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At least 307 records · Page 17

Monitoring Immune System Function and Reactivation of Latent Viruses in the Artificial Gravity Pilot Study

Numerous studies have indicated that dysregulation of the immune system occurs during or after spaceflight. Using 21 day -6 deg. head-down tilt bed rest as a spaceflight analog, this study describes the effects of artificial gravity as a daily countermeasure on immunity, stress and reactivation of clinically important latent herpes viruses. The specific aims were to evaluate psychological and physiological stress, to determine the status of the immune system and to quantify reactivation of latent herpes viruses. Blood, saliva, and urine samples were collected from each participating subject at different times throughout the study. An immune assessment was performed on all treatment and control subjects that consisted of a comprehensive peripheral immunophenotype analysis, intracellular cytokine profiles and a measurement of T cell function. The treatment group displayed no differences throughout the course of the study with regards to peripheral leukocyte distribution, cytokine production or T cell function. Shedding of EBV and CMV was quantified by real time PCR in saliva and urine samples, respectively. There was no significant difference in CMV DNA in the treatment group as compared to the control group. EBV and VZV on the other hand showed a mild reactivation during the study. There were no significant differences in plasma cortisol between the control and treatment groups. In addition, no significant differences between antiviral antibody titers (EBV-VCA, -EA, -EBNA, CMV) or tetramer-positive (EBV, CMV) were found between the two groups. EBV DNA copies in blood were typically undetectable but never exceeded 1,500 copies per 10(exp 6) PBMCs. These data indicate that the artificial gravity countermeasure and the 21 day head-down tilt bed rest regimen had no observable adverse effect on immune function.

Mehta, Satish↗

A systems analysis of the erythropoietic responses to weightlessness. Volume 2: Description of the model of erythropoiesis regulation. Part A: Model for regulation of erythropoiesis. Part B: Detailed description of the model for regulation of erythropoiesis

A mathematical model of the erythropoiesis on total red blood cell mass is presented. The loss of red cell mass has been a consistent finding during space flight. Computer simulation of this phenomenon required a model that could account for oxygen transport, red cell production, and red cell destruction. The elements incorporated into the feedback regulation loop of the model are based on the accepted concept that erythrocyte production is governed by the balance between oxygen supply and demand in the body. The mechanisms and pathways of the control circuit include oxygenation of hemoglobin and oxygenation of tissues by blood transport and diffusional processes. Other features of the model include a variable oxygen-hemoglobin affinity, and time delays which represent time for erythropoietin (erythrocyte-stimulating hormone) distribution in plasma, and time for maturation of the erythrocytes in bone marrow.

Leonard, J. I.↗

Splanchnic Compression Improves the Efficacy of Compression Stockings to Prevent Orthostatic Intolerance

Purpose: Post-spaceflight orthostatic intolerance (OI) is observed in 20-30% of astronauts. Previous data from our laboratory suggests that this is largely a result of decreased venous return. Currently, NASA astronauts wear an anti-gravity suit (AGS) which consists of inflatable air bladders over the calves, thighs and abdomen, typically pressurized from 26 to 78 mmHg. We recently determined that, thigh-high graded compression stockings (JOBST , 55 mmHg at ankle, 6 mmHg at top of thigh) were effective, though to a lesser degree than the AGS. The purpose of this study was to evaluate the addition of splanchnic compression to prevent orthostatic intolerance. Methods: Ten healthy volunteers (6M, 4F) participated in three 80 head-up tilts on separate days while (1) normovolemic (2) hypovolemic w/ breast-high compression stockings (BS)(JOBST(R), 55 mmHg at the ankle, 6 mmHg at top of thigh, 12 mmHg over abdomen) (3) hypovolemic w/o stockings. Hypovolemia was induced by IV infusion of furosemide (0.5 mg/kg) and 48 hrs of a low salt diet to simulate plasma volume loss following space flight. Hypovolemic testing occurred 24 and 48 hrs after furosemide. One-way repeated measures ANOVA, with Bonferroni corrections, was used to test for differences in blood pressure and heart rate responses to head-up tilt, stand times were compared using a Kaplan-Meyer survival analysis. Results: BS were effective in preventing OI and presyncope in hypovolemic test subjects ( p = 0.015). BS prevented the decrease in systolic blood pressure seen during tilt in normovolemia (p < 0.001) and hypovolemia w/o countermeasure (p = 0.005). BS also prevented the decrease in diastolic blood pressure seen during tilt in normovolemia (p = 0.006) and hypovolemia w/o countermeasure (p = 0.041). Hypovolemia w/o countermeasure showed a higher tilt-induced heart rate increase (p = 0.022) than seen in normovolemia; heart rate while wearing BS was not different than normovolemia (p = 0.353). Conclusion: BS may be an effective countermeasure to post-space flight OI. The addition of splanchnic compression is more effective than the previous thigh-high garments. These stockings are readily available, inexpensive, and can be worn for days following landing as astronauts re-adapt to Earth gravity.

