STEM TODAY April 2018, No. 31
STEM TODAY April 2018, No. 31
CONTENTS CV3: Is orthostatic intolerance a potential hazard? PostÂflight orthostatic intolerance, the inability to maintain blood pressure while in an upright position, is an established, spaceflightÂrelated medical problem. Risk definition work was largely accomplished prior to establishment of HRP risks/gaps. Current gaps are heavily focused on mitigation.
Editorial Editor: Mr. Abhishek Kumar Sinha Editor / Technical Advisor: Mr. Martin Cabaniss
STEM Today, April 2018, No.31
Disclaimer ( Non-Commercial Research and Educational Use ) STEM Today is dedicated to STEM Education and Human Spaceflight. This newsletter is designed for Teachers and Students with interests in Human Spaceflight and learning about NASA’s Human Research Roadmap. The opinion expressed in this newsletter is the opinion based on fact or knowledge gathered from various research articles. The results or information included in this newsletter are from various research articles and appropriate credits are added. The citation of articles is included in Reference Section. The newsletter is not sold for a profit or included in another media or publication that is sold for a profit. Cover Page Hubble Makes the First Precise Distance Measurement to an Ancient Globular Star Cluster This ancient stellar jewelry box, a globular cluster called NGC 6397, glitters with the light from hundreds of thousands of stars. Image Credit: NASA, ESA, and T. Brown and S. Casertano (STScI) Acknowledgement: NASA, ESA, and J. Anderson (STScI)
Back Cover Dark Matter Goes Missing in Oddball Galaxy This large, fuzzy-looking galaxy is so diffuse that astronomers call it a "see-through" galaxy because they can clearly see distant galaxies behind it. The ghostly object, catalogued as NGC 1052-DF2, doesn’t have a noticeable central region, or even spiral arms and a disk, typical features of a spiral galaxy. But it doesn’t look like an elliptical galaxy, either. Even its globular clusters are oddballs: they are twice as large as typical stellar groupings seen in other galaxies. All of these oddities pale in comparison to the weirdest aspect of this galaxy: NGC 1052-DF2 is missing most, if not all, of its dark matter. Image Credit: NASA, ESA, and P. van Dokkum (Yale University)
STEM Today , April 2018
Editorial Dear Reader All young people should be prepared to think deeply and to think well so that they have the chance to become the innovators, educators, researchers, and leaders who can solve the most pressing challenges facing our world, both today and tomorrow. But, right now, not enough of our youth have access to quality STEM learning opportunities and too few students see these disciplines as springboards for their careers. According to Marillyn Hewson, "Our children - the elementary, middle and high school students of today - make up a generation that will change our universe forever. This is the generation that will walk on Mars, explore deep space and unlock mysteries that we can’t yet imagine". "They won’t get there alone. It is our job to prepare, inspire and equip them to build the future." STEM Today will inspire and educate people about Spaceflight and effects of Spaceflight on Astronauts.
STEM Today, April 2018, No.31
Editor Mr. Abhishek Kumar Sinha
Editorial Dear Reader The Science, Technology, Engineering and Math (STEM) program is designed to inspire the next generation of innovators, explorers, inventors and pioneers to pursue STEM careers. According to former President Barack Obama, " Science is more than a school subject, or the periodic table, or the properties of waves. It is an approach to the world, a critical way to understand and explore and engage with the world, and then have the capacity to change that world..." STEM Today addresses the inadequate number of teachers skilled to educate in Human Spaceflight. It will prepare , inspire and educate teachers about Spaceflight. STEM Today will focus on NASA’S Human Research Roadmap. It will research on long duration spaceflight and put together latest research in Human Spaceflight in its monthly newsletter. Editor / Technical Advisor Mr. Martin Cabaniss
STEM Today, April 2018, No.31
Human Health Countermeasures (HHC) CV3: Is orthostatic intolerance a potential hazard? Post- ight orthostatic intolerance, the inability to maintain blood pressure while in an upright position, is an established, space ight-related medical problem. Current gaps are heavily focused on mitigation. Countermeasures have been identi ed and implemented with some success ( uid loading, compression garments). It is currently unknown if partial gravity (moon, Mars) will be protective against OI.
PHYSIOLOGY OF UPRIGHT POSTURE
Orthostatic stress is a common daily challenge for humans when posture changes from lying to standing or during prolonged quiet standing. Almost immediately, with the transition from the supine (recumbent) to the upright (erect) position, a gravitational shift of nearly 500 ml of blood away from the chest to the distensible venous capacitance system below the diaphragm (venous pooling) occurs. This results in a rapid decrease in central blood volume and a subsequent reduction of ventricular preload, stroke volume, and mean BP.
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In the vascular system, a reference quantitative determinant of these changes is the venous hydrostatic indifference point (HIP), when pressure is independent of posture. In humans, the venous HIP is approximately at the diaphragmatic level, whereas the arterial HIP lies close to the level of the left ventricle. The venous HIP is dynamic and is significantly affected by venous compliance and muscular activity.
