Modeling human orthostatic responses on the Moon and on Mars.

PURPOSE: Since manned missions to the Moon and Mars are planned, we conducted active standing tests with lunar, Martian, terrestrial, and 1.8 loads of inertial resistance (+Gz) modeled through defined parabolic flight maneuvers. We hypothesized that the cardiovascular response to active standing is proportional to the +Gz load. METHODS: During partial-+Gz parabolic flights, 14 healthy test subjects performed active stand-up maneuvers under 1 +Gz, lunar (0.16 +Gz), Martian (0.38 +Gz), and hyper inertial resistance (1.8 +Gz) while heart rate and finger blood pressure were continuously monitored. We quantified amplitudes and timing of orthostatic response immediately following standing up. RESULTS: The maximum early heart rate increase was 21 (SD ± 10) bpm with lunar, 23 (± 11) bpm with Martian, 34 (± 17) bpm with terrestrial +Gz, and 40 (± 11) bpm hyper +Gz. The time to maximum heart rate increased gradually with increasing loads of inertial resistance. The transient blood pressure reduction was most pronounced with hyper +Gz but did not differ significantly between lunar and Martian +Gz. The mean arterial pressure nadir was reached significantly later with Martian and lunar compared to 1 +Gz. Paradoxically, the time for blood pressure to recover was shortest with terrestrial +Gz. CONCLUSION: While load of inertial resistance directly affects the magnitude of the transient blood pressure reduction and heart rate response to active standing, blood pressure stabilization is most rapidly attained during terrestrial +Gz. The observation might suggest that the human cardiovascular system is tuned to cope with orthostatic stress on earth.

Increased salt consumption induces body water conservation and decreases fluid intake.

BACKGROUND: The idea that increasing salt intake increases drinking and urine volume is widely accepted. We tested the hypothesis that an increase in salt intake of 6 g/d would change fluid balance in men living under ultra-long-term controlled conditions. METHODS: Over the course of 2 separate space flight simulation studies of 105 and 205 days' duration, we exposed 10 healthy men to 3 salt intake levels (12, 9, or 6 g/d). All other nutrients were maintained constant. We studied the effect of salt-driven changes in mineralocorticoid and glucocorticoid urinary excretion on day-to-day osmolyte and water balance. RESULTS: A 6-g/d increase in salt intake increased urine osmolyte excretion, but reduced free-water clearance, indicating endogenous free water accrual by urine concentration. The resulting endogenous water surplus reduced fluid intake at the 12-g/d salt intake level. Across all 3 levels of salt intake, half-weekly and weekly rhythmical mineralocorticoid release promoted free water reabsorption via the renal concentration mechanism. Mineralocorticoid-coupled increases in free water reabsorption were counterbalanced by rhythmical glucocorticoid release, with excretion of endogenous osmolyte and water surplus by relative urine dilution. A 6-g/d increase in salt intake decreased the level of rhythmical mineralocorticoid release and elevated rhythmical glucocorticoid release. The projected effect of salt-driven hormone rhythm modulation corresponded well with the measured decrease in water intake and an increase in urine volume with surplus osmolyte excretion. CONCLUSION: Humans regulate osmolyte and water balance by rhythmical mineralocorticoid and glucocorticoid release, endogenous accrual of surplus body water, and precise surplus excretion. FUNDING: Federal Ministry for Economics and Technology/DLR; the Interdisciplinary Centre for Clinical Research; the NIH; the American Heart Association (AHA); the Renal Research Institute; and the TOYOBO Biotechnology Foundation. Food products were donated by APETITO, Coppenrath und Wiese, ENERVIT, HIPP, Katadyn, Kellogg, Molda, and Unilever.

Agreement between 24-hour salt ingestion and sodium excretion in a controlled environment.

Accurately collected 24-hour urine collections are presumed to be valid for estimating salt intake in individuals. We performed 2 independent ultralong-term salt balance studies lasting 105 (4 men) and 205 (6 men) days in 10 men simulating a flight to Mars. We controlled dietary intake of all constituents for months at salt intakes of 12, 9, and 6 g/d and collected all urine. The subjects' daily menus consisted of 27 279 individual servings, of which 83.0% were completely consumed, 16.5% completely rejected, and 0.5% incompletely consumed. Urinary recovery of dietary salt was 92% of recorded intake, indicating long-term steady-state sodium balance in both studies. Even at fixed salt intake, 24-hour urine collection for sodium excretion (UNaV) showed infradian rhythmicity. We defined a ±25 mmol deviation from the average difference between recorded sodium intake and UNaV as the prediction interval to accurately classify a 3-g difference in salt intake. Because of the biological variability in UNaV, only every other daily urine sample correctly classified a 3-g difference in salt intake (49%). By increasing the observations to 3 consecutive 24-hour collections and sodium intakes, classification accuracy improved to 75%. Collecting seven 24-hour urines and sodium intake samples improved classification accuracy to 92%. We conclude that single 24-hour urine collections at intakes ranging from 6 to 12 g salt per day were not suitable to detect a 3-g difference in individual salt intake. Repeated measurements of 24-hour UNaV improve precision. This knowledge could be relevant to patient care and the conduct of intervention trials.