Platts, Steven H.↗

Exercise training - Blood pressure responses in subjects adapted to microgravity

Conventional endurance exercise training that involves daily workouts of 1-2 hr duration during exposure to microgravity has not proven completely effective in ameliorating postexposure orthostatic hypotension. Single bouts of intense exercise have been shown to increase plasma volume and baroreflex sensitivity in ambulatory subjects through 24 hr postexercise and to reverse decrements in maximal oxygen uptake and syncopal episodes following exposure to simulated microgravity. These physiological adaptations to acute intense exercise were opposite to those observed following exposure to microgravity. These results suggest that the 'exercise training' stimulus used to prevent orthostatic hypotension induced by microgravity may be specific and should be redefined to include single bouts of maximal exercise which may provide an acute effective countermeasure against postflight hypotension.

Convertino, Victor A.↗

Cardiovascular and Body Fluid Adjustments During Bed Rest and Space Flight

Although a few scientific bed rest (BR) studies were conducted soon after World War II, advent of the space program provided impetus for utilizing prolonged (days-months) BR, which employed the horizontal or 6 degree head-down tilt (HDT) body positions, to simulate responses of healthy people to microgravity. Shorter (hours) HDT protocols were used to study initial mechanisms of the acclimation-deconditioning (reduction of physical fitness) syndromes. Of the major physiological factors modified during BR, reduced force on bones, ligaments, and muscles, and greatly reduced hydrostatic pressure within the cardiovascular system, the latter: which involves shifts of blood from the lower extremities into the upper body, increase in central venous pressure, and diuresis, appears to be the initial stimulus for acclimation. Increase in central venous pressure occurs in subjects during weightless parabolic flight, but not in astronauts early during orbital flight. But significant reduction in total body water (hypohydration) and plasma volume (hypovolemia) occurs in subjects during both BR and microgravity. Response of interstitial fluid volume is not as clear, It has been reported to increase during BR, and it may have increased in Skylab II and IV astronauts. Reduction of total body water, and greater proportional reduction of extracellular volume, indicates increased cellular volume which may contribute to inflight cephalic edema. Cerebral pressure abates after a few days of HDT, but not during flight. accompanied by normal (eugravity) blood constituent concentrations suggesting some degree of acclimation had occurred. But during reentry, with moderately increased +Gz (head-to-foot) acceleration and gravitational force, the microgravity "euhydration" becomes functional progressive dehydration contributing to the general reentry syndrome (GRS) which, upon landing the Shuttle, can and often results in gastrointestinal distress, disorientation, vertigo, fatigue, and fainting. Various pre-reentry hyperhydration procedures have been utilized to counteract the GRS. Thus, the somewhat decreased central venous pressure and lack of diuresis early in spaceflight suggests mechanisms other than the Gauer-Henry reflex are more important for maintaining fluid volume homeostasis in astronauts. Inflight hypohydration and hypovolemia are more important for maintaining fluid volume homeostasis in astronauts.

Greenleaf, John E.↗

User's instructions for the erythropoiesis regulatory model

The purpose of the model provides a method to analyze some of the events that could account for the decrease in red cell mass observed in crewmen returning from space missions. The model is based on the premise that erythrocyte production is governed by the balance between oxygen supply and demand at a renal sensing site. Oxygen supply is taken to be a function of arterial oxygen tension, mean corpuscular hemoglobin concentration, oxy-hemoglobin carrying capacity, hematocrit, and blood flow. Erythrocyte destruction is based on the law of mass action. The instantaneous hematocrit value is derived by integrating changes in production and destruction rates and accounting for the degree of plasma dilution.

