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Background: Respiratory sinus arrhythmia (RSA) is characterized by normal fluctuations in heart rate in phase with the respiratory cycle. There are many proposed mechanisms underlying the RSA phenomenon, including respiratory-induced cardiac loading (i.e., Bainbridge reflex), arterial baroreflex activation, vagal feedback from pulmonary stretch receptors, and central neural mechanisms. It is currently unclear to what extent these mechanisms are responsible for eliciting RSA in humans, particularly in response to stressors., Case Report: Here we present a case report of a healthy 26-yr-old woman (BMI 22.95 kg · m(-2)) who developed extreme RSA when exposed to the simultaneous cardiac loading stressors of 45° head-down tilt (HDT) and increased tidal volume during CO2 rebreathing. During baseline breathing in both supine and 45° HDT position, RSA magnitude was similar (mean ∼10-14 bpm). RSA was tidal volume-dependent, whereby in the supine position the RSA magnitude doubled with an approximate doubling in tidal volume during rebreathing (mean ∼20 bpm). However, when HDT and rebreathing were superimposed, extreme RSA was elicited (mean ∼45 bpm; range ∼38-110 bpm), approximately 450% over baseline breathing in the supine position. ECG analysis and follow up medical assessment revealed no underlying cardiac pathology., Discussion: The existence of extreme RSA when HDT and increased inspired volumes were superimposed suggests that the dual cardiac loading stimuli acted synergistically, increasing RSA magnitude over either stimulus alone. This case report may be relevant to situations where orthostatic stress and augmented tidal volumes are superimposed, or more generally when conflicting sympathetic and parasympathetic activation is simultaneous.

Introduction: Skeletal unloading during a spaceflight could result in bone loss and osteopenia, ultimately leading to poor bone strength. The purpose of the present study was to investigate the influence of bone loss on the dynamic behavior of cancellous bone., Methods: Microgravity-induced bone loss and osteopenia were simulated in a macaque head-down bed rest (HDBR) model, in which 20 macaques were laid on a bed tilted by -6 degrees from the horizontal. These macaques were randomly divided into control (Con) and head down bed rest (HDBR) groups. After 28 d, 5 macaques chosen at random from each group were tested for bone density and mechanical properties, and the obtained data was used to develop a density-based constitutive equation; the remaining animals were tested only for bone density in order to attain statistical power. A split Hopkinson bar was used to monitor the dynamic response of cancellous bone. Cancellous bone deformation under high strain rate conditions was recorded by high-speed videos., Results: Compared with the Con group, the Young's modulus of cancellous bone from HDBR macaque lumbar vertebrae were decreased by 6.03%. Based on the static and dynamic experimental results, parameters in the Maxwell nonlinear viscoelasticity material model were estimated., Discussion: This model of cancellous bone under high strain rate was useful to establish the medical tolerance and evolution criteria of impact-related trauma by finite element method calculations.

Background: We studied the effects of 90 d of 6 degrees head-down bed rest (HDBR) on cardiac autonomic and advanced electrocardiographic (ECC) function, especially on repolarization heterogeneity as assessed by beat-to-beat QT interval variability (QTV), T-wave complexity, and 3-dimensional ECG. Based on prior observations of lengthening of the QTc interval during long-duration spaceflight, we hypothesized that abnormalities in ECG repolarization would also occur during long-duration HDBR., Methods: During controlled breathing, 5-min supine high-fidelity 12-lead ECGs were obtained from 20 healthy subjects (14 men and 6 women) together with measurements of plasma volume and electrolytes at 5 points in time: within 10 d before; 28-30, 60, and 90 d into; and 3-5 d after HDBR., Results: By repeated measures ANOVA, 90 d of sedentary HDBR significantly increased the QTV index (from -1.87 +/- 0.33 to - 1.53 +/- 0.39 units), the index of unexplained QTV (from 0.61 +/- 0.48 to 1.21 +/- 0.40 units), the T-wave complexity intradipolar ratio (from 0.344 +/- 0.260 to 2.04 +/- 4.01%), and the spatial QRS-T angle (from 49.1 +/- 23.8 to 58.7 +/- 31.0 degrees), and significantly decreased the spatial ventricular gradient (from 91.3 +/- 26.5 to 59.1 +/- 23.0 mV x ms(-1)). These changes resolved in part by 3-5 d after resumption of ambulation, but unlike concomitant changes in the QTc interval itself and in heart rate variability, they did not significantly relate to changes in electrolytes or plasma volume., Conclusions: Sedentary, long-duration HDBR reversibly increases ECG repolarization heterogeneity and by inference ventricular arrhythmic risk.

