Selected discoveries from human research in space that are relevant to human health on Earth.

A substantial amount of life-sciences research has been performed in space since the beginning of human spaceflight. Investigations into bone loss, for example, are well known; other areas, such as neurovestibular function, were expected to be problematic even before humans ventured into space. Much of this research has been applied research, with a primary goal of maintaining the health and performance of astronauts in space, as opposed to research to obtain fundamental understanding or to translate to medical care on Earth. Some people-scientists and concerned citizens-have questioned the broader scientific value of this research, with the claim that the only reason to perform human research in space is to keep humans healthy in space. Here, we present examples that demonstrate that, although this research was focused on applied goals for spaceflight participants, the results of these studies are of fundamental scientific and biomedical importance. We will focus on results from bone physiology, cardiovascular and pulmonary systems, and neurovestibular studies. In these cases, findings from spaceflight research have provided a foundation for enhancing healthcare terrestrially and have increased our knowledge of basic physiological processes.

Adaptation of the cardiovascular system to weightlessness: Surprises, paradoxes and implications for deep space missions.

Weightlessness in space induces a fluid shift from the dependent to the cephalad parts of the body leading to distension of the cardiac chambers and an accumulation of blood in the veins of the head and neck. Surprisingly, central venous pressure (CVP) during the initial hours of spaceflight decreases compared to being horizontal supine on the ground. The explanation is that the thorax is expanded by weightlessness leading to a decrease in inter-pleural pressure (IPP), which exceeds the measured decrease in CVP. Thus, transmural CVP (TCVP = CVP - IPP) is increased indicating an augmented cardiac preload. Simultaneously, stroke volume and cardiac output (CO) are increased by 18%-26% within the initial weeks and more so by 35%-56% during the subsequent months of flight relative to in the upright posture on the ground. Mean arterial pressure (MAP) is decreased indicating a lower systemic vascular resistance (MAP/CO). It is therefore a surprise that sympathetic nerve activity is not suppressed in space and thus cannot be a mechanism for the systemic vasodilation, which still needs to be explored. Recent observations indicate that the fluid shift during long duration (months) flights is associated with increased retinal thickness that sometimes leads to optical disc oedema. Ocular and cerebral structural changes, increases in left atrial size and decreased flows with thrombi formation in the left internal jugular vein have also been observed. This is of concern for future long duration deep space missions because the health implications are unknown.

Relationship between Sodium Intake and Water Intake: The False and the True.

BACKGROUND: Generally, eating salty food items increases thirst. Thirst is also stimulated by the experimental infusion of hypertonic saline. But, in steady state, does the kidney need a higher amount of water to excrete sodium on a high than on a low sodium intake? This issue is still controversial. The purpose of this review is to provide examples of how the kidney handles water in relation to salt intake/output. It is based on re-analysis of previously published studies in which salt intake was adjusted to several different levels in the same subjects, and in databases of epidemiologic studies in populations on an ad libitum diet. Summary and Key Messages: These re-analyses allow us to draw the following conclusions: (1) In a steady state situation, the urine volume (and thus the fluid intake) remains unchanged over a large range of sodium intakes. The adaptation to a higher sodium excretion rests only on changes in urinary sodium concentration. However, above a certain limit, this concentration cannot increase further and the urine volume may then increase. (2) In population studies, it is not legitimate to assume that sodium is responsible for changes in urine volume, since people who eat more sodium also eat more of other nutrients leading to an increase in the excretion of potassium, urea and other solutes, besides sodium. (3) After an abrupt increase in sodium intake, fluid intake is increased in the first few days, but urine volume does not change. The extra fluid drunk is responsible for an increase in body weight.

Hemodynamic responses to mental stress during salt loading.

