Increased core body temperature in astronauts during long-duration space missions.

Humans' core body temperature (CBT) is strictly controlled within a narrow range. Various studies dealt with the impact of physical activity, clothing, and environmental factors on CBT regulation under terrestrial conditions. However, the effects of weightlessness on human thermoregulation are not well understood. Specifically, studies, investigating the effects of long-duration spaceflight on CBT at rest and during exercise are clearly lacking. We here show that during exercise CBT rises higher and faster in space than on Earth. Moreover, we observed for the first time a sustained increased astronauts' CBT also under resting conditions. This increase of about 1 °C developed gradually over 2.5 months and was associated with augmented concentrations of interleukin-1 receptor antagonist, a key anti-inflammatory protein. Since even minor increases in CBT can impair physical and cognitive performance, both findings have a considerable impact on astronauts' health and well-being during future long-term spaceflights. Moreover, our findings also pinpoint crucial physiological challenges for spacefaring civilizations, and raise questions about the assumption of a thermoregulatory set point in humans, and our evolutionary ability to adapt to climate changes on Earth.

Erythropoietin as a volume-regulating hormone: an integrated view.

The intravascular volume consists of 40% to 45% red cells. Their production is controlled predominantly by erythropoietin (EPO), a hormone that is secreted particularly when tissue hypoxia is present. Because of this high percentage of the total intravascular volume the question comes to mind that, in addition to hypoxia, can volume-regulation mechanisms, known to be responsible for the maintenance of plasma volume, modulate EPO secretion when the total vascular volume changes? Indeed, there is evidence that in situations in which the intravascular volume or specifically the intrathoracic volume is altered, EPO secretion is affected. EPO secretion increases when the intrathoracic volume decreases 24 hours after water immersion or after endurance exercise when a negative water balance prevails. A head-down tilt on the other side induces central engorgement leading to a decrease of EPO concentrations. Under these experimental conditions no hypoxia was seen, supporting the idea that a volume stimulus outgoing from intrathoracic parts of the circulation modulated EPO secretion. Further observations from the clinical side are needed to support these ideas and the consequences need to be implemented into clinical practice.

Anemia and erythropoietin in space flights.

Since the very early manned missions in space, a state of anemia associated with reduced erythropoietin levels and reduced plasma volume was disclosed. The reduction in red blood cell mass is driven by a process of selective hemolysis, which has been named neocytolysis. This phenomenon also occurs in people living at a high altitude who descend rapidly to sea level. The origin of the signal leading to destruction of newly produced red blood cells probably is located in central circulation, but the operating mechanism is unknown. The importance of plasma cell volume reduction in the genesis of a lower red cell mass also is supported by the inverse correlation seen at moderate altitude. People arriving at moderate altitude have increased erythropoietin concentration that decreases after a few days and is in inverse correlation with central venous pressure. Studies under simulated microgravity conditions in human beings (bed rest, head-down tilt at -6 degrees , water immersion) and in rats provide further insight in unraveling the mechanism of astronauts' anemia, a problem difficult to study in space because of the limited availability of spaceflights.

Differential expression of nitric oxide synthases (NOS 1-3) in human skeletal muscle following exercise countermeasure during 12 weeks of bed rest.

Adaptive changes of major body systems in astronauts during spaceflight can be simulated by strict anti-orthostatic head-down tilt (HDT) bed rest (BR), a ground-based microgravity (microG) model that provides a meaningful opportunity to study atrophy mechanisms and possible countermeasures under controlled experimental conditions. As nitric oxide (NO) signaling is linked to muscle activity, we investigated altered expression of the three major isoforms of nitric oxide synthase (NOS 1-3) at cellular compartments during prolonged HDT BR without (control group) and with resistance exercise interventions (exercise group) using a flywheel ergometer (FWE). Atrophy detected in mixed (fast-slow) m. vastus lateralis (VL) and slow-type m. soleus (SOL) myofiber Types I and II (minus 35-40% of myofiber cross-sectional area) was prevented by FWE training. Concomitant to muscle atrophy, reduced NOS 1 protein and immunostaining was found in VL not in SOL biopsies. In trained VL, NOS 1 protein and immunostaining at myofibers II were significantly increased at the end of BR. Exercise altered NOS 2/caveolin 3 co-immunostaining patterns of subsarcolemmal focal accumulations in VL or SOL myofibers, which suggests reorganization of sarcolemmal microdomains. In trained VL, increased capillary-to-fiber (C/F) ratio and NOS 3 protein content were documented. Activity-linked NO signaling may be widespread in skeletal muscle cellular compartments that may be directly or indirectly impacted by adequate exercise countermeasure protocols to offset the negative effects induced by disuse, immobilization, or extended exposure to microgravity.