Introduction: The aim of this study was to investigate the consequences of 20 d of physical inactivity using head-down bed rest (HDBR) at -6 degrees on leptin, ghrelin, and counter-regulatory hormone responses., Methods: Eight male volunteers were subjected to HDBR for 20 d. Variables measured before, during, and after HDBR included plasma cortisol, insulin, glucose, leptin, ghrelin, thyroid stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3)., Results: No changes in ghrelin and leptin concentrations were observed during HDBR. Glucose concentration decreased significantly on the 20th day of HDBR compared to the pre-value (day 0) of HDBR (87.6 +/- 2.0 vs. 93 +/- 1.6 mg x dl(-1)). Significant correlation was observed between glucose and leptin concentrations., Discussion: The results provide the first evidence that 20 d of HDBR is not associated with an alteration in ghrelin concentration. Leptin, insulin, and cortisol concentrations did not differ during 20 d of HDBR.

Introduction: This report is one of a series on the Flight Analogs Project, which is designed to lay the groundwork for a standard bed rest protocol. Behavioral health services, similar to those offered to the U.S. astronauts who undertake 6-mo missions onboard the International Space Station, were provided to 13 long-duration head-down bed rest participants. Long-duration missions pose unique challenges and stressors, including separation from primary support group, monotonous environment, and loss of privacy and autonomy., Methods: The psychological services team, consisting of a psychiatrist, a psychologist, and a master's level psychological support scientist, provided behavioral health services throughout all phases of the Flight Analogs Project (FAP) long-duration head-down bed rest study. During the initial screening phase, potential candidates completed 4 h of psychological testing and a 1.5-h clinical interview with a psychologist to assess their psychological fitness and ability to complete the study successfully. Additionally, the psychological services team provided pre-admission trainings on time management, stress management, and communication skills and conflict resolution. Throughout their stay on the research unit, study participants received regular individual and group visits from the psychological services team. Training was also provided to study personnel to address personality and behavioral management challenges., Results: Psychological support and training provided to both subjects and study personnel have successfully improved the well being of study participants., Discussion: Behavioral health services are indispensable to long-duration head-down bed rest studies.

Introduction: As logistical access for space research becomes more limited and NASA prepares for exploration-class missions, ground-based spaceflight analogs will increase in importance for biomedical countermeasures development. A monitoring of immune parameters was performed during the NASA Flight Analogs Project bed rest study (without countermeasure); to establish 'control' data against which future studies (with countermeasure) will be evaluated. Some of the countermeasures planned to be evaluated in future studies may impact immune function., Methods: The immune assessment consisted of: leukocyte subset distribution, early T cell activation, intracellular cytokine profiles, latent viral reactivation, virus specific T cell levels and function, stress hormone levels, and a behavioral assessment using stress questionnaires., Results: In general, subjects did not display altered peripheral leukocyte subsets, constitutive immune activation, altered T cell function, or significant latent viral reactivation (EBV, VZV). Levels of constitutively activated T cells (CD8+/CD69+) and virus-specific T cells (CMV and EBV) decreased during the study. Cortisol levels (plasma and saliva) did not vary significantly during 90-d bed rest., Conclusions: These data demonstrate the absence of significant immune system alteration and physiological stress during 90-d bed rest, and establish control data against which future studies (including countermeasures) may be compared.

Introduction: Spaceflight has functionally significant effects on sensorimotor behavior, but it is difficult to separate the effects of ascending somatosensory changes caused by postural muscle and plantar surface unloading from descending visual-vestibular neural changes. To differentiate somatosensory changes from graviceptor changes in post-spaceflight sensorimotor behavior, bed rest may serve as an exclusionary analog to spaceflight., Methods: Four separate tests were used to measure changes in sensorimotor performance: 1) the monosynaptic stretch reflex (MSR); 2) the functional stretch reflex (FSR); 3) balance control parameters associated with computerized dynamic posturography (CDP); and 4) a functional mobility test (FMT)., Results: A mixed model regression analysis showed significant increases in median MSR start and peak latencies, while the median FSR latency showed no significant increase. Median MSR peak magnitude showed a significant increase during the middle bed rest period (19-60 d). There were no significant effects of bed rest on balance control, but some indication that dynamic head movements may affect posture after bed rest. Time to complete the course for the FMT increased significantly with bed rest., Discussion: The four primary tests indicate that long-duration head-down bed rest, through unloading and modification of the body's support surface, serves as an exclusionary analog for sensorimotor responses to spaceflight. Furthermore, the data suggest that procedures designed to alleviate modifications to the sensory substrate serving the soles of the feet may provide a countermeasure to help maintain support afferentation of the postural muscles.

