Dynamic change of ERPs related to selective attention to signals from left and right visual field during head-down tilt

To study further the effect of head-down tilt (HDT) on slow positive potential in the event-related potentials (ERPs), the temporal and spatial features of visual ERPs changes during 2 hour HDT (-10 degrees) were compared with that during HUT (+20 degrees) in 15 normal subjects. The stimuli were consisted of two color LED flashes appeared randomly in left or right visual field (LVF or RVF) with same probability. The subjects were asked to make switch response to target signals (T) differentially: switching to left for T in LVF and to right for T in RVF, ignoring non-target signals(N). Five sets of tests were made during HUT and HDT. ERPs were obtained from 9 locations on scalp. The mean value of the ERPs in the period from 0.32-0.55 s was taken as the amplitude of slow positive potential(P400). The main results were as follows. 1) The mean amplitude of P400 decreased during HDT which was more significant at the 2nd, 3rd and 5th set of tests; 2) spatially, the reduction of mean P400 amplitude during HDT was more significant for signals from RVF and was more significant at posterior and central brain regions than that on frontal locations. As that the positive potential probably reflects the active inhibition activity in the brain during attention process, these data provide further evidence showing that the higher brain function was affected by the simulated weightlessness and that this effect was not only transient but also with interesting spatial characteristics.     

Effects of 12 days exposure to simulated microgravity on central circulatory hemodynamics in the rhesus monkey

Central circulatory hemodynamic responses were measured before and during the initial 9 days of a 12-day 10 degrees head-down tilt (HDT) in 4 flight-sized juvenile rhesus monkeys who were surgically instrumented with a variety of intrathoracic catheters and blood flow sensors to assess the effects of simulated microgravity on central circulatory hemodynamics. Each subject underwent measurements of aortic and left ventricular pressures, and aortic flow before and during HDT as well as during a passive head-up postural test before and after HDT. Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure were measured, and dP/dt and left ventricular elastance was calculated from hemodynamic measurements. The postural test consisted of 5 min of supine baseline control followed by 5 minutes of 90 degrees upright tilt (HUT). Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure showed no consistent alterations during HDT. Left ventricular elastance was reduced in all animals throughout HDT, indicating that cardiac compliance was increased. HDT did not consistently alter left ventricular +dP/dt, indicating no change in cardiac contractility. Heart rate during the post-HDT HUT postural test was elevated compared to pre-HDT while post-HDT cardiac output was decreased by 52% as a result of a 54% reduction in stroke volume throughout HUT. Results from this study using an instrumented rhesus monkey suggest that exposure to microgravity may increase ventricular compliance without alternating cardiac contractility. Our project supported the notion that an invasively-instrumented animal model should be viable for use in spaceflight cardiovascular experiments to assess potential changes in myocardial function and cardiac compliance.     

Changes in organ perfusion and weight ratios in post-simulated microgravity recovery

Head-down tilt models have been used as ground-based simulations of microgravity. Our previous animal research has demonstrated that there are significant changes in fluid distribution within 2 h after placement in a 45 degrees head-down tilt (45HDT) position and these changes in fluid distribution were still present after 14 days of 45HDT. Consequently, we investigated changes in fluid distribution during recovery from 16 days of 45HDT. Changes in radioactive tracer distribution and organ/body weight ratio were examined in rats randomly assigned to a 45HDT or prone control group. The 45HDT rats were suspended for 16 days and then allowed to recover at the prone position 0, 77, 101, or 125 h post-suspension. Animals were injected with technetium-labeled diethylenetriamine pentaacetate (99mTcDTPA, MW=492 amu, physical half-life of 6.02 h) and then killed 30 min post-injection. Lungs, heart, liver, spleen, kidneys, and brain were harvested, weighed, and measured for radioactive counts. Statistical analyses included two-way analysis of variance (ANOVA) that compared 45HDT versus controls at the four experimental time points. The organ weight divided by the body weight ratio for the brain, heart, kidneys and liver in the 45HDT rats was significantly different than the control rats, regardless of time (treatment). There was no difference between the different time points (time). The average 99mTcDTPA count divided by the organ weight ratio values for the heart, liver, and spleen were significantly higher in the 45HDT group than the control group. The average counts for the heart and spleen were significantly higher at 77, 101, and 125 h than at time zero. We conclude that the major organs have different recovery patterns after 45HDT for 16 days in the rat.     

