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Background: The goal of this study was to investigate the contribution of splanchnic volume redistribution and lower limb vasoconstriction in the maintenance of blood pressure during progressive central hypovolemia induced by graded lower body negative pressure (LBNP). It was hypothesized that splanchnic blood volume loss during LBNP would buffer decreases in thoracic blood volume., Methods: There were 15 healthy subjects (8 men, 7 women) who participated in the study. We used LBNP of -10, -20, -30, and -40 mmHg with segmental impedance analysis to determine central and splanchnic volume changes, and near infrared spectroscopy (NIRS) to assess calf venous volume changes and vasoconstrictor tone., Results: In relation to baseline, LBNP to -40 mmHg resulted in a 57% increase in deoxygenated blood in the calf, indicating venous pooling in the lower limbs. These events led to a decrease in venous return and a 28% decline in cardiac output. Total upper body impedance increased by 6.6% with a 2.4% change in thoracic and a 13.1% increase in splanchnic impedance with progressive LBNP. Splanchnic blood volume contributed to more than 50% of the volume redistribution to the thoracic compartment during hypovolemia. Both men and women increased their heart rate, but only men vasoconstricted (4.4%) with increasing LBNP. The net result of these events was the maintenance of mean arterial blood pressure with no presyncopal symptoms in these subjects., Discussion: Our results suggest that splanchnic blood volume redistribution--rather than leg vasoconstriction--plays an important role in blood pressure regulation during central hypovolemia.

Introduction: Lower body negative pressure (LBNP) has been used for decades to simulate orthostatic stress and the effects of blood loss in humans. Since the definitive review of LBNP in 1974, new applications have been developed and research has revealed conflicting cardiovascular and neurohormonal responses during and after LBNP., Methods: A search of the literature was conducted for 1964-2007 using the Web of Science and the search terms "cardiovascular system," "orthostasis," "spaceflight," and "methodologies" to identify publications in English that describe human studies where LBNP was used to simulate orthostasis. Publications cited in the earlier review were excluded, leaving a total of 215 articles for consideration., Results: We divided the reported protocols into eight categories based on the pressure, pattern, and duration of the stimulus: 1) mild, constant, short; 2) mild, constant, long; 3) mild, ramp, short; 4) mild, ramp, long; 5) moderate-to-strong, constant, short; 6) moderate, constant, long; 7) moderate-to-strong, ramp, short; and 8) strong, ramp, long. The review showed that these protocols stimulate different reflexes and can be used to produce particular responses., Discussion: Based on the review, we developed guidelines for using LBNP in a predictable and reproducible manner. Variables that must be controlled include subject characteristics, procedures, and environmental conditions as well as specifications for the LBNP chamber and seal positioning. An understanding of the many technical details of such experiments and the nature of elicited cardiovascular and neurohormonal responses is required to design optimal protocols to address specific research questions.

Introduction: The purpose of this study was to identify the combinations of head down tilt (HDT) and lower body negative pressure (LBNP) that would counterbalance each other's effects on cardiovascular and endocrine variables to produce a "neutral point" (NP)., Methods: We conducted 8 30-min experiments in 14 normotensive subjects (2 male, 12 female). Conditions included four levels of HDT (-6 degrees to -24 degrees) and two of LBNP (-15 and -35 mmHg). We determined blood plasma mass density, hematocrit, plasma aldosterone concentration, and plasma renin activity (PRA) before and at the end of stimulation. The effect of stimulus duration was tested using continuous measurements of heart rate (HR), blood pressure (BP), and thoracic electrical impedance (Z0)., Results: NPs were found for all variables except BP, which remained unchanged. NPs were similar for all variables. The 15 mmHg LBNP was compensated by 20 degrees HDT and 35 mmHg LBNP by 27.5 degrees HDT. Longer stimulus duration required increasing HDT angles to balance HR at 35 mmHg LBNP but had no influence on Z0 NP., Discussion: Antiorthostatic positioning can compensate cardiovascular effects of LBNP in a similar fashion for all variables that are significantly influenced by LBNP and body angle, commensurate with stimulus magnitude. Arterial BP remained stable with stimulation and seems to be the primarily defended variable. Why stimulus duration seems to influence the NP for HR remains to be elucidated.