Ketamine in outpatient arthroscopic shoulder surgery: Effects on postoperative pain, hemodynamic stability and process times.

BACKGROUND: Pain after arthroscopic shoulder surgery is often severe, and establishing a pain treatment regimen that does not delay discharge can be challenging. The reported ability of ketamine to prevent opioid-induced hyperalgesia has not been investigated in this particular setting. METHODS: 300 adult patients scheduled for shoulder arthroscopy under general anesthesia were recruited for this observational clinical trial and were allotted to either receive 1mg/kg IV bolus of ketamine before surgery (ketamine group, KG) or to a control group (CG) without ketamine. NRS pain scores were obtained on the operative day and on postoperative days 1 and 2 and compared between groups. Secondary variables were blood pressure, heart rate, process times, satisfaction with the anesthetic and unwanted effects. RESULTS: Pain severity did not differ significantly between the groups at any time. Propofol injection rate and cumulative dose were higher in the KG. Heart rates and blood pressures were similar. Time to emergence and time in PACU were longer and vomiting was more frequent in patients given ketamine. CONCLUSION: Preoperative low-dose ketamine added to a general anesthetic does not reduce perioperative pain after outpatient shoulder arthroscopy. It increases procedural times and the incidence of PONV.

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.

Hypertension, sodium retention, calcium excretion and osteopenia in Dahl rats.

BACKGROUND: Salt-sensitive hypertension in the Dahl rat is associated with abnormalities in both calcium (Ca2+) and sodium (Na) homeostasis. OBJECTIVE: To test the hypothesis that salt-induced abnormal Ca(2+) handling in Dahl salt-sensitive (DSS) rats is associated with negative Ca(2+) balance and bone disease. METHODS: Ca(2+) excretion in acute and chronic Na(+) loading and electrolyte and water balance were determined by balance studies in Dahl salt-resistant (DSR) and salt-sensitive (DSS) rats fed 8 or 0.1% NaCl for 4 weeks. A dry ashing procedure was used to determine Na(+), Ca(2+), and water content and their association with blood pressure in the rats. RESULTS: When fed 8% NaCl, DSS rats initially maintained a positive Ca(2+) balance and showed decreased natriuresis compared with DSR rats. During the course of Na(+) loading, DSS rats increased natriuresis and calciuresis. After 4 weeks of salt loading, cumulative Na balance was greater and cumulative Ca(2+) balance was less in DSS than in DSR rats. In addition, DSS rats developed osteopenia. Bone mineral content correlated inversely with blood pressure in DSS rats. Acute saline volume expansion in DSS rats demonstrated their ability to excrete the Na load fully, but led to an exaggerated renal loss of Ca(2+) compared with DSR rats. CONCLUSION: DSS, but not DSR, develop Ca(2+) loss and ostopenia during chronic Na(+) loading. We speculate that Na retention in DSS rats fed a high Na diet may be in part a compensatory mechanism to maintain Ca(2+) balance.

Long-term sodium balance in humans in a terrestrial space station simulation study.

