Microvascular responses to (hyper-)gravitational stress by short-arm human centrifuge: arteriolar vasoconstriction and venous pooling.

PURPOSE: We hypothesized that lower body microvessels are particularly challenged during exposure to gravity and hypergravity leading to failure of resistance vessels to withstand excessive transmural pressure during hypergravitation and gravitation-dependent microvascular blood pooling. METHODS: Using a short-arm human centrifuge (SAHC), 12 subjects were exposed to +1Gz, +2Gz and +1Gz, all at foot level, for 4 min each. Laser Doppler imaging and near-infrared spectroscopy were used to measure skin perfusion and tissue haemoglobin concentrations, respectively. RESULTS: Pretibial skin perfusion decreased by 19% during +1Gz and remained at this level during +2Gz. In the dilated area, skin perfusion increased by 24 and 35% during +1Gz and +2Gz, respectively. In the upper arm, oxygenated haemoglobin (Hb) decreased, while deoxy Hb increased with little change in total Hb. In the calf muscle, O2Hb and deoxy Hb increased, resulting in total Hb increase by 7.5 ± 1.4 and 26.6 ± 2.6 µmol/L at +1Gz and +2Gz, respectively. The dynamics of Hb increase suggests a fast and a slow component. CONCLUSION: Despite transmural pressures well beyond the upper myogenic control limit, intact lower body resistance vessels withstand these pressures up to +2Gz, suggesting that myogenic control may contribute only little to increased vascular resistance. The fast component of increasing total Hb indicates microvascular blood pooling contributing to soft tissue capacitance. Future research will have to address possible alterations of these acute adaptations to gravity after deconditioning by exposure to micro-g.

Temporal and spatial dispersion of human body temperature during deep hypothermia.

BACKGROUND: Clinical temperature management remains challenging. Choosing the right sensor location to determine the core body temperature is a particular matter of academic and clinical debate. This study aimed to investigate the relationship of measured temperatures at different sites during surgery in deep hypothermic patients. METHODS: In this prospective single-centre study, we studied 24 patients undergoing cardiothoracic surgery: 12 in normothermia, 3 in mild, and 9 in deep hypothermia. Temperature recordings of a non-invasive heat flux sensor at the forehead were compared with the arterial outlet temperature of a heart-lung machine, with the temperature on a conventional vesical bladder thermistor and, for patients undergoing deep hypothermia, with oesophageal temperature. RESULTS: Using a linear model for sensor comparison, the arterial outlet sensor showed a difference among the other sensor positions between -0.54 and -1.12°C. The 95% confidence interval ranged between 7.06 and 8.82°C for the upper limit and -8.14 and -10.62°C for the lower limit. Because of the hysteretic shape, the curves were divided into phases and fitted into a non-linear model according to time and placement of the sensors. During cooling and warming phases, a quadratic relationship could be observed among arterial, oesophageal, vesical, and cranial temperature recordings, with coefficients of determination ranging between 0.95 and 0.98 (standard errors of the estimate 0.69-1.12°C). CONCLUSION: We suggest that measured surrogate temperatures as indices of the cerebral temperature (e.g. vesical bladder temperature) should be interpreted with respect to the temporal and spatial dispersion during cooling and rewarming phases.

Sex differences in stress and immune responses during confinement in Antarctica.