Upon standing, contractions of lower limb muscles, along with the presence of venous valves, provide an intermittent unidirectional flow, moving the venous HIP toward the right atrium. Respiration may also increase venous return because deep inspiration results in both a decline in thoracic pressure and an increase in intraabdominal pressure, which lowers retrograde flow due to compression of both the iliac and femoral veins. To provide an appropriate perfusion pressure to critical organs, an effective set of the neural regulatory system is promptly activated upon standing. The sympathetic nervous system is fast acting and primarily modulated by mechanoreceptors and, to a smaller degree, by chemoreceptors. Arterial baroreceptors (high-pressure receptors) are located in the carotid sinus and the aortic arch and by conveying baroceptive impulses via carotid sinus and aortic depressor nerves to the brainstem, notably in the nucleus of the solitary tract-determine tonic inhibition of vasomotor centers(Figure 1). In contrast, cardiopulmonary baroreceptors (volume receptors) are located in the great veins and the cardiac chambers and detect changes in the filling of the central venous circulation but are not essential for orthostatic cardiovascular homeostasis. A sudden drop in BP in the carotid sinus and the aortic arch triggers baroreceptor-mediated compensatory mechanisms within seconds, resulting in increased heart rate, myocardial contractility, and peripheral vasoconstriction. An additional local axon reflex, the veno-arteriolar axon reflex, results in constriction of arterial flow to the muscles, skin, and adipose tissue, leading to almost one-half of the increase in vascular resistance in the limbs upon standing. Ultimately, orthostatic stabilization is normally achieved in roughly 1 min or less. During prolonged quiet standing, in addition to venous pooling, transcapillary filtration in the subdiaphragmatic space further reduces both central blood volume and cardiac output by approximately 15% to 20%. This transcapillary shift equilibrates after approximately 30 min of upright posture, which can result in a net fall in plasma volume of up to 10% over this time. Continued upright posture also results in activation of neuroendo-
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crine mechanisms, such as the renin-angiotensin-aldosterone system, which may vary in intensity depending on the volume status of the patient. Still, the most important homeostatic response to prolonged orthostatic stress appears to be the carotid baroreflex-mediated increase of peripheral vascular resistance. The inability of any one of these factors to perform adequately or coordinately may result in a failure of the system to compensate for an initial or sustained postural challenge. This may produce a transient or persistent state of hypotension, which, in turn, can lead to symptomatic cerebral hypoperfusion and loss of consciousness, either in the early or late phase of orthostatic challenge.
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Astronauts who have orthostatic intolerance are unable to maintain arterial pressure and cerebral perfusion during upright posture, and may experience presyncope or, ultimately, syncope. This may impair their ability to egress the vehicle after landing. This problem affects about 20-30% of crewmembers that fly short duration missions (4-18 days) and 83% of astronauts that fly long duration missions when subjected to a stand or tilt test. Anecdotal reports, one documented by live media coverage, confirm that some astronauts have difficulty with everyday activities such as press conferences, showering, using the restroom or ambulating after a meal.
The etiology of orthostatic intolerance is complicated and multifactorial, as shown in Figure 3 [Pavy-Le Traon et al.]. While the decrease in plasma volume, secondary to the headward fluid shift that occurs in space, is an important initiating event in the etiology of orthostatic intolerance, it is the downstream effects and the physiological responses (or lack thereof) that may lead to orthostatic intolerance. This is highlighted by the fact that while all crewmembers that have been tested are hypovolemic on landing day, only a fraction of them develop orthostatic intolerance during stand/tilt testing. One physiological mechanism that has been shown to contribute to post-spaceflight orthostatic intolerance is dysfunction of the sympathetic nervous system, with or without failure of the renin-angiotensin-aldosterone system. These two control systems are activated with postural changes to the upright position. As central blood
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volume pools in the lower extremities, aortic-carotid baroreceptors are stimulated by low blood pressure (BP), and cardiopulmonary baroreceptors are stimulated by low blood volume. The baroreflex response via the aorticcarotid pathway is to stimulate the sympathetic nervous system to release norepinephrine, which causes systemic vasoconstriction and increases cardiac contractility, thereby maintaining blood pressure. The baroreflex response via the cardiopulmonary pathway is to stimulate the reninangiotensin- aldosterone system which causes sodium and water reabsorption to maintain central blood volume and blood pressure. If the sympathetic nervous system and/or renin-angiotensin-aldosterone system are inhibited, orthostatic intolerance may occur.
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Another possible mechanism for post-spaceflight orthostatic hypotension is cardiac atrophy and the resulting decrease in stroke volume (SV), as has been shown in multiple bed rest studies and a flight study. Stroke volume is easily altered by mechanical and hydrostatic effects and serves as the primary stimulus to baroreflex regulation of arterial pressure during an orthostatic stress as part of the "triple product" of blood pressure control: BP = HR (heart rate) X SV X TPR (total peripheral resistance). Orthostatic hypotension will ensue if the fall in stroke volume is of sufficient magnitude to overwhelm normal compensatory mechanisms or if the reflex increase in HR and/or TPR is impaired by disease states or by a specific adaptation of the autonomic nervous system. After adaptation to real or simulated microgravity, virtually all individuals studied have an excessive fall in stroke volume in the upright position. Although there are conflicting data regarding changes in baroreflex regulation of heart rate and vascular resistance that may limit the compensatory response to orthostasis, it may be this excessive fall in stroke volume that is the critical factor of microgravity induced orthostatic hypotension. While orthostatic intolerance is perhaps the most comprehensively studied cardiovascular effect of spaceflight, the mechanisms are not well understood. Enough is known to allow for the implementation of some countermeasures, yet none of these countermeasures alone has been completely successful at eliminating spaceflight-induced orthostatic intolerance following spaceflight. The combination of multiple countermeasures (fluid loading, re-entry compression garments and post-landing compression garments) and immediate access to medical care has been successful at controlling this risk for short duration flights. Once the post-landing garments have been validated following long duration flights, it is likely that this risk will also be controlled.