BACKGROUND: Sodium accumulation has been considered to take place in the extracellular space, leading to water retention and weight gain. This traditional view has been questioned by recent studies that showed sodium accumulation in humans without expansion of the extracellular volume. We investigated sodium balance and its impact on body weight (BW) during a long-term balance study. METHODS: Three healthy subjects were confined to a terrestrial MIR simulator for 135 days under conditions simulating a long-term spaceflight. During the entire isolation period, we meticulously measured daily sodium balance and its contribution to BW. RESULTS: During the study period, subjects accumulated between 2,973 and 7,324 mmol of sodium and gained between 5.1 and 9.3 kg in weight. In all subjects, there was a positive correlation between changes in total-body sodium (DeltaTBS) content and BW, reflecting sodium-associated volume expansion. However, toward the end of isolation, sodium gain exceeded weight gain, suggesting that sodium accumulated in an osmotically inactive form. Especially at the onset of the experiment, two subjects showed inverse correlations between DeltaTBS and BW. CONCLUSION: The finding of sodium gain without weight gain is in contradiction to the widely accepted theory that changes in TBS levels are accompanied by changes in extracellular volume. We suggest the existence of a sodium reservoir with the ability to store significant amounts of sodium in an osmotically inactive form. This reservoir might be located in bone, dense connective tissue, or cartilage.

Formation of edema and fluid shifts during a long-haul flight.

BACKGROUND: More than 1.5 billion passengers travel by aircraft every year. Leg edema, as a sign of venous stasis, is a well-known problem among passengers during and after long-haul flights. Until now, no studies have been done on the development of leg edema and fluid shifts under real flight conditions. The aim of our study was to evaluate edema formation in the leg and to investigate possible fluid shifts to the interstitial space under real flight conditions. METHODS: Twenty participants, 10 without risk and 10 with moderate risk for venous thrombosis, were selected. They flew from Vienna to Washington, flight time 9 h, and returned 2 days later. Investigations were done 48 h before the flight, between the fifth and eighth flight hour on board to Washington and back to Vienna, immediately after arrival in Vienna, and 1 and 3 days after arrival. Plethysmographic measurements were carried out using an optoelectronic scanner system (Perometer). Thickness of the skin was measured at the forehead and in front of the tibia. RESULTS: There were no differences in all measurements between both groups. The volume of the leg increased from 8242 +/- 1420 mL to 8496 +/- 1474 mL after the flight (p <.001). Volume accumulation was distributed to the lower leg as well as to the thigh. Skin thickness in front of the tibia increased significantly during the flight (p <.05), and remained elevated 1 day after arrival. CONCLUSION: We have demonstrated that long-haul flights induce significant fluid accumulation in the lower extremity, involving the lower leg and thigh. This increase in tissue thickness was maintained for some days after the flights.

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.

Body mass estimations for Plateosaurus engelhardti using laser scanning and 3D reconstruction methods.

Both body mass and surface area are factors determining the essence of any living organism. This should also hold true for an extinct organism such as a dinosaur. The present report discusses the use of a new 3D laser scanner method to establish body masses and surface areas of an Asian elephant (Zoological Museum of Copenhagen, Denmark) and of Plateosaurus engelhardti, a prosauropod from the Upper Triassic, exhibited at the Paleontological Museum in Tübingen (Germany). This method was used to study the effect that slight changes in body shape had on body mass for P. engelhardti. It was established that body volumes varied between 0.79 m(3) (slim version) and 1.14 m(3) (robust version), resulting in a presumable body mass of 630 and 912 kg, respectively. The total body surface areas ranged between 8.8 and 10.2 m(2), of which, in both reconstructions of P. engelhardti, approximately 33% account for the thorax area alone. The main difference between the two models is in the tail and hind limb reconstruction. The tail of the slim version has a surface area of 1.98 m(2), whereas that of the robust version has a surface area of 2.73 m(2). The body volumes calculated for the slim version were as follows: head 0.006 m(3), neck 0.016 m(3), fore limbs 0.020 m(3), hind limbs 0.08 m(3), thoracic cavity 0.533 m(3), and tail 0.136 m(3). For the robust model, the following volumes were established: 0.01 m(3) head, neck 0.026 m(3), fore limbs 0.025 m(3), hind limbs 0.18 m(3), thoracic cavity 0.616 m(3), and finally, tail 0.28 m(3). Based on these body volumes, scaling equations were used to assess the size that the organs of this extinct dinosaur have.

Voice monitoring to measure emotional load during short-term stress.