PURPOSE: The purpose was to examine whether prolonged moderate stress associated with a student exam would increase the blood pressure response to a salt load in young healthy normotensive individuals. METHODS: Ten healthy young subjects were examined at two different occasions in random order (i) during preparation for a medical exam (prolonged stress) and (ii) outside the exam period (low stress). All subjects consumed a controlled diet for 3 days with low- or high-salt content in randomized order. The subjective stress was measured by Spielberger's State-Trait Anxiety Inventory-Scale, SCL Symptom Checklist for stress and the Visual Analogue Scale. On each level of stress, 24-h ambulatory blood pressure and cardiac output (CO) were measured. Furthermore, plasma norepinephrine (NE), epinephrine (E) and plasma renin activity (PRA) were measured. RESULTS: Twenty-four-hour ABP, 24-h heart rate, CO as well as plasma levels of NE, E and PRA remained unchanged by changes in stress level. Day-night reduction in SAP was significantly larger during moderate stress and high-salt intake; however, no significant difference was observed during daytime and night-time. Individual increase in mental stress correlated significantly with an individual decrease in PRA (SCL-17, r = -0·80, P<0·05, STAIr = -0·64 P<0·05) during high-salt intake. CONCLUSION: Moderate stress over a period of time in young healthy normotensive individuals does not lead to changes in 24-h ABP. However, the augmented reduction in day-to-night systolic blood pressure during high-salt intake and moderate stress may indicate that stress affects blood pressure regulation.

Body height and arterial pressure in seated and supine young males during +2 G centrifugation.

It is known that arterial pressure correlates positively with body height in males, and it has been suggested that this is due to the increasing vertical hydrostatic gradient from the heart to the carotid baroreceptors. Therefore, we tested the hypothesis that a higher gravito-inertial stress induced by the use of a human centrifuge would increase mean arterial pressure (MAP) more in tall than in short males in the seated position. In short (162-171 cm; n = 8) and tall (194-203 cm; n = 10) healthy males (18-41 yr), brachial arterial pressure, heart rate (HR), and cardiac output were measured during +2G centrifugation, while they were seated upright with the legs kept horizontal (+2Gz). In a separate experiment, the same measurements were done with the subjects supine (+2Gx). During +2Gz MAP increased in the short (22 ± 2 mmHg, P < 0.0001) and tall (23 ± 2 mmHg, P < 0.0001) males, with no significant difference between the groups. HR increased more (P < 0.05) in the tall than in the short group (14 ± 2 vs. 7 ± 2 bpm). Stroke volume (SV) decreased in the short group (26 ± 4 ml, P = 0.001) and more so in the tall group (39 ± 5 ml, P < 0.0001; short vs. tall, P = 0.047). During +2Gx, systolic arterial pressure increased (P < 0.001) and SV (P = 0.012) decreased in the tall group only. In conclusion, during +2Gz, MAP increased in both short and tall males, with no difference between the groups. However, in the tall group, HR increased more during +2Gz, which could be caused by a larger hydrostatic pressure gradient from heart to head, leading to greater inhibition of the carotid baroreceptors.

Fluid shifts, vasodilatation and ambulatory blood pressure reduction during long duration spaceflight.

KEY POINTS: Weightlessness in space induces initially an increase in stroke volume and cardiac output, accompanied by unchanged or slightly reduced blood pressure.It is unclear whether these changes persist throughout months of flight.Here, we show that cardiac output and stroke volume increase by 35­41% between 3 and 6 months on the International Space Station, which is more than during shorter flights.Twenty-four hour ambulatory brachial blood pressure is reduced by 8­10 mmHg by a decrease in systemic vascular resistance of 39%, which is not a result of the suppression of sympathetic nervous activity, and the nightly dip is maintained in space.It remains a challenge to explore what causes the systemic vasodilatation leading to a reduction in blood pressure in space, and whether the unexpectedly high stroke volume and cardiac output can explain some vision acuity problems encountered by astronauts on the International Space Station. ABSTRACT: Acute weightlessness in space induces a fluid shift leading to central volume expansion. Simultaneously, blood pressure is either unchanged or decreased slightly. Whether these effects persist for months in space is unclear. Twenty-four hour ambulatory brachial arterial pressures were automatically recorded at 1­2 h intervals with portable equipment in eight male astronauts: once before launch, once between 85 and 192 days in space on the International Space Station and, finally, once at least 2 months after flight. During the same 24 h, cardiac output (rebreathing method) was measured two to five times (on the ground seated), and venous blood was sampled once (also seated on the ground) for determination of plasma catecholamine concentrations. The 24 h average systolic, diastolic and mean arterial pressures (mean ± se) in space were reduced by 8 ± 2 mmHg (P = 0.01; ANOVA), 9 ± 2 mmHg (P < 0.001) and 10 ± 3 mmHg (P = 0.006), respectively. The nightly blood pressure dip of 8 ± 3 mmHg (P = 0.015) was maintained. Cardiac stroke volume and output increased by 35 ± 10% and 41 ± 9% (P < 0.001); heart rate and catecholamine concentrations were unchanged; and systemic vascular resistance was reduced by 39 ± 4% (P < 0.001). The increase in cardiac stroke volume and output is more than previously observed during short duration flights and might be a precipitator for some of the vision problems encountered by the astronauts. The spaceflight vasodilatation mechanism needs to be explored further.

