Effects of daily artificial gravity training on orthostatic tolerance following 60-day strict head-down tilt bedrest.

PURPOSE: Orthostatic intolerance commonly occurs following immobilization or space flight. We hypothesized that daily artificial gravity training through short-arm centrifugation could help to maintain orthostatic tolerance following head-down tilt bedrest, which is an established terrestrial model for weightlessness. METHODS: We studied 24 healthy persons (eight women; age 33.3 ± 9.0 years; BMI 24.3 ± 2.1 kg/m2) who participated in the 60-days head-down tilt bedrest (AGBRESA) study. They were assigned to 30 min/day continuous or 6 × 5 min intermittent short-arm centrifugation with 1Gz at the center of mass or a control group. We performed head-up tilt testing with incremental lower-body negative pressure until presyncope before and after bedrest. We recorded an electrocardiogram, beat-to-beat finger blood pressure, and brachial blood pressure and obtained blood samples from an antecubital venous catheter. Orthostatic tolerance was defined as time to presyncope. We related changes in orthostatic tolerance to changes in plasma volume determined by carbon dioxide rebreathing. RESULTS: Compared with baseline measurements, supine and upright heart rate increased in all three groups following head-down tilt bedrest. Compared with baseline measurements, time to presyncope decreased by 323 ± 235 s with continuous centrifugation, by 296 ± 508 s with intermittent centrifugation, and by 801 ± 354 s in the control group (p = 0.0249 between interventions). The change in orthostatic tolerance was not correlated with changes in plasma volume. CONCLUSIONS: Daily artificial gravity training on a short-arm centrifuge attenuated the reduction in orthostatic tolerance after 60 days of head-down tilt bedrest.

Sixty days of head-down tilt bed rest with or without artificial gravity do not affect the neuromuscular secretome.

Artificial gravity is a potential countermeasure to attenuate effects of weightlessness during long-term spaceflight, including losses of muscle mass and function, possibly to some extent attributable to disturbed neuromuscular interaction. The 60-day AGBRESA bed-rest study was conducted with 24 participants (16 men, 8 women; 33 ± 9 years; 175 ± 9 cm; 74 ± 10 kg; 8 control group, 8 continuous (cAG) and 8 intermittent (iAG) centrifugation) to assess the impact of bed rest with or without daily 30-min continuous/intermittent centrifugation with 1G at the centre of mass. Fasting blood samples were collected before and on day 6, 20, 40 and 57 during 6° head-down tilt bed rest. Concentrations of circulating markers of muscle wasting (GDF-8/myostatin; slow skeletal muscle troponin T; prostaglandin E2), neurotrophic factors (BDNF; GDNF) and C-terminal Agrin Fragment (CAF) were determined by ELISAs. Creatine kinase activity was assessed by colorimetric enzyme assay. Repeated-measures ANOVAs were conducted with TIME as within-subject, and INTERVENTION and SEX as between-subject factors. The analyses revealed no significant effect of bed rest or sex on any of the parameters. Continuous or intermittent artificial gravity is a safe intervention that does not have a negative impact of the neuromuscular secretome.

Gravitational Force-Induced 3D Chromosomal Conformational Changes Are Associated with Rapid Transcriptional Response in Human T Cells.

The mechanisms underlying gravity perception in mammalian cells are unknown. We have recently discovered that the transcriptome of cells in the immune system, which is the most affected system during a spaceflight, responds rapidly and broadly to altered gravity. To pinpoint potential underlying mechanisms, we compared gene expression and three-dimensional (3D) chromosomal conformational changes in human Jurkat T cells during the short-term gravitational changes in parabolic flight and suborbital ballistic rocket flight experiments. We found that differential gene expression in gravity-responsive chromosomal regions, but not differentially regulated single genes, are highly conserved between different real altered gravity comparisons. These coupled gene expression effects in chromosomal regions could be explained by underlying chromatin structures. Based on a high-throughput chromatin conformation capture (Hi-C) analysis in altered gravity, we found that small chromosomes (chr16-22, with the exception of chr18) showed increased intra- and interchromosomal interactions in altered gravity, whereby large chromosomes showed decreased interactions. Finally, we detected a nonrandom overlap between Hi-C-identified chromosomal interacting regions and gravity-responsive chromosomal regions (GRCRs). We therefore demonstrate the first evidence that gravitational force-induced 3D chromosomal conformational changes are associated with rapid transcriptional response in human T cells. We propose a general model of cellular sensitivity to gravitational forces, where gravitational forces acting on the cellular membrane are rapidly and mechanically transduced through the cytoskeleton into the nucleus, moving chromosome territories to new conformation states and their genes into more expressive or repressive environments, finally resulting in region-specific differential gene expression.