BACKGROUND: Antarctica challenges human explorers by its extreme environment. The effects of these unique conditions on the human physiology need to be understood to best mitigate health problems in Antarctic expedition crews. Moreover, Antarctica is an adequate Earth-bound analogue for long-term space missions. To date, its effects on human physiology have been studied mainly in male cohorts though more female expeditioners and applicants in astronaut training programs are selected. Therefore, the identification of sex differences in stress and immune reactions are becoming an even more essential aim to provide a more individualized risk management. METHODS: Ten female and 16 male subjects participated in three 1-year expeditions to the German Antarctic Research Station Neumayer III. Blood, saliva, and urine samples were taken 1-2 months prior to departure, subsequently every month during their expedition, and 3-4 months after return from Antarctica. Analyses included cortisol, catecholamine and endocannabinoid measurements; psychological evaluation; differential blood count; and recall antigen- and mitogen-stimulated cytokine profiles. RESULTS: Cortisol showed significantly higher concentrations in females than males during winter whereas no enhanced psychological stress was detected in both sexes. Catecholamine excretion was higher in males than females but never showed significant increases compared to baseline. Endocannabinoids and N-acylethanolamides increased significantly in both sexes and stayed consistently elevated during the confinement. Cytokine profiles after in vitro stimulation revealed no sex differences but resulted in significant time-dependent changes. Hemoglobin and hematocrit were significantly higher in males than females, and hemoglobin increased significantly in both sexes compared to baseline. Platelet counts were significantly higher in females than males. Leukocytes and granulocyte concentrations increased during confinement with a dip for both sexes in winter whereas lymphocytes were significantly elevated in both sexes during the confinement. CONCLUSIONS: The extreme environment of Antarctica seems to trigger some distinct stress and immune responses but-with the exception of cortisol and blood cell counts-without any major relevant sex-specific differences. Stated sex differences were shown to be independent of enhanced psychological stress and seem to be related to the environmental conditions. However, sources and consequences of these sex differences have to be further elucidated.

Cardiac markers (BNP, NT-pro-BNP, Troponin I, Troponin T, in female amateur runners before and up until three days after a marathon.

PURPOSE: Transient cardiac ventricular dysfunction or sudden cardiac deaths have been reported for male athletes participating in marathon racing. Less is known about the myocardial response in females. We examined natriuretic peptides and cardiac troponins in female athletes after a marathon. METHODS: At the 31st real,- Berlin Marathon plasma levels of NT-pro-BNP, BNP, cTnI and cTnT were measured in 15 women (age 35+/-6 years; finishing times between 3:22 h and 5:21 h) at four different time points (before, immediately after, day one and day three). RESULTS: An increase in [NT-pro-BNP] was observed immediately after the marathon (median [NT-pro-BNP] before: 39.6 pg ml(-1), after: 138.6 pg ml(-1), p=0.003) with a further increase on day one. [BNP] did not increase immediately after the marathon but increased on day one (median [BNP] before: 15 pg ml(-1), day one: 27.35 pg ml(-1), p=0.006). On day three, [NT-pro-BNP] and [BNP] returned to initial values. [cTnI] was under the detection limit prior to the marathon in all runners. [cTnT] was under the detection limit before the marathon except in one runner who presented a concentration of 0.03 ng ml(-1). Cardiac troponins (median [cTnl] after: 0.098 ng ml(-1), p=0.028; median [cTnT] after: 0.032 ng ml(-1), p=0.012) increased immediately after the marathon and returned to initial values on day one [cTnT] and three [cTnI]. DISCUSSION: Parameters representing cardiac stress increased in females after a marathon. Different kinetics of natriuretic peptides BNP and NT-pro-BNP post-marathon could be due to their different half-lives and dependence on renal function. The increase of cTnI and cTnT may result from minor myocardial lesions.

Traveller's thrombosis: international consensus statement.

In 2001, consensus meetings on traveller's thrombosis were held in Vienna and Berlin. The results of these conferences were subsequently published in VASA 2002. In 2006 a follow-up conference was organized in Hall, Tirol, Austria, in order to review new and emerging data and to update the conclusions and recommendations of the 2001 meetings. Prior to the conference key papers from peer-reviewed journals were pre-circulated to all participants. The consensus group discussed the data and drafted an updated statement. Thereafter, the writing group summarised the results including the pre-circulated material and additional papers identified by a formal literature search up to December 2007. In this article current knowledge on the incidence, pathophysiology and prevention of traveller's thrombosis is summarised. The assessment of individual risk is described and recommendations for prevention of traveller's thrombosis are given, based upon the conclusions of the Hall Conference.

Water immersion is associated with an increase in aquaporin-2 excretion in healthy volunteers.