Introduction: Static bone histomorphometry was applied to existing iliac bone sections originating from a 370-d 5 degrees head-down bed rest experiment. This bed rest experiment is the longest ever to have been conducted. We hypothesized that bed rest would decrease cancellous bone volume fraction and that this effect would be reversed by countermeasures., Methods: Eight healthy male subjects underwent 370 d of 5 degrees head-down bed rest. Three subjects were treated with bisphosphonate (Xidifon, potassium salt of ethane-1-hydroxy-1-disphosphonate, EHDP) combined with an exercise regimen (1-2 h x d(-1)) for the entire study period. Five subjects underwent 120 d of bed rest without countermeasures followed by 250 d of bed rest with the exercise regimen. Transiliac bone biopsies were obtained either at baseline and day 366, or at baseline, day 116, and day 366 at alternating sides of the ileum. Static histomorphometry was performed using a computerized method., Results: The 120 d of head-down bed rest without countermeasures resulted in decreased bone volume fraction BV/TV (-6.3%, p = 0.046) and trabecular number (Tb.N; -10.2%, p = 0.080) and increased trabecular separation (Tb.Sp; 14.7%, p = 0.020), whereas the 250 d of subsequent head-down bed rest with exercise treatment prevented further significant deterioration of the histomorphometric measures., Discussion: The 120 d of 5 degrees head-down bed rest without countermeasures induced significant deterioration of iliac crest cancellous bone histomorphometric properties. On average, the countermeasures consisting of either bisphosphonate and exercise, or exercise alone were able to either prevent or stop immobilization-induced changes of the iliac cancellous bone structure.

The effects of long-term spaceflight on inflammatory responses have not been well-studied in either humans or animals. It is thus important to determine if the functions of immune and inflammatory cells are altered in models of spaceflight. One such animal model is antiorthostatic suspension (AOS), in which the experimental animal is subjected to a head-down tilt that mimics both the stress and the cephalad fluid shift experienced in spaceflight. A previous study reported that the peritoneal neutrophils from mice experiencing AOS generated less superoxide than unsuspended controls. We expanded on this study using several different stimuli and measuring the oxidative response of murine neutrophils in a variety of ways. These responses included the rate, lag period, and dose/response characteristics for superoxide generation, FACS analysis with dihydrodichlorofluorescein as a substrate, and a chemiluminescence response with luminol as a substrate. We also examined phagocytosis of three different microorganisms. While some effects of orthostatic suspension (attributable to the stress of the apparatus) were observed, no clear effects of AOS on oxidative function of the peritoneal neutrophils were seen.

Background: Dietary salt is known to increase the excretion of urinary calcium (Ca). To determine the potential role of dietary sodium (Na) on the calciuria associated with a spaceflight simulation model, we evaluated urinary Ca in two groups of bed rest subjects fed either high or low normal amounts of salt., Methods: We analyzed urinary Ca excretion expressed in terms of creatinine (UCa/Cr), fractional Ca excretion (FECa), and urinary cAMP (UCAMP) as an index of parathyroid function, in the urine of 30-50-yr-old male volunteers for 6 degrees head down tilt bed rest studies. Dietary Na was in the high normal range (190 mmol x d(-1)) in 8 men for 7 d (HiNa), and in the low normal range (114 mmol x d(-1)) in 11 men for 30 d (LoNa) bed rest. Dietary Ca averaged 20 mmol x d(-1) in both studies., Results: Within the first 3 bed rest days, subjects in the HiNa study showed increases in UCa/Cr (0.1130 +/- 0.05 to 0.161 +/- 0.05, p < 0.002) and in FECa (1.95 +/- 0.70 to 3.19 +/- 0.93, p < 0.001); those in LoNa showed no change in UCa/Cr (0.125 +/- 0.06 to 0.121 +/- 0.07, NS) or FECa (1.93 +/- 0.75 to 2.22 +/- 0.63). After the 5th bed rest day UCa/Cr stabilized at similar levels in both dietary groups. UCAMP decreased 20% during the first week of bed rest with HiNa, but not until the third week with LoNa diets (p < 0.05)., Conclusion: These findings implicate high salt diets in Ca excretion in a spaceflight model and suggest that low normal salt diets may reduce early calciuria associated with spaceflight.

Background: Women will be included as mission specialists in the upcoming International Space Station program. This paper describes the changes in volume-regulating hormones and determines the degree of degradation in orthostatic tolerance in a group of women after 120 d of bed rest. The aim of this study was to test a countermeasure program to be used by women during long-duration spaceflights., Methods: For 120 d of -6 degrees head-down bed rest (HDBR), eight healthy women were assigned either to a no-countermeasure (No-CM, n = 4), or to a countermeasure (CM, n = 4) group. In the countermeasure group, exercise began after 2 wk, pharmacological agents were given during the 1st and 3rd mo, and the "Centaur" suit was worn on the last day of bed rest and during the day time for several days after bed rest. Diet supplements were taken during the 1st and 4th mo of HDBR. Tilt tests were run before and after HDBR., Results: After the HDBR, none of the CM subjects, had pre-syncopal or syncopal symptoms during tilt tests: BP was well maintained in the CM group, while heart rate and BP changed in the No-CM group. In plasma, atrial natriuretic peptide (ANP) increased in both groups and remained high throughout HDBR, while aldosterone increased and remained elevated in the No-CM group. Natriuresis was decreased during HDBR., Conclusion: The CM protocols used during this study were efficient and prevented orthostatic intolerance for the four CM subjects. It would be necessary to obtain more data regarding this set of CM protocols on female subjects to lead to statistical and formal conclusions.