Gender differences in organ density in a rat simulated microgravity model

Research investigating the physiological effects of microgravity on the human body has demonstrated a shift of body fluids in actual spaceflight and in simulated Earth-based microgravity models in both males and females, possibly causing many deleterious physiological effects. Twenty-five anatomically normal female (NF) and 20 ovariectomized (OE) Fischer 344 rats were randomly selected to be in an experimental (1 h of 45 degrees head-down tilt, 45HDT) or control (1 h of prone position) group. At the end of the hour experimental period, the density of the brain, lungs, heart, liver, and left and right kidneys were measured using spiral computed tomography (SCT) while the rats remained in their experimental positions. A sub-group of OE rats (N=6) was administered estrogen replacement therapy on a daily basis (5 micrograms/kg body weight, s.c.) for 4 days and then underwent 1 h of 45HDT and SCT analysis at one day, 2 days, and 5 days to determine if estrogen replacement therapy would alter organ densities. Our data demonstrate that 1 h of 45HDT produced significant increases (p<0.05) in the organ densities of the brain, liver, left kidney, and lung of the OE female group compared to their prone controls. However, only the brain density was significantly increased in the NF group. Estrogen replacement therapy caused a significant decrease in brain organ density at the 5 day time point compared to the 24 h time point. We conclude that estrogen plays a role in fluid distribution in a rat 45HDT model.     

Effect on the cardiac function of repeated LBNP during a 1-month head down tilt

Cardiovascular assessment by ultrasound methods was performed during two long duration (1 month) Head Down Tilt (HDT) on 6 healthy volunteers. On a first 1 month HDT session, 3 of the 6 subjects (A, B, C) had daily several lower body negative pressure tests (LBNP), whereas the 3 subjects remaining (D, E, F) rested without LBNP. On a second 1 month HDT session subjects D, E, and F had daily LBNP tests and the A, B and C subjects did not. The cardiac function was assessed by Echocardiography, (B mode, TM mode). On all the "6 non LBNP" subjects the left ventricule diastolic volume (LVDV), the stroke volume (SV) and the cardiac output (CO) increase (+10%, -15%) after HDT then decrease and remain inferior (-5%, -5%) or equal to the basal value during the HDT. Immediately after the end of the HDT the heart rate (HR) increase (+10%, +30%) whereas the cardiac parameters decrease weakly (-5%, -10%) and normalize after 3 days of recovery. On the "6 LBNP" subjects the LVDV, SV and CO increase (+10%, 15%) after 1 h HDT as in the previous group then decrease but remain superior (+5%, +15%) or equal to the basal value. After the HDT session, the HR is markedly increased (+20%, +40%) the LVDV and SV decrease (-15%, -20%) whereas the CO increases or decreases depending on the amplitude of the HR variations. These parameters do not completely normalize after 3 day's recovery. Repeated LBNP sessions have a significant effect on the cardiovascular function as it maintains all cardiac parameters above the basal value. The LBNP manoeuvre can be considered as an efficient countermeasure to prevent cardiac disadaptation induced by HDT position and probably microgravity.     

Efficacy of periodic centrifugation of primates during 4-week head-down tilt.

Creation of artificial force of gravity (AFG) to counteract the negative consequences of microgravity in manned space missions of extended duration is one of the high-priority problems of space biology and medicine. However, there are a number of especial effects of AFG (namely, structural changes in muscles and bones, and some other system) which need implantation of electrodes and sensors and are possible only with animals. That is why it is of particular interest to make studies with monkeys whose reactions to changed gravity bear much resemblance with human. The purpose of the investigation was development of a protocol of periodic gravity loads as a counter-measure against the hypokinetic syndrome in Macaca mulatta. Two series of experiments were performed. In the series, animals were split into two groups of 6 species each who were motor restrained with the head end tilted downward at 5 degrees (HDT) for 28 days. Monkeys of group-2 were periodically subjected to centrifugation (HDT+G). During the first series of experiments rotation was conducted in the +Gz direction at g-loads from 1.2 to 1.6 units for 30-40 minutes 4-5 times a week. In the second series, g-load was equal to 1.2 units and the animals were rotated 30 min. 2-3 time a week. The criterion of Y-training protocol efficacy was a test +Gz run at 3 units for 30 s. during which functioning of the cardiovascular systems and its controls was evaluated. The test run was performed prior to and after HDT. Following HDT the animals of group HDT+G were more resistant to the test than their counterparts who had not been trained on the centrifuge. Data of the investigation imply that following HDT and HDT+G alike reduced the amount of total bodily fluids (by approximately 5%), the intracellular component (approximately 4%), and plasma volume (by 6-7%). Yet, there are radical differences between the groups in the levels of reduction in extracellular fluids (by 11% and 6.5%, respectively, P<0.05) and the interstitial component (by 11.5% and 6.5, respectively, P<0.05). Prophylactic centrifugation during HDT was also positive to the muscular blood flow in lower extremities.     

