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All sourcesNASA NTRSDOE OSTI
NASA NTRS1993

Physiological Anatomical Rodent Experiment (PARE) .04 Feasibility Test 1

The objective of this feasibility study was to investigate the environmental/treatment stresses in the proposed PARE.04 experiments in a ground based study to determine if these stresses were of sufficient magnitude to compromise the planned shuttle experiments. Eighty pregnant Sprague-Dawley rats were received on day 2 (day l equals day of vaginal plug) of gestation (G2) and on G7 60 were laparotomized to determine the condition of pregnancy and allow assignment to test groups. The five test groups (N equals 10 each group) were as follows: Group 1, nominal flight; Group 2, laparotomy control; Group 3, hysterectomy control; Group 4, vivarium control; Group 5, caesarean delivery. On G17, groups 1, 2, and 5 were subjected to unilateral hysterectomy to obtain fetuses for evaluation. There was no difference in fetal crown-rump length, fetal weight, or placental weight in any of the test groups subjected to unilateral hysterectomy at G17. Animals were allowed to go to term and animals in each group delivered between the morning of G22 and the afternoon of G23. Rats assigned to Group 5 began delivering vaginally prior to the designated time for caesarean section, thus only 2 animals in this group were delivered by caesarean section. After delivery, a blood sample was taken from the dam, and they were euthanized and the thymus and adrenal glands weighed. Pups from experimental dams were tattooed for identification, the anogenital distance of male pups was photographed for later measurement, and all pups placed with foster dams and litter sizes were standardized to 10. On day 7, all pups were euthanized, and pup adrenal glands and thymus weighed. Laparotomy at G7 with or without unilateral hysterectomy at G17, had no effect on pregnancy maintenance or vaginal delivery. There was no difference in maternal adrenal or thymus weights or plasma levels of catecholamines, estradiol, progesterone, or corticosterone. Likewise, there was no difference in the anogenital distance (index of fetal stress) of neonatal male pups, between any of the experimental groups. From days 0-7, weight gain from dams in all experimental groups was similar. Lastly, there was no difference in weights of thymus and adrenal glands in pups euthanized at day 7. Collectively, these data indicate that treatment stresses inherent in the proposed PARE.04 experimental design should not compromise the planned shuttle experiments.

Burden, Hubert W.↗
NASA NTRS1994

The anemia of primary autonomic failure and its reversal with recombinant erythropoietin

OBJECTIVE: To determine if chronic sympathetic deprivation is associated with anemia and a low erythropoietin response. DESIGN: Survey of the prevalence and characteristics of anemia in patients with severe primary autonomic failure. SETTING: A referral service for autonomic failure in a tertiary teaching hospital. PATIENTS: 84 patients with primary autonomic failure who had symptomatic orthostatic hypotension. INTERVENTION: Open-label trial with human recombinant erythropoietin. RESULTS: Anemia was present in 32 of 84 patients (38%; 95% Cl, 27% to 50%). Plasma norepinephrine levels, measured in patients standing upright, were lower in the patient group with lower hemoglobin levels. Mean values in 22 patients with a hemoglobin level of less than 120 g/L were as follows: hemoglobin, 108 g/L (range, 87 to 118 g/L); hematocrit, 0.33; corrected reticulocyte counts, 0.008; mean corpuscular volume, 89 fL (89 microns 3); serum iron, 16.5 mumol/L (92 micrograms/dL); total iron binding capacity, 43.3 mumol/L (242 micrograms/dL); ferritin, 184 micrograms/L; serum vitamin B12, 410 pmol/L (556 pg/mL); and serum folate, 22.7 nmol/L (10 ng/mL). No relation was found between serum erythropoietin and blood hemoglobin levels. In seven of nine patients with autonomic failure who had hemoglobin levels less than 120 g/L, serum erythropoietin levels decreased below the 95% confidence interval corresponding to patients with iron deficiency anemia. Therapy with recombinant erythropoietin improved mean hemoglobin levels (from 108 to 133 g/L) in all patients treated (n = 5) at relatively low doses (25 to 50 units/kg body weight, subcutaneously, three times a week). CONCLUSIONS: Our data support the hypothesis that the sympathetic nervous system stimulates erythropoiesis in humans because anemia is a frequent occurrence in patients with severe autonomic failure and is associated with a blunted erythropoietin response.

