Evidence for central venous pressure resetting during initial exposure to microgravity.

We measured central venous pressure (CVP); plasma volume (PV); urine volume rate (UVR); renal excretion of sodium (UNa); and renal clearances of creatinine, sodium, and osmolality before and after acute volume infusion to test the hypothesis that exposure to microgravity causes resetting of the CVP operating point. Six rhesus monkeys underwent two experimental conditions in a crossover counterbalance design: 1) continuous exposure to 10 degrees head-down tilt (HDT) and 2) a control, defined as 16 h/day of 80 degrees head-up tilt and 8 h prone. After 48 h of exposure to either test condition, a 120-min course of continuous infusion of isotonic saline (0.4 ml. kg(-1). min(-1) iv) was administered. Baseline CVP was lower (P = 0.011) in HDT (2.3 +/- 0.3 mmHg) compared with the control (4.5 +/- 1.4 mmHg) condition. After 2 h of saline infusion, CVP was elevated (P = 0.002) to a similar magnitude (P = 0.485) in HDT (DeltaCVP = 2.7 +/- 0.8 mmHg) and control (DeltaCVP = 2.3 +/- 0.8 mmHg) conditions and returned to preinfusion levels 18 h postinfusion in both treatments. PV followed the same pattern as CVP. The response relationships between CVP and UVR and between CVP and UNa shifted to the left with HDT. The restoration of CVP and PV to lower preinfusion levels after volume loading in HDT compared with control supports the notion that lower CVP during HDT may reflect a new operating point about which vascular volume is regulated. These results may explain the ineffective fluid intake procedures currently employed to treat patients and astronauts.

Blood pressure changes during orthostatic stress: evidence of gender differences in neuroeffector distribution.

BACKGROUND: Research has demonstrated that exogenous adrenergic agonists produce dose-related vasoconstriction in men but not women. This suggests that the distribution of adrenergic receptor sites differ with gender. Women may have a higher density of receptor sites in the arterioles (fast acting with low gain) while men may have higher density in the larger vessels (slow acting with high gain). METHODS: To partially test this hypothesis, the time course in beat-to-beat responses in systolic and diastolic BP, and heart rate was compared between six men and six women during the transition from a supine to an upright posture and during prolonged standing. RESULTS: The transient change in systolic and diastolic BP was very rapid in women, but completed within 15 to 30 s after assuming an upright position. Men increased BP at a much slower rate, but continued to produce higher BPs over the complete testing session (up to 15 min). The rate of change for men (15 mm Hg systolic and 10 mm Hg diastolic) was approximately half that for women (30 mm Hg systolic and 15 mm Hg diastolic) during the first 30 s of upright posture. However, after 60 s of standing, absolute change in systolic BP for the men exceeded that of the women by approximately 5 mm Hg for both systolic and diastolic BP. While men's heart rate remained relatively constant during standing, women compensated for the lower change in BP by a continual increase in heart rate throughout the duration of the test. Although both men and women demonstrated increases in norepinephrine at 5 and 15 min during standing, no difference between genders was observed. Similarly, there were no differences in dominant periodicity of heart rate during standing, although women demonstrated slightly higher beat-to-beat variation (RMS) than men. CONCLUSION: The results support the hypothesis of distributional differences in neuroeffector responses between men and women and have implications for how men and women respond to orthostatic stress across a variety of environmental conditions.

Laser dosimetry control for retinal surgery.

We discuss the initial stages of the development of a feedback control system to provide consistent lesions across a non-uniform retina during laser photocoagulation therapy. The system will control the power supplied to the irradiating laser in the Hybrid Retinal Photocoagulation System, a system which will robotically assist an ophthalmologist in performing laser photocoagulation. Adding automation to this process will make the procedure less tedious and time-consuming for both patient and ophthalmologist. [1] Research performed during the summer of 2000 to determine a suitable microprocessor for this subsystem is the subject. The results explain the choice of microprocessor. Research continues on this subsystem which will use the reflectance signal to generate real time laser power control.

Left ventricular, systemic arterial, and baroreflex responses to ketamine and TEE in chronically instrumented monkeys.