Circulatory responses to lower body negative pressure in young Afghans and Danes: implications for understanding ethnic effects on blood pressure regulation.

PURPOSE: We have previously shown that Afghans residing in Denmark for at least 12 years exhibit a lower 24-h ambulatory blood pressure compared to Danes. The purpose of this study was to test the hypothesis that the lower blood pressure reflects attenuated compensatory baroreflex responses in the Afghans. METHODS: On a controlled diet (2,822 cal/day, 55-75 mmol + 2 mmol Na+/kg/day), 12 young males of Afghan (Afghans) and 12 young males of Danish (Danes) origin were exposed to a two-step lower body negative pressure (LBNP) protocol of -20 and -50 mmHg, respectively, each of 10-min duration. RESULTS: Afghans had lower 24-h systolic blood pressure compared to Danes (115 ± 2 vs. 123 ± 1 mmHg, p < 0.05). Cardiac output and stroke volume were significantly lower in Afghans compared to Danes prior to and during each level of LBNP. However, it decreased to the same extent in both groups during LBNP. During LBNP of -20 mmHg, plasma noradrenaline concentration and plasma renin activity (PRA) increased significantly only in the Afghans. At LBNP of -50 mmHg plasma noradrenaline concentration and PRA both increased significantly and similarly in the two groups. CONCLUSION: The lower 24-h ambulatory blood pressure in the Afghans is probably caused by a lower stroke volume, which augmented the circulatory and vasoactive hormonal responses to LBNP in the Afghans. The lower stroke volume in Afghans residing in Denmark compared to that of matched native Danes remains to be explained.

Blood pressure regulation IV: adaptive responses to weightlessness.

During weightlessness, blood and fluids are immediately shifted from the lower to the upper body segments, and within the initial 2 weeks of spaceflight, brachial diastolic arterial pressure is reduced by 5 mmHg and even more so by some 10 mmHg from the first to the sixth month of flight. Blood pressure thus adapts in space to a level very similar to that of being supine on the ground. At the same time, stroke volume and cardiac output are increased and systemic vascular resistance decreased, whereas sympathetic nerve activity is kept surprisingly high and similar to when ground-based upright seated. This was not predicted from simulation models and indicates that dilatation of the arteriolar resistance vessels is caused by mechanisms other than a baroreflex-induced decrease in sympathetic nervous activity. Results of baroreflex studies in space indicate that compared to being ground-based supine, the carotid (vagal)-cardiac interaction is reduced and sympathetic nerve activity, heart rate and systemic vascular resistance response more pronounced during baroreflex inhibition by lower body negative pressure. The future challenge is to identify which spaceflight mechanism induces peripheral arteriolar dilatation, which could explain the decrease in blood pressure, the high sympathetic nerve activity and associated cardiovascular changes. It is also a challenge to determine the cardiovascular risk profile of astronauts during future long-duration deep space missions.

Blood pressure in Afghan male immigrants to Denmark.