Rapid Cellular Perception of Gravitational Forces in Human Jurkat T Cells and Transduction into Gene Expression Regulation.

Cellular processes are influenced in many ways by changes in gravitational force. In previous studies, we were able to demonstrate, in various cellular systems and research platforms that reactions and adaptation processes occur very rapidly after the onset of altered gravity. In this study we systematically compared differentially expressed gene transcript clusters (TCs) in human Jurkat T cells in microgravity provided by a suborbital ballistic rocket with vector-averaged gravity (vag) provided by a 2D clinostat. Additionally, we included 9× g centrifuge experiments and rigorous controls for excluding other factors of influence than gravity. We found that 11 TCs were significantly altered in 5 min of flight-induced and vector-averaged gravity. Among the annotated clusters were G3BP1, KPNB1, NUDT3, SFT2D2, and POMK. Our results revealed that less than 1% of all examined TCs show the same response in vag and flight-induced microgravity, while 38% of differentially regulated TCs identified during the hypergravity phase of the suborbital ballistic rocket flight could be verified with a 9× g ground centrifuge. In the 2D clinostat system, doing one full rotation per second, vector effects of the gravitational force are only nullified if the sensing mechanism requires 1 s or longer. Due to the fact that vag with an integration period of 1 s was not able to reproduce the results obtained in flight-induced microgravity, we conclude that the initial trigger of gene expression response to microgravity requires less than 1 s reaction time. Additionally, we discovered extensive gene expression differences caused by simple handling of the cell suspension in control experiments, which underlines the need for rigorous standardization regarding mechanical forces during cell culture experiments in general.

Autophagy protects HUVECs against ER stress-mediated apoptosis under simulated microgravity.

Astronauts exposed to a gravity-free environment experience cardiovascular deconditioning that causes post-spaceflight orthostatic intolerance and other pathological conditions. Endothelial dysfunction is an important factor responsible for this alteration. Our previous study showed enhanced autophagy in endothelial cells under simulated microgravity. The present study explored the cytoprotective role of autophagy under microgravity in human umbilical vein endothelial cells (HUVECs). We found that clinorotation for 48 h induced apoptosis and endoplasmic reticulum (ER) stress in HUVECs. ER stress and the unfolded protein response (UPR) partially contributed to apoptosis under clinorotation. Autophagy partially reduced ER stress and restored UPR signaling by autophagic clearance of ubiquitin-protein aggregates, thereby reducing apoptosis. In addition, the ER stress antagonist 4-phenylbutyric acid upregulated autophagy in HUVECs. Taken together, these findings indicate that autophagy plays a protective role against apoptosis under clinorotation by clearing protein aggregates and partially restoring the UPR.

Space headache on Earth: head-down-tilted bed rest studies simulating outer-space microgravity.