Background: Exercise thermoregulation 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., Hypothesis: We hypothesized that 24 h of head down tilt (HDT24) would alter thermoregulatory responses to a submaximal exercise test and result in a higher exercise rectal temperature (Tre) when compared with exercise Tre after 1 h of head down tilt (HDT1)., Methods: Seven men (31+/-SD 6 yr, peak oxygen uptake (VpO2peak) of 44+/-6 ml x kg(-1) x min(-1)) were studied during 70 min of supine cycling at 58+/-SE 1.5% VO2peak at 22.0 degrees C Tdb and 47% rh., Results: Relative to pre-tilt sitting chair rest data, HDT1 resulted in a 6.1+/-0.9% increase and HDT24 in a 4.3+/-2.3% decrease in PV (delta = 10.4% between experiments, p<0.05) while plasma osmolality remained unchanged (NS). Pre-exercise Tre was elevated after HDT24 (36.71 degrees C +/-0.06 HDT1 vs. 36.93 degrees C+/-0.11 HDT24, p<0.05). The 70 min of exercise did not alter this relationship (p<0.05) with respective end exercise increases in Tre to 38.01 degrees C and 38.26 degrees C (degrees = 1.30 degrees C (HDT1) and 1.33 degrees C (HDT24)). While there were no pre-exercise differences in mean skin temperature (Tsk), a significant (p<0.05) time x treatment interaction occurred during exercise: after min 30 in HDT24 the Tsk leveled off at 31.1 degrees C, while it continued to increase reaching 31.5 degrees C at min 70 in HDT1. A similar response (NS) occurred in skin blood velocity. Neither local sweating rates nor changes in body weight during exercise of -1.63+/-0.24 kg (HDT1) or - 1.33+/-0.09 kg (HDT24) were different (NS) between experiments., Conclusion: While HDT24 resulted in elevated pre-exercise Tre, reduced PV, attenuation of Tsk and skin blood velocity during exercise, the absolute increase in exercise Tre was not altered. But if sweat rate and cutaneous vascular responses were similar at different core temperatures (unchanged thermoregulation), the Tre offset could have been caused by the HDT-induced hypovolemia.

Background: Alterations in autonomic function are commonly seen during and after spaceflight, and its ground-based analog, 6 degrees head-down bed rest (HDBR). They may include peripheral vascular regulation, but vasomotor sympathetic efferent nerve discharges to peripheral vasculatures have not been examined. The aim of our study was to examine changes in vasomotor sympathetic nerve activity during HDBR and under orthostasis after HDBR., Methods: We performed 6 d of HDBR on six male subjects, and measured muscle sympathetic nerve activity (MSNA) together with plasma norepinephrine concentrations in the supine position before HDBR and in 6 degrees head-down position on the sixth day (HDBR6) of HDBR. We also measured MSNA in head-up tilt (HUT) test before and after HDBR., Results: On HDBR6, MSNA burst rate was the same (17+/-4 bursts x min(-1)) as that in supine position before HDBR (15+/-2 bursts min(-1)), but plasma norepinephrine concentrations were decreased to 1.14+/-0.10 pmol x ml(-1) compared with the supine value before HDBR (1.56+/-0.20 pmol x ml(-1), p<0.05). After HDBR, supine MSNA burst rate significantly increased by 58% to 24+/-4 bursts x min(-1). MSNA increment in response to HUT was similar between before (34+/-3 bursts min(-1) x sin HUT(-1)) and after (40+/-6 bursts x min(-1) x sin HUT(-1)) HDBR., Conclusions: Our findings suggest that: a) the relationship between MSNA and plasma norepinephrine concentrations was altered on the sixth day during HDBR; b) the vasomotor sympathetic nerve activity was enhanced after HDBR; and c) the augmentation of vasomotor sympathetic outflow to muscles under orthostasis was preserved after HDBR.

This study explored changes of the cerebral circulation and evaluated the responses to weightlessness in 12 volunteers (18-22 yr of age). The velocities, diameters and blood flow volume of the common carotid artery (CCA), internal carotid artery (ICA), vertebral artery (VA) and internal jugular vein (IJV) were measured with color Doppler echogram before and during simulated weightlessness. -30 degrees head-down tilt (HDT) for 45 min was used as a weightlessness simulation model. When the subjects' positions were changed from the supine to -30 degrees HDT, blood flow velocities along the CCA, ICA and IJV decreased significantly (p< 0.05), and their diameters were increased. The subjects were divided into two groups according to measured changes in flow volume of the ICA and IJV: group I with a net in-flow of cerebral blood flow (CBF) and group II with a net out-flow of CBF during HDT. Symptoms were recorded in the two groups during HDT (nasal congestion, sensation of head fullness, headache, and others) and graded on a four-point scale, from absent to serious. Results showed that group I had a higher symptoms score while group II had a lower symptoms score. Although this difference did not reach statistical significance, it suggests that cerebral blood flow changes may be partly responsible for the symptoms observed in subjects during HDT.