Clinical Trial↗
NASA NTRS1992

Effect of hemorrhage on cardiac output, vasopressin, aldosterone, and diuresis during immersion in men

The purpose of this research was to test the hypotesis that a reduction in blood volume would attenuate or eliminate immersion-induced increases in cardiac output (Q(sub co)) and urine excretion, and to investigate accompanying vasoactive and fluid-electrolyte hormonal responses. Eight men (19-23 yr) were supine during a 2-hr control period in air, and then sat for 5-hr test periods in air at 20 C (dry control, DC); water at 34.5 C (wet control, WC); and water (34.5 C) after hemorrhage (WH) of 14.8 plus or minus 0.3 percent of their blood volume. Blood volume was -11.6 plus or minus 0.6 percent at immersion (time 0). Mean (bar-X hrs 1-5) Q(sub co) was unchanged in WC (5.3 plus or minus 0.01 l/min) and in WH (4.5 plus or minus 0.1 l/min), but decreased (P less than 0.05) in DC to 3.6 plus or minus 0.1 l/min. Mean urine excretion rates were 1.0 plus or minus 0.2 ml/min for DC and 1.1 plus or minus 0.2 ml/min for WH; both were lower (P less than 0.05) than that for WC of 2.0 plus or minus 0.4 ml/min. Plasma (Na+) and (Osm) were unchanged in all experiments. Mean plasma vasopressin (PVP) (bar-X hrs 1-5) was 1.1 plus or minus 0.1 pg/ml in WC, and higher (P less than 0.05) in DC (2.1 plus or minus 0.2 pg/ml)and WH (2.1 plus or minus 0.1 pg/ml); it was unchanged during air and water test periods. Thus, hemorrhage attenuated the immersion-induced increase in Q(sub co), eliminated the WC diuresis, maintained plasma renin activity and PVP at DC levels and did not change immersion-induced aldosterone suppression; the osmotic diuresis during control immersion is apparently not due to either aldosterone suppression or vasopressin suppression.

Greenleaf, J. E.↗
NASA NTRS2000

Decreased NK-Cell Cytotoxicity after Short Flights on the Space Shuttle

Cytotoxic activity of natural killer (NK) cells and cell surface marker expression of peripheral blood mononuclear cells (PBMCs) isolated from 11 U.S. astronauts on two different missions were determined before and after 9 or 10 days of spaceflight aboard the space shuttle. Blood samples were collected 10 and 3 days before launch, within 3 hours after landing, and 3 days after landing. All PBMC preparations were cryopreserved and analyzed simultaneously in a 4-hour cytotoxicity "Cr-release assay using NK-sensitive K-562 target cells. Compared to preflight values, NK-cell cytotoxicity (corrected for lymphopenia observed on landing day) was significantly decreased at landing (P < 0.0125). It then apparently began to recover and approached preflight values by 3 days after landing. Consistent with decreased NK-cell cytotoxicity, significant increases from preflight values were found in plasma adrenocorticotropic hormone at landing. Plasma and urinary cortisol levels did not change significantly from preflight values. Expression of major lymphocyte surface markers (CD3, CD4, CD8, CD14, CD16, CD56), determined by flow cytometric analysis, revealed no consistent phenotypic changes in relative percent of NK or other lymphoid cells after 10 days of spaceflight.

Mehta, Satish K.↗
NASA NTRS1992

Design of potent substrate-analogue inhibitors of canine renin

Through a systematic study of structure-activity relationships, we designed potent renin inhibitors for use in dog models. In assays against dog plasma renin at neutral pH, we found that, as in previous studies of rat renin inhibitors, the structure at the P2 position appears to be important for potency. The substitution of Val for His at this position increases potency by one order of magnitude. At the P3 position, potency appears to depend on a hydrophobic side chain that does not necessarily have to be aromatic. Our results also support the approach of optimizing potency in a renin inhibitor by introducing a moiety that promotes aqueous solubility (an amino group) at the C-terminus of the substrate analogue. In the design of potent dog plasma renin inhibitors, the influence of the transition-state residue 4(S)-amino-3(S)-hydroxy-5-cyclohexylpentanoic acid (ACHPA)-commonly used as a substitute for the scissile-bond dipeptide to boost potency-is not obvious, and appears to be sequence dependent. The canine renin inhibitor Ac-paF-Pro-Phe-Val-statine-Leu-Phe-paF-NH2 (compound 15; IC50 of 1.7 nM against dog plasma renin at pH 7.4; statine, 4(S)-amino-3(S)-hydroxy-6-methylheptanoic acid; paF, para-aminophenylalanine) had a potent hypotensive effect when infused intravenously into conscious, sodium-depleted, normotensive dogs. Also, compound 15 concurrently inhibited plasma renin activity and had a profound diuretic effect.