Source record↗

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

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

Golin, Raffaello M. A.↗

Treatment of hypertension with perindopril reduces plasma atrial natriuretic peptide levels, left ventricular mass, and improves echocardiographic parameters of diastolic function

BACKGROUND: Hypertension is a major independent risk factor for cardiac deaths, and diastolic dysfunction is a usual finding during the course of this disease. HYPOTHESIS: This study was designed to investigate the effects of chronic therapy with perindopril on left ventricular (LV) mass, left atrial size, diastolic function, and plasma level of atrial natriuretic peptide (ANP) in patients with hypertension. METHODS: Twenty four patients who had not been previously taking any antihypertensive medication and without prior history of angina pectoris, myocardial infarction, congestive heart failure, dysrhythmias, valvular heart disease, or systemic illnesses received 4-8 mg/day of perindopril orally. Echocardiographic studies were acquired at baseline and 6 months after the initiation of therapy. RESULTS: Systolic and diastolic blood pressure decreased from 174 +/- 19.7 and 107.5 +/- 7.8 mmHg to 134 +/- 10.6 and 82 +/- 6.7 mmHg, respectively (p < 0.001). Left ventricular mass decreased from 252.4 +/- 8.3 to 205.7 +/- 7.08 g and left atrial volume from 20.4 +/- 5.1 to 17.6 +/- 5.2 ml, respectively (p < 0.001). Transmitral Doppler early and atrial filling velocity ratio (E/A) increased from 0.69 +/- 0.06 to 0.92 +/- 0.05 m/s and plasma ANP level decreased from 71.9 +/- 11.7 to 35.3 +/- 7.8 pg/ml (p < 0.001). Reduction of LV mass correlated positively with a reduction in ANP levels (r = 0.66, p < 0.0005). CONCLUSIONS: Perindopril caused a significant reduction of LV mass, left atrial volume, and plasma ANP levels, as well as improvement in Doppler parameters of LV filling in this group of patients with hypertension.

NASA Program Biomedical Research and Countermeasur↗

Validation of Spectral Analysis as a Noninvasive Tool to Assess Autonomic Regulation of Cardiovascular Function

A major focus of our program has been to develop a sensitive noninvasive procedure to quantify early weightlessness-induced changes in cardiovascular function or potential dysfunction. Forty studies of healthy young volunteers (10 men and 10 women, each studied twice) were conducted to determine changes in the sympatho-vagal balance of autonomic control of cardiovascular regulation during graded headward and footward blood volume shifts. Changes in sympatho-vagal balance were classified by changes in the mean levels and spectral content of cardiovascular variables and verified by changes in circulating levels of catecholamines and pancreatic polypeptide. Possible shifts in intra/extravascular fluid were assessed from changes in hematocrit and plasma mass density while changes in the stimulus to regulate plasma volume were determined from Plasma Renin Activity (PRA). Autonomic blockade was used to unmask the relative contribution of sympathetic and parasympathetic efferent influences in response to 10 min each of 0, 20 and 40 mmHg Lower Body Negative Pressure (LBNP) and 15 and 30 mmHg Positive Pressure (LBPP). The combination of muscarinic blockade with graded LBNP and LBPP was used to evoke graded increases and decreases in sympathetic activity without parasympathetic contributions. The combination of beta blockade with graded LBNP and LBPP was used to produce graded increases and decreases in parasympathetic activity without beta sympathetic contributions. Finally, a combination of both beta and muscarinic blockades with LBNP and LBPP was used to determine the contribution from other, primarily alpha adrenergic, sources. Mean values, spectral analyses and time frequency analysis of R-R interval (HR), Arterial Pressure (AP), peripheral blood flow (RF), Stroke Volume (SV) and peripheral resistance (TPR) were performed for all phases of the study. Skin blood Flow (SF) was also measured in other studies and similarly analyzed. Spectra were examined for changes in three frequency regions (low 0.006 - 0.005 Hz (LF), mid 0.05 - 0.15 Hz (W), and high 0.15 - 0.45 Hz (EF)). The primary objective of the study was to indicate which changes in the mean values and/or spectra of cardiovascular variables consistently correlated with changes in sympatho-vagal balance in response to headward and footward fluid shifts. A secondaey objective was to quantify the vascular and extravascular fluid shifts evoked by LBNP and LBPP. The principal hypothesis being tested was that headward fluid shifts would evoke an increase in parasympathetic activity and footward fluid shifts would evoke an increase in sympathetic activity both of which would be detected by spectral analysis and verified by circulating hormones. Hematocrit (HCT), plasma mass density and plasma renin activity increased with muscarinic blockade and with LBNP, a response indicative of a plasma shift to extravascular spaces. Beta blockade alone or after muscarinic blockade had no effect on HCT or plasma mass density. With respect to intravascular fluid volume distribution, LBNP and LBPP produced sufficient upper body vascular fluid shifts to evoke appropriate autonomic regulatory responses.