PURPOSE: Immigration from a Third-World society to a Western society can be associated with higher blood pressure and salt sensitivity. We therefore tested whether immigrants from Afghanistan to Denmark compared with non-immigrant Danes exhibit a (i) higher 24-h ambulatory blood pressure (24-h ABP) and (ii) blunted renin response to a change in salt intake. METHODS: Twenty-four-hour ABP was measured in 40 men of Afghan (Afghans) and 40 men of Danish (Danes) origin. Each group was divided into young (20-30 years, n = 20) and middle aged (40-60 years, n = 20). A 3-day low (70 mmol per 24-h) and a 3-day high (250 mmol per 24-h) salt intake were in addition instituted in subgroups of the young groups (n = 18). RESULTS: Young and middle-aged Afghans exhibited a lower 24-h mean arterial pressure (24-h MAP) than the same respective age groups of Danes (83 ± 1 versus 90 ± 1 mm Hg, P<0·05, and 89 ± 2 versus 100 ± 1 mm Hg, P<0·05). 24-h ABP did not change in any of the young groups during increased salt intake, whereas the Danes exhibited a greater decrease in plasma renin activity (PRA) (P<0·05). Plasma noradrenaline (PNA ) was significantly higher among the young Afghans. CONCLUSIONS: Afghan immigrants to Denmark exhibit a lower 24-h ABP than Danes. In young Afghans, PRA is less sensitive to changes in salt intake, while PNA is higher and may reflect their lower systolic blood pressure and/or arterial pulse pressure. Whether these hormonal differences can explain the lower 24-h ABP in Afghans should be further explored.

Mechanisms and management of exercise-induced asthma in elite athletes.

OBJECTIVE AND METHODS: Asthma is often reported by elite athletes, especially endurance athletes. The aim of this article is to review current knowledge of mechanisms and management of exercise-induced asthma (EIA) in adult elite athletes. RESULTS: The mechanisms underlying EIA is incompletely understood, but the two prevailing hypotheses are the hyper-osmolarity and the thermal hypothesis. Both hypotheses consider inflammation and activation of mast cells as being crucial for the development of EIA, although the assumed mechanisms triggering the inflammatory response differ. Objective testing is of utmost importance in the diagnosis of EIA in elite athletes. Management of EIA can be divided into pharmacologic and non-pharmacologic treatment. The basic principles for the treatment of EIA in elite athletes should be as for any asthmatic individual, including use of inhaled corticosteroids (ICS), ß(2)-agonists, and leukotriene antagonists. However, evidence suggests that daily use of ß(2)-agonists might lead to the development of tolerance. ICS therapy is, due to its anti-inflammatory effects, the recommended primary therapy for EIA also in elite athletes. All doctors treating individuals with asthma, especially elite athletes, should remain updated on doping aspects of asthma therapy. Non-pharmacologic management of EIA in elite athletes includes physical warm-up, which takes advantage of the refractory period following an attack of EIA, whereas high intake of antioxidants may reduce airway inflammation. Wearing heat masks, specially designed for outdoor winter athletes, might protect against bronchoconstriction triggered by inhalation of cold and dry air. CONCLUSION: EIA in elite athletes should be managed as in any individual with asthma, but the risk of developing tolerance to bronchodilators as well as doping aspects should always be taken into account.

Body height and blood pressure regulation in humans during anti-orthostatic tilting.

The hypothesis was tested that the cardiovascular changes during an upper body anti-orthostatic maneuver in humans are more pronounced in tall than in short individuals, because of the larger intravascular hydrostatic pressure gradients. In 34 males and 41 females [20-30 yr, body height (BH) = 147-206 cm], inter-individual multiple linear regression analyses adjusted for gender and body weight were conducted between changes in cardiovascular variables versus BH during tilting of the upper body from vertical to horizontal while keeping the legs horizontal. In all the subjects, tilting induced increases in stroke volume and arterial pulse pressure and a decrease in heart rate, which each correlated significantly with BH. In males (n = 51, BH = 163-206 cm), 24-h ambulatory mean arterial pressure increased significantly with BH (P = 0.004, r = 0.40, α = 0.15 mmHg/cm) so that systolic/diastolic blood pressure increased by 2/2 mmHg per 15 cm increase in BH. There was no significant correlation between mean arterial pressure and BH in females (n = 53, BH = 147-193 cm). In conclusion, a larger BH induces larger cardiovascular changes during anti-orthostatic tilting, and in males 24-h ambulatory mean arterial pressure increases with BH. The lack of a mean arterial pressure to BH correlation in females is probably because of their lower BH and greater variability in blood pressure.