Non-NASA Center↗
NASA NTRS1991

Carotid-cardiac baroreflex: Relation with orthostatic hypotension following simulated microgravity and implications for development of countermeasures

In a series of studies, we have examined the effects of exposure to simulated microgravity, varying states of vascular volume, and acute exercise on the function of the carotid-cardiac baroreflex in man. In the first study, exposure to simulated microgravity (6 degree headdown bedrest) reduced the sensitivity and buffer capacity of the vagal baroreceptor-cardiac reflex mechanisms and this impaired baroreflex function was associated with orthostatic hypotension. Since the reduction in plasma volume during BR was not correlated with impaired baroreflex function, a second study was conducted which demonstrated that the carotid-cardiac baroreflex response was not affected by either acute hypovolemia or hypervolemia. These results suggest that acute fluid replacement prior to reentry may not reverse impaired baroreflex function associated with postflight hypotension. In a third study, we demonstrated that one bout of maximal exercise increased baroreflex sensitivity and buffer capacity through 24 h post-exercise. These baroreflex changes were opposite to those observed following BR. Taken together, these data suggest that the contributions of reduced blood volume and impaired carotid-cardiac baroreflex function to orthostatic hypotension following exposure to microgravity are probably separate and additive; maximal exercise in addition to fluid replacement may provide an acute effective countermeasure against postflight hypotension.

Convertino, Victor A.↗
NASA NTRS1992

Vasopressin responses to unloading arterial baroreceptors during cardiac nerve blockade in conscious dogs

We examined the relative contributions of afferent input from the heart and from arterial baroreceptors in the stimulation of arginine vasopressin (AVP) secretion in response to hypotension caused by thoracic inferior vena caval constriction (TIVCC). Afferent input from cardiac receptors was reversibly blocked by infusing 2% procaine into the pericardial space to anesthetize the cardiac nerves. Acute cardiac nerve blockade (CNB) alone caused a rise in mean arterial pressure (MAP) of 24 +/- 3 mmHg but no change in plasma AVP. If the rise in MAP was prevented by TIVCC, plasma AVP increased by 39 +/- 15 pg/ml, and if MAP was allowed to increase and then was forced back to control by TIVCC, plasma AVP increased by 34 +/- 15 pg/ml. Thus the rise in MAP during CNB stimulated arterial baroreceptors, which in turn compensated for the loss of inhibitory input from cardiac receptors on AVP secretion. These results indicate that the maximum secretory response resulting from complete unloading of cardiac receptors at a normal MAP results in a mean increase in plasma AVP of 39 pg/ml in this group of dogs. When MAP was reduced 25% below control levels (from 95 +/- 5 to 69 +/- 3 mmHg) by TIVCC during pericardial saline infusion, plasma AVP increased by 79 +/- 42 pg/ml. However, the same degree of hypotension during CNB (MAP was reduced from 120 +/- 5 to 71 +/- 3 mmHg) led to a greater (P less than 0.05) increase in plasma AVP of 130 +/- 33 pg/ml. Because completely unloading cardiac receptors can account for an increase of only 39 pg/ml on average in this group of dogs, the remainder of the increase in plasma AVP must be due to other sources of stimulation. We suggest that the principal stimulus to AVP secretion after acute CNB in these studies arises from unloading the arterial baroreceptors.