BACKGROUND: Headache is a common symptom during space travel, both isolated and as part of space motion syndrome. Head-down-tilted bed rest (HDTBR) studies are used to simulate outer space microgravity on Earth, and allow countermeasure interventions such as artificial gravity and training protocols, aimed at restoring microgravity-induced physiological changes. OBJECTIVES: The objectives of this article are to assess headache incidence and characteristics during HDTBR, and to evaluate the effects of countermeasures. METHODS: In a randomized cross-over design by the European Space Agency (ESA), 22 healthy male subjects, without primary headache history, underwent three periods of -6-degree HDTBR. In two of these episodes countermeasure protocols were added, with either centrifugation or aerobic exercise training protocols. Headache occurrence and characteristics were daily assessed using a specially designed questionnaire. RESULTS: In total 14/22 (63.6%) subjects reported a headache during ≥1 of the three HDTBR periods, in 12/14 (85.7%) non-specific, and two of 14 (14.4%) migraine. The occurrence of headache did not differ between HDTBR with and without countermeasures: 12/22 (54.5%) subjects vs. eight of 22 (36.4%) subjects; p = 0.20; 13/109 (11.9%) headache days vs. 36/213 (16.9%) headache days; p = 0.24). During countermeasures headaches were, however, more often mild (p = 0.03) and had fewer associated symptoms (p = 0.008). CONCLUSIONS: Simulated microgravity during HDTBR induces headache episodes, mostly on the first day. Countermeasures are useful in reducing headache severity and associated symptoms. Reversible, microgravity-induced cephalic fluid shift may cause headache, also on Earth. HDTBR can be used to study space headache on Earth.

Short-arm human centrifugation with 0.4g at eye and 0.75g at heart level provides similar cerebrovascular and cardiovascular responses to standing.

BACKGROUND AND PURPOSE: Orthostatic intolerance continues to be a problem with astronauts upon return to Earth as a result of cerebral and cardiovascular adaptations to weightlessness. We tested the hypothesis that artificial gravity from a short-arm human centrifuge (SAHC) could provide cerebral and cardiovascular stimuli similar to upright posture and thereby serve as a suitable countermeasure. METHODS: We compared cardiovascular and cerebrovascular responses before, during, and after exposure to hyper-G with that of standing in healthy young participants. The head was positioned such that the middle cerebral artery (MCA) was 0.46 m from the center of rotation. Two levels of hyper-G that provided 1g and 2g at foot level were investigated. Continuous blood pressure, heart rate, calf blood volume, MCA mean blood flow velocity (MFV) and end-tidal CO2 were measured. RESULTS: Blood pressure at the level of the MCA (BP-MCA) and MFV was reduced during stand and at 2g. The relationship between MFV and BP-MCA at 2g was different from supine and similar to standing, while 1g centrifugation was not different from supine. The cardiovascular system was also not different from supine at 1g but was similarly challenged in 2g compared to stand. CONCLUSIONS: Our data suggest that short-arm centrifugation 2g at the feet, with the head offset 0.5 m from the center, provides similar cardiovascular and cerebral responses to standing. This supports the hypothesis that passive 2g SAHC exposure at the feet could be used as a countermeasure for in-flight cardiovascular and cerebrovascular deconditioning.

[MORPHOLOGICAL ASPECTS OF CHANGES IN THE SPINAL GRAY MATTER DUE TO G-LOADS IN EXPERIMENT].

To study changes in spinal cord structures brought about by g-loads, laboratory animals (rats) were rotated on a centrifuge following a special procedure. Systematic g-loads along the craniocaudal axis resulted in reactive alterations, and also obvious destructive processes in the spinal gray matter (SGM). Light optical microscopy discovered that part of neurons had bodies with less intensive dying. Electron microscopy showed that among the cytoplasmic structures mitochondria were particularly sensitive to g-loads, which could affect mitochondrial oxidation. In the lumbar, these changes were observed in every segment under study; they were more significant in comparison with those found in cervical and thoracic segments of the spinal cord. Interneuron disintegration at neural centers revealed itself by the "light" type degeneration of synapses. Changes in capillaries included nuclei deformations and destruction of organelles in endotheliocytes, pericapillary edema, and erythrocytes sludge in the lumen. Inequality of spinal cord changes suggests the mosaic pattern of their distribution. Furthermore, their manifestation grew with the cranicaudal gradient so that the most conspicuous destructive developments occurred in the lumbar but not in the thoracic let alone the cervical segment. Acute g-loads gave rise to reactive changes in neurons and interneuron synapses that were the morphological markers of increased functional activity of neurons and activation of interneuron firing. In addition to the reactive changes, chronic g-loading also produced destructive disorders in GSM structures. These changes were not observed following acute g-loads and, therefore, resulted from multiple g-exposures and were cumulative.