Does mental arithmetic before head up tilt have an effect on the orthostatic cardiovascular and hormonal responses?

Passive head up tilt (HUT) and mental arithmetic (MA) are commonly used for providing mental and orthostatic challenges, respectively. In animal experiments, even a single exposure to a stressor has been shown to modify the response to subsequent stress stimulus. We investigated whether MA applied before HUT elicits synergistic responses in orthostatic heart rate (HR), cardiac output (CO), heart rate variability and arterial blood pressure. The 15 healthy young males were subjected to two randomized protocols: (a) HUT and (b) HUT preceded by MA, with sessions randomized and ≥2 weeks apart. Beat to beat continuous hemodynamic variables were measured and saliva samples taken for hormonal assay. HUT alone increased HR from 59±7 (baseline) to 80±10 bpm (mean±SD) and mean blood pressure (MBP) from 88±10 to 91±14 mmHg. HUT results after MA were not different from those with HUT alone. The activity of alpha amylase showed differences during the experiments irrespective of the protocols. We conclude that mental challenge does not affect orthostatic cardiovascular responses when applied before; the timing of mental loading seems to be critical if it is intended to alter cardiovascular responses to upright standing.     

Early renal changes in 45 degrees HDT rats

Background: Both microgravity and simulated microgravity models, such as the 45HDT (45 degrees head-down tilt), cause a redistribution of body fluids indicating a possible adaptive process to the microgravity stressor. Understanding the physiological processes that occur in microgravity is a first step to developing countermeasures to stop its harmful effects, i.e., (edema, motion sickness) during long-term space flights. Hypothesis: Because of the kidneys' functional role in the regulation of fluid volume in the body, it plays a key role in the body's adaptation to microgravity. Methods: Rats were injected intramuscularly with a radioactive tracer and then lightly anesthetized in order to facilitate their placement in the 45HDT position. They were then placed in the 45HDT position using a specially designed ramp (45HDT group) or prone position (control group) for an experimental time period of 1 h. During this period, the 99mTc-DTPA (technetium-labeled diethylenepentaacetate, MW=492 amu, physical half-life of 6.02 h) radioactive tracer clearance rate was determined by measuring gamma counts per minute. The kidneys were then fixed and sectioned for electron microscopy. A point counting method was used to quantitate intracellular spaces of the kidney proximal tubules. Results: 45HDT animals show a significantly (p=0.0001) increased area in the interstitial space of the proximal tubules. Conclusions: There are significant changes in the kidneys during a 1 h exposure to a simulated microgravity environment that consist primarily of anatomical alterations in the kidney proximal tubules. The kidneys also appear to respond differently to the initial periods of head-down tilt.     

Increased urinary excretion rates of serotonin and metabolites during bedrest

Astronauts are often on a voluntarily reduced energy intake during space missions, possibly caused by a metabolic or emotional stress response with involvement of the central serotonergic system (SES). We investigated 24 h urinary excretion (24 h-E) of serotonin (5-HT) and 5-hydroxyindol acidic acid as indicators of the SES in healthy males under two different normocaloric conditions: normal physical activity (NPA) and -6 degree head-down-tilt (HDT). HDT or NPA were randomly arranged with a recovery period of 6 months in between. 24 h-E of hormones varied widely among individuals. Values were higher in HDT compared to NPA. Assuming that the 24 h-E values are, beside being indicators for alterations in the number and metabolism of platelets. Also indicators of central SES, HDT condition seems to activate central SES in a higher degree compared to NPA. Therefore, changes in central SES might be involved in the mechanisms associated with space flight or microgravity, including possible maladaptations such as voluntary undernutrition.     

Effect of a venotonic agent on the main arteries and veins during a 5 day HDT.

Objective: To evaluate the cardiac, arterial and venous effect of a venotonic drug (Cirkan "Ck") administrated orally daily to 6 subjects in HDT position during 5 days. These subjects underwent a second 5d HDT without Ck treatment one month later. Pre and post HDT the subjects were submitted to a stand test. Method: The cardiovascular parameters were measured by echography and Doppler. Results and discussion: The Cirkan treatment contributed to reduce the increase in cerebral resistance, and to maintain the lower limb resistance at a higher level than on controls. It reduces the vein section at the extremities (Jugular, femoral) and in the central vein system connected to the right heart (sub hepatics). On the other hand it increases the portal vein section which means that the blood stagnation at the splanchnic level is increased. Despite these arterial and venous significant modifications the clinical and ECG and Blood pressure response to the Stand test was similar in both groups.     