NASA Center ARC↗
NASA NTRS2017

Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

BACKGROUND: Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. Astronauts participating in long-duration missions may be at an increased risk of oxidative stress and inflammatory damage due to radiation, psychological stress, altered physical activity, nutritional insufficiency, and hyperoxia during extravehicular activity. By studying one identical twin during his 1-year ISS mission and his ground-based twin, this work extends a current NASA-funded investigation to determine whether these spaceflight factors contribute to an accelerated progression of atherosclerosis. This study of twins affords a unique opportunity to examine spaceflight-related atherosclerosis risk that is independent of the confounding factors associated with different genotypes. PURPOSE: The purpose of this investigation was to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and determine if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. These physiological and biochemical data will be extended by using an exploratory approach to investigate the relationship between intermediate phenotypes and risk factors for atherosclerosis and the metabolomic signature from plasma and urine samples. Since metabolites are often the indirect products of gene expression, we simultaneously assessed gene expression and DNA methylation in leukocytes. HYPOTHESIS: We predict that, compared to the ground-based twin, the space-flown twin will experience elevated biomarkers of oxidative stress and inflammatory damage, altered arterial structure and function, accelerated telomere shortening, dysregulation of genes associated with oxidative stress and inflammation, and a metabolic profile shift that is associated with elevated atherosclerosis risk factors. METHODS: In the space-flown twin, a panel of biomarkers of oxidative and inflammatory stress were measured in venous blood samples and in 24-h (in-flight) and 48-h (pre- and post-flight) urine pools collected twice before flight, six times during the mission (~FD15, 75, 180, 240, 300, 335), and early in the post-flight recovery phase (3-5 days after landing). We also measured metabolomic (targeted and untargeted approaches) and genomic markers (DNA methylation, mRNA gene expression, telomere length) in these samples. Arterial structure, assessed from measures of intima-media thickness, also were measured using standard clinical ultrasound at the same time points. Arterial function was assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and a sensitive predictor of atherosclerotic risk, only before and after spaceflight. All of the same measures were obtained in the ground-based twin, but less frequently. DISCUSSION: All data collection has been completed for both the space-flown twin and the ground-based twin. Vascular structure and function measures have been analyzed, blood and urine samples have been batch-processed. Results from these individuals will be compared to each other, to data from other Twin Study investigations, and to the larger complement of subjects participating in the companion study currently ongoing in ISS astronauts.

Lee, Stuart M. C.↗
NASA NTRS2009

Microfluidic Mixing Technology for a Universal Health Sensor

A highly efficient means of microfluidic mixing has been created for use with the rHEALTH sensor an elliptical mixer and passive curvilinear mixing patterns. The rHEALTH sensor provides rapid, handheld, complete blood count, cell differential counts, electrolyte measurements, and other lab tests based on a reusable, flow-based microfluidic platform. These geometries allow for cleaning in a reusable manner, and also allow for complete mixing of fluid streams. The microfluidic mixing is performed by flowing two streams of fluid into an elliptical or curvilinear design that allows the combination of the flows into one channel. The mixing is accomplished by either chaotic advection around micro - fluidic loops. All components of the microfluidic chip are flow-through, meaning that cleaning solution can be introduced into the chip to flush out cells, plasma proteins, and dye. Tests were performed on multiple chip geometries to show that cleaning is efficient in any flowthrough design. The conclusion from these experiments is that the chip can indeed be flushed out with microliter volumes of solution and biological samples are cleaned readily from the chip with minimal effort. The technology can be applied in real-time health monitoring at patient s bedside or in a doctor s office, and real-time clinical intervention in acute situations. It also can be used for daily measurement of hematocrit for patients on anticoagulant drugs, or to detect acute myocardial damage outside a hospital.