Simulations of gravitational stress on normovolemic and hypovolemic men and women.

BACKGROUND: Earth-based simulations of physiologic responses to space mission activities are needed to develop prospective countermeasures. To determine whether upright lower body positive pressure (LBPP) provides a suitable space mission simulation, we investigated the cardiovascular responses of normovolemic and hypovolemic men and women to supine and orthostatic stress induced by head-up tilt (HUT) and upright LBPP, representing standing in lunar, Martian, and Earth gravities. METHODS: Six men and six women were tested in normovolemic and hypovolemic (furosemide, intravenous, 0.5 mg x kg(-1)) conditions. Continuous electrocardiogram, blood pressure, segmental bioimpedance, and stroke volume (echocardiography) were recorded supine and at lunar, Martian, and Earth gravities (10 degrees, 20 degrees, and 80 degrees HUT vs. 20%, 40%, and 100% bodyweight upright LBPP), respectively. Cardiovascular responses were assessed from mean values, spectral powers, and spontaneous baroreflex parameters. RESULTS: Hypovolemia reduced plasma volume by approximately 10% and stroke volume by approximately 25% at supine, and increasing orthostatic stress resulted in further reductions. Upright LBPP induced more plasma volume losses at simulated lunar and Martian gravities compared with HUT, while both techniques induced comparable central hypovolemia at each stress. Cardiovascular responses to orthostatic stress were comparable between HUT and upright LBPP in both normovolemic and hypovolemic conditions; however, hypovolemic blood pressure was greater during standing at 100% bodyweight compared to 80 degree HUT due to a greater increase of total peripheral resistance. CONCLUSIONS: The comparable cardiovascular response to HUT and upright LBPP support the use of upright LBPP as a potential model to simulate activity in lunar and Martian gravities.

Cerebrovascular autoregulation: lessons learned from spaceflight research.

This review summarizes our current understanding of cerebral blood flow regulation with exposure to microgravity, outlines potential mechanisms associated with post-flight orthostatic intolerance, and proposes future directions for research and linkages with cerebrovascular disorders found in the general population. It encompasses research from cellular mechanisms (e.g. hind limb suspension: tissue, animal studies) to whole body analysis with respect to understanding human responses using space analogue studies (bed rest, parabolic flight) as well as data collected before, during, and after spaceflight. Recent evidence indicates that cerebrovascular autoregulation may be impaired in some astronauts leading to increased susceptibility to syncope upon return to a gravitational environment. The proposed review not only provides insights into the mechanisms of post-flight orthostatic intolerance, but also increases our understanding of the mechanisms associated with pathophysiological conditions (e.g. unexplained syncope) with clinical applications in relation to postural hypotension or intradialytic hypotension.

Psychoneuroendocrine alterations during 5 days of head-down tilt bed rest and artificial gravity interventions.

This study aimed to investigate psychological stress and endocrine responses during 5 days of head-down tilt bed rest (HDTBR) with or without the impact of artificial gravity (AG). Participants were assigned to one of three bed-rest-protocols either with (i) no centrifugation, (ii) continuous 30 min (AG1) or (iii) discontinuous 6 × 5 min (AG2) centrifugation periods at 1G in the center of mass periods. Centrifugations were performed daily in one session. Questionnaires for assessing psychological stress and the corresponding biological sample collection were performed before, during and after HDTBR or centrifugation. Overall, questionnaires showed no significant changes of anxiety or emotional stress during HDTBR. In the AG1-group, salivary cortisol levels were significantly higher after centrifugation irrespective of the progress of the HDTBR and day of intervention. The AG2-group showed higher cortisol concentrations after centrifugation only on the first days of head-down tilt but no more on day 5 of HDTBR. During bed rest, urine epinephrine excretion increased in all groups, but showed the highest day concentrations in the AG1-group, which were also significantly higher when compared with AG2. These results indicate that 5 days of HDT alone is not a major stressor and accordingly resulted only in moderate changes of neuroendocrine responses over time. However, daily centrifugation for a continuous duration of 30 min induced a significant neuroendocrine response, which was not subject to a habituation as compared with daily but intermittent centrifugation for 6 × 5 min. Discontinuous centrifugation is better tolerated and associated with lower adrenocortical stress responses during HDTBR.