Here, we report the alterations in renal water handling in healthy volunteers during a 6 h thermoneutral water immersion at 34 to 36 degrees C. We found that water immersion is associated with a reversible increase in total urinary AQP2 excretion.

Erythropoietin regulations in humans under different environmental and experimental conditions.

In the adult human, the kidney is the main organ for the production and release of erythropoietin (EPO). EPO is stimulating erythropoiesis by increasing the proliferation, differentiation and maturation of the erythroid precursors. In the last decades, enormous efforts were made in the purification, molecular encoding and description of the EPO gene. This led to an incredible increase in the understanding of the EPO-feedback-regulation loop at a molecular level, especially the oxygen-dependent EPO gene expression, a key function in the regulation loop. However, studies in humans at a systemic level are still very scanty. Therefore, it is the purpose of the present review to report on the main recent investigations on EPO production and release in humans under different environmental and experimental conditions, including: (i) studies on EPO circadian, monthly and even annual variations, (ii) studies in connection with short-, medium- and long-term exercise at sea-level which will be followed (iii) by studies performed at moderate and high altitude.

Observation of serum erythropoietin concentrations in female athletes for up to eight days after a marathon run.

Erythropoietin (EPO) was studied in 13 female marathon runners before and up to 8 days after a competition marathon run. The median baseline control value was 13.7 U/l. No change in EPO concentration was found immediately (15 min.) and one day after the run. However, a median increase in EPO concentration (18.1 U/l) was found on day three post-exercise (p< 0.05). On day 8 no change was found compared to pre-exercise values. This late increase in EPO concentration would seem to be responsible for the well known increase of red blood cell mass in long distance runners.

A hypothesis: autonomic rhythms are reflected in growth lines of teeth in humans and extinct archosaurs.

A major determinant of tooth architecture is the arrangement of lines in dentin and in the enamel following the contour of the surface. Since the original description of these lines in the 19th century, they have been attributed to recurring events during tooth development. They have also attracted the attention of dental scientists and anthropologists; however, to date, studies of these structures have been largely theoretical and microscopic. We show here that the statistical properties of the spacing between the lines are similar in teeth from both ancient and modern humans and from extinct archosaurs, reptiles that lived tens or hundreds of millions of years ago-they also resemble heart rate variability of living humans. We propose that the deposition of these recurring structures is controlled by the autonomic nervous system. This control accounts for their regularity and recurrent nature and implies that the lines are an expression of a biologic rhythm which has been conserved throughout evolution. Details of the rhythms give clues to life styles in ancient civilizations and to the physiology of extinct archosaurs.

Influence of maximal ergometric exercise on endothelin concentrations in relation to molecular markers of the hemostatic system.

The effects of moderate 30 min cycle ergometer exercise (aerobic metabolism; 0.85-3.71 mmol.1(-1) lactate) followed by short-term exercise at maximal capacity (anaerobic metabolism; 5.09 to 17.75 mmol.1(-1) lactate) on endothelin (ET) and hemostatic variables (tissue plasminogen activator [t-PA] antigen, prothrombin fragments [F1,2], thrombin-antithrombin III complex [TAT], prothrombin time and partial thromboplastin time) were investigated in 15 male healthy subjects of varying fitness levels. Endothelin was measured twice before and immediately after maximal cycle exercise. The results show an increase in endothelin concentration [10.0 pg.ml-1 (baseline) + 6.1 pg.ml-1 (increase post exercise)]. ET did not increase under control conditions. Moderate 30 min exercise caused an increase in t-PA antigen concentration (3.66 + 3.15 ng.ml-1) and short-term maximal exercise produced a markedly higher elevation in this variable (+10.6 ng.ml-1). F1,2 increased (810 + 40 pmol.l-1) under moderate and by 150 pmol.l-1 under anaerobic exercise. TAT increased only at maximal exercise levels (1.01 + 0.32 ng.l-1). No changes were found in any of these variables under control conditions. No correlation of endothelin and the hemostatic variables was found. It is concluded that endothelin and hemostatic markers increase independently during moderate and maximal exercise.

Time course of erythropoietin, triiodothyronine, thyroxine, and thyroid-stimulating hormone at 2,315 m.