Prediction of Human Orthostatic Tolerance by Changes in Arterial and Venous Hemodynamics in the Microgravity Environment
The human body is evolutionarily adapted to the conditions of the earth’s gravity. The high tone of blood vessels of the lower half of the human body and the low resistance of cerebral, coronary, pulmonary, and renal vessels ensure full blood supply of the vital organs. Vessels of the lower extremities, conversely, have a high vascular resistance. This distribution of the vascular tone ensures the human’s body stability in the vertical position. Under exposure to microgravity, the blood is redistributed from the regions of high vascular resistance to the regions of low resistance, which initiates all subsequent changes in the cardiovascular system, including the changes in the arterial and venous hemodynamics and vascular tone. The first 3-5 days in space are the most difficult for humans. During this time, the cosmonaut feels a rush of blood to the head, swelling of the mucous membrane of the nose, facial swelling, and a headache. These symptoms are often accompanied by dizziness, loss of appetite, and illusions of the body position. These symptoms are associated with the movement of body fluids to the upper part of the body and are observed in all cosmonauts. Blood redistribution leads to an increased flow of blood to the right heart. According to the hypothesis of Henry-Gower , the receptors located in this area indicate hypervolemia and initiate unloading reflexes aimed at reducing the volume of circulating blood plasma (fluid excretion by the kidneys and the movement of part of the fluid from the bloodstream into the interstitial space, i.e., the reduction of volemia). The redistribution of blood in microgravity initiates all subsequent hemodynamic changes in humans. Hemodynamic changes and the mechanisms of their occurrence in microgravity were described in detail by many researchers. In this research, A. R. Kotovskaya and G. A. Fomina focus only on those changes in the arterial and venous hemodynamics that are relevant to the assessment and individual prediction of human orthostatic tolerance during and after space flight. Arterial hemodynamics was studied by ultrasonic methods at rest and under the functional effect of negative pressure to the lower half of the body (lower body negative pressure, LBNP), which was created with the Chibis pneumatic vacuum suit (PVS), which, to some extent, simulates the orthostatic blood redistribution.
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The LBNP test was performed as follows: rest before exposure for 5 min, vacuum -25 mm Hg for 5 min, vacuum -35 mm Hg for 1 min, vacuum -45 mm Hg for 5 min, and rest after exposure for 5 min. Throughout the study (before, during, and after exposure to LBNP), the electrocardiogram (ECG), blood pressure (BP) on the finger according to Penjaz and on the brachial artery according to Korotkoff, and dopplerograms of the blood flow in the ascending aorta and middle cerebral and femoral arteries were continuously recorded.
Before the beginning of the study of hemodynamics of cosmonauts under exposure to LBNP during and after space flights by ultrasonic methods, in the early 1980s, the same methods were used to determine the physiological norm of the arterial hemodynamic response to orthostatic impact (passive postural test) in healthy volunteers under terrestrial conditions. These studies showed that the response of human arterial hemodynamics to orthostatic effects consists in the increase in the resistance of the femoral arteries, which limits the movement of blood to the vessels of the lower extremities and prevents the reduction of the cerebral blood flow. At the same time, the resistance to the blood flow in the intracranial vessels decreases. The oppositely directed changes in the tone of femoral and brain arteries provide the best conditions for the redistribution of the cardiac output in such a way that the relative proportion of the cerebral blood flow in the cardiac output increased. In other words, the changes in the peripheral hemodynamics during orthostasis are aimed at maintaining the blood supply of the brain. The joint research of Russian and French scientists in microgravity was the first to establish the parameters that make it possible to assess the orthostatic tolerance by ultrasonic data: the femoral artery resistance index (the ratio between the retrograde and antegrade blood flow rates), the blood flow redistribution index (the ratio of the blood flow volume in the cerebral and femoral arteries), and the cerebral blood flow deficit (CBFD) index. The last index is particularly important because it make it possible to quantitatively assess the reduction in the volume of the blood flowing in the middle cerebral artery under LBNP compared toan equal time interval at rest before the test. The hemodynamic response to LBNP during longterm flights significantly changed in all cosmonauts. The changes in the arterial hemodynamics parameters at a vacuum of -45 mm Hg in the Chibis PVS at different periods of space flight are shown in Fig. 2. In the initial period of long term space flight (first month), the dynamics of the heart rate (HR) and the blood pressure under exposure to LBNP did not differ from the preflight data. However, as can be seen in Fig. 2, the vasoconstrictive response of the femoral arteries to the exposure to negative pressure was observed in this period, whereas the changes in the cerebral blood flow during the test were close to the preflight data. Therefore, at this stage of space flight, the body still retained the ability to redistribute the blood flow in favor of the brain. Then, the ability of the femoral arteries to respond to exposure to LBNP by increased resistance continued to deteriorate throughout the flight. This phenomenon was accompanied by a decrease in the effectiveness of redistribution of the blood flow during the test, as a result of which the cerebral blood flow deficit increased. In other words, during a 6 month space flight, the femoral artery resistance index in the LBNP test clearly decreased, whereas the cerebral blood flow deficit index increased with the duration of exposure to microgravity. The data obtained in this study suggest that the earliest sign of a change in the arterial hemodynamics response to LBNP was the reduced ability of the femoral arteries to impede the blood movement in the lower half of the body. This meant that the regulation of the arterial tone of the lower extremities, which was constantly stimulated on Earth by the earth’s gravity, suffered in microgravity in the first place. During the first few months of space flight, the regulation of the cerebral blood flow allowed the body to compensate for the movement of
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blood to the lower extremity vessels: the resistance of the cerebral arteries was reduced and the cerebral blood flow remained at an acceptable level. It should be noted that, at this stage, the changes in the conventional integral parameters, such as blood pressure and heart rate, during the test remained within the preflight values. However, upon further reduction in the vasoconstrictive ability of the femoral arteries during space flight, the blood flow redistribution could no longer compensate for the reduced circulating blood volume (CBV) in the LBNP test, which led to an increase in the cerebral blood flow deficit (CBFD) of varying degrees. In other words, the human body was doing everything possible to maintain the cerebral blood flow at all costs. The reduction in the cerebral blood flow meant that the body’s ability to preserve it was exhausted.