Chan, Eugene Y.↗
NASA NTRS1997

Regulation of body fluid volume and electrolyte concentrations in spaceflight

Despite a number of difficulties in performing experiments during weightlessness, a great deal of information has been obtained concerning the effects of spaceflight on the regulation of body fluid and electrolytes. Many paradoxes and questions remain, however. Although body mass, extracellular fluid volume, and plasma volume are reduced during spaceflight and remain so at landing, the changes in total body water are comparatively small. Serum or plasma sodium and osmolality have generally been unchanged or reduced during the spaceflight, and fluid intake is substantially reduced, especially during the first of flight. The diuresis that was predicted to be caused by weightlessness, has only rarely been observed as an increased urine volume. What has been well established by now, is the occurrence of a relative diuresis, where fluid intake decreases more than urine volume does. Urinary excretion of electrolytes has been variable during spaceflight, but retention of fluid and electrolytes at landing has been consistently observed. The glomerular filtration rate was significantly elevated during the SLS missions, and water and electrolyte loading tests have indicated that renal function is altered during readaptation to Earth's gravity. Endocrine control of fluid volumes and electrolyte concentrations may be altered during weightlessness, but levels of hormones in body fluids do not conform to predictions based on early hypotheses. Antidiuretic hormone is not suppressed, though its level is highly variable and its secretion may be affected by space motion sickness and environmental factors. Plasma renin activity and aldosterone are generally elevated at landing, consistent with sodium retention, but inflight levels have been variable. Salt intake may be an important factor influencing the levels of these hormones. The circadian rhythm of cortisol has undoubtedly contributed to its variability, and little is known yet about the influence of spaceflight on circadian rhythms. Atrial natriuretic peptide does not seem to play an important role in the control of natriuresis during spaceflight. Inflight activity of the sympathetic nervous system, assessed by measuring catecholamines and their metabolites and precursors in body fluids, generally seems to be no greater than on Earth, but this system is usually activated at landing. Collaborative experiments on the Mir and the International Space Station should provide more of the data needed from long-term flights, and perhaps help to resolve some of the discrepancies between U.S. and Russian data. The use of alternative methods that are easier to execute during spaceflight, such as collection of saliva instead of blood and urine, should permit more thorough study of circadian rhythms and rapid hormone changes in weightlessness. More investigations of dietary intake of fluid and electrolytes must be performed to understand regulatory processes. Additional hormones that may participate in these processes, such as other natriuretic hormones, should be determined during and after spaceflight. Alterations in body fluid volume and blood electrolyte concentrations during spaceflight have important consequences for readaptation to the 1-G environment. The current assessment of fluid and electrolyte status during weightlessness and at landing and our still incomplete understanding of the processes of adaptation to weightlessness and readaptation to Earth's gravity have resulted in the development of countermeasures that are only partly successful in reducing the postflight orthostatic intolerance experienced by astronauts and cosmonauts. More complete knowledge of these processes can be expected to produce countermeasures that are even more successful, as well as expand our comprehension of the range of adaptability of human physiologic processes.

NASA Discipline Number 18-10↗
NASA NTRS2010

Immune System Dysregulation and Herpesvirus Reactivation Persist During Long-Duration Spaceflight

Background: Immunity, latent herpesvirus reactivation, physiological stress and circadian rhythms were assessed during six month spaceflight onboard ISS. Blood and saliva samples were collected early, mid and late in-flight and returned for immediate analysis. Mid-point study data (10 of 17 planned subjects) will be presented. Results: Some shifts in leukocyte distribution occurred during flight, including alterations in CD8+ T cell maturation. General T cell function was consistently reduced early in-flight. Levels CD8+/IFNg+ producing T cells were depressed early in-flight, and immediately upon landing. Persistent mitogen-dependant reductions were observed in IFNg, IL-17a, IL-10, TNFa and IL-6 production. Monocyte production of IL-10 was reduced, whereas IL-8 levels were increased. Levels of mRNA for the TNFa, IL-6 and IFNg were transiently elevated early in-flight, and the dynamics of TNF and IL-6 gene expression were somewhat antagonistic to their corresponding receptors during flight. The number of virus-specific CD8+ T-cells was measured using MHC tetramers, while their function was measured using intracellular cytokine analysis following peptide stimulation. Both the number and function of EBV-specific cells decreased during flight as compared to preflight levels. The number of CMV-specific T-cells generally increased as the mission progressed while their function was variable. Viral (EBV) load in blood was elevated postflight. Anti-EBV VCA antibodies were significantly elevated by R+0; anti-EA antibodies were not significantly elevated at landing; and anti-CMV antibodies were somewhat elevated during flight. Higher levels of salivary EBV DNA were found during flight. VZV DNA reactivation occurred in ~50 % of astronauts during flight, continuing for up to 30 days post-flight. CMV was shed in 35 % the in-flight and 30% of postflight urine samples of the crewmembers. There was generally a higher level of cortisol as measured in urine and saliva in the astronauts during flight, but plasma cortisol was relatively unchanged during flight. Circadian rhythm of salivary cortisol was altered during flight. Conclusion. Some alterations in immunity do not resolve during six month spaceflight, consequentially resulting in persistent herpesvirus reactivation. Ongoing immune dysregulation may represent specific clinical risks for exploration-class space missions.