Mechanisms of increase in cardiac output during acute weightlessness in humans.

Based on previous water immersion results, we tested the hypothesis that the acute 0-G-induced increase in cardiac output (CO) is primarily caused by redistribution of blood from the vasculature above the legs to the cardiopulmonary circulation. In seated subjects (n = 8), 20 s of 0 G induced by parabolic flight increased CO by 1.7 ± 0.4 l/min (P < 0.001). This increase was diminished to 0.8 ± 0.4 l/min (P = 0.028), when venous return from the legs was prevented by bilateral venous thigh-cuff inflation (CI) of 60 mmHg. Because the increase in stroke volume during 0 G was unaffected by CI, the lesser increase in CO during 0 G + CI was entirely caused by a lower heart rate (HR). Thus blood from vascular beds above the legs in seated subjects can alone account for some 50% of the increase in CO during acute 0 G. The remaining increase in CO is caused by a higher HR, of which the origin of blood is unresolved. In supine subjects, CO increased from 7.1 ± 0.7 to 7.9 ± 0.8 l/min (P = 0.037) when entering 0 G, which was solely caused by an increase in HR, because stroke volume was unaffected. In conclusion, blood originating from vascular beds above the legs can alone account for one-half of the increase in CO during acute 0 G in seated humans. A Bainbridge-like reflex could be the mechanism for the HR-induced increase in CO during 0 G in particular in supine subjects.

Impact of diuretic treatment and sodium intake on plasma volume in patients with compensated systolic heart failure.

AIMS: In patients with heart failure (HF), the use of diuretics may be a double-edged sword that can alleviate symptoms of congestion, but also result in over-diuresis and intravascular volume depletion. The purpose of the present study was to examine plasma volume (PV) in HF patients receiving from 0 to 160 mg of furosemide and to investigate whether determination of plasma N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) concentrations can predict PV-status. METHODS AND RESULTS: Plasma volume, extracellular volume, glomerular filtration rate, NT-proBNP, and daily renal sodium excretion were measured in 18 patients with medically treated, compensated HF and in 27 healthy volunteers. Cardiac function was examined by non-invasive cardiac output determination and echocardiography. Exercise capacity was evaluated by 6 min walk test. There was a borderline significant difference in PV between patients with HF and control subjects (37.3 +/- 6.0 and 40.2 +/- 5.8 mL/kg, respectively, P = 0.092) with a significant tendency towards a contraction of PV with increasing use of diuretics (P = 0.031). There was no difference in extracellular volume between patients with HF and control subjects (P = 0.844). NT-proBNP plasma concentrations had no correlation to either sodium excretion (P = 0.193) or PV (P = 0.471) in patients with HF. CONCLUSION: Plasma volume in patients with HF was within normal limits, but patients treated with high doses of loop-diuretics tended to have subnormal PV. Single measurement of NT-proBNP plasma concentration could not be used to estimate intravascular volume status in patients with HF.

Estimating changes in cardiac output using an implanted hemodynamic monitor in heart failure patients.