Effects of prescribed doses of ketamine five minutes after application and influences of transesophageal echocardiography (TEE) on left ventricular, systemic arterial, and baroreflex responses were investigated to test the hypothesis that ketamine and/or TEE probe insertion alter cardiovascular function. Seven rhesus monkeys were tested under each of four randomly selected experimental conditions: (1) intravenous bolus dose of ketamine (0.5 ml), (2) continuous infusion of ketamine (500 mg/kg/min), (3) continuous infusion of ketamine (500 mg/kg/min) with TEE, and (4) control (no ketamine or TEE). Monkeys were chronically instrumented with a high fidelity, dual-sensor micromanometer to measure left ventricular and aortic pressure and a transit-time ultrasound probe to measure aortic flow. These measures were used to calculate left ventricular function. A 4-element Windkessel lumped-parameter model was used to estimate total peripheral resistance and systemic arterial compliance. Baroreflex response was calculated as the change in R-R interval divided by the change in mean aortic pressure measured during administration of graded concentrations of nitroprusside. The results indicated that five minutes after ketamine application heart rate and left ventricular diastolic compliance decreased while TEE increased aortic systolic and diastolic pressure. We conclude that ketamine may be administered as either a bolus or continuous infusion without affecting cardiovascular function 5 minutes after application while the insertion of a TEE probe will increase aortic pressure. The results for both ketamine and TEE illustrate the classic "Hawthorne Effect," where the observed values are partly a function of the measurement process. Measures of aortic pressure, heart rate, and left ventricular diastolic pressure should be viewed as relative, as opposed to absolute, when organisms are sedated with ketamine or instrumented with a TEE probe.

Is there resetting of central venous pressure in microgravity?

In the early phase of the Space Shuttle program, NASA flight surgeons implemented a fluid-loading countermeasure in which astronauts were instructed to ingest eight 1-g salt tablets with 960 ml of water approximately 2 hours prior to reentry from space. This fluid loading regimen was intended to enhance orthostatic tolerance by replacing circulating plasma volume reduced during the space mission. Unfortunately, fluid loading failed to replace plasma volume in groundbased experiments and has proven minimally effective as a countermeasure against post-spaceflight orthostatic intolerance. In addition to the reduction of plasma volume, central venous pressure (CVP) is reduced during exposure to actual and groundbased analogs of microgravity. In the present study, we hypothesized that the reduction in CVP due to exposure to microgravity represents a resetting of the CVP operating point to a lower threshold. A lower CVP 'setpoint' might explain the failure of fluid loading to restore plasma volume. In order to test this hypothesis, we conducted an investigation in which we administered an acute volume load (stimulus) and measured responses in CVP, plasma volume and renal functions. If our hypothesis is true, we would expect the elevation in CVP induced by saline infusion to return to its pre-infusion levels in both HDT and upright control conditions despite lower vascular volume during HDT. In contrast to previous experiments, our approach is novel in that it provides information on alterations in CVP and vascular volume during HDT that are necessary for interpretation of the proposed CVP operating point resetting hypothesis.

Effects of background field-of-view and depth-plane on the oculogyral illusion.

This study examined the effects of background field-of-view and depth plane on the oculogyral illusion. Seven subjects viewed a stationary fixation stimulus during the postrotatory interval following a 45-sec constant-velocity chair rotation. The duration of the illusory movement of the fixation stimulus during the postrotatory interval was measured, along with the duration of the illusion of whole-body rotation (known as the somatogyral illusion) and the duration of the subject's slow-phase vestibular nystagmus. Subjects viewed the fixation stimulus by itself in a No-background condition or when surrounded by six background fields formed by the combination of two fields-of-view (35 degrees and 115 degrees) and three depth-planes (near, coplanar, and far). The different background fields inhibited the oculogyral illusion relative to the No-background condition but did not differ statistically from each other. The somatogyral durations better matched the oculogyral ones than did nystagmus decay, especially when a background field was present. These results suggest that the oculogyral illusion is more related to the experience of whole-body rotation than to oculomotor mechanisms and that the inhibitory effect of a background scene is only modestly affected by its field-of-view and depth plane.

Renal responsiveness to aldosterone during exposure to simulated microgravity.