Background: This study determined the efficacy of venoconstrictive thigh cuffs, inflated to 50 mmHg, on impeding fluid redistributions during simulated microgravity., Methods: There were 10 healthy male subjects who were exposed to a 2-h tilt protocol which started in the standing position, and was followed by 30 min supine, 30 min standing, 30 min supine, 30 min of -12 degrees head down tilt (HDT, to simulate microgravity), 15 min of HDT with venoconstrictive thigh cuffs inflated, a further 10 min of HDT, 5 min supine, and 10 min standing. To increase the sensitivity of the techniques in an Earth-based model, 12 degrees HDT was used to simulate microgravity effects on body fluid shifts. Volume changes were measured with anthropometric sleeve plethysmography., Results: Transition to the various tilt positions resulted in concomitant decrements in leg volume (Stand [STD] to Supine [SUP], -3.0%; SUP to HDT, -2.0%). Inflation of the venoconstrictive thigh cuffs to 50 mmHg, during simulated microgravity, resulted in a significant 3.0% increase in leg volume from that seen in HDT (p < 0.01). No significant changes in systemic cardiovascular parameters were noted during cuff inflation., Conclusions: We conclude that venoconstrictive thigh cuffs, inflated to 50 mmHg for 15 min during 12 degrees HDT, can create a more Earth-like fluid distribution. Cuffs could potentially be used to ameliorate the symptoms of cephalad edema seen with space adaptation syndrome and to potentiate existing fluid volume countermeasure protocols.

Hypothesis: The responses of the carotid baroreflex and of the peripheral sympathetic system to stimulations induced by either lower body negative pressure (LBNP -40 mmHg) or cold pressor test were investigated in eight volunteers before and after 48 h in the -6 degrees head-down tilt (HDT)., Methods: Geometry (diastolic diameter and pulsatile distention) and dynamics (cross-sectional compliance and tangential tension) of the bulb and the common carotid artery were investigated using ultrasonic devices, echotracking and aplanation tonometry. The activity of the sympathetic system was evaluated through measurements of plasma concentrations of catecholamines (CAs) and 3,4-dihydroxyphenyl glycol (DHPG)., Results: During LBNP -40 mmHg, the pulsed tangential tension was decreased and the pressure amplification, induced by the reflexion of the pressure wave, was increased with no difference between before and after HDT. Since cross-sectional compliance and distensibility coefficient remained unchanged and the carotid contour of the waveform unaltered, it is concluded that the carotid reflexogenic area reads the same message during LBNP whether the cardiovascular system was deconditioned or not. Nonetheless, during LBNP after 48 h HDT, the heart rate accelerated faster and CAs and DHPG concentrations increased out of proportion, suggesting that the peripheral sympathetic activity was more reactive after HDT than before. Finally, forearm vascular resistances were measured in response to cold pressor test; they increased in the same proportion after HDT when compared with before., Conclusion: Results indicate that the carotid baroreflex and the peripheral sympathetic system were not deficient after 48 h HDT.

Background: On exposure to microgravity, astronauts lose up to 12% of their plasma volume which may contribute to post-flight orthostatic intolerance., Hypothesis: Whole-body dehydration during prolonged microgravity, simulated by 6(0) head-down tilt (HDT), may increase plasma colloid osmotic pressure (COP)., Methods: There were seven healthy male subjects (30-55 yr of age) were placed in 6(0) HDT for 16 d. Plasma COP was measured from blood samples drawn immediately before HDT, on day 14 of HDT, and 1 h following bed rest termination using a 20 muL colloid osmometer. Plasma volume was determined before HDT, on day 16 of HDT, and 1 h following bed rest termination using a modified Evans blue dye technique., Results: Plasma COP on day 14 of bed rest (29.9 +/- 0.7 mm Hg) was higher (p = 0.01) than pre-HDT value (23.1 +/- 0.8 mm Hg), coinciding with a decrease of plasma volume. At 1 h of upright recovery following HDT, plasma volume stayed below baseline and plasma COP remained elevated (26.6 +/- 0.6 mm hg; p = 0.003) as compared with the pre-HDT value., Conclusion: Our results indicate that reduced plasma volume and significantly elevated plasma COP probably reflect an overall loss of extracellular fluids during simulated microgravity.