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It was noted that the degree of increase in the CBFD in the LBNP test was clearly associated with the tolerability of this test: (1) If the CBFD during flight increased compared to the preflight data but did not exceed 8%, the tolerability of LBNP changed slightly. (2) When the CBFD value increased by 8 to 15%, the reduction in the LBNP tolerability became prominent, including the heart rate and blood pressure dynamics, but was still not accompanied by the appearance of obvious signs of a deterioration in orthostatic tolerance (pallor, hyperhidrosis, and complaints of feeling unwell). (3) With a significant increase in the CBFD (by more than 15%), the signs of deterioration of the orthostatic tolerance became more pronounced. In some cases, the LBNP test was stopped for medical reasons in accordance with the criteria adopted in aviation and space medicine for test termination. According to the results of studies of the cerebral blood flow, in such cases the CBFD in the LBNP tests exceeded 20%. This study was the first to distinguish three degrees of changes in the CBFD in the LBNP test, which corresponded to the three degrees of tolerability of this procedure. The changes in the vasoconstrictive response of the femoral arteries and the cerebral blood flow deficit in LBNP tests during space flight made it possible to evaluate the physiological reserve of the human body and identify the deterioration of toleration in cases where the change in the conventional parameters (blood pressure and heart rate) during the test were close to the pre-flight data. In other words, the study of the peripheral hemodynamics under exposure to LBNP using ultrasonic methods allowed us to identify the earliest initial signs of changes in the response of the cardiovascular system to the redistribution of blood to the lower half of the body. The analysis of the dynamics of these changes during the flight allowed not only evaluating but also predicting the state of human orthostatic tolerance during space flight. Venous Hemodynamics and Prognosis of Orthostatic Tolerance The majority of researchers believe that changes in the venous hemodynamics, especially in the lower extremities, play an important role in reducing the orthostatic tolerance during space. The hemodynamic of the veins of the lower extremities was studied by the occlusion plethysmography of the lower legs, which allowed recording the changes in the lower leg volume after creating discrete levels of dosed occlusion of the venous outflow of 10 to 60 mm Hg with a step of 10 mm Hg on the hip. Given the necessity to perform studies in each cosmonaut both under conditions of the earth’s gravity before flight and in microgravity, where the pressure in the veins of the lower extremities is reduced, a combined stage was introduced to the method, with the creation of occlusion pressure (OP) of 20 mm Hg at the first stage and an increase in the OD to 60 mm Hg after stabilization of the lower leg volume. This allowed authors to assess the distensibility of veins as the ratio of the change in the lower leg volume to the change in the venous pressure (∆V/∆P) in the same range of changes in the venous pressure for all studies. During the study of the veins of the lower extremities in microgravity, the information of changes in the capacity, distensibility, and the rate of filling of veins of varying severity were accumulated, which required an analysis of their significance and determination of the relationship between the detected changes and the tolerability of the LBNP test during space flight. In this case, a question arose as to changes in which index (capacity, distensibility, or rate of filling) of the veins are important and most significant for subsequent prediction of the tolerability of the LBNP test. With the accumulation of the data, it appeared that it is impossible to distinguish one most significant predictor. All predictors are important and informative; the indicator is not as important as the severity of its changes and the combination of changes in all predictors in each case. This was the key position. To rule out the bias in the plethysmography data assessment during space flight, the veins of the lower extremities were studied 3-5 days before the LBNP test, i.e., when the results of plethysmography were evaluated,
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the results of the LBNP test were not yet known. Based on the results of the study of veins, a preliminary prediction of the tolerability of the test with an exposure to LBNP was made, which was then compared to the actual assessment of the tolerability of the test. The results of the analysis of the accumulated data allowed us to distinguish three degrees of changes in the veins of the lower extremities during space flight, by which the different degree of reduction to tolerability of the LBNP, corresponding to three gradations, were forecast: (1) When the venous capacity and distensibility increased by less than 25-30% relative to the baseline values before space flight in combination with a strong (50% or greater) decrease in the rate of filling of veins, a slight decrease in the LBNP test tolerability was predicted. (2) When two signs were identified (a substantial increase in the venous capacity and distensibility (40% or more)), but the rate of filling of veins did not increase, a moderate decrease in the tolerability of the LBNP test was predicted. (3) When all three signs (a marked increase in the venous capacity (50%), a significant increase in the distensibility of the veins of the lower extremities (50%), and an increase in the rate of vein filling) were combined, a significant reduction in the LBNP test tolerability was predicted.