We measured renal functions and hormones associated with fluid regulation after a bolus injection of aldosterone (Ald) during head-down tilt (HDT) bed rest to test the hypothesis that exposure to simulated microgravity altered renal responsiveness to Ald. Six male rhesus monkeys underwent two experimental conditions (HDT and control, 72 h each) with each condition separated by 9 days of ambulatory activities to produce a crossover counterbalance design. One test condition was continuous exposure to 10 degrees HDT; the second was a control, defined as 16 h per day of 80 degrees head-up tilt and 8 h prone. After 72 h of exposure to either test condition, monkeys were moved to the prone position, and we measured the following parameters for 4 h after injection of 1-mg dose of Ald: urine volume rate (UVR); renal Na(+)/K(+) excretion ratio; renal clearances of creatinine, Na(+), osmolality, and free water; and circulating hormones [Ald, renin activity (PRA), vasopressin (AVP), and atrial natriuretic peptide (ANP)]. HDT increased Na(+) clearance, total renal Na(+) excretion, urine Na(+) concentration, and fractional Na(+) excretion, compared with the control condition, but did not alter plasma concentrations of Ald, PRA, and AVP. Administration of Ald did not alter UVR, creatinine clearance, Ald, PRA, AVP, or ANP but reduced Na(+) clearance, total renal Na(+) excretion, urinary Na(+)/K(+) ratio, and osmotic clearance. Although reductions in Na(+) clearance and excretion due to Ald were greater during HDT than during control, the differential (i.e., interaction) effect was minimal between experimental conditions. Our data suggest that exposure to microgravity increases renal excretion of Na(+) by a natriuretic mechanism other than a change in renal responsiveness to Ald.

Validity of VO(2 max) in predicting blood volume: implications for the effect of fitness on aging.

A multiple regression model was constructed to investigate the premise that blood volume (BV) could be predicted using several anthropometric variables, age, and maximal oxygen uptake (VO(2 max)). To test this hypothesis, age, calculated body surface area (height/weight composite), percent body fat (hydrostatic weight), and VO(2 max) were regressed on to BV using data obtained from 66 normal healthy men. Results from the evaluation of the full model indicated that the most parsimonious result was obtained when age and VO(2 max) were regressed on BV expressed per kilogram body weight. The full model accounted for 52% of the total variance in BV per kilogram body weight. Both age and VO(2 max) were related to BV in the positive direction. Percent body fat contributed <1% to the explained variance in BV when expressed in absolute BV (ml) or as BV per kilogram body weight. When the model was cross validated on 41 new subjects and BV per kilogram body weight was reexpressed as raw BV, the results indicated that the statistical model would be stable under cross validation (e.g., predictive applications) with an accuracy of +/- 1,200 ml at 95% confidence. Our results support the hypothesis that BV is an increasing function of aerobic fitness and to a lesser extent the age of the subject. The results may have implication as to a mechanism by which aerobic fitness and activity may be protective against reduced BV associated with aging.

Renal responsiveness to aldosterone during exposure to head-down tilt bedrest.

The kidneys represent a fundamental organ system responsible in part for the control of vascular volume. A 10% to 20% reduction in plasma volume is one of the fundamental adaptations during exposure to low gravity environments such as bedrest and space flight. Bedrest-induced hypovolemia has been associated with acute diuresis and natriuresis. Elevated baseline plasma renin activity and aldosterone levels have been observed in human subjects following exposure to head-down tilt and spaceflight without alterations in renal sodium excretion. Further, attempts to restore plasma volume with isotonic fluid drinking or infusion in human subjects exposed to head-down bedrest have failed. One explanation for these observations is that renal distal tubular cells may become less sensitive to aldosterone following exposure to head-down tilt, with a subsequent reduction in renal capacity for sodium retention. We hypothesized that elevated sodium and water excretion observed during prolonged exposure to bedrest and the subsequent inability to restore body fluids by drinking might be reflected, at least in part, by reduced renal tubular responsiveness to aldosterone. If renal tubular responsiveness to aldosterone were reduced with confinement to bedrest, then we would expect measures of renal sodium retention to be reduced when a bolus of aldosterone was administered in head-down tilt (HDT) bedrest compared to a control experimental condition. In order to test this hypothesis, we conducted an investigation in which we administered an acute bolus of aldosterone (stimulus) and measured responses in renal functions that included renal clearances of sodium and free water, sodium/potassium ratio in urine, urine sodium concentration, and total and fractional renal sodium excretion.

