System identification of dynamic closed-loop control of total peripheral resistance by arterial and cardiopulmonary baroreceptors.

Prolonged exposure to microgravity in space flight missions (days) impairs the mechanisms responsible for defense of arterial blood pressure (ABP) and cardiac output (CO) against orthostatic stress in the post-flight period. The mechanisms responsible for the observed orthostatic intolerance are not yet completely understood. Additionally, effective counter measures to attenuate this pathophysiological response are not available. The aim of this study was to investigate the ability of our proposed system identification method to predict closed-loop dynamic changes in TPR induced by changes in mean arterial pressure (MAP) and right atrial pressure (RAP). For this purpose we designed and employed a novel experimental animal model for the examination of arterial and cardiopulmonary baroreceptors in the dynamic closed-loop control of total peripheral resistance (TPR), and applied system identification to the analysis of beat-to-beat fluctuations in the measured signals. Grant numbers: NAG5-4989.     

Correlation of macro and micro cardiovascular function during weightlessness and simulated weightlessness

The investigation of cardiovascular function necessarily involves a consideration of the exchange of substances at the capillary. If cardiovascular function is compromised or in any way altered during exposure to zero gravity in space, then it stands to reason that microvascular function is also modified. We have shown that an increase in cardiac output similar to that reported during simulated weightlessness is associated with a doubling of the number of post-capillary venules and a reduction in the number of arterioles by 35%. If the weightlessness of space travel produces similar changes in cardiopulmonary volume and cardiac output, a reasonable expectation is that astronauts will undergo venous neovascularization. We have developed an animal model in which to correlate microvascular and systemic cardiovascular function. The microcirculatory preparation consists of a lightweight, thermo-neutral chamber implanted around intact skeletal muscle on the back of a rat. Using this technique, the performed microvasculature of the cutaneous maximus muscle may be observed in the conscious, unanesthetized animal. Microcirculatory variables which may be obtained include venular and arteriolar numbers, lengths and diameters, single vessel flow velocities, vasomotion, capillary hematocrit anastomoses and orders of branching. Systemic hemodynamic monitoring of cardiac output by electromagnetic flowmetry, and arterial and venous pressures allows correlation of macro- and microcirculatory changes at the same time, in the same animal. Observed and calculated hemodynamic variables also include pulse pressure, heart rate, stroke volume, total peripheral resistance, aortic compliance, minute work, peak aortic flow velocity and systolic time interval. In this manner, an integrated assessment of total cardiovascular function may be obtained in the same animal without the complicating influence of anesthetics.     

CCISS,Vascular and BP Reg: Canadian space life science research on ISS

A comprehensive goal of the Canadian Space Agency studies (CCISS, Vascular and BP Reg) has been to investigate the efficacy of current exercise countermeasures to maintain cardiovascular and cerebrovascular health on return to Earth after up to 6-months in space. Results from the CCISS experiments revealed no significant change of in-flight heart rate during daily activities or sleep, and small, but variable between astronauts, post-flight elevation. The between astronaut differences were exaggerated during measurement of spontaneous baroreflex slope, which was reduced post-flight (P<0.05) during paced breathing with 3 astronauts having significant correlations between reduced baroreflex and reduced RR-interval (consistent with reduced fitness). Cerebrovascular autoregulation and CO₂ response were mildly impaired after flight. Some loss of in-flight fitness of astronauts in Vascular was reflected by the increase in HR at a work rate of 161±46 W of 12.3±10.5 bpm, 10.4±5.9 bpm and 13.4±5.7 bpm for early-flight, late-flight and R+1, respectively. On return to gravity, changes in resting heart rate for supine (5.9±3.5 bpm), sit (8.1±3.3 bpm) and stand (10.3±10.0 bpm) were small but variable between individuals (from −5 bpm to +20 bpm in post-flight standing) and not related to the change in exercise heart rate. In Vascular astronauts, pulse wave transit time measured to the finger tended to be reduced post-flight and carotid artery distensibility was significantly reduced (P=0.03, and n=6). The heart rate and baroreflex data suggest that some astronauts return with cardiovascular deconditioning in spite of the exercise regimes. However, greater arterial stiffness is common among all astronauts studied to date. The new CSA project, BP Reg, will monitor inflight blood pressure in an attempt to identify astronauts in greater need for countermeasures. Future research should focus on whether Vascular changes in astronauts might make them an appropriate model to study the mechanisms of arterial aging on Earth.     