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These predictions were confirmed by the results of real studies of the tolerability of the LBNP test in 14 out of 16 cases (in 88% of cases). Thus, the study of the state of human venous hemodynamics during 6 month space flights on the ISS RS and the changes in the veins of the lower extremities and orthostatic tolerance of cosmonauts, found in microgravity. In the majority of cosmonauts, a clear dependence of the tolerability of the LBNP test on the state of the veins of the lower extremities was found. However, in 2 out of 16 cosmonauts, the real tolerability of the LBNP test was worse than expected based on the studies of veins of the lower extremities. This can be explained by the fact that the mechanism of deterioration of the orthostatic tolerance is multifactorial and, in these cases, given the small changes in the capacity vessels of the lower extremities, the decrease in the orthostatic tolerance could be due to significant changes in the resistant vessels. The possibility of such a combination of changes in the arterial and venous vessels of the lower extremities was demonstrated in ground based experiments performed by V.M. Hayutin and confirmed this assumption in microgravity by this study. According to authors observations, when making individual predictions of the orthostatic tolerance on the basis of the data on the plethysmography of an occlusion of the lower leg, not only the results of the study of the veins of the lower extremities, immediately preceding the LBNP test, but also the results of all previous studies using the plethysmography of an occlusion of the lower leg of a given cosmonaut should be taken into account. The presence of pronounced changes in the veins of the lower extremities, at least one of the plethysmographic studies performed during space flight, should be regarded as an unfavorable prognostic sign indicating a certain individual natural weakness of hemodynamic mechanisms responsible for maintaining the orthostatic tolerance in the given person, which increases the risk of orthostatic disorders in him. Prediction of Changes in Human Orthostatic Tolerance during and after Space Flight according to the Preflight Research Data The toleration of exposure to LBNP (and, hence, orthostatic tolerance) during space flight, according to the data, declined in all cosmonauts, but the degree of individual changes in the orthostatic tolerance was different. It was necessary to determine whether the degree of changes in the orthostatic tolerance during and after space flight can be predicted based on the results of pre-flight studies of the orthostatic tolerance and LBNP test tolerability. For this purpose, authors analyzed changes in the orthostatic tolerance in a group of 43 cosmonauts who had completed 53 long term space flights. The cosmonauts who participated in the studies of the arterial hemodynamic response to exposure to LBNP by ultrasonic methods before, during, and after space flight were included in this group. In order to assess the state of orthostatic tolerance of cosmonauts before and after space flight, the experts of the Gagarin Cosmonaut Training Center (CTC) performed the following standard tests: the active orthostatic test (AOT, maintaining the upright posture for 10 min) and the passive postural test (PPT, 20 min suspension head up on a tilt table at an angle of 70â—Ś ). During the tests, the ECG, blood pressure, and heart rate were recorded. After the flight, the AOT was performed on days 1, 2 and 3; and PPP, on days 3-5. The orthostatic tolerance was assessed by the standard criteria adopted in the aviation and space medicine practice. Hemodynamic studies by ultrasonic methods were performed 30 and 60 days before the space flight and at
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an interval of 1.5- 2 months during the space flight. Before the flight, the orthostatic tolerance of the majority of cosmonauts was estimated as good or excellent. However, in 21% of the cases according to the results of the AOT and in 11% of cases according to the results of PPT, the preflight orthostatic tolerance was estimated as satisfactory. After the flight, one day after touchdown, when the AOT was performed in the morning after the first night on Earth, a decrease in the orthostatic tolerance was observed in all cosmonauts (100% of cases). In 53% of the cosmonauts, this decrease was pronounced (up to early termination of the test), which greatly limited the physical capabilities of the cosmonauts. The decrease in the orthostatic tolerance on the first day after a long term space flight accounted for 26.7 ± 8.2% at an excellent preflight estimate, 39.1 ± 2.9% at a good estimate, and 57.6 ± 4.9% at a satisfactory estimate; i.e., it was more pronounced the lower the pre-flight estimation of the orthostatic tolerance.
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After the space flight, PPT was performed in the cosmonauts who reached at least the satisfactory level of orthostatic tolerance according to the AOP data. This state of the orthostatic tolerance was observed in cosmonauts usually on days 3-4 after a long term flight. During the performance of PPT, the decrease in the orthostatic tolerance compared to the preflight data was retained (100%) in all cosmonauts. On the whole, for the general sample, this decrease was 20.1 ± 1.2%. The decrease in the orthostatic tolerance evaluation relative to the preflight was highly statistically significant (p < 0.001). The state of the orthostatic tolerance in the groups of cosmonauts with different preflight orthostatic tolerance (excellent, good, and satisfactory) on days 3-4 after space flight was markedly different; the difference between groups was statistically significant (p < 0.05). The changes in the orthostatic tolerance after long term space flights in the groups of cosmonauts with different preflight orthostatic tolerance are shown in Fig. 3.
Author note that the comparison of data of preflight and postflight studies of the orthostatic tolerance using postural tests showed a close correlation ( r = 0.81 ± 0.5) of the changes in the orthostatic tolerance after completion of the space flight with the individual preflight orthostatic tolerance. Thus, according to the orthostatic tests, the degree of deterioration of the orthostatic tolerance after long term space flights depended on its preflight level. Surprisingly a similar clear dependence of the changes during space flight on the preflight level was also found for the cerebral blood flow deficit (CBFD) in the LBNP test. During the space flight, studies of the arterial hemodynamics under exposure to LBNP revealed a very important dependence; the lower the cerebral blood flow deficit in the preflight LBNP tests the smaller the changes in the hemodynamic response to this effect during the flight. If the CBFD under exposure to LBNP before the flight was small (less than 8%; on average, 3.85 ± 0.88%) compared to the state of rest before the test, then the changes in the hemodynamic response to this effect during the flight were moderate: CBFD increased but did not exceed
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8%, and no marked reduction in the LBNP test tolerance was observed. Conversely, an expressed deterioration of the hemodynamic response to LBNP during the flight and the increase in the CBFD to 21.78 ± 5.8% during the flight in this test was observed in those cosmonauts who had high CBFD values (8 to 15%; on average, 12.1% ± 3) in the preflight LBNP tests. The changes in the cerebral blood flow developing under exposure to LBNP were clearly correlated to the tolerability of this test. The better the LBNP tolerability before the flight the weaker the impact that exposure to microgravity exerted on it.
BP Reg: Predicting fainting in astronauts
The Canadian science experiment Blood Pressure Regulation and Risk of Fainting on Return from Space (BP Reg) studied why some astronauts are more likely to faint or experience dizziness after their missions by observing how their bodies react to changes in blood pressure.