Crucian, B. E.↗
NASA NTRS2001

Marked exacerbation of orthostatic intolerance after long- vs. short-duration spaceflight in veteran astronauts

OBJECTIVE: The incidence of postflight orthostatic intolerance after short-duration spaceflight is about 20%. However, the incidence after long-duration spaceflight was unknown. The purpose of this study was to test the hypothesis that orthostatic intolerance is more severe after long-duration than after short-duration flight. METHODS: We performed tilt tests on six astronauts before and after long-duration (129-190 days) spaceflights and compared these data with data obtained during stand tests before and after previous short-duration missions. RESULTS: Five of the six astronauts studied became presyncopal during tilt testing after long-duration flights. Only one had become presyncopal during stand testing after short-duration flights. We also compared the long-duration flight tilt test data to tilt test data from 20 different astronauts who flew on the short-duration Shuttle missions that delivered and recovered the astronauts to and from the Mir Space Station. Five of these 20 astronauts became presyncopal on landing day. Heart rate responses to tilt were no different between astronauts on long-duration flights and astronauts on short-duration flights, but long-duration subjects had lower stroke volumes and cardiac outputs than short-duration presyncopal subjects, suggesting a possible decrease in cardiac contractile function. One subject had subnormal norepinephrine release with upright posture after the long flight but not after the short flight. Plasma volume losses were not greater after long flights. CONCLUSION: Long-duration spaceflight markedly increases orthostatic intolerance, probably with multiple contributing factors.

STS Shuttle Project↗
NASA NTRS1985

Effects of thermal stress and exercise on blood volume in humans

The available experimental data base on the effects of exercise, posture and the environment (heat) on the blood volume, composition and concentration in humans is surveyed in depth to synthesize supportable conclusions. A large disparity is noted in the effective controls which were initiated in previous experimental conditions, resulting in contradictory findings regarding, e.g., hemoconcentrations and hemodilution in response to exercise. Comparisons between the results of exercise and of supine, seated and upright subjects has underscored the importance of gravity in hemoconcentration, particularly in the legs, and the generation of aldotestosterone. Hemoconcentration has been confirmed to increase with exercise in a seated or supine position. Exercise in a heated environment transfers cardiac output from core areas and reduces filtration efficiencies. Also, plasma volume increases, an action which cannot yet be associated with crystalloidal or colloidal influences on the osmotic behavior of cell walls.

Harrison, M. H.↗
NASA NTRS2002

Exercise Versus +Gz Acceleration Training

Decreased working capacity and "orthostatic" intolerance are two major problems for astronauts during and after landing from spaceflight in a return vehicle. The purpose was to test the hypotheses that (1) supine-passive-acceleration training, supine-interval-exercise plus acceleration training, and supine exercise plus acceleration training will improve orthostatic tolerance (OT) in ambulatory men; and that (2) addition of aerobic exercise conditioning will not influence this enhanced OT from that of passive-acceleration training. Seven untrained men (24-38 yr) underwent 3 training regimens (30 min/d x 5d/wk x 3wk on the human-powered centrifuge - HPC): (a) Passive acceleration (alternating +1.0 Gz to 50% Gzmax); (b) Exercise acceleration (alternating 40% - 90% V02max leg cycle exercise plus 50% of HPCmax acceleration); and (c) Combined intermittent exercise-acceleration at 40% to 90% HPCmax. Maximal supine exercise workloads increased (P < 0.05) by 8.3% with Passive, by 12.6% with Exercise, and by 15.4% with Combined; but maximal V02 and HR were unchanged in all groups. Maximal endurance (time to cessation) was unchanged with Passive, but increased (P < 0.05) with Exercise and Combined. Resting pre-tilt HR was elevated by 12.9% (P < 0.05) only after Passive training, suggesting that exercise training attenuated this HR response. All resting pre-tilt blood pressures (SBP, DBP, MAP) were not different pre- vs. post-training. Post-training tilt-tolerance time and HR were increased (P < 0.05) only with Passive training by 37.8% and by 29.1%, respectively. Thus, addition of exercise training attenuated the increased Passive tilt tolerance. Resting (pre-tilt) and post-tilt cardiac R-R interval, stroke volume, end-diastolic volume, and cardiac output were all uniformly reduced (P < 0.05) while peripheral resistance was uniformly increased (P < 0.05) pre-and post-training for the three regimens indicating no effect of any training regimen on those cardiovascular variables. Plasma volume (% delta) was uniformly decreased by 8% to 14% (P < 0.05) at tilt-tolerance pre- vs. post-training for all regimens indicating no effect of these training regimens on the level of vascular fluid shifts.