Background: This is the first simulation of a 14-d lunar mission including 6 d on the Moon., Hypothesis: We hypothesized that a lunar gravity simulation in the middle of a head-down tilt (HDT) might result in some reversal of body fluid/hormonal responses, and influence cardiovascular deconditioning., Methods: Six men (28 +/- 2.5 yr) were placed in bed rest (BR): in (HDT) (-6 degrees) to simulate microgravity during the travel (two 4-d periods), and in head-up tilt (HUT) (+10 degrees) (6-d period) to simulate lunar gravity (1/6 g). Muscular exercise was performed during the HUT period to simulate 6 h of lunar EVA. Heart rate variability (HRV) and hormonal responses were studied., Results: An orthostatic arterial hypotension was observed after the BR (tilt test) in 4 of the 6 subjects. Plasma volume measured at D14 decreased by -11.1% (vs. D-3, sitting position). A decrease in atrial natriuretic peptide (26 +/- 3.5 pg.ml-1 (D14) vs. 37.9 +/- 3.5 pg.ml-1 (D-3, sitting) and an increase in plasma renin activity (198 +/- 9.2 mg.L-1.min-1 (D14) vs. 71 +/- 9.2 mg.L-1.min-1 (D-3, sitting) were observed during the BR, more pronounced in HUT at 7:00 p.m. Sympathetic-parasympathetic balance (HRV) at rest showed a decrease in parasympathetic indicator and an increase in sympathetic indicator in BR (p < 0.05), without differences within HDT and HUT periods., Conclusion: These changes were mostly similar to those reported in spaceflights, and HDT. Although the exposure to 1/6 g with exercise modified some hormonal and body fluid responses, this partial gravity simulation was not sufficient to prevent the decrease in orthostatic tolerance observed here as well as after Apollo lunar missions.

Background: Acute fluid shifts initiate chronic cardiovascular acclimation to altered posture or gravity., Hypothesis: We hypothesized that neck volume increases with acute tilt from vertical to horizontal and head-down positions, and that neck volume correlates negatively with leg volume during tilting., Methods: Strain gauges measured changes in calf and neck volumes in 9 subjects during the following tilt table protocol: 90 degrees (upright control), 54 degrees, 30 degrees, 12 degrees, 0 degree (horizontal supine), -6 degrees (head-down tilt), -12 degrees, -6 degrees, 0 degree, 12 degrees, 30 degrees, 54 degrees, and 90 degrees. Each position was held for 30 s., Results: Tilting from 90 degrees upright to 0 degree supine increased neck volume 3.09 +/- 0.37% (mean +/- SE); neck volume increased further above upright control to 4.26 +/- 0.39% at -12 degrees head-down tilt. In the calf, tilting produced significant volume decrements of 1.66 +/- 0.36% below 90 degrees control at 0 degree supine, and 2.03 +/- 0.50% below control at -12 degrees tilt. Neck volume elevation consistently exceeded the absolute magnitude of calf volume reduction at a given tilt angle by a factor of about 1.5, and the two were linearly correlated (r2 = 0.60)., Conclusions: Responses of body segment volumes to tilt were practically instantaneous, indicating that venous blood volume translocation accounted for the changes. We conclude that leg and neck volume changes provide a convenient, non-invasive, and sensitive means of assessing acute regional fluid shifts in humans.

Introduction: Changes in radioactive tracer distribution were examined in rats after exposure to a simulated microgravity model of 45 degrees head down tilt (45HDT) or 45 degrees hind limb unweighting (45HU) for up to 24 h., Methods: Rats were randomly assigned to either 45HDT (or 45HU) experimental groups or control groups for each time point of 0.5 h, 1 h, 2 h, 4 h, 8 h, or 24 h. The 0.5-h through 8-h experimental rats were anesthetized and placed head-down on a ramp at 45 degrees, while control rats were placed in a prone position. Non-anesthetized rats in the 24-h experimental group were tail-suspended at 45 degrees, while control rats were allowed unrestrained movement. Technetium-labeled diethylenetriamine pentaacetate (99mTcDTPA, physical half-life of 6.02 h, MW = 492 amu) and indium-labeled diethylenetriamine pentaacetate (111In DTPA, physical half-life of 3.5 d, MW = 545 amu) were used to measure body organ distributions of the radioactive tracers at the 0.5-h-8-h and 24-h time points, respectively. Major organs were harvested after each time period and measured for radioactive counts. Light and electron micrographs were examined., Results: Mean 111InDTPA counts for the lungs, kidneys, and brains of the 24 h 45HU groups were significantly higher than control counts. Light and electron microscopy demonstrated the development of pulmonary edema in the alveolar septal areas after 2 h of 45HDT, and a shift in edema to the pulmonary airways and pulmonary arteries after 24 h of 45HU., Conclusions: Pulmonary edema development, accompanied by a significant increase in 111InDTPA lung, kidney, and brain counts in the 24-h 45HU groups, suggests vascular injury in the microcirculation of these organs.

Background: The effects of exercise on postural control during walking were evaluated following exposure to head-down bed rest (BR)., Methods: Two groups of male subjects (N = 18, mean age = 21.4 yr +/- SE 1.0) were exposed to 5 d of 6 degrees head-down bed rest. The experimental group (E) exercised 90 min.d-1 (n = 12 subjects) during the BR while the control group received no intervention (n = 6). The exercise treatment consisted of a combination of isotonic and isokinetic lower extremity exercise training. Electromyographic (EMG) activity in the tibialis anterior, gastrocnemius, vastus lateralis, and biceps femoris was measured during walking before and after BR., Results: Following BR, EMG activity increased in both test subject groups for all muscles (p < 0.05). However, there were no significant differences in EMG activity between the C and E groups either before or after BR., Conclusions: These data suggest that the ability of the postural control system to adjust to the gravitational environment was compromised as a result of BR. In addition, we conclude that the exercise protocol used was not an effective countermeasure to the alterations in the postural control system.