OBJECTIVES: The aim of this study was to evaluate an algorithm that estimates changes in cardiac output (CO) from right ventricular (RV) pressure waveforms derived from an implantable hemodynamic monitor (IHM) in heart failure patients. DESIGN: Twelve heart failure patients (NYHA II-III, EF 32%) with an implantable hemodynamic monitor (Chronicle) were included in this study. Changes in cardiac output were provoked by body position change at rest (left lateral supine, horizontal supine, sitting, and standing) and a steady state bicycle exercise at 20 watts. Estimated CO derived from the IHM (CO(IHM)) was compared to CO measured with inert gas rebreathing (CO(RB)), echocardiography (CO(ECHO)) and impedance cardiography (CO(ICG)). CO(RB) was considered the reference method. RESULTS: The median intra-patient correlation coefficient comparing CO(RB) and CO(IHM) was 0.83 (range: 0.63-0.98). Comparing CO(RB) with CO(ECHO) and CO(ICG) resulted in mean intra-patient correlation coefficients of 0.73 (-0.29-0.94) and 0.63 (-0.29-0.96). In a statistical model where slope and intercept was considered random between patients the coefficient of determination (R2) comparing CO(RB) and CO(IHM) was 0.91. Mean bias was -0.39 L/min (11%). Limits of agreement were +/-1.56 L/min and relative error was 21%. CONCLUSIONS: A simple algorithm based on RV pressure wave form characteristics derived from an IHM can be used to estimate changes in CO in heart failure patients. These findings encourage further research aiming to improve and validate the algorithm.

The paradox of systemic vasodilatation and sympathetic nervous stimulation in space.

Cardiac output is increased by some 18% by weightlessness during the initial week of spaceflight compared to upright standing or sitting on the ground and more so during the initial days of flight than at the end. In addition, mean 24-h diastolic, but not systolic pressure, is significantly decreased by 5mmHg. This is in accordance with observations that very acute weightlessness during parabolic airplane flights and a week of weightlessness in space leads to a decrease in systemic vascular resistance. That the arterial resistance vessels are dilated in space is in contrast to the augmented sympathetic nervous activity and decreased urine production, which have consistently been observed in astronauts in space. These contrasting observations require further investigation.

Cardiac output response to changes of the atrioventricular delay in different body positions and during exercise in patients receiving cardiac resynchronization therapy.

AIMS: The aim of this study was to study the haemodynamic effect of atrioventricular delay (AVD) modifications within a narrow range in different body positions and during exercise in patients receiving cardiac resynchronization therapy (CRT). METHODS: The previously optimized AVD was shortened and prolonged by 40 ms in 27 CRT patients and 9 controls without heart failure. Cardiac output (CO) was measured by inert gas rebreathing (Innocor) as the average over different body positions (left-lateral, supine, sitting, standing, and exercise). In eight CRT patients with an implantable haemodynamic monitor, the estimated pulmonary artery diastolic pressure (ePAD) was analysed. RESULTS: The magnitude of CO response to AVD changes was greater in CRT patients than in controls (0.25 vs. 0.20 L/min, P<0.05), varied substantially between individuals (range: 0.12-0.56 L/min), and correlated with left atrial size (r=0.61, P<0.001). On average, AVD shortening decreased CO slightly (0.07+/-0.17 L/min) and increased ePAD (1.1+/-0.8 mmHg, both P<0.05), whereas prolongation had no significant effect. CONCLUSION: The haemodynamic response to AVD modifications within a narrow range is larger in CRT patients than in normal controls and varies substantially between individuals. These findings suggest that optimal AVD tuning is clinically important in selected patients.

ESSC-ESF position paper--science-driven scenario for space exploration: report from the European Space Sciences Committee (ESSC).