It is well known that there is a relationship between the voice the human emotional status. Previous studies have demonstrated that changes of fundamental frequency ( f(0)), in particular, have a significant relationship with emotional load. The aim of the present study was to investigate how f(0) changes in response to an unknown emotionally stressful task under real-life conditions. A further question was whether repetitions of this task lead to an adaptation of f(0), indicating a lower emotional load. The participants of this study included 26 healthy males. f(0) and heart rate ( f(c)) were recorded for baseline testing (BLT) under relaxed laboratory conditions. Then the participants were asked to negotiate a natural obstacle by way of sliding down a rope hanging from a handlebar without any safety provisions, thus being exposed to the danger of a fall from a height of up to 12 m into shallow water (guerrilla slide I, GSI). The task was repeated after 30 min (GSII) and after 3 days of physical strain (GSIII). Immediately before starting the task the participants were asked to give a standardised speech sample, during which f(c) was recorded. The mode value of f(0) ( f(0,mode)) of the speech samples was used for further analysis. The mean (SD) value of f(0,mode) at BLT was 114.9 (14.8) Hz; this increased to 138.8 (19.6) Hz at GSI ( P<0.000), decreased to 135.9 (19.6) Hz at GSII and to 130.0 (21.5) Hz at GSIII ( P=0.012). The increase in f(c) was significantly different from BLT to GSI ( P<0.000). The repetitions of the task did not produce significant changes in f(c). It was shown that f(0,mode) is a sensitive parameter to describe changes in emotional load, at least in response to short-term psychoemotional stress, and seems to throw light upon the amount of adaptation caused by increased experience.

Reduced osmotically inactive Na storage capacity and hypertension in the Dahl model.

Recent evidence suggested that Na can be stored in an osmotically inactive form. We investigated whether osmotically inactive Na storage is reduced in a rat model of salt-sensitive (SS) hypertension. SS and salt-resistant (SR) Dahl-Rapp rats as well as Sprague-Dawley (SD) rats were fed a high (8%)- or low (0.1%)-NaCl diet for 4 wk (n = 10/group). Mean arterial pressure (MAP) was measured at the end of the experiment. Wet and dry weights, water content, total body Na (TBS), and bone Na content were measured by dessication and dry ashing. MAP was higher in both Dahl strains than in SD rats. In SS rats, 8% NaCl led to Na accumulation, water retention, and hypertension due to impaired renal Na excretion. There was no dietary-induced Na retention in SR and SD rats. TBS was variable; nevertheless, TBS was significantly correlated with body water and MAP in all strains. However, the extent of Na-associated volume and MAP increases was strain specific. Osmotically inactive Na in SD rats was threefold higher than in SS and SR rats. Both SS and SR Dahl rat strains displayed reduced osmotically inactive Na storage capacity compared with SD controls. A predisposition to fluid accumulation and high blood pressure results from this alteration. Additional factors, including impaired renal Na excretion, probably contribute to hypertension in SS rats. Our results draw attention to the role of osmotically inactive Na storage.

Osmotically inactive skin Na+ storage in rats.

Compared with age-matched men, women are resistant to the hypertensive effects of dietary NaCl; however, after menopause, the incidence of salt-sensitive hypertension is similar in women and men. We recently suggested that osmotically inactive Na+ storage contributes to the development of salt-sensitive hypertension. The connective tissues, including those immediately below the skin that may serve as a reservoir for osmotically inactive Na+ storage, are affected by menopause. We tested the hypothesis that ovariectomy (OVX) might reduce osmotically inactive Na+ storage capacity in the body, particularly in the skin. Male, female-fertile, and female OVX Sprague-Dawley (SD) rats were fed a high (8%)- or low (0.1%)-NaCl diet. The groups received the diet for 4 or 8 wk. At the end of the experiment, subgroups received 0.9% saline infusion and urinary Na+ and K+ excretion was measured. Wet and dry weight (DW), water content in the body and skin, total body Na+ (rTBNa+) and skin Na+ (rSKNa+) content were measured relative to DW by desiccation and dry ashing. There were no gender differences in osmotically inactive Na+ storage in SD rats. All SD rats accumulated Na+ if fed 8% NaCl, but rTBNa+ was lower in OVX rats than in fertile rats on a low (P < 0.001)- and a high (P < 0.05)-salt diet. OVX decreased rSKNa+ (P < 0.01) in the rats. A high-salt diet led to Na+ accumulation (DeltaSKNa+) in the skin in all SD rats. Osmotically inactive skin Na+ accumulation was approximately 66% of DeltaSKNa+ in female and 82% in male-fertile rats, but there was no osmotically inactive Na+ accumulation in OVX rats fed 8% NaCl. We conclude that skin is an osmotically inactive Na+ reservoir that accumulates Na+ when dietary NaCl is excessive. OVX leads to an acquired reduction of osmotically inactive Na+ storage in SD rats that predisposes the rats to volume excess despite a reduced Na+ content relative to body weight.