Background/hypothesis: To simulate exposure to microgravity and to determine the effectiveness of intermittent exposure to passive and active +1 Gz force (head-to-foot) in preventing head-down bed rest (HDBR) deconditioning, 4 d of 6 degrees HDBR were used., Methods: Volunteers were 9 males, 30-50 yr, who performed periodic standing or controlled walking for 2 or 4 h.d-1 in 15-min bouts, one bout per hour, or remained in a continuous HDBR control condition (0 Gz)., Results: Standing 4 h (S4) completely prevented, and standing 2 h (S2) partially prevented, decreases in post-HDBR orthostatic tolerance (survival rates with 30 min of upright tilt at 60 degrees). Walking, both 2 h (W2) and 4 h (W4), and S4 attenuated decreases in peak oxygen uptake compared to 0 Gz. Compared to 0 Gz, both S4 and W4 attenuated plasma volume loss during HDBR. Urinary Ca2+ excretion increased over time with HDBR; the quadratic trend for urinary Ca2+, however, was attenuated with W2 and W4., Conclusions: We concluded that various physiological systems benefit differentially from passive +1 Gz or activity in +1 Gz and, in addition to the duration of the stimulus, the number of exposures to postural stimuli may be an important moderating factor.

Background: Hindquarter suspension in rats has been used as a model of simulated weightlessness (SW) for ground based study of the effects of microgravity on the cardiovascular system (CVS)., Methods: Using this rat model of SW we tested the hypothesis that CVS deconditioning following spaceflight results, in part, from a decrease in the circulating concentration of sodium-potassium pump inhibitor (SPI). Control rats similarly prepared were not suspended., Results: During the first hour of suspension, central venous pressure (CVP), blood pressure (BP), heart rate (HR), cardiac output (CO), plasma volume (PV), extracellular fluid volume (ECFV), urine output (UV), atrial natriuretic peptide (ANP), and the plasma level of SPI increased. Plasma renin activity (PRA) and myocardial Na+, K(+)-ATPase activity (NKA) decreased. By the end of 4 h of SW, the changes in CVP, BP, HR, ECFV, and UV persisted, but PV, plasma ANP and SPI, and myocardial NKA activity returned to control levels. By the end of 1 d of SW, ECFV and plasma SPI levels had decreased but the myocardial NKA had not increased. At day 4, CVP and BP were the same as in control sham treated rats. Plasma SPI levels were decreased at day 4 but the myocardial NKA was not different, whereas renal NKA was increased. At day 7, myocardial NKA and renal NKA were increased and vascular smooth muscle cell (VSMC) membrane potentials were hyperpolarized., Conclusions: These data indicate that prolonged SW causes a decrease in plasma SPI level which, by hyperpolarizing VSMC, may play a role in the CVS deconditioning seen in astronauts following spaceflight.

Background: Maintaining intermediary metabolism is necessary for the health and well-being of astronauts on long-duration spaceflights. While peak oxygen uptake (VO2) is consistently decreased during prolonged bed rest, submaximal VO2 is either unchanged or decreased., Methods: Submaximal exercise metabolism (61 +/- 3% peak VO2) was measured during ambulation (AMB day-2) and on bed rest days 4, 11, and 25 in 19 healthy men (32-42 yr) allocated into no exercise (NOE, N = 5) control, and isotonic exercise (ITE, N = 7) and isokinetic exercise (IKE, N = 7) training groups. Exercise training was conducted supine for two 30-min periods per day for 6 d per week: ITE training was intermittent at 60-90% peak VO2; IKE training was 10 sets of 5 repetitions of peak knee flexion-extension force at a velocity of 100 degrees s-1. Cardiac output was measured with the indirect Fick CO2 method, and plasma volume with Evans blue dye dilution., Results: Supine submaximal exercise VO2 decreased significantly (*p < 0.05) by 10.3%* with ITE and by 7.3%* with IKE; similar to the submaximal cardiac output decrease of 14.5%* (ITE) and 20.3%* (IKE), but different from change in peak VO2 (+1.4% with ITE and -10.2%* with IKE) and decrease in plasma volume of -3.7% (ITE) and -18.0%* (IKE). Reduction of submaximal VO2 during bed rest correlated 0.79 (p < 0.01) with submaximal Qc, but was not related to change in peak VO2 or plasma volume., Conclusion: Reduction in submaximal oxygen uptake during prolonged bed rest is related to decrease in exercise but not resting cardiac output; perturbations in active skeletal muscle metabolism may be involved.