Immobilization induces a very rapid increase in osteoclast activity

We studied in a randomized, strictly controlled cross-over design, the effects of 6 days 6 degrees head-down tilt bed rest (HDT) in eight male healthy subjects in our metabolic ward. The study consisted of two periods (phases) of 11 days each in order to allow for the test subjects being their own controls. Both study phases were identical with respect to environmental conditions, study protocol and diet. Two days before arriving in the metabolic ward the subjects started with a diet. The diet was continued in the metabolic ward. The metabolic ward period (1l days) was divided into three parts: 4 ambulatory days, 6 days either HDT or control and 1 recovery day. Continuous urine collection started on the first day in the metabolic ward to analyze calcium excretion and bone resorption markers. On the 2nd ambulatory day in the metabolic ward and on the 5th day in HDT or control blood was drawn to analyze serum calcium, parathyroid hormone, and bone formation markers. Urinary calcium excretion was, as early as the first day in immobilization, increased (p<0.01). CTX- and NTX-excretion stayed unchanged in the first 24 h in HDT compared to the control. But already on the 2nd day of immobilization, both bone resorption markers significantly increased. We conclude from these results--pronounced rise of bone resorption markers--that already 24 h of immobilization induce a significant rise in osteoclast activity in healthy subjects. Thus, it appears possible to use short-term bed rest studies as a first step for the development of countermeasures to immobilization.     

Impaired T-wave amplitude adaptation to heart-rate induced by cardiac deconditioning after 5-days of head-down bed-rest

The study of QT/RR relationship is important for the clinical evaluation of possible risk of acquired or congenital ventricular tachyarrhythmias. In the hypothesis that microgravity exposure could induce changes in the repolarization mechanisms, our aim was to test if a short 5-days strict 6° head-down bed-rest (HDBR) could induce alterations in the QT/RR relationship and spatial repolarization heterogeneity. Twenty-two healthy men (mean age 31±6) were enrolled as part of the European Space Agency HDBR studies. High fidelity (1000 Hz) 24 h Holter ECG (12-leads, Mortara Instrument) was acquired before (PRE), the last day of HDBR (HDT5), and four days after its conclusion (POST). The night period (23:00–06:30) was selected for analysis. X, Y, Z leads were derived and the vectorcardiogram computed. Selective beat averaging was used to obtain averages of P–QRS–T complexes preceded by the same RR (10 ms bin amplitude, in the range 900–1200 ms). For each averaged waveform (i.e., one for each bin), T-wave maximum amplitude (Tmax), T-wave area (Tarea), RTapex, RTend, ventricular gradient (VG) magnitude and spatial QRS-T angle were computed. Non-parametric Friedman test was applied. Compared to PRE, at HDT5 both RTapex and RTend resulted shortened (−4%), with a decrease in T-wave amplitude (−8%) and area (−13%). VG was diminished by 10%, and QRS-T angle increased by 14°. At POST, QT duration and area parameters, as well as QRS-T angle were restored while Tmax resulted larger than PRE (+5%) and VG was still decreased by 3%. Also, a marked loss in strength of the linear regression with RR was found at HDT5 in Tmax and Tarea, that could represent a new dynamic marker of increased risk for life-threatening arrhythmias. Despite the short-term HDBR, ventricular repolarization during the night period was affected. This should be taken into account in astronauts for risk assessment during space flight.     

航天器浮动电位的初步分析

为了研究表面充电引起的浮动电位情况,我们采用等效电容的方法分析了近赤道低轨道高度条件下航天器的等效电容及充电时间问题,初步总结了浮动电位对航天器可能产生的影响。根据计算结果可以认为在低轨道等离子体环境中航天器会达到浮动电位的平衡状态。
     

Positive pressure breathing by total body negative pressure: a new simulation model for fluid balance in weightlessness?

A systems study is proposed to explore correctly the effects of the combination of HDT (Head Down Tilt) and TBNP (Total Body Negative Pressure).     

Evaluation of spontaneous baroreflex response after 28 days head down tilt bedrest

The spontaneous baroreflex response was evaluated during supine rest and head up tilt (60 degrees) before and immediately after a 28 day 6 degrees HDT bedrest in 6 healthy adult men (age 30-42 years). Sequences of 3 or more beats where RR-interval and systolic blood pressure changed in the same direction were used to evaluate baroreflex response slope (BRS). Prior to bedrest, the mean BRS and RR-interval were 18.0 +/- 3.9 ms/mm Hg and 926 +/- 61 ms at rest and 10.5 +/- 2.5 ms/mm Hg and 772 +/- 63 ms during the first 10 min of 60 degrees tilt. Following bedrest, these values changed to 15.6 +/- 2.7 ms/mm Hg and 780 +/- 53 ms at rest, and to 6.5 +/- 1.2 ms/mm Hg and 636 +/- 44 ms during tilt. Thus, (1) the spontaneous baroreflex can be evaluated in human subjects during experiments of orthostatic stress; (2) the baroreflex slope was reduced on going from supine to the head up tilt position; and (3) 28 days of bedrest reduced the spontaneous baroreflex slope.     