Alterations in the volume stimulus-renal response relationship during exposure to simulated microgravity.

We measured central venous pressure (CVP), plasma volume (PV), urine volume rate (UVR), and circulating hormones (renin activity (PRA), vasopressin (AVP), atrial natriuretic peptide (ANP), and cortisol) before and after acute volume infusion (Dextran-40) to test the hypotheses that head-down tilt bedrest (HDT) caused (1) a resetting of the CVP operating point and (2) attenuated urine excretion. Six rhesus monkeys underwent two experimental conditions (HDT and control, each of 48 hour duration) with each condition separated by nine days of ambulatory activities to produce a cross-over counterbalance design. One test condition was continuous exposure to 10 degrees HDT and the second test condition was a control, defined as approximately 12-14 hours per day of 80 degrees head-up tilt and 10-12 hours prone. Following 48 hours of exposure to either test condition, 20-minute continuous infusion of Dextran-40 was administered. CVP in HDT was lower than the control condition. Similar elevations in CVP occurred 30 min post-infusion in both test conditions, and returned to pre-infusion baseline levels between 22 and 46 h post-infusion in both treatments. The UVR response during infusion was attenuated by HDT despite similar elevation in CVP. Elevation in ANP and reduction in PRA at the end of infusion were greater in Control compared to HDT. No differences between control and HDT were detected for AVP and cortisol responses to infusion. Since CVP returned to its pre-infusion levels following volume loading in HDT and control conditions, it appeared that the lower CVP may reflect a new operating point about which vascular volume is regulated. Further, attenuated ANP and PRA responses during vascular volume loading may contribute to depressed UVR in low gravity exposure.

Active lifestyle offsets HRT-induced suppression of T cell reactivity to mitogens.

OBJECTIVE: The purpose of the study was to investigate the combined impact of hormone replacement therapy (HRT) and active lifestyle on the phenotypic profile and in vitro activities of specific immune cells in postmenopausal women. METHODS: Healthy postmenopausal women aged 45-70 were assigned to one of four groups: (a) HRT/sedentary (n = 9); (b) HRT/active (n = 12); (c) no HRT/sedentary (n = 10); and (d) no HRT/active (n = 9). Blood samples were collected from each subject on 3 days within 1 week. The mean value of three samples was used to assess the in vitro response of T lymphocytes to the mitogens phytohemagglutinin and concanavalin A and natural killer cell activity. One of three blood samples was utilized for phenotypic analysis of circulating leukocytes. RESULTS: The mitogenic reactivity of T lymphocytes in whole blood cultures for the groups receiving HRT was lower than from the groups not receiving HRT. There also was a trend for T lymphocyte reactivity to be higher in the active women when compared to the sedentary women. In contrast, the phenotypic profile of leukocytes and natural killer cell activity were not significantly different for samples collected from the four groups. CONCLUSIONS: These data suggest that the suppressive effect of HRT on T cell function in postmenopausal women may be attenuated by a physically active lifestyle.

Evidence for increased cardiac compliance during exposure to simulated microgravity.