Erythropoietin (EPO), triiodothyronine, thyroxine, thyroid-stimulating hormone (TSH), hemoglobin (Hb), reticulocytes, packed cell volume, and plasma volume changes were studied in 29 male Austrian mountain rescue soldiers before and several days after an ascent from 744 to 2,315 m in the Alps. EPO concentrations showed a remarkable increase 48 h after the ascent (P < 0.01). No significant changes were found in triiodothyronine, thyroxine, and TSH. Reticulocytes increased only slightly. Hb decreased during the week (P < 0.01). Packed cell volume did not change, whereas plasma volume showed a slight decrease for 48 h after the ascent but then increased constantly (P < 0.01). It seems that thyroid hormones, TSH, and Hb play only a minor role in the regulation of EPO production and release under mild hypobaric-hypoxic conditions (2,315 m).

Erythropoietin under real and simulated microgravity conditions in humans.

The aim of this study was to analyze the time course of erythropoietin (EPO) during Earth-bound microgravity simulations such as bed rest, isolation and confinement (IC), head-down tilt (HDT; -6 degrees), and immersion to evaluate which factors could contribute to alterations in EPO under real microgravity conditions during and after short- (< 10 days) and long-term (> 6 mo) spaceflights. During bed rest (24h), no significant changes in EPO could be observed. Subjects confined in a diving chamber facility for 60 days showed a decrease in EPO. In the recovery period a slight increase was observed, but EPO concentrations did not reach the pre-IC control level. In the control period before HDT, subjects showed normal resting values for EPO, but on day 2 of HDT the EPO concentrations were decreased (P < 0.01). Later the EPO levels remained below the control value and were increased after HDT (P < 0.05). After immersion (24 h) increased EPO concentrations could be determined (P < 0.05). During a short-term spaceflight the astronauts showed in-flight (day 4) decreased and unchanged EPO concentrations. During a long-term spaceflight, 24 h after recovery, the cosmonaut showed slightly elevated EPO concentration, which increased markedly during the following days. It is concluded that 1) HDT (-6 degrees) causes a rapid decrease in EPO in humans, 2) IC per se leads to diminished EPO concentrations, 3) EPO regulation in humans during short- and long-term spaceflights might be different, 4) changes in central blood volume, i.e., central venous pressure, seem to be involved in the modulation of EPO production and release under simulated and real microgravity conditions, and 5) the HDT (-6 degrees) Earth-bound simulation reflects mostly the changes in EPO production and release observed under real microgravity conditions in humans.

Shift working in the Chilean Andes (> 3,600 m) and its influence on erythropoietin and the low-pressure system.

It was hypothesized that, in shift workers with a history of intermittent hypoxic stress (working 10 days at > 3,600 m, then resting for 4 days at sea level) for > 5 yr, the initial erythropoietin (EPO) response and the changes in central venous pressure (CVP) are different from those in Caucasian lowlanders. We studied the kitchen personnel (n = 11) of a mine (3,600 m) and a group of Caucasian lowlanders (n = 5). Blood samples were taken, and CVP was determined several times before, during, and after a typical shift. At baseline data collection (BDC) before transition, the shift workers had EPO concentrations of 5.2 +/- 2.4 mU/ml, which increased at altitude (P < 0.01) and returned to BDC values on the recovery (day 16). The Caucasians showed the same time course. Serum transferrin receptor concentrations did not change in either group. CVP values were generally higher in the shift workers than in the Caucasians. In conclusion, the hypothesis that the initial EPO response to a hypoxic stimulus is altered in these shift workers has to be refuted. Higher hemoglobin concentrations and/or CVP values in shift workers might be responsible for the rather low EPO concentrations in shift workers at BDC.

Fluid regulation during prolonged physical strain with water and food deprivation in healthy, trained men.