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The Canadian Space Agency (CSA) has supported three experiments: Cardio- vascular and Cerebrovascular control on return from the International Space Station (CCISS); Cardiovascular Health Consequences of Longduration Spaceflight (Vascular) and Blood Pressure Regulation and Risk of Fainting on Return from Space (BP Reg). Arterial baroreflex The CCISS experiments measured the arterial baroreflex before, during and after long-duration spaceflight from the sequence method that related to spontaneous changes in RR-interval with finger arterial blood pressure measured in space with the continuous blood pressure device (CBPD). Pre- and post-flight, astronauts were studied in supine and seated postures. The arterial baroreflex slope was not different inflight compared to pre-flight baseline in either the supine or seated postures. Post-flight, a significant reduction was observed only in paced breathing (10 breaths/min). Large changes in baroreflex slope were observed in individuals who did the most aerobic exercise sessions while on ISS. While this observation seems contrary to expectations, it is probable that the individuals who did the most aerobic exercise while on ISS were also the same astronauts who incorporated large quantities of aerobic exercise into their pre-flight routines. That is, they had the lowest heart rate prior to spaceflight due to high parasympathetic tone, but were unable to maintain their high aerobic fitness on ISS due to lack of loading of the treadmill device. These astronauts also reported frequent dizziness that might have been related to post-flight orthostatic hypotension. Arterial stiffness Increased arterial stiffness, normally observed with aging, has recently been observed during and after spaceflight including long-duration ISS missions as well as short-duration shuttle flights. Baevsky et al. measured the pulse wave transit time from the R-wave of the ECG to the arrival of the finger pressure wave. The observations of faster transit time from pre- to post-flight in the Vascular experiment (P = 0.07) were almost identical to previous data. However, preliminary new data from the first 6 astronauts in the Vascular study revealed reductions in carotid artery distensibility after approximately 6 months in space. Given the observations in older sedentary individuals that 3 months of walking or jogging for 40 min/day reduced carotid and peripheral artery stiffness, possibly through enhanced bioavailability of nitric oxide, authors investigated whether astronauts who maintained physical fitness would have less change in pulse wave transit time to the finger. There was no relationship between the change in pulse wave transit time and the change in heart rate at a fixed work rate (mean pre-flight heart rate approximately 145 ±17 bpm) as shown in Fig. 2. It is established that multiple factors could contribute to increased arterial stiffness with aging including increased vasoconstrictor or reduced vasodilator factors, structural breakdown of elastin, accumulation of collagen,
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Vascular smooth muscle cell proliferation and increased cross-linking in the extracellular matrix. The possible roles of these factors related to the increased arterial stiffness with spaceflight have not been investigated. The animal model of hindlimb suspension, used as an analog of spaceflight, revealed cellular hypertrophy in the middle cerebral artery with a potential role for activation of Vascular wall reninangiotensin system. Other experiments with a similar animal model suggested increased cross-linkage in the major elastic arteries. The Vascular experiment provides data to test these mechanisms.
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It is not clear from the cosmonaut data of Baevsky et al. whether the increased stiffness is an acute or long-term effect of spaceflight.
Lifelong increased arterial stiffness in aging has important health consequences associated with increased systolic arterial blood pressure that can lead to target organ damage such as increased cerebrovascular resistance with a reduction in brain blood flow in otherwise healthy elderly individuals. These data reveal that, like bone loss, cardiovascular health consequences of spaceflight require further research to establish effective countermeasures.
Microgravity induced changes in aortic stiffness and their role in orthostatic intolerance
Microgravity induced orthostatic intolerance (OI) in astronauts is characterized by a marked decrease in cardiac output (CO) in response to an orthostatic stress. Since CO is highly dependent on venous return, alterations in the resistance to venous return (RVR) may be important in contributing to OI. The RVR is directly dependent on arterial compliance (Ca), where aortic compliance (Cao) contributes up to 60% of Ca. All human astronaut data were from previously published studies [Meck et al.] . The data set consisted of supine hemodynamic measures taken from 57 astronauts usually 10 days before launch, on landing day, and 3 days after landing. Tilt tests were used todetermine whether astronauts were orthostatically intolerant before and after spaceflight. Detailed methods are available from Meck et al. and Fritsche-Yelle et al.; briefly, blood pressure was measured every minute using an automated arm cuff concurrently with beat-to-beat wrist cuff. Aortic cross-sectional area, determined using two-dimensional echocardiography, and ascending aortic flow, sampled with pulsed Doppler, were used to determine the stroke volume. OT was evaluated using a 10-min tilt protocol that brought the subject to an 80â&#x2014;Ś upright position from supine. The subjects remained in a vertical position for 10 min or until presyncopal symptoms manifested. A subject was determined to be intolerant if the tilt was prematurely ended due to the manifestation of presyncopal symptoms. Ca was estimated as the stroke volume divided by the arterial pulse pressure (systolic minus diastolic blood pressure). Astronaut Ca. Figure 1 summarizes the Ca in astronauts preflight, on landing day, and post landing (in general, preflight measures were taken 10 days before flight, missions lasted between 5 and 18 days, and post landing measures were taken 3 days after landing).
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As demonstrated in Fig. 1A, and consistent with the hypothesis, there is a significant decrease in Ca in OT astronauts between preflight and landing day (2.0 ± 0.097 to 1.7 ± 0.083 ml/mmHg; P = 0.0011; n = 40). The Ca then returns toward normal 3 days following landing (2.0 ± 0.095 ml/mmHg). In marked contrast, there is no significant decrease in compliance in OI astronauts at landing day (1.9 ± 0.13 to 2.3 ± 0.39 ml/mmHg; P = 0.36; n = 17) (Fig. 1B).