Austrian Moderate Altitude Study (AMAS 2000) - fluid shifts, erythropoiesis, and angiogenesis in patients with metabolic syndrome at moderate altitude (congruent with 1700 m).

It was hypothesized that subjects with metabolic syndrome (hypertension, obesity, hyperlipidemia, diabetes mellitus): (1) develop measurable peripheral edema at moderate altitude and (2) might show differences on erythropoiesis, iron status and vascular endothelial growth factor (VEGF) in comparison to healthy subjects during and after a long-term stay (3-week exposure) at moderate altitude (congruent with 1700 m). Twenty-two male subjects with metabolic syndrome were selected. Baseline investigations (t1) were performed in Innsbruck (500 m). All participants were transferred by bus to 1700 m (Alps) and remained there for 3 weeks with examinations on day 1 (after the first night at altitude, t2), day 4 (t3), day 9 (t4) and day 19 (t5). After returning to Innsbruck, post-altitude examinations were conducted after 7-10 days (t6) and 6-7 weeks (t7), respectively. Body mass was decreased from t1 to t7 (P<0.01). Total body water was decreased at t2 (P<0.01), returned to control level (t3, t4), and was found elevated at t7 (P<0.01). Lean body mass did not change, but body fat decreased during the study (P<0.01). Tissue thickness at the forehead decreased during and after altitude exposure (P<0.01), whereas tissue thickness at the tibia did not alter. Erythropoietin (EPO) was elevated as early as t2 and remained increased until t5. Reticulocyte count was increased at t3 and remained above pre-altitude values. VEGF levels were unchanged. After a 3-week exposure to moderate altitude, patients with metabolic syndrome had reduced their body mass, mainly because of a reduction in body fat. The moderate altitude was found to stimulate erythropoiesis in these patients but this was not sufficient to increase serum VEGF concentration.

Austrian Moderate Altitude Study 2000 (AMAS 2000). The effects of moderate altitude (1,700 m) on cardiovascular and metabolic variables in patients with metabolic syndrome.

We investigated the changes in the cardiovascular system [resting blood pressure (BP) and heart rate (HR), measured by means of a 24-h ambulatory BP and a holter-electrocardiogram (ECG)], glycemic parameters, and lipid metabolism of subjects suffering from metabolic syndrome during a 3-week sojourn at 1,700 m in the Austrian Alps. A total of 22 male subjects with metabolic syndrome were selected. Baseline investigations were performed at Innsbruck (500 m above sea level). During the 3-week altitude stay the participants simulated a holiday with moderate sports activities. Examinations were performed on days 1, 4, 9, and 19. After returning to Innsbruck, post-altitude examinations were conducted after 7-10 days and 6-7 weeks, respectively. The 24-h ambulatory BP and holter ECG revealed a decrease in average HR, BP, and rate pressure product (RPP: systolic blood pressure x HR) after 3 weeks of altitude exposure. In some patients, an increase in premature ventricular beats was observed at the end compared to the beginning of the exposure to moderate altitude. The ECG revealed no ischemic ST-segment changes. Maximal physical capacity as measured by symptom-limited maximal cycle ergometry tests remained unchanged during the study. Six weeks after the altitude exposure the blood pressure increased again and returned to pretest levels. The Homeostasis Model Assessment index, which is a measure of insulin resistance, decreased significantly and glucose concentrations obtained after an oral glucose tolerance test were significantly lower after the stay at altitude compared to the basal values. We conclude that after a 3-week exposure to moderate altitude, patients with metabolic syndrome (1) tolerated their sojourn without any physical problems, (2) exhibited short-term favorable effects on the cardiovascular system, and (3) had significant improvements in glycemic parameters that were paralleled by a significant increase in high-density-lipoprotein-cholesterol.