We measured hemodynamic responses during 4 days of head-down tilt (HDT) and during graded lower body negative pressure (LBNP) in invasively instrumented rhesus monkeys to test the hypotheses that exposure to simulated microgravity increases cardiac compliance and that decreased stroke volume, cardiac output, and orthostatic tolerance are associated with reduced left ventricular peak dP/dt. Six monkeys underwent two 4-day (96 h) experimental conditions separated by 9 days of ambulatory activities in a crossover counterbalance design: 1) continuous exposure to 10 degrees HDT and 2) approximately 12-14 h per day of 80 degrees head-up tilt and 10-12 h supine (control condition). Each animal underwent measurements of central venous pressure (CVP), left ventricular and aortic pressures, stroke volume, esophageal pressure (EsP), plasma volume, alpha1- and beta1-adrenergic responsiveness, and tolerance to LBNP. HDT induced a hypovolemic and hypoadrenergic state with reduced LBNP tolerance compared with the control condition. Decreased LBNP tolerance with HDT was associated with reduced stroke volume, cardiac output, and peak dP/dt. Compared with the control condition, a 34% reduction in CVP (P = 0.010) and no change in left ventricular end-diastolic area during HDT was associated with increased ventricular compliance (P = 0.0053). Increased cardiac compliance could not be explained by reduced intrathoracic pressure since EsP was unaltered by HDT. Our data provide the first direct evidence that increased cardiac compliance was associated with headward fluid shifts similar to those induced by exposure to spaceflight and that reduced orthostatic tolerance was associated with lower cardiac contractility.

Female exposure to high G: chronic adaptations of cardiovascular functions.

INTRODUCTION: Exposure to microgravity is associated with increased leg venous compliance and reductions in cardiac output, baroreflex functions, and tolerance to orthostatism. However, the effects of chronic exposure to high-G environments are unknown. In addition, there is evidence that females have lower orthostatic tolerance than males, although the underlying mechanisms are unclear. Therefore, we tested the hypotheses that high-G training will enhance baroreflex and orthostatic functions and that females will demonstrate similar adaptations compared with males. METHODS: Calf venous compliance, baroreflex function, and orthostatic performance were measured in six men and seven women before and after repeated exposures on the centrifuge (G-training) for 4 wk, 3 times/wk, with gradual levels of G starting with +3 Gz without G-suit protection during week 1 and advancing to +9 Gz with G-suit protection by the end of week 4. Calf venous compliance was measured by occlusion plethysmography using impedance rheographic recordings of volume change. Baroreflex function was assessed from beat-by-beat changes in heart rate (HR) and mean arterial pressure (MAP) that were measured before, during, and after a Valsalva maneuver strain at 30 mmHg expiratory pressure. The orthostatic performance of reflex responses was assessed from beat-by-beat changes in HR, MAP, stroke volume (SV), cardiac output (Q; by impedance plethysmography), and systemic peripheral resistance during the last 10 cardiac beats of a 4-min squat position and during the initial 10 cardiac beats in a standing position. RESULTS: G-training increased calf compliance in both men and women. SV and Q were increased during the squat-to-stand test in the males, but not in the females, following G-training and provided protection against the development of acute hypotension in the men. CONCLUSIONS: G-training caused adaptations in orthostatic functions opposite to those observed following exposure to microgravity environments. However, adaptations to G-training were limited in females, a finding that may provide a physiological basis for their lower simulated combat tracking performance during simulated aerial combat maneuvers compared with males.

Mediating effect of onset rate on the relationship between +Gz and LBNP tolerance and cardiovascular reflexes.

INTRODUCTION: Research attempting to establish a relationship between human response to lower body negative pressure (LBNP) and +Gz acceleration has in general, disregarded the moderating effects of negative pressure and +Gz onset rates. Many of the past studies designed to examine the relationship between lower body decompression and +Gz acceleration tolerances have also ignored the problem of differences in body position typically encountered during LBNP and +Gz testing (supine LBNP vs. seated +Gz). METHODS: There were 17 male subjects (24-34 yr) who were tested in a seated LBNP chamber and received 3 pressure onset rates of 0.067, 0.33, and 2.0 mm Hg x s(-1). Relaxed acceleration tolerance was assessed on a 6.1 -m centrifuge using three gradual onset rates of 0.01, 0.05, and 0.2 +Gz x s(-1). LBNP and +Gz tolerances were subjected to principle components (factor) analysis, and the resulting factors correlated with variables derived from autonomic reflex control tests (Valsalva and carotid-cardiac baroreflex responsiveness) and height. RESULTS: The factor model suggested a two-dimensional solution consisting of an acceleration factor and an orthostatic factor. The general pattern of the factor loadings indicates the relationship between tolerances of the two forms of orthostatic stress (acceleration and LBNP) is a function of how fast each stress is delivered. The correlation between LBNP tolerance and acceleration tolerance increases as LBNP onset rate is increased, or +Gz onset rate is decreased. Height was highly correlated (-0.71) and carotid-cardiac baroreflex responsiveness moderately correlated (0.54) with general orthostatic tolerance. Valsalva measures of autonomic reflex control had low correlations with general orthostatic tolerance (<0.30). CONCLUSIONS: Although both LBNP and +Gz exposure can lead to eventual loss of consciousness, syncopal events associated with intolerance to either stress are a function of somewhat different cardiovascular mechanisms. There are however, specific situations where LBNP may constitute a viable substitute for +Gz.

