrate that carry-over of media supplemented with fetal bovine serum enhances the production of reactive oxygen species (ROS), providing mechanistic insights to 405 nm light-mediated viral inactivation. Overall, 405 nm light successfully inactivates HCVcc, further strengthening this method as a novel PRT for platelets and plasma.

Science & Technology - Other Topics↗

NMR of laser-polarized 129Xe in blood foam

Laser-polarized 129Xe dissolved in a foam preparation of fresh human blood was investigated. The NMR signal of 129Xe dissolved in blood was enhanced by creating a foam in which the dissolved 129Xe exchanged with a large reservoir of gaseous laser-polarized 129Xe. The dissolved 129Xe T1 in this system was found to be significantly shorter in oxygenated blood than in deoxygenated blood. The T1 of 129Xe dissolved in oxygenated blood foam was found to be approximately 21 (+/-5) s, and in deoxygenated blood foam to be greater than 40 s. To understand the oxygenation trend, T1 measurements were also made on plasma and hemoglobin foam preparations. The measurement technique using a foam gas-liquid exchange interface may also be useful for studying foam coarsening and other liquid physical properties.

Non-NASA Center↗

Effect of hypovolemia, infusion, and oral rehydration on gradual onset +Gz acceleration tolerance

The purpose of this study was to determine the effect of blood withdrawal, blood infusion, and oral fluid intake on +Gz tolerance at an acceleration rate of 0.5 G/min. Six healthy men aged 21-27 yr were centrifuged after the withdrawal of 400 ml of blood (hypovolemia) from each man; they were centrifuged again following blood infusion (Phase I). Three weeks later the men were accelerated after similar hypovolemia and again after consuming 800 ml of an isotonic NaCl drink (Phase II). Phase I hypovolemia resulted in a reduction in tolerance in all subjects from a mean control level of 6.42 + or - 0.35 min to 5.45 + or - 0.17 min (-15.1%, p less than 0.05). Both infusion and drinking returned tolerances to control levels. During acceleration there were significant (p less than 0.05) increases in plasma vasopressin levels to 35 pg/ml; these were not influenced appreciably by infusion or drinking. In all acceleration runs there was an obligatory shift (loss) of plasma volume and electrolytes, especially potassium, regardless of the experimental treatments. Oral rehydration is shown to be as effective as blood replacement in restoring +Gz acceleration tolerance decrements due to hypovolemia.

Greenleaf, J. E.↗

Magnetic Storms

One of the oldest mysteries in geomagnetism is the linkage between solar and geomagnetic activity. The 11-year cycles of both the numbers of sunspots and Earth geomagnetic storms were first noted by Sabine. A few years later, speculation on a causal relationship between flares and storms arose when Carrington reported that a large magnetic storm followed the great September 1859 solar flare. However, it was not until this century that a well-accepted statistical survey on large solar flares and geomagnetic storms was performed, and a significant correlation between flares and geomagnetic storms was noted. Although the two phenomena, one on the Sun and the other on the Earth, were statistically correlated, the exact physical linkage was still an unknown at this time. Various hypotheses were proposed, but it was not until interplanetary spacecraft measurements were available that a high-speed plasma stream rich in helium was associated with an intense solar flare. The velocity of the solar wind increased just prior to and during the helium passage, identifying the solar ejecta for the first time. Space plasma measurements and Skylab's coronagraph images of coronal mass elections (CMES) from the Sun firmly established the plasma link between the Sun and the Earth. One phenomenon associated with magnetic storms is brilliant "blood" red auroras, as shown.

Tsurutani, Bruce T.↗

Exercise Thermoregulation in Men after One and 24-hours of 6 Degree Head-Down Tilt

Exercise thermoregulation exercise is dependent on heat loss by increased skin blood flow (convective and conductive heat loss) and through enhanced sweating (evaporative heat loss). Reduction of plasma volume (PV), increased plasma osmolality, physical deconditioning, and duration of exposure to simulated and actual microgravity reduces the ability to thermoregulate during exercise.

Ertl, A. C.↗

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.↗