In 2005 the then ESA Directorate for Human Spaceflight, Microgravity and Exploration (D-HME) commissioned a study from the European Science Foundation's (ESF) European Space Sciences Committee (ESSC) to examine the science aspects of the Aurora Programme in preparation for the December 2005 Ministerial Conference of ESA Member States, held in Berlin. A first interim report was presented to ESA at the second stakeholders meeting on 30 and 31 May 2005. A second draft report was made available at the time of the final science stakeholders meeting on 16 September 2005 in order for ESA to use its recommendations to prepare the Executive proposal to the Ministerial Conference. The final ESSC report on that activity came a few months after the Ministerial Conference (June 2006) and attempted to capture some elements of the new situation after Berlin, and in the context of the reduction in NASA's budget that was taking place at that time; e.g., the postponement sine die of the Mars Sample Return mission. At the time of this study, ESSC made it clear to ESA that the timeline imposed prior to the Berlin Conference had not allowed for a proper consultation of the relevant science community and that this should be corrected in the near future. In response to that recommendation, ESSC was asked again in the summer of 2006 to initiate a broad consultation to define a science-driven scenario for the Aurora Programme. This exercise ran between October 2006 and May 2007. ESA provided the funding for staff support, publication costs, and costs related to meetings of a Steering Group, two meetings of a larger ad hoc group (7 and 8 December 2006 and 8 February 2007), and a final scientific workshop on 15 and 16 May 2007 in Athens. As a result of these meetings a draft report was produced and examined by the Ad Hoc Group. Following their endorsement of the report and its approval by the plenary meeting of the ESSC, the draft report was externally refereed, as is now normal practice with all ESSC-ESF reports, and amended accordingly. The Ad Hoc Group defined overarching scientific goals for Europe's exploration programme, dubbed "Emergence and co-evolution of life with its planetary environments," focusing on those targets that can ultimately be reached by humans, i.e., Mars, the Moon, and Near Earth Objects. Mars was further recognized as the focus of that programme, with Mars sample return as the recognized primary goal; furthermore the report clearly states that Europe should position itself as a major actor in defining and leading Mars sample return missions. The report is reproduced in this article. On 26 November 2008 the Ministers of ESA Member States decided to give a high strategic priority to the robotic exploration programme of Mars by funding the enhanced ExoMars mission component, in line therefore with the recommendations from this ESSC-ESF report.

Altered sodium intake affects plasma concentrations of BNP but not proBNP in healthy individuals and patients with compensated heart failure.

AIMS: Plasma B-type natriuretic peptide (BNP) and proBNP are promising markers for treatment of heart failure (HF), but the intra-individual biological variation is high. We investigated whether changes in sodium intake and posture contribute to this variation. METHODS AND RESULTS: A total of 12 healthy individuals and 12 patients with medically treated compensated HF were examined after 1 week of low (70 mmol [1.61 g] per day) and 1 week of high (250 mmol [5.75 g] per day) sodium intake. Plasma volume and plasma concentrations of BNP and proBNP were determined after 1 h in seated and 1 h in supine position. In healthy individuals, the plasma BNP concentration increased significantly on high sodium intake with a ratio (high sodium/low sodium) of 2.00 (1.32-3.03, P = 0.004). The corresponding values for HF patients were 1.69 (1.25-2.29, P = 0.003). The plasma BNP concentration changed modestly by a posture change, with a plasma BNP ratio (supine/seated) of 1.15 (1.07-1.14, P = 0.001) and 1.06 (0.99-1.24, P = 0.088) in healthy subjects and HF patients, respectively. Plasma proBNP concentrations were neither significantly affected by posture nor by sodium intake. CONCLUSION: Sodium intake has a considerable effect on plasma BNP and therefore contributes to the intra-individual variability. We suggest dietary sodium intake to be standardized at least 3 days prior to blood sampling for the determination of plasma BNP.

Effect of spaceflight on the subcutaneous venoarteriolar reflex in the human lower leg.

Whenever the legs are lowered in humans, a venoarteriolar reflex is activated by the hydrostatic distension of the venules. Through local axon reflexes, the adjacent arterioles are contracted to decrease blood flow and prevent formation of edema. Because the venoarteriolar reflex is activated by gravity, we tested the hypothesis that long-term weightlessness would attenuate it. The reduction in subcutaneous blood flow was measured by the (133)Xe washout technique just proximal to the ankle joint in dependent lower legs of eight supine astronauts, where the knee joint was passively bent by 90 degrees . The measurements were conducted before spaceflight and 3-6 h on landing following 4-6.5 mo in space. Activation of the venoarteriolar reflex reduced subcutaneous blood flow by 37 +/- 9% (P = 0.016) before flight and by 64 +/- 8% (P < 0.001) following landing with no statistical significant difference between the two reductions (P = 0.062). Therefore, our results show that the venoarteriolar reflex is not attenuated by weightlessness and therefore does not need the everyday stimulus of gravity to maintain efficiency.