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In fact, although not statistically significant, there is a trend toward an increase in OI astronaut Ca between preflight and landing day. Interestingly, there is no significant difference between OI and OT Ca preflight [1.9 ± 0.13 (n = 17) and 2.0 ± 0.097 ml/mmHg (n = 40), respectively; P = 0.53].
However, on landing day, the Ca values are dramatically different [2.3 ± 0.39 (n = 17) and 1.7 ± 0.083 ml/mmHg (n = 40), respectively; P = 0.046; Fig. 1C]. The data presented are consistent with the hypothesis that exposure to actual or simulated microgravity induces a change in Ca. This is demonstrated by the fact that an estimate of Ca was seen to change in astronauts (Fig. 1).
The data also support the hypothesis that a decrease in Ca (increase in stiffness) maybe an adaptive change that protects astronauts from OI by decreasing the resistance to venous return.
The astronaut hemodynamic data indicates that while the OI astronauts had a slight, nonsignificant increase in Ca, the OT astronauts demonstrated a large decrease in Ca after spaceflight.
This may explain why these astronauts were able to maintain adequate cardiac output and blood pressure during an orthostatic challenge. On the other hand, OI astronauts failed to decrease their Ca. Potts et al. showed that a reduction of Ca was partly responsible for minimizing a baroreflex-evoked increase in resistance to venous return. Additionally, Hatanaka et al. demonstrated that a decrease in Ca effectively decreases the resistance to venous return. Thus a stiffer, or less compliant, arterial bed will allow for less accumulation of blood volume in the arterial circulation and consequently shift the extra volume to the venous side, aiding in venous return. Therefore, it is reasonable to conclude that the decrease in Ca seen in the OT astronauts is, in part, responsible for maintaining OT, while failure to decrease compliance contributes to OI. The decreases in stroke volume, cardiac output, and mean arterial blood pressure are not as great as reported from OI astronauts during an upright tilt test [∼30-50% decrease for stroke volume and cardiac output and ∼25% for mean arterial blood pressure].
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Compression Garments as Countermeasures to Orthostatic Intolerance
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The ability to remain upright or egress from the space vehicle after landing may be compromised by an inability to maintain adequate arterial pressure and cerebral perfusion. Many astronauts experience postflight orthostatic intolerance, and its severity and incidence appear to increase as the length of microgravity exposure is extended.
Approximately 20-60% of astronauts returning from short-duration(4-18d) spaceflights and up to 83% of astronauts returning from long-duration (>1 mo) spaceflights become presyncopal during postflight orthostatic challenges. Reduced postflight plasma volume and altered distribution of blood while upright, particularly to the abdomen and lower body, is thought to contribute to postflight orthostatic intolerance. Orthostatic intolerance may be caused by an impaired ability to constrict the splanchnic vasculature. To provide protection against spaceflight-induced orthostatic intolerance during re-entry and landing, both NASA and the Russian Federal Space Agency require that astronauts and cosmonauts wear compression garments. During Space Shuttle landings, NASA astronauts used an inflatable antigravity suit (AGS) that consisted of five interconnected bladders that cover the abdomen, thigh, and calf. The bladders could be inflated to pressures ranging from 0.5 psi (25.9 mmHg) to 2.5 psi (129.3 mmHg) in increments of 0.5 psi. The purpose of this study was to evaluate a three-piece abdomen-high, elastic gradient compression garment (GCG) as a countermeasure to post-spaceflight orthostatic intolerance. There were 14 Space Shuttle astronauts (7 treatment, 7 controls) who volunteered to participate in this study. Astronauts participated in a short 3.5-min stand test before flight without compression garments as a measure of preflight baseline condition. Seven treatment astronauts (seven men, 47 ± 1 yr, 174 ± 2 cm, 83 ± 3 kg, mean ± SE; flight duration 12-16 d) completed the same stand test on landing day while wearing the compression garments. Seven astronauts (five men, two women,44 ± 2 yr, 178 ± 1 cm, 76 ± 3 kg, mean ± SE; flight duration 10-15 d) who completed an identical stand test in a separate study served as control subjects. Astronauts serving as control subjects did not wear the compression garments before or after flight. Approximately 30 d before launch (L-30) and on landing day, astronauts participated in a 3.5-min stand test.
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No astronauts wore the GCG during preflight testing and only the countermeasure subjects wore the GCG on landing day. Preflight testing was conducted in the Cardiovascular Laboratory at the Johnson Space Center, Houston, TX.
Postflight testing was conducted in the Baseline Data Collection Facility at the Kennedy Space Center, FL, or at the Dryden Flight Research Center, Edwards, CA. Testing on landing day was conducted approximately 2 h after wheel stop.
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Astronauts were instrumented to measure continuous ECG and beat-to-beat blood pressure in the finger during the stand test. The stand test began with the astronaut lying prone on a foam mat for 3 to 5 min. After baseline measurements were obtained, astronauts stood up as quickly as possible in response to a verbal cue, and stood quietly for 3.5 min (210 s).
During standing, the astronauts were discouraged from movement, muscle contractions, and talking (except to report symptoms), and were encouraged to breathe normally. Astronauts were asked to abstain from caffeine, nicotine, and alcohol for 12 h prior to testing, refrain from exercise within 4 h of testing, and avoid maximal exercise for 24 h prior to testing. Astronauts also were asked to avoid heavy meals in the 4 h prior to testing.