Artificial gravity with ergometric exercise as a countermeasure against cardiovascular deconditioning during 4 days of head-down bed rest in humans.

We have shown previously that combined short-arm centrifuge and aerobic exercise training preserved several physiologically important cardiovascular functions in humans. We hypothesized that artificial gravity (AG) and exercise is effective to prevent changes of physical problems during head-down bed rest (HDBR). To test this hypothesis, 12 healthy male subjects had undergone 4 days of 6° HDBR. Six of them were exposed to AG of an alternating 2-min intervals of +1.0 and +2.0 Gz at foot level for 30 min twice per day with ergometric exercise of 40 W as a countermeasure during bed rest (CM group), while the remaining six served as untreated controls (no-CM group). Before and after 4 days of bed rest, leg venous hemodynamics was assessed by venous occlusion plethysmography and autonomic cardiovascular control estimated by power spectral analysis of blood pressure and heart rate. Further, orthostatic tolerance was evaluated by a 75° head-up tilt test and physical working capacity was surveyed by near maximal physical working capacity test before and after bed rest. The data showed that combined centrifuge and exercise applied twice daily for a total of 60 min during 4 days of HDBR prevented (a) a decrease in working capacity, (b) autonomic dysfunction (a decrease in the activity of parasympathetic cardiac innervation) and (c) an increase in leg venous flow resistance. The combination of a 30 min alternating of +1.0 and +2.0 Gz for twice per day of AG with 40 W ergometric exercise may offer a promising countermeasure to short duration simulated microgravity.

[Indicators of innate and adaptive immunity of cosmonauts after long-term space flight to international space station].

Results of innate and adaptive immunity indicators research at 12 cosmonauts who took part in long (128-215 days) expeditions to the International space station (ISS) are presented. It is shown that a space flight can lead to deflection of deviations in human immune system. These shifts occurred in decrease of phagocytes, NK, T-lymphocytes functional activity and also in abilities of immunocompetent cells to synthesize cytokines. Significant individual changes are noted in reaction of immune system to the long term space flight conditions specifying on individual predisposition to development of immune reactance infringements in the conditions of varying gravitational influences.

Tolerability of daily intermittent or continuous short-arm centrifugation during 60-day 6o head down bed rest (AGBRESA study).

Artificial gravity through short-arm centrifugation has potential as a multi-system countermeasure for deconditioning and cranial fluid shifts that may underlie ocular issues in microgravity. However, the optimal short-arm centrifugation protocol that is effective whilst remaining tolerable has yet to be determined. Given that exposure to centrifugation is associated with presyncope and syncope and in addition motion sickness an intermittent protocol has been suggested to be more tolerable. Therefore, we assessed cardiovascular loading and subjective tolerability of daily short arm centrifugation with either an intermittent or a continuous protocol during long-term head-down bed rest as model for microgravity exposure in a mixed sex cohort. During the Artificial Gravity Bed Rest with European Space Agency (AGBRESA) 60 day 6° head down tilt bed rest study we compared the tolerability of daily +1 Gz exposure at the center of mass centrifugation, either performed continuously for 30 minutes, or intermittedly (6 x 5 minutes). Heart rate and blood pressure were assessed daily during centrifugation along with post motion sickness scoring and rate of perceived exertion. During bed rest, 16 subjects (6 women, 10 men), underwent 960 centrifuge runs in total. Ten centrifuge runs had to be terminated prematurely, 8 continuous runs and 2 intermittent runs, mostly due to pre-syncopal symptoms and not motion sickness. All subjects were, however, able to resume centrifuge training on subsequent days. We conclude that both continuous and intermittent short-arm centrifugation protocols providing artificial gravity equivalent to +1 Gz at the center of mass is tolerable in terms of cardiovascular loading and motion sickness during long-term head down tilt bed rest. However, intermittent centrifugation appears marginally better tolerated, albeit differences appear minor.

