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.     

Considerations for development of countermeasures for physiological decrements associated with long-duration space missions

Countermeasures are necessary to offset or minimize the deleterious changes in human physiology resulting from long duration space flight. Exposure to microgravity alters musculoskeletal, neurosensory, and cardiovascular systems with resulting deconditioning that may compromise crew health and performance. Maintaining health and fitness at acceptable levels is critical for preserving performance capabilities required to accomplish specific mission tasks (e.g.—extravehicular activity) and to optimize performance after landing. To enable the goals of the exploration program, NASA is developing a new suite of exercise hardware such as the improved loading device, the SchRED. This presentation will update the status of current countermeasures, correlate hardware advances with improvements in exercise countermeasures, and discuss future activities for safe and productive exploration missions.     

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.     

Artificial gravity: a possible countermeasure for post-flight orthostatic intolerance

Four payload crewmembers were exposed to sustained linear acceleration in a centrifuge during the Neurolab (STS-90) flight. In contrast to previous studies, otolith–ocular reflexes were preserved during and after flight. This raised the possibility that artificial gravity may have acted as a countermeasure to the deconditioning of otolith–ocular reflexes. None of the astronauts who were centrifuged had orthostatic intolerance when tested with head-up passive tilt after flight. Thus, centrifugation may also have helped maintain post-flight hemodynamic responses to orthostasis by preserving the gain of the otolith–sympathetic reflex. A comparison with two fellow Neurolab orbiter crewmembers not exposed to artificial gravity provided some support for this hypothesis. One of the two had hemodynamic changes in response to post-flight tilt similar to orthostatically intolerant subjects from previous missions. More data is necessary to evaluate this hypothesis, but if it were proven correct, in-flight short-radius centrifugation may help counteract orthostatic intolerance after space flight.     

Accomplishments in bioastronautics research aboard International Space Station

The tenth long-duration expedition crew is currently in residence aboard International Space Station (ISS), continuing a permanent human presence in space that began in October 2000. During that time, expedition crews have been operators and subjects for 18 Human Life Sciences investigations, to gain a better understanding of the effects of long-duration space flight on the crewmembers and of the environment in which they live. Investigations have been conducted to study: the radiation environment in the station as well as during extravehicular activity (EVA); bone demineralization and muscle deconditioning; changes in neuromuscular reflexes; muscle forces and postflight mobility; causes and possible treatment of postflight orthostatic intolerance; risk of developing kidney stones; changes in pulmonary function caused by long-duration flight as well as EVA; crew and crew–ground interactions; changes in immune function, and evaluation of imaging techniques. The experiment mix has included some conducted in flight aboard ISS as well as several which collected data only pre- and postflight. The conduct of these investigations has been facilitated by the Human Research Facility (HRF). HRF Rack 1 became the first research rack on ISS when it was installed in the US laboratory module Destiny in March 2001. The rack provides a core set of experiment hardware to support investigations, as well as power, data and commanding capability, and stowage. The second HRF rack, to complement the first with additional hardware and stowage capability, will be launched once Shuttle flights resume. Future years will see additional capability to conduct human research on ISS as International Partner modules and facility racks are added to ISS. Crew availability, both as a subject count and time, will remain a major challenge to maximizing the science return from the bioastronautics research program.     

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.     

Quantitative electrocardiography during extended space flight

To assess the effects of prolonged space flight on the electrophysiological properties of the heart, vectorcardiograms (VCG) were obtained on the Skylab crews at regular intervals during flight and the pre- and postflight periods. The VCG signals were telemetered from Skylab and analyzed by digital computer. Conventional 12-lead electrocardiograms were derived from the VCG signals by a lead transformation program. Standardized exercise loads were incorporated into the experiment protocol to increase the sensitivity of the VCG for effects of deconditioning and to detect susceptibility for arrhythmias. In Skylab II, 24 preflight, 21 inflight, and 19 postflight experiments were analyzed. Statistically significant inflight changes observed in two or more crew members included: decreased resting heart rate, increased QRS duration, anterior shift QRS vector, increased QRS vector magnitude, anterior shift T vector, and increased T vector magnitude. One astronaut had occasional premature ventricular contractions (PVC) during the pre- and postflight phases. He had a single episode of multiple PVC's during heavy-load exercise testing in flight. A second astronaut had no arrhythmia during pre- or inflight testing. On postflight day 21 he had multiple PVC's and salvos of ectopic ventricular beats. He has had no recurrence of the arrhythmia. With the exception of the cardiac arrhythmias, no deleterious electrophysiological changes were observed during Skylab II.     

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.     

Cardiovascular deconditioning during weightlessness simulation and the use of lower body negative pressure as a countermeasure to orthostatic intolerance

The cardiovascular function is one of the main disturbed by weightlessness: it is particularly affected by the astronaut's return to Earth, where symptoms linked to the cardiovascular deconditioning syndrom appear in the following forms: (1) orthostatic intolerance with its risk of syncope: (2) higher submaximal oxygen consumption for an equivalent work load. Lower Body Negative Pressure (LBNP) is intended to stimulate the venous system of the lower limbs; however, the specific effects of periodical LBNP sessions on the orthostatic intolerance have never been studied. With this objective in mind, 5 volunteers took part in two recent antiorthostatic bedrest experiments for 30 days. In the first experiment 3 subjects were submitted to several sessions of LBNP experiment per day and 2 others were controls; in the second experiment the LBNP group of the 1st one became controls and vice-versa. Two orthostatic investigations were performed: (1) 5 days before the bedrest; (2) at the end of the 30 day bedrest period. The results showed: (1) when the subjects were control, a high orthostatic intolerance post bedrest with 3 syncopes and one presyncopal state during the first minutes of the tilt test; (2) when the subjects were submitted to LBNP sessions, no orthostatic intolerance.     

