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.

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.

The Double Sensor-A non-invasive device to continuously monitor core temperature in humans on earth and in space.

The objective of our study was to establish whether rectal temperature recordings in humans could be replaced by a non-invasive skin temperature sensor combined with a heat flux sensor (Double Sensor) located at the forehead to monitor core body temperature changes due to circadian rhythms. Rectal and Double Sensor data were collected continuously for 24h in seven men undertaking strict head-down tilt bed-rest. Individual differences between the two techniques varied between -0.72 and +0.55 degrees C. Nonetheless, when temperature data were approximated by cosinor analysis in order to compare circadian rhythm profiles between methods, it was observed that there were no significant differences between mesor, amplitude, and acrophase (P>0.310). It was therefore concluded that the Double Sensor technology is presently not accurate enough for performing single individual core body temperature measurements under resting conditions at normal ambient room temperature. Yet, it seems to be a valid, non-invasive alternative for monitoring circadian rhythm profiles.

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.

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.

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.

Improvement of metabolic syndrome markers through altitude specific hiking vacations.

To study the influence of a 3-week hiking vacation at moderate (1700 m) and low altitude (LA) (200 m) on key-markers of the metabolic syndrome, 71 male volunteers (age 36-66 yr old) with the metabolic syndrome [according to the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) - or World Health Organization (WHO) - definition] participated in the study and were randomly assigned into a moderate altitude (MA) group (1700 m, no. 36) and a low altitude (LA) group (200 m, no. 35). The 3-week vacation program included 12 moderate- intensity guided hiking tours [4 times/week, 55-65% heart rate maximum (HRmax)] with a total exercise time of 29 h plus moderate recreational activities. Both study groups had a comparable and balanced nutrition with no specific dietary restrictions. Anthropometric, metabolic and cardiovascular parameters were measured 10-14 days before vacation, several times during the 3-week vacation, 7-10 days and 6-8 weeks after return. All participants tolerated the vacation without any adverse effects. Body weight, body fat, waist-circumference, fasting glucose, total cholesterol, LDL-cholesterol (LDL-C), plasma fibrinogen, resting systolic and diastolic blood pressure were significantly decreased over time in both study groups. In the LA group, fasting insulin and homeostasis model assessment (HOMA)-index were significantly decreased one week after return. Relative cycle ergometry performance was significantly increased after return compared to baseline. In both study groups, waist-to-hip ratio (WHR), 2-h oral glucose tolerance test (OGTT), HDL-cholesterol (HDL-C), and triglycerides remained unchanged. The 3-week vacation intervention at moderate and LA had a positive influence on all key-markers of the metabolic syndrome. No clinically relevant differences could be detected between the study groups. A hiking vacation at moderate and LA can be recommended for people with stable, controlled metabolic and cardiovascular risk factors.

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.

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.

Markers of coagulation, fibrinolysis and angiogenesis after strenuous short-term exercise (Wingate-test) in male subjects of varying fitness levels.

It was the aim of the study to analyse the haemostatic system during a high standardized intensive short-term (30 s) exercise (anaerobic Wingate test). Blood samples were taken from 15 male subjects before (t0 ), and within 2 (t1 ), 9 (t2 ) and 30 min (t3 ) after the test. We found that the partial thromboplastin time was markedly shortened, whereas the prothrombin time increased slightly from t0 to t1 (p < 0.002) and remained elevated (t3, p < 0.046). Factor VIII increased from t0 to t1 (p < 0.001) and remained elevated as well (t3, p < 0.001). Fibrin monomers were approximately 15 times higher immediately post-exercise (t1, p < 0.001) and continued to be elevated (t3, p < 0.004). The tissue plasminogen activator increased by 4 times after exercise (t1, p < 0.001) and remained elevated (t3, p < 0.002). The d-dimers increased from t0 to t1 (p < 0.001) as well and remained elevated (t3, p < 0.005). Thrombopoietin concentrations were unchanged, whereas the vascular endothelial growth factor increased immediately post-exercise (t0 to t1, p < 0.011 resp. at t2 p < 0.019) and returned to the control level at t3 (p < 0.878). In conclusion, it was found that prothrombotic markers and, even more pronounced, those of the fibrinolytic system were increased. The study provides evidence that due to intensive short-term exercise the balance of the haemostatic system is shifted to a higher equilibrium. Theoretically, the data show that in the case of a subject with risk factors such as impaired fibrinolysis, unfavourable conditions cannot be excluded.

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.

Activation of blood platelets in response to maximal isometric exercise of the dominant arm.