Motion sickness symptoms during jumping exercise on a short-arm centrifuge.

Artificial gravity elicited through short-arm human centrifugation combined with physical exercise, such as jumping, is promising in maintaining health and performance during space travel. However, motion sickness symptoms could limit the tolerability of the approach. Therefore, we determined the feasibility and tolerability, particularly occurrence of motion sickness symptoms, during reactive jumping exercises on a short-arm centrifuge. In 15 healthy men, we assessed motion sickness induced by jumping exercises during short-arm centrifugation at constant +1Gz or randomized variable +0.5, +0.75, +1, +1.25 and +1.5 Gz along the body axis referenced to center of mass. Jumping in the upright position served as control intervention. Test sessions were conducted on separate days in a randomized and cross-over fashion. All participants tolerated jumping exercises against terrestrial gravity and on the short-arm centrifuge during 1 Gz or variable Gz at the center of mass without disabling motion sickness symptoms. While head movements markedly differed, motion sickness scores were only modestly increased with jumping on the short-arm centrifuge compared with vertical jumps. Our study demonstrates that repetitive jumping exercises are feasible and tolerable during short-arm centrifugation. Since jumping exercises maintain muscle and bone mass, our study enables further development of exercise countermeasures in artificial gravity.

Parabolic flight primes cytotoxic capabilities of polymorphonuclear leucocytes in humans.

BACKGROUND: Previously performed in vitro studies suggested that gravitational stress may alter functions of immune cells. This study investigated the in vivo effects of parabolic flight manoeuvres as a short-term model of micro- and hypergravity on the cytotoxic and microbicidal polymorphonuclear leucocyte (PMN) functions as the key element of innate immunity. MATERIAL AND METHODS: Twenty-one healthy male volunteers underwent 30 subsequent parabolic flight manoeuvres. Each manoeuvre produced 22-s periods of nearly weightlessness close to <<0g>>, with each parabola starting with a pull-up and ending with a pull-out (hypergravity) at 1.8 g for about 20 s each. Blood samples were drawn 24 h prior to take off (T0), after 25-30 parabolas (T1), and 24 h (T2) and 48 h (T3) after flight for determination of (i) leucocyte number and subpopulations, (ii) PMNs' capabilities to produce hydrogen peroxide (H(2)O(2)) and to adhere and phagocytose particles and (iii) plasma cytokines known to prime PMN functions [interleukin-8 (IL-8), tumour necrosis factor-alpha (TNF-alpha), granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF)]. RESULTS: Parabolic flight induced an increase in leucocyte number with a significant elevation of the PMN fraction. The spontaneous H(2)O(2) production by PMNs did not change; however, the capability of PMNs to produce H(2)O(2) in response to soluble stimuli [N-formyl-methionyl-leucyl-phenylalanine (fMLP), fMLP and TNF-alpha, calcium ionophore (A23187), phorbol myristate acetate (PMA)] was increased. Adhesive and phagocytic properties of PMNs were not altered. Regarding priming cytokines, IL-8 and G-CSF were significantly elevated. CONCLUSIONS: Our data indicate that parabolic flight induces priming of the cytotoxic capabilities of PMNs without affecting microbicidal functions.

A standardized, incremental protocol to increase human tolerance to the cross-coupled illusion.

BACKGROUND: Humans can adapt to the "Coriolis" cross-coupled illusion with repeated exposure, improving the tolerability of faster spin rates and enabling short-radius, intermittent centrifugation for artificial gravity implementation. OBJECTIVE: This investigation assesses the criticality of personalization in acclimation to the cross-coupled illusion. METHODS: We used the median stimulus sequence of our previous effective and tolerable personalized, threshold-based protocol to develop a standardized (non-personalized) approach. During each of 10, 25-minute sessions, the spin rate was incremented independent of whether each subject reported experiencing the cross-coupled illusion. RESULTS: In comparison to the previous personalized protocol, the standardized protocol resulted in significantly reduced acclimation to the cross-coupled illusion (17.7 RPM threshold for the personalized protocol versus 11.8 RPM threshold for the standardized) and generally increased motion sickness reports (average reporting of 1.08/20 (personalized) versus 1.98/20 (standardized)), on average. However, the lack of individualization also leads to significantly less variance in subjects' acclimation. CONCLUSIONS: These findings are critical for future missions that may require several astronauts to be acclimated concurrently, due to resource and time constraints. Assessing feasibility of fast spin rate, short-radius centrifugation is crucial for the future of artificial gravity implementation during spaceflight.