Effects of exposure to simulated microgravity on neuronal catecholamine release and blood pressure responses to norepinephrine and angiotensin.

We tested the hypothesis that exposure to microgravity reduces the neuronal release of catecholamines and blood pressure responses to norepinephrine and angiotensin. Eight men underwent 30 days of 6 degrees head-down tilt (HDT) bedrest to simulate exposure to microgravity. Plasma norepinephrine and mean arterial blood pressure (MAP) were measured before and after a cold pressor test (CPT) and graded norepinephrine infusion (8, 16 and 32 ng/kg/min) on day 6 of a baseline control period (C6) and on days 14 and 27 of HDT. MAP and plasma angiotensin II (Ang-II) were measured during graded Ang-II infusion (1, 2 and 4 ng/kg/min) on C8 and days 16 and 29 of HDT. Baseline total circulating norepinephrine was reduced from 1017ng during the baseline control period to 610 ng at day 14 and 673ng at day 27 of HDT, confirming a hypoadrenergic state. An elevation of norepinephrine (+178 ng) to the CPT during the baseline control period was eliminated by HDT days 14 and 27. During norepinephrine infusion, similar elevations in plasma norepinephrine (7.7 pg/ml/ng/kg/min) caused similar elevations in MAP (0.12 mmHg/ng/kg/min) across all test days. Ang-II infusion produced higher levels of plasma Ang-II during HDT (47.3 pg/ml) than during baseline control (35.5 pg/ml), while producing similar corresponding elevations in blood pressure. While vascular responsiveness to norepinephrine appears unaffected, impaired neuronal release of norepinephrine and reduced vascular responsiveness to Ang-II might contribute to the lessened capacity to vasoconstrict after spaceflight. The time course of alterations indicates effects that occur within two weeks of exposure.

Effects of vestibular and oculomotor stimulation on responsiveness of the carotid-cardiac baroreflex.

Twelve healthy men underwent measurement of their carotid-cardiac baroreflex response during varying conditions of vestibulo-oculomotor stimulation to test the hypothesis that vestibular and/or oculomotor stimulation associated with head movements in the yaw plane inhibit baroreflex control of heart rate. We assessed the carotid-cardiac baroreflex response by plotting R-R intervals (in milliseconds) at each of eight neck pressure steps with their respective carotid distending pressures (in millimeters mercury). Baroreflex sensitivity was measured under four experimental conditions: 1) sinusoidal whole body yaw rotation of the subject in the dark without visual fixation (combined vestibular-oculomotor stimulation); 2) yaw oscillation of the subject while tracking a small head-fixed light moving with the subject (vestibular stimulation without eye movements); 3) subject stationary while fixating on a small light oscillating in yaw at the same frequency, peak acceleration, and velocity as the chair (eye movements without vestibular stimulation); and 4) subject stationary in the dark (no eye or head motion). Head motion alone reduced baseline baroreflex responsiveness by 30% from 3.8 +/- 0.5 to 2.6 +/- 0.5 ms/mmHg. Eye motion alone also reduced the baroreflex response by 13% (0.5 ms/mmHg) to 3.3 +/- 0.5 ms/mmHg. During head motion, the effect of eye motion was negligible (2.7 +/- 0.4 ms/mmHg). These results suggest that vestibular stimulation associated with head movements in yaw inhibits vagally mediated baroreflex control of heart rate, whereas oculomotor stimulation is less of a factor and only in the absence of vestibular stimulation.

Effect of standing or walking on physiological changes induced by head down bed rest: implications for spaceflight.

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.

Restoration of plasma volume after 16 days of head-down tilt induced by a single bout of maximal exercise.