The aim of this study was to investigate fluidregulating mechanisms, with special regard to the role of plasma proteins in the control of plasma volume (PV), and the role of the superficial tissues as a water storage organ of the body during prolonged physical strain. 29 male subjects (mean age 22.2 +/- 2.8 years) were studied during a 5 day period of survival training with multifactorial strain including restricted water intake (11 H2O.day-1) and food intake (628 kJ.day-1) additionally to physical exercise and sleep deprivation (20 h within 5 days). Under field conditions the heart rate was monitored continuously, and body mass, body composition, thickness of the shell tissues, and blood parameters were measured at (T1), after 72 h (T2), after 120 h (T3) and in the recovery period after 48 h (T4) and 72 h (T5). The estimated energy expenditure was approximately 24,000 kJ.day-1. The mean decrease of body mass was 6.77 kg (9.5%) at T3 (p < 0.001), 0.95 kg (1.3%) at T4 (p < 0.05) and 0.68 kg (0.9%) at T5 (n.s.). A reduction of total body water of 3.8 1 was estimated at T3. Serum creatinine ([Cr]) was raised at T3 by 18.5% (p < 0.0001). No relationship was found between [Cr] and other parameters. The PV decreased by 3.7% (p < 0.0001) at T2, increased by 1.6% (p < 0.0001) at T3 and was not different to baseline at T4 (+0.2%; n.s.). Total protein concentration ([TP]) increased at T2 (11.7%; p < 0.0001) and T3 (2.6%; p < 0.01), and decreased (p < 0.0001) at T4 (8.2%) and T5 (5.7%). Plasma proteins shifted into the intravascular space at T2 and T3 and moved out of the intravascular space at T4 and T5. This gives support to the hypothesis that one of the counterregulatory mechanisms maintaining PV during prolonged exercise is provided by protein shifts from the extravascular into the intravascular space. Our data provide evidence that this mechanism assists PV homeostasis efficiently over a period of 120 h with multifactorial strain, even under conditions with a fluid loss of almost 8% of the total body water.

Nathan Zuntz (1847-1920)--a German pioneer in high altitude physiology and aviation medicine, Part I: Biography.

Nathan Zuntz (1847-1920) was a key person in the history of high altitude physiology and aviation medicine. As a professor of animal physiology at the Landwirtschaftliche Hochschule (Agricultural University) in Berlin from 1881 until 1918, he carried out laboratory studies on the changes in metabolism at rest and during exercise. To this end he, together with August Julius Geppert, developed the famous "Zuntz-Geppert'schen Respirationsapparat" (Zuntz-Geppert respiratory apparatus) in 1885. In the early 1890's, Zuntz extended his research to the field of high altitude physiology. In view of the variety of questions, and despite considerable methodological problems, Zuntz first studied the effects of lowered PO2 on the human body in a Pneumatischen Kammer (hypobaric chamber). In 1893 the newly completed Capanna Regina Margherita, an international research station at the top of Monte Rosa, Italy (4,500 m), became the site of Zuntz's extensive field studies, where he worked together with his close co-worker Adolf Loewy (1862-1936), the Italian Angelo Mosso (1846-1910), and the Austrian Arnold Durig (1872-1961). For their investigations Zuntz invented the transportable Gasuhr (a gas exchange measuring device). In 1902 Zuntz and the Austrian Hermann von Schroetter (1870-1928) made two balloon ascents up to 5,000 m in Berlin. A synopsis of these studies was published by Zuntz in 1906: his famous book "Höhenklima und Bergwanderungen" (High altitude climate and mountain-touring). A few years later Zuntz undertook further expeditions to the Canary Islands (Pico de Teide), conducting studies in airships and planes until 1914. Zuntz retired in 1916 and died in Berlin on March 22, 1920.

Nathan Zuntz (1847-1920)--a German pioneer in high altitude physiology and aviation medicine, Part II: Scientific work.