Tolerable acclimation to the cross-coupled illusion through a 10-day, incremental, personalized protocol.

BACKGROUNDArtificial gravity (AG) has the potential to provide a comprehensive countermeasure mitigating deleterious effects of microgravity. However, the cross-coupled "Coriolis" illusion has prevented using a more feasible and less costly short-radius centrifuge, as compared to large, slowly spinning systems.OBJECTIVEWe assessed tolerability of a personalized, incremental protocol to acclimate humans to the cross-coupled illusion, enabling faster spin rates.METHODSTen subjects were exposed to the illusion by performing roll head tilts while seated upright and spun about an Earth-vertical axis. The spin rate was incremented when head tilts did not subjectively elicit the illusion. Subjects completed one 25-minute session on each of 10 days.RESULTSThe spin rate at which subjects felt no cross-coupled illusion increased in all subjects from an average of 1.8 rotations per minute (RPM) (SD: ±0.9) at the beginning of the protocol to 17.7 RPM (SD: ±9.1) at the end. For off-axis centrifugation producing 1G at the rider's feet, this corresponds to a reduction in the required centrifuge diameter from 552.2 to 5.7 meters. Subjects reported no more than slight motion sickness.CONCLUSIONSAcclimation to the cross-coupled illusion, such as that accomplished here, is critical for feasibility of short-radius centrifugation for AG implementation.

[The problem of artificial gravity: the present status and possible approaches].

The author reviews the Russian and international literature on the potentialities of artificial gravity in extended piloted space flights, especially in view of the declared initiatives to set forth on exploration missions in the first part of this century. Physical deconditioning and loss of tolerance to the gravitational loads consistently have their effects on cosmonauts despite the large assortment of in-flight preventive procedures. Effectiveness of artificial gravity generated by the short-arm centrifuge (SAC) has been assessed in experiments simulating the physiological consequences of microgravity by immersion or HDT, and flown aboard the dedicated satellites. It is emphasized that all the data indiscriminately indicate effectiveness of SAC as a preventive and therapeutic instrument alleviating the negative effects of modeled microgravity. Open issues and research objectives are presented.

Effect of G-force on bicuspid aortic valve in aviators.

BACKGROUND AND AIMS: Bicuspid aortic valve (BAV) is a common congenital cardiac malformation. The major complications are aortic stenosis (AS), aortic regurgitation (AR), infectious endocarditis and aortic dissection. This paper aims to assess the hemodynamic importance of incidentally-found BAV in military aviators and evaluate the effect of high G-force on disease progression. METHODS: Aviators with BAV were detected by reviewing all cardiac assessment records between 1987 and 2005. All aviators underwent annual flight surgeon examination. Echocardiography was performed as recommended by our cardiologists and flight surgeons. RESULTS: Eight newly diagnosed cases of BAV were found. All of the aviators continued active aviation throughout the study period. Repeat echocardiography demonstrated progressive widening of the aortic diameter in five of the eight aviators. No worsening of valve dysfunction was seen in those with mild aortic regurgitation at diagnosis. Left ventricular dimensions and function did not deteriorate. No new valve complications, including infectious endocarditis, were seen. The age at diagnosis strongly correlated with the root diameter change; both total (r = 0.74, p = 0.02) and annualized (r = 0.78, p = 0.02) change. Over a mean follow-up period of 12.1 years, no difference was seen in the progression of BAV in high-performance as compared to low-performance aviators. CONCLUSIONS: Exposure to G-force and anti-G maneuvers does not appear to worsen cardiac and valve function in aviators with BAV.