Knapp, Charles F.↗

Plasma Hormone Concentrations in Monkeys after Spaceflight

The aim of this study was to determine the effects of a 12.5 day spaceflight on the endocrine status of Rhesus monkeys. Male monkeys (three to four years old; 4 kg) were adapted to chair restraint and trained for 20 months. Blood samples were obtained from four control (C) and two flight (F) monkeys preflight (PF), post-flight (Recovery-R; days 0, 3, 11, and 17), and before and after a mission length simulation (S). Cortisol, T4, T3, testosterone (T), and IGF-1 were measured by RIA (radioimmunassay). Growth hormone (GH) was measured by an in vitro bioassay. Cortisol (16-34 ug/dl), T4 (3.9-7.4 ug/dl), and T (0.2-0.4 mg/ml) did not differ between F and C or between PF, R, and S samples. The low T values reflect the immaturity of the animals. In F, T3 fell from C levels of 208 +/- 4 ng/dl to 44 on R+0 and 150 on R+3, then returned to C. F showed a 55% decrease in GH at R+0 and decreases of 93, 89, and 80%, respectively, at R+3, 11, and 17. IGF-1 decreased from PF levels of 675 ng/ml to 365 (R+0) and 243 (R+3), but returned to C at R+11. GH and IGF-1 levels before and after S did not differ from each other or from C. The cause of the transitory decrease in T3 is unknown. The suppressed GH levels for 17 days after flight may reflect reduced proprioceptive input during flight. The faster recovery of IGF-1 suggests that factors other than reduced GH secretion are involved.

Grindeland, Richard E.↗

Evidence of thyroxine formation following iodine administration in Sprague-Dawley rats

Iodine (I2) has been proposed to be used as a water disinfectant on the manned space station. Previous work has shown that subchronic administration of I2 to Sprague-Dawley rats in drinking water significantly increases plasma thyroxine/triiodothyronine (T4/T3) levels. This is not observed with iodide (I-) treatment. The present study addresses the possibility that I2 reacts with deiodinated T4 metabolites in the gastrointestinal tract to resynthesize T4. Incubation of diiodothyronine (T2), T3, or reverse T3 with I2 in phosphate-buffered saline resulted in the formation of T4 as measured by radioimmunoassay. Washes from the initial segments of the small intestine of the rat show that substrates are present that react with I2 to produce T4. Single oral doses of I2 to rats produced significant dose-related increases in serum T4 and decreases in T3 concentrations after 2 h. Administration of an equivalent dose of I- did not alter significantly plasma T4 concentrations. Higher concentrations of a radioactive substance that bound a T4-specific antibody are present in plasma of animals treated with 125I2 compared to 125I-. These data support the hypothesis that I2 reacts with metabolites of thyroid hormone in the gastrointestinal tract to resynthesize T4 and elevate its levels in blood.

NASA Discipline Environmental Health↗

Examining Individual Differences in Temporal Profiles of Cardiovascular Responses to the Head Down Tilt during Fluid Loading

Upon returning to Earth after an extended exposure to micro-gravity in space many astronauts have experienced symptoms of light headedness and fainting associated with post-flight orthostatic intolerance (low blood pressure). The main reason for this condition is the reduced fluid volume in the body while in space. A preventative treatment was proposed to prevent this condition by fluid loading to restore lost plasma volume by giving crew members salt tablets and water prior to re-entry. In order to simulate micro-gravity effects on earth test subjects are placed in a supine position with their head below the level of their heart (6 head down tilt-HDT). The purpose of the present study is to define individual differences in the time course of cardiac stroke volume responses to HDT (6 hours) and the effectiveness of fluid loading for mitigating orthostatic intolerance when standing . Echocardiography and impedance cardiography data will be collected on 8 men and 8 women to examine heart function to HDT. A second objective is to determine if the effects of fluid loading vary due to individual differences (e.g., age, gender, height, weight, physical fitness, etc.).

orthostatic intolerance↗

Cardiovascular responses during orthostasis - Effect of an increase in maximal O2 uptake

A study is described which tests the hypothesis that changes in aerobic activity (increases in maximum oxygen uptake) will reduce the effectiveness of cardiovascular reflexes to regulate blood pressure during orthostasis. The hypothesis was tested by measuring heart rate, blood pressure and blood volume responses in eight healthy male subjects before and after an eight-day endurance regimen. The results of the study suggest that the physiologic responses to orthostasis are dependent upon the rate of plasma volume loss and pooling, and are associated with training-induced hypervolemia. It is indicated that endurance type exercise training enhances cardiovascular adjustments during tilt. The implications of these results for the use of exercise training as a countermeasure and/or therapeutic method for the prevention of cardiovascular instability during orthostatic stress are discussed.