For over 52 years, the work of Nathan Zuntz (1847-1920) covered an amazingly wide spectrum of research fields; metabolism, nutrition, respiration, blood gases, exercise, and high altitude physiology were the main themes. Zuntz achieved fame for his invention of the Zuntz-Geppert respiratory apparatus in 1886 and the first Laufband (treadmill) in 1889. To this experimental setup Zuntz later added an X-ray apparatus in 1914 to determine the changes in heart volume during exercise. Moreover, he constructed a climate chamber to study exercise under varying and sometimes extreme climates. For field studies Zuntz invented a transportable Gasuhr (dry gas measuring device). Zuntz was the first to describe the difference between laboratory data gained in a hypobaric chamber and the measurements at high altitude. He found that the barometric formula is not applicable in the field. Two balloon expeditions in 1902 by Zuntz and his pupil, v. Schroetter, marked the step from terrestrial physiology towards aviation medicine. An outline of the development of scientific aviation in Berlin from 1880-1918 elucidates how closely the aviation union, army, and scientific departments were connected with and dependent upon each other. In cooperation with these institutions Zuntz and v. Schroetter constructed an oxygen supply system and planned a pressure cabin for extreme altitudes above 10,000 m, a forerunner of modern systems in aviation and astronautics. In 1912, Zuntz and v. Schroetter each published papers on aviation medicine, both publications internationally unique in style and extent. Zuntz's work in its empirical approach was the counterpart to the established formal mathematical-physical reductionism of the German Physiological Society.(ABSTRACT TRUNCATED AT 250 WORDS)

Voice stress monitoring in space--possibilities and limits.

An overview of experimental investigations into the use of the voice pitch mode (F0 m) as a distance tool for the monitoring of emotional stress reactions is given. Seven experiments are summarized describing the relations between voice reaction and psychological and physical load in laboratory and field applications. The reactivity of F0 m to mental load depends on psychological personality traits. F0 m is less related to physical load. The evaluation of F0 m as voice stress indicator requires an individual calibration. This calibration has to include the assessment of the individual Autonomic Outlet Type (AOT) because the physiological relevance of voice reactions depends on the individual AOT. The calibration is based on statistical reference data which have to be improved in the future. The calibration has to be done under comparable environmental circumstances. A 3-yr application of the method on board Mir station documents the applicability of the procedure.

Effects of 28-day isolation (ESA-ISEMSI'90) on blood pressure and blood volume regulating hormones.

The aim of this study was to determine what effects social isolation and confinement stress had on the volume regulating hormones. In six healthy male subjects, during a 28-d isolation and confinement study (ESA-ISEMSI'90), hematocrit, blood pressure and resting heart rate, plasma cortisol, renin, aldosterone, arginine vasopressin levels besides the electrolyte (Na+, K+) balance and plasma creatinine were measured. During the confinement, an elevated systolic blood pressure (p < 0.01) was observed together with an increase in MHPG corresponding to an elevated mental work load. The pattern displayed by volume regulating hormones (increased values for renin, aldosterone (p < 0.05) and arginine vasopressin) was not only characteristic of confinement stress but also reflected changes in the water and electrolyte metabolism. The increased creatinine levels seen throughout the study were regarded as consequences of hypohydration, and an enhanced muscular catabolism due to reduced physical activity. A similar pattern of hormone modifications was obtained in a head down tilt of the same duration, indicating that some of the described modifications are probably related to isolation and confinement stress.

Blood volume regulating hormones response during two space related simulation protocols: four-week confinement and head-down bed-rest.

The volume of regulating hormones (renin, aldosterone, arginine vasopressin and atrial natriuretic factor), electrolytes and creatinine concentrations, and blood pressure were measured in two different four-week experimental protocols: respectively -6 degrees head-down bed-rest (5 subjects) and confinement (6 subjects). We observed a significant increase (P < 0.01 at D2 vs D-5) of systolic blood pressure during confinement and a different level of response for some hormones, especially for arginine vasopressin (300% increase during confinement instead of 50% during bed-rest). The renin-angiotensin-aldosterone system was enhanced during confinement and head-down bed-rest. In both conditions, we obtained a similar pattern of response for blood volume regulating hormones. During confinement, two main factors were inactivity and stress activation of the sympathetic nervous system. In the bed-rest study the response is principally due to the fluid shift and blood volume adaptation but it is not possible to exclude the role of inactivity and stress.