Interaction of mental and orthostatic stressors

We assessed hemodynamic responses induced by orthostatic and mental stressors, using passive head up tilt (HUT) and mental arithmetic (MA), respectively. The 15 healthy males underwent three protocols: (1) HUT alone, (2) MA in supine position and (3) MA+HUT, with sessions randomized and ≥2 weeks apart. In relation to baseline, HUT increased heart rate (HR) (+20.4±7.1 bpm; p<0.001), mean blood pressure (MBP) (+4.7±11.3 mmHg; p<0.05), diastolic blood pressure (DBP) (+6.1±11.6 mmHg; p<0.05) and total peripheral resistance (TPR) (+155±232 dyne*s/cm⁵; p<0.001) but decreased stroke volume (SV) (?33.1±13.4 ml; p<0.001) and cardiac output (CO) (?0.6±1.0 l/min; p<0.01). MA increased HR (+8.0±6.0 bpm; p<0.001), systolic blood pressure (SBP) (+9.0±7.7 mmHg; p<0.001), MBP (+10.0±6.5 mmHg; p<0.001), DBP (+9.5±7.2 mmHg; p<0.001) and CO (+0.6±0.8 l/min; p<0.01). MA+HUT increased HR (+28.8±8.4 bpm; p<0.001), SBP (+4.6±14.3 mmHg; p<0.05), MBP (+11.2±11.6 mmHg; p<0.001), DBP (+13.5±10.1 mmHg; p<0.001) and TPR (+160±199 dyne*s/cm⁵; p<0.001) but SV (?34.5±14.6 ml; p<0.001) decreased. Mental challenge during orthostatic challenge elicited greater increases in heart rate, despite similar reductions in stroke volume such as those during orthostatic stress alone. Overall, cardiac output decreases were less with combinations of mental and orthostatic challenges in comparison to orthostasis alone. This would suggest that carefully chosen mental stressors might affect orthostatic responses of people on standing up. Therefore, additional mental loading could be a useful countermeasure to alleviate the orthostatic responses of persons, particularly in those with histories of dizziness on standing up or on return to earth from the spaceflight environment of microgravity.     

Gender specific changes in cortical activation patterns during exposure to artificial gravity

Keeping astronauts healthy during long duration spaceflight remains a challenge. Artificial gravity (AG) generated by a short arm human centrifuges (SAHC) is proposed as the next generation of integrated countermeasure devices that will allow human beings to safely spend extended durations in space, although comparatively little is known about any psychological side effects of AG on brain function.     

Executive function on the 16-day of bed rest in young healthy men

Microgravity due to prolonged bed rest may cause changes in cerebral circulation, which is related to brain function. We evaluate the effect of simulated microgravity due to a 6° head-down tilt bed rest experiment on executive function among 12 healthy young men. Four kinds of psychoneurological tests—the table tapping test, the trail making test, the pointing test and losing at rock–paper–scissors—were performed on the baseline and on day 16 of the experiment. There was no significant difference in the results between the baseline and day 16 on all tests, which indicated that executive function was not impaired by the 16-day 6° head-down tilting bed rest. However, we cannot conclude that microgravity did not affect executive function because of the possible contribution of the following factors: (1) the timing of tests, (2) the learning effect, or (3) changes in psychophysiology that were too small to affect higher brain function.     

The properties of alamethicin incorporated into planar lipid bilayers under the influence of microgravity.

During evolution, life on earth had adapted to the gravity of 1g. Due to space flight, in the last decades the question arose what happens to the brain under microgravity on the molecular level. Ion channels among others are the molecular basis of brain function. Therefore, the investigation of ion channel function under microgravity seems to be a promising approach to gather knowledge on brain function during space flight. In a first step, the ion channel forming peptide Alamethicin was used as a model channel in an artificial membrane. It is well suitable for this kind of investigation, since its properties are well described under standard gravity. For that reason, changes due to microgravity can be detected easily. All experiments were performed in the German drop tower at ZARM-FAB, Bremen. A special set-up was constructed based on the bilayer technique introduced by Mueller and Rudin. All functions of this set-up can be observed and controlled remotely. In the first set of experiments, a dramatic change of electrical properties of Alamethicin under microgravity could be observed. Mainly, the pore frequency is significantly reduced.