Isometric exercise is a popular form of physical activity for many people. Only few studies exist on the effects of this type of exercise on the hemostatic system. Eleven male healthy subjects (21-42 years) of varying fitness levels were investigated before, immediately after and 10 min after strenuous isometric exercise of the dominant arm. Blood samples were drawn by repetitive puncture from both the exercising and the contralateral arm. The following variables were studied: Prothrombin time and partial thromboplastin time as group tests for the plasmatic coagulation system; platelet count as well as p-selectin expression for the platelet system; tissue plasminogen activator (t-PA) activity and antigen for the fibrinolytic system. The partial thromboplastin time was shortened immediately after maximal isometric exercise of the dominant arm, the prothrombin time remained unchanged. No change was found in the platelet count, but a marked p-selectin expression was observed immediately after maximal isometric exercise of the dominant arm (p < 0.05) and even in the resting contralateral arm. Values returned to baseline after 10 min. There was a slight increase of t-PA antigen concentration and white blood cell count at maximal isometric contraction which did not occur in the resting arm, although changes over the 3 time points were significant in both arms. Maximal isometric exercise leads to platelet activation in both arms, a slight aPTT decrease and t-PA antigen increase in local blood stream. As compensatory fibrinolytic changes do not occur, it is an open question whether isometric exercise increases the potential risk of thromboembolism.

Vascular endothelial growth factor in exercising humans under different environmental conditions.

It was the aim of this study to investigate the time course of changes in the serum concentrations of vascular endothelial growth factor (VEGF) during a regular survival training programme combined with food and fluid deprivation and during a high altitude marathon run. We studied soldiers of the Austrian Special Forces performing survival training at sea-level and marathon runners of the Posta Atletica who crossed the border between Chile and Argentina at altitudes up to 4722 m. Baseline data collected before the 1-week of survival training showed that the soldiers had normal VEGF [n = 8, 246.7 (SD 118.5) pg.ml(-1)] serum concentrations which remained unchanged during the course of the study. Before the high altitude marathon the subjects showed normal VEGF serum concentrations [178 (SD 84.5) pg.ml(-1)]. After the run VEGF concentrations were found to be significantly decreased [41.0 (SD 41.6) pg ml(-1), P < 0.01]. It was concluded that prolonged physical stress during normobaric-normoxia did not alter the VEGF concentrations whereas during severe hypobaric-hypoxia decreased VEGF serum concentrations were measured, at least temporarily, after prolonged physical exercise which might have been due to changes in production, release, removal and/or binding of circulating VEGF.

Muscle and bone-aging and space.

One of the major concerns of aging, but also during and after spaceflight, is loss of muscle and bone mass. In aging, this is associated with an increasing risk of fractures. Recently, the possibility of aged and aging astronauts has been arisen. Thus considering the perspectives of aging and space we want to discuss, in how far the adaptations during spaceflight and during aging interfere. In other words: does spaceflight push the astronauts along the irreversible axis of aging? And which of the spaceflight effects will be reversible? Bones adapt to their mechanical function. For convenience, a simple model has been proposed: Bone, as a 'mechanostat', keeps the strains within certain thresholds, namely one threshold for modeling, i.e. formation of new bone, and one for remodeling, i.e. repair and removal. These thresholds are usually expressed as strains. A crucial role in physiological strain detection is obviously played by the osteocytes. The largest forces in the musculo-skeletal systems arise from muscle contractions. The reason for this are the poor levers, against which the muscles pull. For example: during a one-leg vertical jump, a young subject (body weight 70 kg) exerts a vertical ground reaction force of 2500 N. Due to the lever ratio of os calcis and forefoot around the tibio-talar joint, the calf muscles must exert a force 3 times greater, so that together with the body weight the bones of the lower leg are loaded with 10000 N, i.e. 14 times the body weight. Accordingly, good correlations can be observed between muscle strength and bone strength, or muscle mass and bone mass. It is therefore reasonable to discuss the accumulated knowledge about loss of muscle and bone in a combined approach. In this respect, two points must be considered: (i) for structural adaptation of bone, the muscular variable of interest arc force and rate of force development, but not power, and (ii) women before menopause have a greater bone to muscle ratio than men.

Regulatory changes at high altitudes in comparison with post-space-flight reactions.

This report will compare results of applications of the psychophysiological method "Assessment of Autonomic Outlet Type" (AOT) in space as well as at high altitudes. The aim was to find out whether it is possible to differentiate a subject's reaction to different environments by this method (Johannes et.al. 1995). This assessment as described below was first applied to clinically well defined cohorts and to healthy subjects. By means of cluster analysis it could be demonstrated that different reaction patterns exist. These different patterns were correlated to two groups of normal controls ([I] = non-responder/voice-responder and [II] = heart-responder) and two groups of patients with different clinical diagnoses (rheumatic diseases ([III] = autonomic-responder) and [IV] = hypertensives). Based on these clinical reference data the method provides for each "new" experiment a common classification of the complex regulatory reaction pattern of the autonomic nervous system (ANS) and the Cardiovascular system (CVS) to psychological stressors by means of a discriminant function. Since August 1997 the experiment has been applied to all Russian cosmonauts continuously each month. (Johannes et.al. 1998). At the same time numerous terrestrial experiments have been running parallel for comparison with the results from space. This report will focus on a study at altitudes of 3600 m.