Seven healthy men performed maximal exercise 24 h before the end of 16 days exposure to 6 degrees head-down tilt (HDT) to test the hypothesis that such an exercise technique could restore plasma volume (PV) at the end of a simulated space mission. Exercise consisted of supine cycling with graded work rates increasing by 16 W/min to volitional fatigue and required an average of 16 min. The experimental protocol was a standard cross-over design in which the order of treatment (exercise or control) was counterbalanced across all seven subjects. PV, fluid intake (ad libitum), urine output, renal function, and hormones associated with fluid homeostasis were measured before HDT, 24 h before the end of HDT just prior to exercise, and at the end of HDT 24 h after exercise. HDT reduced PV by 16% in both control and exercise conditions. Maximal exercise completely restored plasma volume within 24 h to 3.9 +/- 3.2% of pre-HDT levels despite continued HDT. Compared with control, exercise induced a 660-ml larger positive fluid balance because of greater fluid intake and reduced urine volume during the 24 h after exercise. These results suggest that one bout of maximal leg exercise before return from 16 days of spaceflight may be completely effective in stimulating thirst and restoring plasma volume to preflight levels.

Effect of simulated microgravity on cardiopulmonary baroreflex control of forearm vascular resistance.

The stimulus-response characteristics of cardiopulmonary baroreflex control of forearm vascular resistance (FVR) were studied in 11 healthy men before and after 7 days of 6 degrees head-down bedrest to test the hypothesis that microgravity alters this reflex response. We assessed the relationship between stimulus [changes in central venous pressure (delta CVP)] and reflex response (delta FVR) during unloading of cardiopulmonary baroreceptors with lower body negative pressure (LBNP; 0 to -20 mmHg). delta CVP during bedrest and LBNP was estimated from peripheral vein pressures in the dependent right arm. Compared with prebedrest baseline, plasma volume and estimated CVP were decreased by 13 and 33%, respectively, at 7 days of bedrest. Progressive reflex forearm vasoconstriction occurred in response to graded reductions in estimated CVP during LBNP, and delta FVR per unit delta CVP was doubled after bedrest. The increase in sensitivity of the cardiopulmonary baroreflex control of FVR was related to reduced circulating blood volume, suggesting that enhanced peripheral vasoconstriction in individuals adapted to microgravity can be attributed, in part, to hypovolemia. In addition, microgravity appears to alter the stimulus for cardiopulmonary baroreceptors to a lower operational range of CVP, suggesting the possibility of chronic resetting.

Predicting orthostatic intolerance: physics or physiology?

To adequately assess the viability of any particular causal theory of orthostatic intolerance, physical and physiological parameters thought to be associated with orthostasis must be evaluated simultaneously within the same individual. Time, cost, and complexity of instrumentation generally limit studies of orthostatic intolerance to a single independent effect for any given sample of subjects. We, therefore, measured 6 key physical and physiological variables associated with various theories of orthostatic intolerance in 14 males to test the hypothesis that physical factors rather than physiological reflex mechanisms were dominant in contributing to orthostatic tolerance. Measurements included height, plasma volume (expressed as percent of total weight), variation in R-R interval, leg compliance, and carotid-cardiac (high pressure), and cardiopulmonary (low pressure) baroreflex sensitivity. Subjects' orthostatic intolerance was quantified by time to syncope during progressive supine lower body decompression. Correlations, regression coefficients, and indices of replicability were calculated using 500 to 1,000 bootstrap resamplings of the original 14 observations. Although all six measurements correlated with time to syncope when evaluated individually, only height (negative), percent plasma volume weight (positive), and, to a lesser extent, carotid-cardiac baroreflex sensitivity yielded consistent (reproducible) results when all measures were tested simultaneously. These results suggest that while orthostatic intolerance may be dependent upon a variety of physiological reflexes, physical factors such as height and plasma volume tend to dominate the prediction of time to syncope during lower body negative pressure (LBNP). Physiological reflexes, which act to maintain adequate profusion to the brain during normal terrestrial posture in humans, may be overwhelmed by the additional orthostatic challenge imposed by progressive lower body decompression.