Greenleaf, John E.↗
NASA NTRS2006

Hypovolemia Induced Orthostatic Hypotension in Presyncopal Astronauts and Normal Subjects Related to Hypoadrenergic Responsiveness

Circulating blood volume is reduced during spaceflight, making astronauts hemodynamically compromised. After landing, astronauts separate into two groups. One group compensates for the hypovolemia with a hyper-sympathetic response during upright tilt testing and can complete a tilt test with few symptoms. The other group is unable to mount a hyper-sympathetic response and experiences orthostatic hypotension and presyncope during upright tilt tests. We tested the hypothesis that hypovolemia alone, in the absence of spaceflight, also would cause subjects to separate into presyncopal and non-presyncopal groups according to their sympathetic responses during tilt. We studied 20 subjects, including 10 veteran astronauts, on three occasions. On Days 1 (normovolemia) and 3 (hypovolemia), plasma volume, tilt tolerance and supine and standing plasma norepinephrine levels were measured. Forty hours prior to Day 3, subjects were given intravenous furosemide, followed by 36 hours of a 10MEq Na diet. Statistical comparisons were made between normovolemia and hypovolemia responses. This protocol reproduced landing day tilt test outcomes with 100% fidelity in the astronauts. Similarly to patterns reported after flight, non-presyncopal subjects had greater norepinephrine responses to tilt during hypovolemia compared to normovolemia (580 plus or minus 79 vs. 298 plus or minus 37 pg/ml, P less than 0.05), but presyncopal subjects had no increase (180 plus or minus 44 vs. 145 plus or minus 32 pg/ml, P=NS). This model can be used to predict astronauts who will become presyncopal on landing day, so that prospective, individualized countermeasures can be developed. Within patient populations, it can be used to study the interaction of volemic state and the sympathetic nervous system.

Meck, Janice V.↗
NASA NTRS2001

Decreased non-MHC-restricted (CD56+) killer cell cytotoxicity after spaceflight

Cytotoxic activity of non-major histocompatibility complex-restricted (CD56+) (NMHC) killer cells and cell surface marker expression of peripheral blood mononuclear cells were determined before and after spaceflight. Ten astronauts (9 men, 1 woman) from two space shuttle missions (9- and 10-day duration) participated in the study. Blood samples were collected 10 days before launch, within 3 h after landing, and 3 days after landing. All peripheral blood mononuclear cell preparations were cryopreserved and analyzed simultaneously in a 4-h cytotoxicity (51)Cr release assay using K562 target cells. NMHC killer cell lytic activity was normalized per 1,000 CD56+ cells. When all 10 subjects were considered as one study group, NMHC killer cell numbers did not change significantly during the three sampling periods, but at landing lytic activity had decreased by approximately 40% (P < 0.05) from preflight values. Nine of ten astronauts had decreased lytic activity immediately after flight. NMHC killer cell cytotoxicity of only three astronauts returned toward preflight values by 3 days after landing. Consistent with decreased NMHC killer cell cytotoxicity, urinary cortisol significantly increased after landing compared with preflight levels. Plasma cortisol and ACTH levels at landing were not significantly different from preflight values. No correlation of changes in NMHC killer cell function or hormone levels with factors such as age, gender, mission, or spaceflight experience was found. After landing, expression of the major lymphocyte surface markers (CD3, CD4, CD8, CD14, CD16, CD56), as determined by flow cytometric analysis, did not show any consistent changes from measurements made before flight.