Introduction: Exposure to spaceflight or simulations of microgravity reduce human postflight orthostatic tolerance. Exercise training and volume loading can reduce associated losses of plasma volume and muscle strength, but are not successful in maintaining postflight orthostatic tolerance. A preliminary study (16) indicated that short bouts of artificial gravity (AG) training on a centrifuge could increase orthostatic tolerance in healthy, ambulatory volunteers. We tested the same AG protocol for its tolerance effect on 14 men who underwent a 3-wk exposure to Gz acceleration training on NASA-Ames' (Moffet Field, CA) human-powered centrifuge., Methods: Subjects trained supine (head near the center of rotation) and in pairs (one subject rode passively while the other provided power to operate the 1.9-m centrifuge). The acceleration profile consisted of 7 min at 1 Gz before alternating between 1 and 2.5 Gz at 2-min intervals for 28 min. Each subject's presyncopal orthostatic tolerance limit (to a combination of 70 degrees head-up tilt and increasing lower body negative pressure) was determined before and after training., Results: There were no significant differences between training groups, but presyncopal orthostatic tolerance time was improved 17 +/- 10% (p < 0.05) for the combined groups. Mechanisms associated with increased tolerance included: increased cardiac output (p < 0.04), stroke volume (p < 0.01) and low-frequency spectral power of arterial pressure (p < 0.006), and decreased arterial pressure (p < 0.05) and vascular resistance (p < 0.04). Artificial gravity training in this group of men appears to increase orthostatic tolerance through a combination of decreased vascular resistance and enhanced cardiac function.

Hypothesis: Measurements of plasma volume (PV) and its changes (delta%PV) by Evans blue (EB) dye are presumed to be valid only in fasting subjects. In addition, delta%PVEB with acute altitude exposure has not been compared with other methods employing the concentration or dilution of naturally occurring blood (hematocrit (Hct), hemoglobin (Hb)) and plasma (density, proteins) components, but should be similar if capillary permeability and the sampled vein/whole body Hct ratio remain unchanged., Methods: PVEB was determined in six subjects while fasting or eating on different days, with injection and sampling in the same arm, 4-h extrapolation to time zero and correcting readings with the 620-740 A method. For 93 experiments at altitude, delta%PVEB was obtained similarly from a 3-h extrapolation near the end of a 12-h chamber exposure to 426 mm Hg (-4,880 m =16,000 ft) and at the same time on the preceding control day., Results: Mean PVEB with and without eating was not significantly different (SE of absolute difference = +/- 2.8%). The EB decay curves had significantly more scatter with eating than fasting. The fasting vs. non-fasting values for the single 20-min post-injection point also gave a close comparison (r = +0.97). At altitude the loss in PV measured with EB was significantly greater (delta%PVEB = -6.3%) than losses estimated from Hct-Hb (-2.9%), plasma protein (-3.7%), and plasma density (-3.9%). The expected larger PV loss in subjects tolerant to altitude sickness compared with intolerant ones was most clearly shown by delta%PVEB (8.8%)., Conclusions: Obtaining more samples can offset reproducibility lost by eating. The delta%PVEB were largest and nearest to values previously reported at altitude, perhaps because the single baseline and altitude samples utilized by the other methods are more sensitive to subtle, transient fluctuations in body water and vasomotor tone associated with apprehension, vomiting, fluid intake, and regional vasodilation and constriction.

Purpose: To study hormonal factors that may account for the dissociation between beverage-induced plasma sodium p[Na+] and osmotic p[Osm] concentrations that appear to refute the high theoretical correlation between p[Na+] and p[Osm]., Methods: Ten men (24 +/- SD 3 yr of age) sat reclining (head up) for 12 h in a chamber (21-23 degrees C dry bulb, 25-33% relative humidity) at 2800 m (9184 ft, 539 mm Hg) altitude (ALT), and at 321 m (1053 ft, 732 mm Hg) on the ground (GND). During 1000-1030 hours they consumed 3 fluids (12 ml x kg(-1),X = 948 ml x d(-1)) with large differences in sodium and osmotic contents: AstroAde (AA) with 185 mEq x L(-1) Na+ and 283 mOsm x kg(-1), Performance 1 (Shaklee) (P1) with 22 mEq x L(-1) Na+ and 365 mOsm kg(-1), or H2O at ALT; and only H2O on the GND., Results: After drinking: plasma volume (PV) increased at 1200 hours by 8.3% (p < 0.05) with AA but was not significantly (NS) changed in the other sessions (Xdelta = +0.9%, range -0.9 to 2.8%); p[Na+] and p[Osm] were unchanged. Urinary rates and free-water clearances were attenuated with AA and P1 vs. those with H2O. Correlations between and among p[Na+] and p[Osm] suggest that the pNa+ ion is more tightly controlled than pOsm; and that there was no clear hormonal response that could account for this dissociation from theoretical considerations., Conclusions: There is significant dissociation between plasma sodium and osmotic concentrations after fluid intake. Induction and maintenance of hypervolemia requires increased (near isotonic) drink Na+ osmols rather than increased non-ionic osmols.