EMG and heart rate responses decline within 5 days of daily whole-body vibration training with squatting.

In this study, we examined the acute effects of a 5-day daily whole-body vibration (WBV) training on electromyography (EMG) responses of the m. rectus femoris and m. gastrocnemius lateralis, heart rate (HR, continuously recorded), and blood lactate levels. The purpose of the study was to investigate the adaptation of muscle activity, heart rate and blood lactate levels during 5 days of daily training. Two groups of healthy male subjects performed either squat exercises with vibration at 20 Hz on a side alternating platform (SE+V, n = 20, age  = 31.9±7.5 yrs., height  = 178.8±6.2 cm, body mass  = 79.2±11.4 kg) or squat exercises alone (SE, n = 21, age  = 28.4±7.3 years, height  = 178.9±7.4 cm, body mass  = 77.2±9.7 kg). On training day 1, EMG amplitudes of the m. rectus femoris were significantly higher (P<0.05) during SE+V than during SE. However, this difference was no longer statistically significant on training days 3 and 5. The heart rate (HR) response was significantly higher (P<0.05) during SE+V than during SE on all training days, but showed a constant decline throughout the training days. On training day 1, blood lactate increased significantly more after SE+V than after SE (P<0.05). On the following training days, this difference became much smaller but remained significantly different. The specific physiological responses to WBV were largest on the initial training day and most of them declined during subsequent training days, showing a rapid neuromuscular and cardiovascular adaptation to the vibration stimulus.

Pulse contour methods to estimate cardiovascular indices in micro- and hypergravity.

BACKGROUND: The importance of noninvasive health monitoring in space increased as a result of the long-duration missions on the International Space Station (ISS). In order to monitor changes in cardiovascular indices such as cardiac output (CO) and total peripheral resistance (TPR), many methods have been developed using signal processing and mathematical modeling techniques. However, their performance in various gravitational conditions has not been known. METHODS: The present study compared 10 methods to estimate CO and TPR by processing peripheral arterial blood pressure signals recorded from 8 subjects in multiple gravity levels (1 G, 0 G, and 1.8 G) during parabolic flights. For reference data sets, CO and TPR were simultaneously obtained by an inert gas rebreathing technique. Root normalized mean square errors and Bland-Altman plots were used to evaluate the estimation methods. RESULTS: The corrected impedance method achieved the lowest estimation errors (20.0% CO error and 23.5% TPR error) over the three gravity levels. In microgravity, mean arterial pressure was also demonstrated to be an indicator of CO (24.5% error). DISCUSSION: The corrected impedance method achieved low estimation errors for a wide range of the gravity levels. Gravity-dependent performance was observed in the mean arterial pressure method that achieved low errors in the short-term 0 G.

Long-term space flight simulation reveals infradian rhythmicity in human Na(+) balance.

The steady-state concept of Na(+) homeostasis, based on short-term investigations of responses to high salt intake, maintains that dietary Na(+) is rapidly eliminated into urine, thereby achieving constant total-body Na(+) and water content. We introduced the reverse experimental approach by fixing salt intake of men participating in space flight simulations at 12 g, 9 g, and 6 g/day for months and tested for the predicted constancy in urinary excretion and total-body Na(+) content. At constant salt intake, daily Na(+) excretion exhibited aldosterone-dependent, weekly (circaseptan) rhythms, resulting in periodic Na(+) storage. Changes in total-body Na(+) (±200-400 mmol) exhibited longer infradian rhythm periods (about monthly and longer period lengths) without parallel changes in body weight and extracellular water and were directly related to urinary aldosterone excretion and inversely to urinary cortisol, suggesting rhythmic hormonal control. Our findings define rhythmic Na(+) excretory and retention patterns independent of blood pressure or body water, which occur independent of salt intake.

Upright cardiac output measurements in the transition to weightlessness during parabolic flights.

OBJECTIVE: Aims of this study were: 1) to determine cardiac output by inert gas rebreathing (CO(reb)) during transition into 0 Gz in the standing position; and 2) to compare impedance cardiography (ICG) and pulse contour method (PCM) with CO(reb) as a reference method. METHODS: We measured baseline CO(reb) and heart rate (HR) on the ground, and CO(reb), CO(pcm), CO(icg), and HR in standing and supine positions in the transition to weightlessness in six subjects. We conducted repeated measures ANOVA, Bland and Altman analysis, and analysis of percentage error of each data set. RESULTS: CO(reb) rose from 5.03 +/- 0.7 upright ground control to 11.45 +/- 3.6 L x min(-1) in 0 Gz. HR and stroke volume (SV) rose from 83 +/- 14 to 113 +/- 19 bpm and from 61 +/- 6 to 99 +/- 18 ml, respectively. Mean CO(reb), CO(pcm), and CO(icg) across all conditions were 10.45 +/- 3.04, 7.42 +/- 1.71, and 6.57 +/- 2.46 L x min(-1), respectively. Overall Bland and Altman analysis showed poor agreement for CO(pcm) and CO(icg) compared to CO(reb). DISCUSSION: Large bias for both comparisons indicated that both PCM and ICG underestimate the true CO value. Paired CO values of individual subjects showed a better correlation between methods and a broad bias range, indicating a preponderant role for large between-subjects variability. Repeated CO(reb) determinations in 1 Cz (i.e., when the cardiovascular system is in a steady state) should be used for calibration of the PCM and of ICG data. PCM and ICG can then be used to track CO dynamics during rapid changes of acceleration profiles.