The physical price of a ticket into space

As a direct consequence of exposure to microgravity astronauts experience a number of physiological changes, which can have serious medical implications when they return to Earth. Most immediate and significant are the head-ward shift of body fluids and the removal of gravitational loading from bone and muscles, which lead to progressive changes in the cardiovascular and musculoskeletal systems. Cardiovascular adaptations result in an increased incidence of orthostatic intolerance (fainting) post-flight, decreased cardiac output and reduced exercise capacity. Changes in the musculoskeletal system contribute significantly to the impaired functions experienced in the post-flight period. The underlying factor producing these changes is the absence of gravity. Countermeasures, therefore, are designed primarily to simulate Earth-like movements, stresses and system interactions. Exercise is one approach that has received wide operational use and acceptance in both the US and Russian space programmes, and has enabled humans to stay relatively healthy in space for well over a year. Although it remains the most effective countermeasure currently available, significant physiological degradation still occurs. The development of other countermeasures will therefore be necessary for longer duration missions, such as the human exploration of Mars.     

Cardiovascular effects of simulated zero-gravity in humans

Head-down and head-up [correction of heat-up] tilted bedrest (5 degrees) and head out water immersion (HOWI) for 6 hr were compared. Parameters: Cardiac output (rebreathing method), blood pressure (arm cuff), forearm blood flow (venous occlusion plethysmography), total peripheral (TPR), and forearm vascular (FVR) resistances, Hct, Hb, relative plasma volume (PV) changes, and plasma catecholamines (single-isotope assay). During HOWI there was as expected a decrement in TPR, FVR, Mean arterial pressure (MAP, from 100 to 80 mmHg), Hct, and PV, and--as a new finding--catecholamines, which were 30-50% lower compared with both +5 and -5 degrees bedrest. During head down tilt, MAP was elevated (to 100-110 mmHg) and catecholamines did not fall, while TPR and EVR slowly decreased over 6 hr. HOWI is a stronger stimulus than -5 degrees bedrest, probably because HOWI elevates central venous pressure more markedly emptying the peripheral veins, while bedrest permits a distension of veins, which induces an increase in sympathetic nervous activity.     

Vascular functions in humans following cardiovascular adaptations to spaceflight

Purpose: Diminished vascular function is a primary cardiovascular risk of spaceflight identified in the 2004 NASA Bioastronautics Critical Path Roadmap based on: (1) structural and functional alterations in arterial vessels of animals undergoing hindlimb unloading and; (2) lower peripheral vascular resistance (PVR) in astronauts who became presyncopal after spaceflight.Methods: We conducted a critical review of published data obtained from spaceflight and relevant ground-based microgravity simulations in an effort to interpret the meaning of altered responses in PVR and their relationship to postflight presyncope.Results: Presyncope reported in astronauts on landing day was associated with lower peripheral resistance. However, non-presyncopal astronauts demonstrated significantly elevated vascular resistance in the upright posture after compared with before spaceflight. Results from both space and ground experiments suggest that preflight maximal vasoconstrictor capacity is inherently lower in presyncopal astronauts, but unaltered by spaceflight.Conclusions: Vasoconstrictor reserve is associated with lower blood volume adaptation to microgravity. Rather than reduced vascular function, low inherent maximal vasoconstrictor capacity and reduced vasoconstrictor reserve secondary to decreased circulating vascular volume explain lower peripheral vascular resistance in astronauts who experience presyncopal episodes on landing day.     