Purpose: To get a more complete picture of cardiovascular regulation after postural changes, this investigation directly monitored volume-related, hemodynamic, and endocrine variables during and after 30 min of passive head-up tilt (HUT) of various degrees. It was hypothesized that the return of variables to pre-tilt control level is of system-specific duration and different from what is found after lower body negative pressure (LBNP)., Design: We tested 7 persons on 5 different days using, in random order, no (HUT0) or different intensity (12 degrees , 30 degrees , 53 degrees , and 70 degrees ) of passive orthostasis (HUT12, HUT30, HUT53, HUT70). Data were collected before (supine), during, and after (supine) HUT and compared with synchronous data from HUT0., Results: There was graded alteration with the sine of tilt angle for all hormones and directly volume-related variables. The effects of HUT70 were of the same magnitude as previously documented by others. After HUT, hemodynamic variables and catecholamines returned to control levels most rapidly. Heart rate depression, as observed in a companion LBNP study in the same subjects, did not occur. Vasopressin, PRA, plasma volume and Z0 returned to nominal values more slowly. Plasma aldosterone was still elevated 50 min after reassuming supine posture., Conclusion: Besides specific dose-responses within hemodynamic, volume-dependent, and hormonal variables after orthostatic loading of different degree, the return to control levels after HUT occurs with distinctly different time-courses, which are not identical with those seen after LBNP-simulated orthostasis.

We investigated basal levels and lower body negative pressure (LBNP)-induced changes of volume regulating (PRA, aldosterone, AVP, ANP99-126) and other stress-sensitive hormones (catecholamines, cortisol, ACTH) in venous plasma from one cosmonaut before (-45 d), during (3, 170, 287, 430 d) and after (+4, +90 d) a record-breaking long-term (438 d) spaceflight. Blood was taken at the beginning and immediately after ending LBNP (-15/-30/-35 mm Hg for 15/15/10 min, respectively) preflight supine, inflight, and postflight supine. PRA, aldosterone, and vasopressin levels stayed within normal boundaries during the entire flight and after landing. Catecholamines exceeded reference limits (epinephrine > 140 pg x ml(-1), norepinephrine >1000 pg x ml(-1) 5 and 9 mo inflight, and 4 d postflight. ANP and cGMP were lower inflight (p<0.04) than pre- or postflight. Cortisol and ACTH were not consistently altered. LBNP-induced hormonal changes were not different (p>0.05) in microgravity and 1-G. Based on data from one cosmonaut, we conclude that long-term spaceflight up to 430 d duration appeared to lower plasma ANP and cGMP during flight and occasionally elevate catecholamine levels, without significantly altering LBNP-induced relative hormone changes as compared with those observed on the ground.

Background: The mechanism for reduction and restoration of total body water and plasma volume (PV) during initial exposure to acute altitude (ALT) is not clear but may involve involuntary dehydration; i.e., delayed voluntary fluid intake., Method: Ten men (24 +/- SD 3 yr, 180.8 +/- 8.1 cm height, 78.8 +/- 12.8 kg weight, 1.99 +/- 0.19 m2 surface area, and 12.2 +/- 4.0% body fat) were in a semi-reclining position for 12 h in a chamber at 2800 m (539 mmHg) ALT or at 321 m (732 mmHg; ground). They ate a controlled breakfast (450 kcal + 3 ml x kg(-1) H2O) on the ground, and lunch and dinner at ALT (or on the ground) for a total daily intake of 2850 kcal (14% PRO, 67% CHO, 16% fat, 2.6g NaCl). At hour 10 they consumed fluid-electrolyte beverages or water (12 ml x kg(-1), 948 ml x d(-1)) in 4 sessions at weekly intervals. Beverage compositions were: a) 185 mEq x L(-1) Na+, 283 mOsm x kg(-1); b) 21.6 mEq x L(-1) Na+, 365 mOsm x kg(-1); c) water at ALT; and d) water on the ground., Results: After 10 h at ALT % deltaPV (Hb-Hct) decreased (p < 0.05) by: a) 9.0 +/- SE 1.5%; b) 6.2 +/- 1.7%; c) 7.4 +/- 2.2%; and d) by 9.0 +/- 2.4%, respectively. After drinking from 1000-1030 h, PV at 1200 h changed by: a) +8.3 +/- SE 2.0% (p < 0.05); b) +2.8 +/- 2.7% (NS); c) -0.9 +/- 1.5% (NS); and d) by +0.8 +/- 3.5% (NS), respectively. The similar ground-induced hypovolemia suggests a response to confinement rather than an ALT effect and involuntary dehydration does not appear to be implicated., Conclusion: The significant increase in PV after consuming the (a) NaCl-NaCitrate beverage indicates that drink ionic composition appears to be more important than its osmolality for restoring PV in these conditions. Practical considerations: Because this hypovolemia was probably due to the confinement rather that reduced ambient pressure, appropriate countermeasures could be consumption of isotonic beverages, elastic stockings, leg exercise, and leg elevation.