Biomedical support of man in space

In its broadest sense, biomedical support of man in space must not be limited to assisting spacecraft crew during the mission; such support should also ensure that flight personnel be able to perform properly during landing and after leaving the craft. Man has developed mechanisms that allow him to cope with specific stresses in his normal habitat; there is indisputable evidence that, in some cases, the space environment, by relieving these stresses, has also allowed the adaptive mechanisms to lapse, causing serious problems after re-entry. Inflight biomedical support must therefore include means to simulate some of the normal stresses of the Earth environment. In the area of cardiovascular performance, we have come to rely heavily on complex feedback mechanisms to cope with two stresses, often combined: postural changes, which alter the body axis along which gravitational acceleration acts, and physical exercise, which increases the total load on the system. Unless the appropriate responses are reinforced continuously during flight, crew members may be incapacitated upon return. The first step in the support process must be a study of the way in which changes in g, even of short duration, affect these responses. In particular we should learn more about effects of g on the "on" and "off" dynamics, using a variety of approaches: increased acceleration on one hand at recumbency, immersion, lower body positive pressure, and other means of simulating some of the effects of low g, on the other. Once we understand this, we will have to determine the minimal exposure dose required to maintain the response mechanisms. Finally, we shall have to design stresses that simulate Earth environment and can be imposed in the space vehicle. Some of the information is already at hand; we know that several aspects of the response to exercise are affected by posture. Results from a current series of studies on the kinetics of tilt and on the dynamics of readjustment to exercise in different postures will be presented and discussed.     

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.     

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.     

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.     

Usefulness of daily +2Gz load as a countermeasure against physiological problems during weightlessness.

Adaptation to head-down-tilt bed rest as a simulated microgravity leads to an abnormality of reflex control of circulation, hypovolemia and reduction of exercise capacity. We hypothesized that this cardiovascular deconditioning and reduction of exercise capacity could be prevented by a daily 1 hr centrifugation at +2Gz. To test this hypothesis, twenty healthy male subjects underwent 4 day of 6 degrees head-down-tilt bed rest. Ten of them were exposed to a +2Gz load for up to 30 min twice per day (the Gz group). The remaining 10 were not exposed to a Gz load (the no-Gz group). We estimated autonomic cardiovascular control by power spectral analysis of blood pressure and R-R interval variability, and baroreflex regulation by the transfer function analysis and the sequence method, before and after bed rest. Further, we measured hematocrit as an index of changes in plasma volume and maximal oxygen consumption as an index of exercise capacity, before and after bed rest. Result: In the no-Gz group, heart rate increased after bed rest. The high frequency power of R-R interval variability as an index of cardiac parasympathetic nervous activity, baroreflex gains estimated by transfer function analysis and the sequence method as index of the integrated arterial-cardiac baroreflex function decreased significantly. Associated with these changes, the ratio of low to high frequency power of R-R as an indicator of cardiac sympathovagal balance tended to increase after bed rest in the no-Gz group. However, those showed no significant changes after bed rest in the Gz group. Hematocrit increased after bed rest in the no-Gz group. It also tended to increase in the Gz group, however it did not achieve statistical significance. Maximal oxygen consumption decreased significantly to similar extent in both the groups. Conclusion: This result suggested that 1) a daily 1hr +2Gz load produced by a centrifuge might eliminate the changes in autonomic cardiovascular control during simulated weightlessness; 2) furthermore, it might partly reverse hypovolemia induced by bed rest; 3) however, it could not prevent the decreases in exercise capacity.     

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.     

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.     

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.     

Lower body negative pressure (LBNP) as a countermeasure for long term spaceflight

The article presents the current status of lower body negative pressure (LBNP) as a countermeasure for preventing orthostatic intolerance after space flight or bed rest. Devices discussed include the Chibis vacuum suit, the Anthrorack device, a collapsible device, and an inflatable device. Two bed rest studies examined the effect of LBNP and exercise on orthostatic tolerance; plasma volume; vasopressin, plasma renin activity, and catecholamines; and side effects.     

The human cardiovascular system during space flight

Purpose of the work is to analyze and to summarize the data of investigations into human hemodynamics performed over 20 years aboard orbital stations Salyut-7 and Mir with participation of 26 cosmonauts on space flights (SF) from 8 to 438 days in duration. The ultrasonic techniques and occlusive plethysmography demonstrated dynamics of changes in the cardiovascular system during SF of various durations. The parameters of general hemodynamics, the pumping function of the heart and arterial circulation in the brain remained stable in all the space flights; however, there were alterations in peripheral circulation associated with blood redistribution and hypovolemie in microgravity. The anti-gravity distribution of the vascular tone decayed gradually as unneeded. The most considerable changes were observed in leg vessels, equally in arteries (decrease in resistance) and veins (increase in maximum capacity). The lower body negative pressure test (LBNP) revealed deterioration of the gravity-dependent reactions that changed for the worse as SF duration extended. The cardiovascular deconditioning showed itself as loss of descent acceleration tolerance and orthostatic instability in the postflight period.     

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.