Autonomic function testing aboard the ISS using “PNEUMOCARD”

Investigations of blood pressure, heart rate (HR), and heart rate variability (HRV) during long term space flights on board the “ISS” have shown characteristic changes of autonomic cardiovascular control. Therefore, alterations of the autonomic nervous system occurring during spaceflight may be responsible for in- and post-flight disturbances. The device “Pneumocard” was developed to further investigate autonomic cardiovascular and respiratory function aboard the ISS. The hard-software diagnostic complex “Pneumocard” was used during in-flight experiment aboard ISS for autonomic function testing. ECG, photoplethysmography, respiration, transthoracic bioimpedance and seismocardiography were assessed in one male cosmonaut (flight lengths six month). Recordings were made prior to the flight, late during flight, and post-flight during spontaneous respiration and controlled respiration at different rates.HR remained stable during flight. The values were comparable to supine measurements on earth. Respiratory frequency and blood pressure decreased during flight. Post flight HR and BP values increased compared to in-flight data exceeding pre-flight values. Cardiac time intervals did not change dramatically during flight. Pulse wave transit time decreased during flight. The maximum of the first time derivative of the impedance cardiogram, which is highly correlated with stroke volume was not reduced in-flight.Our results demonstrate that autonomic function testing aboard the ISS using “Pneumocard” is feasible and generates data of good quality. Despite the decrease in BP, pulse wave transit time was found reduced in space as shown earlier. However, cardiac output did not decrease profoundly in the investigated cosmonaut.Autonomic testing during space flight detects individual changes in cardiovascular control and may add important information to standard medical control. The recent plans to support a flight to Mars, makes these kinds of observations all the more relevant and compelling.     

Hemodynamic and neurohormonal responses to extreme orthostatic stress in physically fit young adults

Blood pressure stability may be jeopardized in astronauts experiencing orthostatic stress. There is disagreement about cardiovascular and endocrine stress responses that emerge when a critical (presyncopal) state is reached. We studied hemodynamic and neurohormonal changes as induced by an orthostatic stress paradigm (head-up tilt combined with lower body negative pressure) that leads to a syncopal endpoint. From supine control to presyncope, heart rate increased by 78% and thoracic impedance by 12%. There was a 49% fall in stroke volume index, 19% in mean arterial blood pressure, 14% in total peripheral resistance index and 11% in plasma volume. Plasma norepinephrine rose by 107, epinephrine by 491, plasma renin activity by 167, and cortisol by 25%. Hemodynamic and hormonal changes of clearly different magnitude emerge in presyncope as compared to supine rest. Additional studies are warranted to reveal the exact time course of orthostatic changes up to syncopal levels.     

Cardiovascular reflexes during rest and exercise modified by gravitational stresses.

The hypotheses tested were whether variations in central venous pressure via the low pressure baroreceptors would take over or modify the arterial baroreceptor function, and further to which extent local and "whole body" hydrostatic stresses influence blood flow distribution. We investigated total forearm and skin blood flow (venous occlusion plethysmography and 133-Xe clearance) and cardiac output (rebreathing method) among other parameters. Hypo- and hyper-gravitational stresses were simulated by LBNP, LBPP, water immersion and lowering of the arm. The changes in flow distribution in the arm were ascribed to arterial baroreceptor function and not to low pressure baroreceptor activity. The enhancement of venous return during water immersion increased exercise tolerance during heat stress presumably due both to increased stroke volume and decreased venous pooling. The response to sustained handgrip exercise during LBNP and LBPP was not different from control measurements and the effects explained by arterial baroreceptor function. Application of exercise and local hydrostatic stresses in combination with gravitational stresses represent an interesting model for further study of the mechanisms behind the distribution of cardiac output to the peripheral organs.     

First results from experiments performed with the ESA Anthrorack during the D-2 Spacelab mission

In 1993 four astronauts performed physiological experiments on the payload "Anthrorack" during the second German Spacelab mission D-2. The Anthrorack set-up is a Spacelab double rack developed under the management of the European Space Agency. It consists of an ECHO machine, a respiratory monitoring system (gas analyzer with flow meter), a blood centrifuge, an ergometer, a finger blood pressure device, ECG, body impedance measurement device and a respiratory inductance plethysmograph. Experiment-specific equipment was used as well. Nineteen investigators performed experiments in the cardiovascular, pulmonary, fluid-renal and nutritional physiology area. Results on central venous pressure, ocular pressure, vascular resistance, cardiac output, tissue thickness and orthostatic intolerance are presented in the cardiovascular area. In the pulmonary area first results are mentioned on O2 transport perfusion and ventilation distribution and breathing pattern. From the fluid-renal experiments, data from diuresis, sodium excretion and hormonal determinations are given. Finally results from glucose metabolism and nitrogen turnover experiments are presented.     