Background: The purpose for this study was to evaluate various carbohydrate (CHO)-electrolyte fluid formulations for consumption by astronauts to maintain or restore their plasma volume (PV) and total body water (TBW) during and after extravehicular activity (exercise experiment, EE) and for a few hours before reentry and immediately after landing (rest experiment RE)., Hypothesis: That fluid formulation electrolyte content would be more important than osmotic (Osm) content for increasing or maintaining PV during the RE and EE., Methods: In the RE, 5 healthy men (23-44 yr), previously dehydrated for 24 h, drank 6 fluid formulations (Water, 19.6 Na, 157 Na, 19.6 Na + glucose, and the prepared drinks Performances and Power)--one each at weekly intervals, and then sat for 70 min. In the EE, four healthy 24-h dehydrated men (30-46 yr) exercised for 70 min supine on a cycle ergometer (load = 71 +/- 1% peak VO2)., Results: Rest: Subjects who consumed formulations with total Osm concentrations nearer the normal range (157 Na - 270 mOsm x kg(-1), Performance with 19.6 mEq x L(-1) Na - 380 mOsm, and to some extent Power with 23.5 mEq x L(-1) Na - 390 mOsm) had the greater increases in PV; intake of drink 157 Na, with the largest Na content, induced the greatest hypervolemia of 7.6% (p < 0.05). The various additional ions, in addition to 19.6 Na, probably contributed to the 4.6% (p < 0.05) hypervolemia with Performance. Water was not effective. Exercise: Stabilization of PV between 15-70 min was not related to drink total CHO, Na or Osm content. Performance and 157 Na were no more effective than 19.6 Na or 19.6 Na + glu for PV stabilization. Water was the least effective. Regulatory mechanisms controlling PV during exercise appear to be independent of oral fluid formulation Osm-electrolyte content., Conclusions: Drink cation (sodium) content is more important that its total osmotic content for increasing plasma volume at rest. Fluid formulations with greater hypervolemic action in resting subjects may not be as effective during exercise; therefore different formulations for use during exercise appear to be necessary.

Background: This study quantifies hemodynamic and thoracic impedance (TI) changes with four levels of lower body negative pressure (LBNP) from -15 to -65 mm Hg in seven healthy men in supine position 20 min before (pre-LBNP), 30 min during, and 20 min after suction (post-LBNP) as well as without suction (LBNP-0, rest control)., Results: LBNP > 15 mm Hg increased basic TI by up to 2.2 omega (+9.5%). TI-computed stroke volume index (SVI) continuously decreased with time up to -12%, -28%, -36%, and -40% at the end of LBNP-15, -35, -55, and -65. TI-computed cardiac index decreased most (-14%) at LBNP-15 and -35, resulting in a 19% increase of calculated total peripheral resistance index at those intensities. Mean arterial pressure (MAP) did not change in any systematic way with lower LBNP levels, but increased +4.7% and +7.4% at the end of LBNP-55 and -65, respectively. Heart rate remained unchanged at LBNP-15, but continuously increased to reach +22%, +42%, and +55% at the end of LBNP-35, -55, and -65. After finishing LBNP, heart rate fell to values below both pre-LBNP and rest control for > or = 5 min (post-LBNP bradycardia). SVI transiently returned to, and MAP increased above, pre-LBNP levels after suction., Conclusion: In conclusion, different levels of lower body subatmospheric pressure produced quantitatively different time course and dose-response patterns and remained non-hypotensive up to -65 mm Hg suction. Further, heart rate was depressed after LBNP, while arterial BP and TI-computed total peripheral resistance exceeded pre-stimulus levels, indicating an altered cardiovascular state after 30 min of simulated orthostasis.