NASA Center JSC↗
NASA NTRS2001

Maximal exercise as a countermeasure to orthostatic intolerance after spaceflight

Previous investigators have suggested that maximal exercise performed 24 h before the end of bed rest, a spaceflight analog, restores prebed rest plasma volume, baroreflex responses, and orthostatic tolerance. PURPOSE: In this case report, we examined the effect of a similar exercise protocol 24 h before a Shuttle landing on the orthostatic responses of four crewmembers (EX) after spaceflights of 8-14 d. Four additional crewmembers (CON) served as controls and did not perform exercise during the final day of the flight. METHODS: Each crewmember performed a 10-min stand test approximately 10 d before launch (L-10) and within 1-2 h of landing (R+0). Cardiac stroke volume was measured (Doppler ultrasound) supine and during each min of standing for three EX and three CON subjects. RESULTS: Preflight, all crewmembers completed the stand test and each group had similar heart rate and blood pressure responses. Postflight, all subjects also completed the 10-min stand test. Each group had similarly elevated supine and standing heart rates, elevated diastolic and mean arterial blood pressures, and reduced pulse pressures compared to L-10. However, postflight cardiac output, mean +/- SEM, (EX: 4.5+/-0.6 L x min(-1); CON: 3.1+/-0.3 L x min(-1)) and stroke volume (EX: 43+/-7 mL x beat; CON: 30+/-6 mL x beat) were higher after 10 min standing in the EX subjects compared to CON subjects. CONCLUSIONS: For these four crewmembers, maximal exercise performed 24 h before landing may have helped maintain stroke volume but did not maintain heart rate and blood pressure responses during standing compared to preflight.

Flight Experiment↗
NASA NTRS2001

Exercise Thermoregulation Following 13 Days of Bed Rest

This investigation examined two potential mechanisms, altered skin blood flow (SBF) and sweating rate (SR) responses, that may be responsible for an elevated core temperature during exercise after bed rest (BR) and space flight. Seven healthy men (29 +/- 5 yr, 179.6 +/- 7.1 cm, 77.2 +/- 17.0kg; mean +/- SD) underwent 13 days of 6 deg head-down BR. Pre- and post-BR, subjects completed supine submaximal cycle ergometry (20 min at 40% and 20 min at 65% of pre-BR supine VO2pk) in a thermoneutral room (23.4 +/- 0.5 C, 56 +/- 8 %RH) during, heat production (VO2 ; indirect calorimetry), intestinal temperature (T(sub in) ; ingestible pill), SBF (laser Doppler velocimetry), local SR (dew point hygrometry), and total sweat loss (TSL; Delta body weight) were measured. Pre- and post- BR plasma volume (PV) was measured using I-125 dilution. After BR, T(sub in) was elevated at rest (36.99 +/- 0.14 vs. 37.30 +/- 0.06 C; p<_0.05) and at the end of exercise (37.57 +/- 0.13 vs. 37.90 +/- 0.09 C; P less than or equal to 0.05). However, the increase in T(sub in) from rest to the end of exercise was not different after BR (0.59 +/- 0.07 vs. 0.60 +/- 0.07 C). There was no difference in VO2 pre- to post-BR during rest (0.28 +/- 0.04 vs. 0.24 +/- 0.03 1 multiplied by min(exp -1) ) or 40% VO2pk (0.95 +/- 0.08 vs. 0.96 +/- 0.05 1 multiplied by min(exp -1)), but VO2 was significantly less at the end of the 65% VO2pk stage (1.53 +/- 0.09 vs. 1.42 +/- 0.11 1 multiplies by min(exp - 1); p less than or equal to 0.05). The percent change in SBF from rest to end of exercise was less after BR (211 +/- 53 vs. 96 +/- 31%; p less than or equal to 0.05), the threshold for the onset of SBF was greater (37.17 +/- 0.18vs. 37.51 +/- 0.17 C; p less than or equal to 0.05), and the slope of the response tended to be reduced (536 +/- 184 vs. 201 +/- 46 %A PC; p=0.08). TSL was not different after BR (0.42+0.06 vs. 0.44 +/- 0.08 kg), but the T in threshold at the onset of sweating was delayed significantly (37.06 +/- 0.1 1 vs. 37.34 +/- 0.06 C; p less than or equal to 0.05). However, the slope of SR was not changed after BR (3.45 +/- 1.22 vs. 2.58 +/- 0.71 mg multiplied by min(exp -1) multiplied by cm sq). PV was decreased by 11% after BR (3,259 +/- 177 vs. 2,894 +/- 138 ml; p less than or equal to 0.05). These results suggest that exercise SBF and SR responses after BR are altered, and heat production is unchanged or reduced, consistent with observations following space flight. The higher resting T(sub in) with a proportional increase in T(sub in) during exercise and delayed onset of SBF and SR suggest a centrally-mediated elevation in the thermoregulatory set point during microgravity exposure.

Lee, Stuart M. C.↗