Biomedical performance monitoring and assessment of astronauts by means of an ocular–vestibular monitoring system

The paper focuses on the strong correlation between unmitigated symptoms exhibited by post Space flight astronauts, and symptoms associated with postural deficiency syndrome (PDS) that can be correctly assessed, identified, and monitored via a neurophysiological ocular–vestibular monitoring system (OVMS). From examining clinical data taken over a 10-year period from patients experiencing PDS related acute and chronic post-traumatic medical conditions, the authors show the potential for current assessment and monitoring techniques to examine better the impacts on astronaut neurophysiology. The data presented provide strong evidence that this biomedical monitoring and assessment methodology along with appropriate technology can lead to a better understanding of astronaut post-flight neurophysiology, which is necessary if human exploration in Space is to continue on a successful path.     

Universal values of Canadian astronauts

Values are desirable, trans-situational goals, varying in importance, that guide behavior. Research has demonstrated that universal values may alter in importance as a result of major life events. The present study examines the effect of spaceflight and the demands of astronauts' job position as life circumstances that affect value priorities. We employed thematic content analysis for references to Schwartz’s well-established value markers in narratives (media interviews, journals, and pre-flight interviews) of seven Canadian astronauts and compared the results to the values of National Aeronautics and Space Administration (NASA) and Russian Space Agency (RKA) astronauts.Space flight did alter the level of importance of Canadian astronauts’ values. We found a U-shaped pattern for the values of Achievement and Tradition before, during, and after flight, and a linear decrease in the value of Stimulation. The most frequently mentioned values were Achievement, Universalism, Security, and Self-Direction. Achievement and Self Direction are also within the top 4 values of all other astronauts; however, Universalism was significantly higher among the Canadian astronauts. Within the value hierarchy of Canadian astronauts, Security was the third most frequently mentioned value, while it is in seventh place for all other astronauts. Interestingly, the most often mentioned value marker (sub-category) in this category was Patriotism. The findings have important implications in understanding multi-national crew relations during training, flight, and reintegration into society.     

Cardiac and vascular adaptation to 0g with and without thigh cuffs (Antares 14 and Altair 21 day Mir spaceflights)

Cardiovascular Actaptation was evaluated on 2 astronauts: one wearing thigh cuffs from flight day 1 to 8 (14d flight), the second without cuffs (21d flight). Ultrasound investigations were performed at rest and during LBNP. Results: Without thigh cuffs the cardiovascular Actaptation consists in (1) the development of a hypovolemia with an increase of the heart rate and the cardiac output, (2) the decrease of the vascular tone in the deep (mesenteric and splanchnic) and peripheral (Lower limbs) vascular areas. The use of thigh cuffs maintains the volemia and the cardiac output at the preflight level (without heart rate increase) and prevents the loss of vascular tone in the deep and peripheral areas. Moreover the adaptative process changes since the cuffs are removed and even the volemia seems to be unaffected at this stage the vascular tone decreases to a comparable extend as during the flight without cuffs. Nevertheless during the flight without cuffs or 3 days after removing the cuffs hemodynamic signs of decreased orthostatic tolerance are present during the inflight and the 3 days post flight LBNP. Presently the possible contribution of the thigh cuffs to the reduction of the vascular deconditioning has not been tested yet.     

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.     

Effect of the thigh-cuffs on the carotid artery diameter jugular vein section and facial skin edema: HDT study.

Objective: To evaluate the distal arterial, venous and skin changes in a group using thigh cuffs during daytime and in a control group. Method: Cardiac, arterial, venous parameters were measured by echography and Doppler. Skin thickness was measured by high frequency echography. Results & discussion: Head down position induced plasma volume reduction, increased cerebral resistance, reduced lower limb resistance. The jugular vein increased whereas the femoral and popliteal veins decreased. All these changes were already observed in previous HDT. Common carotid diameter decreased, Front head skin thickness increased and Tibial skin thickness decreased. Eight hours with thigh cuffs increased the cardiac and carotid sizes which is in agreement with the plasma volume increase. Conversely they reduced the cerebral vascular resistance, jugular section and front head edema which may explain the sensation of comfort reported by the subjects. At the lower limb level the thigh cuffs restored the skin thickness to pre-HDT level but enlarged markedly the femoral and popliteal veins. HR, BP, CO, TPR did not change.     