Purpose: To determine weight (water) loss levels for onset of muscular strength and endurance changes during deconditioning., Methods: Seven men (27-40 yr) performed maximal shoulder-, knee-, and ankle-joint isometric (0 degree.s(-1) load) and isokinetic (60 degrees, 120 degrees, 180 degrees.s(-1) velocity) exercise tests during ambulatory control (AC), after 6 h of 6 degrees head-down tilt (HDT; dry-bulb temp. = 23.2 +/- SD 0.6 degrees C, relative humidity = 31.1+/- 11.1%) and after 6 h of 80 degrees foot-down head-out water immersion (WI; water temp. = 35.0 +/- SD 0.1 degree C) treatments., Results: Weight (water) loss after HDT (1.10 +/- SE 0.14 kg, 1.4 +/- 0.2% body wt) and WI (1.54+/- 0.19 kg, 2.0 +/- 0.2% body wt) were not different, but urinary excretion with WI (1,354 +/- 142 ml.6 h(-1)) was 28% greater (p < 0.05) than that of 975 +/- 139 ml.6 h(-1) with HDT. Muscular endurance (total work; maximal flexion-extension of the non-dominant knee at 180 degrees.s(-1) for 30 s) was not different between AC and the WI or HDT treatments. Shoulder-, knee-, and ankle-joint strength was unchanged except for three knee-joint peak torques: AC torque (120 degrees.s(-1), 285 +/- 20 Nm) decreased to 268 +/- 21 Nm (delta = -6%, p < 0.05) with WI; and AC torques (180 degrees.s(-1), 260 +/- 19 Nm) decreased to 236 +/- 15 Nm (delta = -9%, p < 0.01) with HDT, and to 235 +/- 19 Nm (delta = -10%, p < 0.01) with WI., Conclusion: Thus, the total body hypohydration threshold level for shoulder- and ankle-joint strength and endurance decrements is more than 2% body weight (water) loss, while significant reduction in knee-joint muscular strength-endurance occurred only at moderate (120 degrees.s(-1) and lighter (180 degrees.s(-1)) loads with body weight loss of 1.4-2.0% following WI or HDT, respectively. These weight (water) losses and knee-joint strength decrements are somewhat less than the mean weight loss of 2.6% and knee-joint strength decrements of 6-20% of American astronauts after Skylab flights to 84 d.

This study was performed to determine the effects of 28 d of head-down tilt (HDT) (simulated weightlessness) on cardiovascular responses to orthostatic stress induced by lower body negative pressure (LBNP) (before, during, and after HDT) and +60 degrees head-up tilt (before and after HDT) in 12 subjects. Half of them underwent countermeasures (CM) of regular muscular exercise (isometric and isokinetic training) and LBNP sessions (-30 mm Hg) as generally performed during spaceflight; the other six were a control group (C). The countermeasure effect on the orthostatic responses to LBNP and tilt test was assessed by studying the changes after HDT in the two groups. Essentially, blood pressure was better maintained in group CM in the tilt test after HDT (MBP at the end of the tilt vs. baseline value: +16% (CM); -19% (C)). LBNP and muscular exercise may have contributed to this improvement. One of the probable contributing factors is the relative conservation of plasma volume, at the end of HDT, in group CM (-2.2%), compared to group C (-11.2%). Transcranial Doppler (TCD) recordings of middle cerebral artery (MCA) velocities permitted indirect evaluation of cerebral blood flow changes during the orthostatic tests. MCA velocities decreased significantly although slightly (-7 to -12%) during LBNP sessions without changes along the HDT showing that the cerebral circulation was well preserved in each group. On the other hand, subjects undergoing presyncopal symptoms presented a drop in MCA velocities, suggesting a decrease in cerebral blood flow.

Astronauts often experience back pain during spaceflight. Retrospectively, Wing et al. (14) found that during spaceflight, 14 of 19 Shuttle crewmembers experienced back pain, which they described as dull (62%), localized to the lower back (50%), and with an intensity of 2 on a 5-point scale. Further, the spine lengthens 4-7 cm in microgravity. Our objective was to compare back pain and spinal lengthening (body height increase) during simulated microgravity (6 degrees head-down tilt, HDT) with the same parameters during actual microgravity. Eight male subjects completed a modified McGill pain questionnaire with intensity graded from zero (no pain) to five (intense and incapacitating pain) each day at 7:00 pm during 2 d pre-HDT control, 16 d HDT, and 1 d post-HDT recovery periods. Also, the subjects' heights were measured each day while supine (control and recovery) and during HDT. Back pain increased from zero (pre-tilt control period) to 2.3 +/- 0.4 at days 1 to 3 of HDT, and was categorized as dull and/or burning pain in subjects' lower backs. Only 2 subjects reported any pain after day 9 of HDT and during recovery. Heights increased 2.1 +/- 0.5 cm by day 3 of HDT and remained at that level until the end of the HDT period. Although spinal lengthening in space is greater than that during HDT, the HDT model approximates the level, type, distribution, and time course of back pain associated with actual microgravity. In the HDT model, pain subsides in intensity when spinal lengthening stops.(ABSTRACT TRUNCATED AT 250 WORDS)