Convertino, V. A.↗

Cardiovascular adaptation to spaceflight

This article reviews recent flight and ground-based studies of cardiovascular adaptation to spaceflight. Prominent features of microgravity exposure include loss of gravitational pressures, relatively low venous pressures, headward fluid shifts, plasma volume loss, and postflight orthostatic intolerance and reduced exercise capacity. Many of these short-term responses to microgravity extend themselves during long-duration microgravity exposure and may be explained by altered pressures (blood and tissue) and fluid balance in local tissues nourished by the cardiovascular system. In this regard, it is particularly noteworthy that tissues of the lower body (e.g., foot) are well adapted to local hypertension on Earth, whereas tissues of the upper body (e.g., head) are not as well adapted to increase in local blood pressure. For these and other reasons, countermeasures for long-duration flight should include reestablishment of higher, Earth-like blood pressures in the lower body.

Review, Tutorial↗

Field Immune Assessment during Simulated Planetary Exploration in the Canadian Arctic

Dysregulation of the immune system has been shown to occur during space flight, although the detailed nature of the phenomenon and the clinical risks for exploration class missions has yet to be established. In addition, the growing clinical significance of immune system evaluation combined with epidemic infectious disease rates in third world countries provides a strong rationale for the development of field-compatible clinical immunology techniques and equipment. In July 2002 NASA performed a comprehensive field immunology assessment on crewmembers participating in the Haughton-Mars Project (HMP) on Devon Island in the high Canadian Arctic. The purpose of the study was to evaluate mission-associated effects on the human immune system, as well as to evaluate techniques developed for processing immune samples in remote field locations. Ten HMP-2002 participants volunteered for the study. A field protocol was developed at NASA-JSC for performing sample collection, blood staining/processing for immunophenotype analysis, wholeblood mitogenic culture for functional assessments and cell-sample preservation on-location at Devon Island. Specific assays included peripheral leukocyte distribution; constitutively activated T cells, intracellular cytokine profiles and plasma EBV viral antibody levels. Study timepoints were L-30, midmission and R+60. The protocol developed for immune sample processing in remote field locations functioned properly. Samples were processed in the field location, and stabilized for subsequent analysis at the Johnson Space Center in Houston. The data indicated that some phenotype, immune function and stress hormone changes occurred in the HMP field participants that were largely distinct from pre-mission baseline and post-mission recovery data. These immune changes appear similar to those observed in Astronauts following spaceflight. The sample processing protocol developed for this study may have applications for immune assessment during exploration-class space missions or in remote terrestrial field locations. The data validate the use of the HMP as a ground-based spaceflight/planetary exploration analog for some aspects of human physiology.

Crucian, Brian↗

Orthostatic stress is necessary to maintain the dynamic range of cardiovascular control in space

In the upright position, gravity fills the low-pressure systems of human circulation with blood and interstitial fluid in the sections below the diaphragm. Without gravity one pressure component in the vessels disappears and the relationship between hydrostatic pressure and oncotic pressure, which regulates fluid passage across the capillary endothelium in the terminal vascular bed, shifts constantly. The visible consequences of this are a puffy face and "bird" legs. The plasma volume shrinks in space and the range of cardiovascular control is reduced. When they stand up for the first time after landing, 30-50% of astronauts suffer from orthostatic intolerance. It remains unclear whether microgravity impairs cardiovascular reflexes, or whether it is the altered volume status that causes the cardiovascular instability following space flight. Lower body negative pressure was used in several space missions to stimulate the cardiovascular reflexes before, during and after a space flight. The results show that cardiovascular reflexes are maintained in microgravity. However, the astronauts' volume status changed in space, towards a volume-retracted state, as measurements of fluid-regulating hormones have shown. It can be hypothesized that the control of circulation and body fluid homeostasis in humans is adapted to their upright posture in the Earth's gravitational field. Autonomic control regulates fluid distribution to maintain the blood pressure in that posture, which most of us have to cope with for two-thirds of the day. A determined amount of interstitial volume is necessary to maintain the dynamic range of cardiovascular control in the upright posture; otherwise orthostatic intolerance may occur more often.

manned↗

Analyses of plasma for metabolic and hormonal changes in rats flown aboard Cosmos 2044

Plasmas samples from rats flown aboard Cosmos 2044 were analyzed for the levels of key metabolites, electrolytes, enzymes, and hormones. The major differences between the flight group and the synchronous control were elevations in glucose, cholesterol, phosphate, creatinine, blood urea nitrogen, lactate dehydrogenase, and aspartate aminotransferase and decreased levels of thyroxine. Most of these differences were not mimicked by tail suspension of ground-based rats; however, both flight and suspended rats exhibited inhibited testosterone secretion. Corticosterone, immunoreactive growth hormone, and prolactin showed inconsistent differences from the various control groups, suggesting that the levels of these hormones were not due to actual or simulated microgravity.

Merrill, Alfred H., Jr.↗