Psychological adaptation and salutogenesis in space: Lessons from a series of studies

Individuals who adapt positively to an inhospitable or extreme environment can derive benefit from their experiences. This positive effect may include an initial improvement in mental health as someone adjusts to the environment (adaptation) as well as more sustained personal growth during the mission (salutogenesis). We review relevant findings from our prior work, including two post-mission surveys of astronauts and cosmonauts, and three studies of crewmembers during missions in a space station simulator, the Mir space station, and the International Space Station (ISS). We also present new analyses showing evidence for adaptation to ISS missions. This finding replicates our previous results from the simulation study, but this effect was not found on the Mir. A better understanding of psychological adaptation and salutogenesis during space flight should help us develop strategies to enhance crewmembers’ in-flight stress tolerance and post-flight adjustment.     

Influence of graviceptives cues at different level of visual information processing: the effect of prolonged weightlessness

We evaluated the influence of prolonged weightlessness on the performance of visual tasks in the course of the Russian-French missions ANTARES, Post-ANTARES and ALTAIR aboard the MIR station. Eight cosmonauts were subjects in two experiments executed pre-flight, in-flight and post-flight sessions.

In the first experiment, cosmonauts performed a task of symmetry detection in 2-D polygons. The results indicate that this detection is locked in a head retinal reference frame rather than in an environmentally defined one as meridional orientations of symmetry axis (vertical and horizontal) elicited faster response times than oblique ones. However, in weightlessness the saliency of a retinally vertical axis of symmetry is no longer significantly different from an horizontal axis. In the second experiment, cosmonauts performed a mental rotation task in which they judged whether two 3-D objects presented in different orientations were identical. Performance on this task is basically identical in weightlessness and normal gravity.     

Effects of repeated long duration +2Gz load on man's cardiovascular function

Usefulness of a short-arm human centrifuge is expected when it is used in space as a countermeasure against cardiovascular deconditioning, problem of bone-calcium metabolism, etc. However, nothing is solidly established regarding the most desirable program for artificial G application. Accordingly, this study was designed to analytically evaluate the effects of repeated long duration +Gz load on human cardiovascular function. Recently heart rate spectral analysis has been recognized as a powerful tool for quantitatively evaluating parasympathetic and sympathetic activity separately in human. It is reported that power of the high frequency component (HF-p) is mediated selectively by parasympathetic activity and the power ratio of low to high frequency components(LF/HF) is indicative of cardiac sympathetic activity or cardiac sympathovagal balance. Sequence method is developed to examine spontaneous baroreceptor reflex sensitivity (BRS). We studied cardiovascular control function by using these methods in 9 healthy men before and after 7 days of daily repeated 1hour +2Gz load. When compared with the data of pre-G load period, post-G load period, decrease of HR, increases of HF-p and BRS were statistically significant. SBP, DBP and LF/HF tended to decrease, however, these changes were not statistically significant. This results indicate that repeated +2Gz load increases parasympathetic activity and arterial baroreceptor-cardiac reflex sensitivity. In recent years, many investigators suggest that space flight and head-down bedrest leads to impaired baroreceptor-cardiac reflex responses and decrease of parasympathetic activity, which may contribute to orthostatic intolerance. So our results suggest that daily repeated 1hour +2Gz load would be useful in preventing post-flight orthostatic intolerance.     

Effects of space flights on human allergic status (IgE-mediated sensitivity)