Increasing sodium intake from a previous low or high intake affects water, electrolyte and acid-base balance differently.

Contrasting data are published on the effects of high salt intake (between 300 and 660 mmol/d) on Na balance and fluid retention. In some studies high levels of NaCl intake (400, 440, 550 and 660 mmol/d) led to positive Na balances without fluid retention. To test the relevance of different baseline NaCl intake levels on changes in metabolic water, Na, K, chloride and acid-base balance, a 28 d clinical trial ('Salty Life 6') was carried out in a metabolic ward. Nine healthy male volunteers (aged 25.7 (SD 3.1) years; body mass (BM) 71.4 (SD 4.0) kg) participated in the present study. Four consecutive levels of NaCl intake: low (6 d, 0.7 mmol NaCl/kg BM per d), average normal (6 d, 2.8 mmol NaCl/kg BM per d), high (10 d, 7.7 mmol NaCl/kg BM per d), and low again (6 d, 0.7 mmol NaCl/kg BM per d) were tested. Urine osmolality, extracellular volume (ECV) and plasma volume (PV), cumulative metabolic Na, K, chloride and fluid balances, mRNA expression of two glycosaminoglycan (GAG) polymerisation genes, capillary blood pH, bicarbonate and base excess were measured. During average normal NaCl intake, 193 (SEM 19) mmol Na were retained and ECV (+2.02 (SEM 0.31) litres; P<0.001) and PV (+0.57 (SEM 0.13) litres; P<0.001) increased. During high NaCl intake, 244 (SEM 77) mmol Na were retained but ECV did not increase (ECV -0.54 (SEM 0.30) litres, P=0.+89; PV +0.27 (SEM 0.25) litres, P=0.283). mRNA expression of GAG polymerisation genes increased with rise in NaCl intake, while pH (P<0.01) and bicarbonate (P<0.001) levels decreased. We conclude that a high NaCl intake may increase GAG synthesis; this might play a role in osmotically inactive Na retention in humans.

Effect of change in intrathoracic pressure on thermoregulatory responses during -6 degree head-down bed rest.

We investigated the effect of change in intrathoracic pressure by total body negative pressure (TBNP) or positive pressure (TBPP) on thermoregulatory responses during -6 degree head-down bed rest (HDBR). Eight healthy male subjects participated to three of the following interventions in a randomised sequence: 1) HDBR, 2) HDBR with TBNP of -15 cmH2O, 3) HDBR with TBPP of +15 cmH2O. A rapid decrease of cutaneous blood flow occurred after the start of TBNP. In contrast, cutaneous blood flow increased slightly at TBPP. Sweat rate decreased immediately after the start of TBNP. Immediately after the TBPP was started, tympanic temperature greatly decreased. It is concluded that combination of HDBR and intrathoracic pressure changes thermoregulatory responses through the cardiopulmonary baroreceptor to reduce the wall stretch.

Influence of salt intake on renin-angiotensin and natriuretic peptide system genes in human adipose tissue.

We tested the hypothesis that changes in sodium intake modulate adipose-tissue renin-angiotensin and natriuretic peptide system gene expression in humans. We studied 9 healthy young men in a metabolic ward at constant room temperature, humidity, and water, potassium, and calcium intake. Subjects were submitted to 4 different periods of sodium intake, and blood samples, microdialysis samples (interstitial fluid), and biopsies from subcutaneous abdominal adipose tissue were obtained at the end of the low-sodium period (0.7 mmol Na/kg per day) and at the end of the high-sodium period (7.7 mmol Na/kg per day). Urinary sodium excretion was 64+/-4 mmol per day with the low-sodium diet and 521+/-8 mmol per day with the high-sodium diet. Systemic and microdialysate sodium concentrations were similar with both interventions. With high-sodium intake, systemic renin activity and aldosterone levels were suppressed, angiotensin-converting enzyme activity did not change, and systemic levels of the atrial natriuretic peptide increased. High-sodium diet increased angiotensin-converting enzyme and atrial natriuretic peptide gene expression in adipose tissue. None of the other genes tested were influenced by changes in dietary sodium intake. Our findings suggest that the adipose-tissue renin-angiotensin system is not part of a feedback mechanism regulating sodium homeostasis and blood pressure. Systemic and adipose-tissue renin-angiotensin systems are regulated at least in part independently from each other. In contrast, systemic atrial natriuretic peptide and adipose-tissue atrial natriuretic peptide respond similarly to changes in sodium intake.