In one cosmonaut, we investigated lower body negative pressure (LBNP)-induced capillary fluid shifts which we hypothesized would be changed by microgravity (micrograms) adaptation. Sound pulse velocity (SV) was determined in whole blood and plasma samples, using a new method that could detect 0.1% protein concentration changes. Experiments were performed 3 months preflight (supine), during space flight (6th day in orbit), and postflight (supine; 4th day after landing). Antecubital blood was taken at the beginning (3 min: time a) and after shut-down (+2 min: time b) of 40 min LBNP (-15/-30/-35 mm Hg for 15/15/10 min, respectively), since in control experiments with multiple sampling on Earth, the largest difference (increase) between blood and plasma SV was observed between a and b. Our cosmonaut had a 1.6 m/s increase in blood sound pulse velocity (BSV) preflight and a 4.0 m/s increase postflight, whereas BSV stayed unchanged in flight. Plasma sound pulse velocity (PSV) increased 1.2 m/s preflight and 1.7 m/s postflight, whereas PSV did not rise (-0.4 m/s) in flight. This would indicate profoundly altered LBNP-induced fluid dynamics in flight, compared to control (1-g) conditions. On the 4th day postflight, blood and plasma sound velocity increased more with LBNP than preflight, indicating greater hemoconcentration than under control conditions. In summary, the data suggest: 1) altered fluid shifts between blood and interstitial compartments during LBNP with 6 d adaptation to microgravity; and 2) increased hemoconcentration during LBNP early after a 10-d spaceflight.(ABSTRACT TRUNCATED AT 250 WORDS)

We measured volume regulating and stress hormones (AVP, aldosterone, ANP, c-GMP, angiotensin II, PRA, epinephrine, norepinephrine, ACTH, cortisol) in venous blood twice during a lower body negative pressure (LBNP) maneuver in one cosmonaut (31 years, 75 kg, 180 cm) preflight (supine), inflight (6th d in orbit), and on the 4th d (supine) after a 10-d flight. Antecubital blood was taken at the beginning (3 min: "a") and after ceasing (2 min: "b") 40 min LBNP (-15/-30/-35 mm Hg for 15/15/10 min). At the beginning of LBNP, no big changes of resting hormone levels are to be expected. Comparison of "a" values: Inflight, there was a 4-5-fold increase in vasopressin and epinephrine, a slight increase in aldosterone, ANP, norepinephrine, cortisol and ACTH, and a decrease in PRA levels. Postflight, vasopressin was almost as much increased as inflight, and aldosterone and ANP levels were higher than pre- or inflight. PRA, epinephrine, norepinephrine, and cortisol were moderately increased, whereas ACTH and angiotensin II were diminished. Comparison of "b" to "a" values (2 min after LBNP to 3 min intra-LBNP): Preflight, ANP, PRA, and epinephrine rose more than 100%. The inflight response was higher for aldosterone but lower for all other volume active hormones. Postflight, the increase in PRA was pronounced, whereas little change occurred in other hormones. Cortisol and ACTH fell similarly during LBNP under all conditions. In summary, the data provide evidence that not only the endocrine status but also the neuroendocrine responsiveness to stimulation; i.e., the hormone response during cardiovascular load, are altered by the stay in microgravity and readaptation to normal conditions.

Using the "mechanical oscillator technique," the mass density of antecubital venous blood and plasma samples was measured 5-20 times in order to study the influence of postural changes (gravity dependence) on human blood mass density with 0.01 g.L-1 precision, while performing tilt table tests in 17 men. Hemoglobin concentration was measured in 10, and hematocrit in all subjects. Postural fluid shifts were mirrored by accompanying changes in all variables. Blood density (BD) was monitored continuously in five additional experiments from one vein each using two independent densitometers. There were linear relations (p less than 0.01) between all possible combinations of BD, plasma density (PD), blood hemoglobin concentration (Hb), and hematocrit (Ht). Hb can be directly computed from BD (range +/- 10%); the accuracy of Ht determinations from BD increases (range +/- 0.02) if the individual erythrocyte density (ED) and the sample PD are used for calculation. ED was calculated and did not change with body position. ED values of different persons ranged between 1085 g.L-1 and 1095 g.L-1 and did not vary in 15 out of 17 individuals with time (5-75 d). We conclude that ED is closely regulated to an individual set point, that Ht can be computed from BD with higher accuracy if the individual ED and the actual PD values are known, and that BD allows for direct Hb calculation. On-line BD monitoring can be performed with high precision and reveals the individual time-course of spontaneous and postural capillary fluid shifts.