Suppression of the immune system after space flights of different duration has been reported earlier by Konstantinova [Immune system in extreme conditions, Space immunology. B. 59. M. Science 1988. 289p. (in Russian) [4]; Immunoresistance of man in space flight, Acta Astronautica 23 (1991) 123–127 [5]]. Changes in T- and B-mediated activities of the immune system were demonstrated during and after space flight. However, the influence of the space flight conditions on the allergic status of cosmonauts and astronauts is still unclear. The goal of this investigation was to analyze total blood IgE levels, specific IgE-antibodies and interleukin-4 in blood of Russian crew members before and after space flights to the International Space Station (ISS) and during a long-term isolation study. For this purpose, we used the ELISA assays as well as other special kits. It was noticed that four out of nine cosmonauts had high total serum IgE (more than normal clinical values of 120 IU/ml). At the same time, there were no statistically significant changes in serum IgE levels before and after long-term space flights (128–195 days). A similar situation was observed regarding preflight IgE levels of cosmonauts who performed short-term flights (7–11 days). However, seven out of 11 cosmonauts had increased IgE level in blood post short flights as compared with pre-flight values. We also measured specific IgE-antibodies, because their high concentration may cause the increased production of total IgE indicating sensitization of cosmonauts. This becomes more important when humans spend a longer time in the closed environment of a space vehicle. Also our ground-based investigations showed that a stay in such conditions does not enhance sensitization to allergens (total number of tested allergens 27) including food, inhalants and cross-reactive proteins. Serum interleukin-4 level measured after short- and long-term space flights was identical. A linear correlation between levels of immunoglobulin E and interleukin-4 also was not significant. Despite the fact that our investigations did not establish any influence of space flight on sensitization and development of immediate-type allergic reactions, they demonstrated the necessity to control the allergic status of cosmonauts very carefully both before and after space flights. At the same time, it is necessary to pay special attention to outcomes of atopic individuals with high pre-flight level of total blood IgE.     

Spacelab Life Sciences flight experiments: an integrated approach to the study of cardiovascular deconditioning and orthostatic hypotension

The microgravity environment of spaceflight produces rapid cardiovascular changes which are adaptive and appropriate in that setting, but are associated with significant deconditioning and orthostatic hypotension on return to Earth's gravity. The rapidity with which these space flight induced changes appear and disappear provides an ideal model for studying the underlying pathophysiological mechanisms of deconditioning and orthostatic hypotension, regardless of etiology. Since significant deconditioning is seen after flights of very short duration, muscle atrophy due to inactivity plays, at most, a small role. These changes in circulatory control associated with cephalad fluid shifts, rather than inactivity per se, are probably more important factors. In order to test this hypothesis in a systematic way, a multidisciplinary approach which defines and integrates inputs and responses from a wide variety of circulatory sub-systems is required. The cardiovascular experiments selected for Spacelab Life Sciences flights 1 and 2 provide such an approach. Both human and animal models will be utilized. Pre- and post-flight characterization of the payload crew includes determination of maximal exercise capacity (bicycle ergometry), orthostatic tolerance (lower body negative pressure), alpha and beta adrenergic sensitivity (isoproterenol and phenylephrine infusions), baroreflex sensitivity (ECG-gated, stepwise changes in carotid artery transmural pressure with a pneumatic neck collar), and responses to a 24 h period of 5 deg head-down tilt. Measurements of cardiac output (CO2 and C2H2 rebreathing), cardiac chamber dimensions (phased-array 2-dimensional echocardiography), direct central venous pressure, leg volume (Thornton sock), limb blood flow and venous compliance (occlusion plethysmography), blood and plasma volumes, renal plasma flow and glomerular filtration rates, and various hormonal levels including catecholamines and atrial natriuretic factor will also be obtained. The central venous catheter will be inserted immediately pre-launch and monitored with heart rate and blood pressure in-flight until cardiac output, respiratory gas exchange and quantitative 2D echocardiography measurements can be performed. In-flight hemodynamic measurements will be repeated at rest and during submaximal exercise daily and also during maximal exercise midway through the flight to document the timecourse and extent of cardiovascular changes in the payload crew. Parallel studies are planned for the animals. In addition to measurements of right atrial and aortic pressures and cardiac output, a dorsal micro-circulatory chamber will allow determinations of changes in capillary and venular architecture and function in six of the rats. The techniques and findings from many of the SLS-1 and 2 supporting studies have already yielded significant information about circulatory regulation in patients with both hypo- and hypertension. The flight experiments themselves will provide new data to test the validity of both animal and human models currently used for simulating the fluid shifts of a micro-gravity environment. The development of effective countermeasures, not only for short and long duration space travellers, but also for Earth-bound medical patients can then be physiologically based on experimental data rather than anecdote.