Abdomen, thigh, calf, and ankle circumferences were measured during each test session to measure changes in body segments that might influence the fit of the garments after spaceflight. Test operators also queried the astronauts regarding garment comfort and fit while the astronauts were wearing the garments on landing day. Astronauts scored the garment fit of the shorts and thigh stockings separately on a scale of 1 to 5, with 1 being "very comfortable" and 5 being "very uncomfortable". A score of 3 was considered to be "neutral"’. Result No subjects in either the GCG or control group became presyncopal during the 3.5-min stand test before or on landing day. Mean (± SE) heart rate and blood pressure values during prone rest and while standing for the GCG and control subjects are displayed in Table I. Mean (± SE) stroke volume, cardiac output, and total peripheral resistance values for the GCG subjects are shown in Table II . There was a significant Group × Time interaction (Z= -3.77, P <0.01) in subjects’ heart rate response to standing (Fig. 2). The postflight heart rate response to standing was not different from preflight in the GCG group [χ2 (1)=0.37,P=0.55], while the postflight heart rate response to standing was greater than preflight in the control group [χ2 (1)=7.08,P < 0.01]. The analysis of blood pressure revealed no significant effects; however, the data revealed somewhat lower overall systolic blood pressure among the controls relative to our GCG group (Z=1.87,P=0.06).
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GCG subjects’ total peripheral resistance response to standing was signifi cantly greater (Z= 2.32,P= 0.02) on landing day; however, stroke volume response was not significantly different on landing day (Z= -0.69,P=0.49). Calf, thigh, and abdominal circumference in GCG subjects were 1.7±0.8% (Z=-2.14,P=0.033), 2.4±1.0% (Z= -2.46,P= 0.014), and 2.6±0.9% (Z= -2.85,P= 0.004) lower, respectively, on landing day than preflight (Table III). The circumference of the ankle on landing day (-1.6±1.1%) was not significantly different (Z= -1.30,P= 0.193) than preflight.
The majority of the astronauts described the shorts and thigh-high garments as being comfortable on landing day. Specifically, five of the seven astronauts described the shorts as being comfortable or very comfortable, while two of the seven described them as being uncomfortable. Of the seven astronauts, six reported the thigh high garments as comfortable or very comfortable. The lowest comfort rating for the thigh-highs was 3, which would be neither comfortable nor uncomfortable "‘neutral"). None of the astronauts described the garments as being very uncomfortable.
The three-piece, abdomen-high compression garments effectively prevent post-spaceflight tachycardia, increase total peripheral response to standing, and are comfortable to wear. Tachycardia is a common finding after spaceflight and authors observed an elevated heart rate response to standing in the control subjects on landing day. However, the change in heart rate from prone to standing was similar from pre- to postflight in the GCG
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subjects. Also, stroke volume and cardiac output are normally reduced after spaceflight, likely due to decreased circulating blood volume, pooling in the lower extremities, or reduced cardiac effectiveness. In contrast, the decreases in stroke volume and cardiac output with standing after spaceflight were not different from preflight in astronauts who wore the three-piece GCG. Overall, the astronauts in the GCG group judged the three-piece compression garments to be comfortable to wear, even after completing the NASA standard fluid loading protocol.
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Evaluation of Compression Garments as Countermeasures to Orthostatic Intolerance (Compression_Garments) the NASA Anti-Gravity Suit (AGS) and the Russian Kentavr compression garment were effective countermeasures to orthostatic intolerance in subjects whose plasma volume was reduced pharmacologically to a similar degree as experienced by astronauts. While these compression garments were effective in these conditions, two observations led to the evaluation of other compression garments/conditions. First, although the AGS and Kentavr appeared to be equally effective in the initial study, the level of compression provided by the two garments were very different. The Kentavr provided compression of â&#x2C6;ź30 mmHg but the AGS was inflated to a pressure of â&#x2C6;ź78 mmHg. Thus, one objective of this study was to determine whether the AGS could provide a similar level of protection as the Kentavr when the AGS was inflated to provide a similar level of compression (â&#x2C6;ź26 mmHg). Second, astronauts have reported uncomfortable levels of abdominal compression while using the AGS, which may be particularly problematic after completing the pre-landing fluid loading protocol. Therefore, the second objective of this study was to determine the efficacy of a thigh-high compression garment, which might be more effective than either the AGS or the Kentavr because it provided a gradient compression to promote venous return. Both the AGS and Kentavr apply approximately the same level of compression across the entire length of the garment, but a commercially - available garment provides the highest pressure at the ankle, and the pressure decreases up the leg to the top of the thigh.
G-tolerance of female cosmonauts during descent in space flights of 8 up to 169 days in duration
The authors analyzed g-tolerance of female cosmonauts during descent in space flights based on the data about 4 female cosmonauts in 5 space flights The space flights were conventionally divided into short-term (8-16 days) and long-term (169 days). In two space flights (16 and 169-d long), tubeless anti-g suit Centaur was warn during descent. In these space flights, g-tolerance of females was quite satisfactory advocating for the possibility for women to fly to space without any constraints. When the anti-g suit was not used, female physiological systems were stressed heavier than male. The spacesuit smoothed away this difference. A distinct positive effect of wearing the anti-g suit by female cosmonauts during descent as it reduces stress to their physiological systems.
Tolerance of +Gz loads by space physician Poliakov VV during the active phases of his 438-days space mission
Tolerance of +Gz loads was assessed in space physician V.V. Polyakov during the active phases of his record, 438-day space mission. On the phases of insertion into orbit the +Gz-tolerance of the space physician was good; a fairly satisfactory g-tolerance during departure of orbit was extenuated by wearing of two anti-g suits (KARKAS-3 and CENTAUR) and administration of countermeasures against the unfavorable effects of space microgravity. His general health state and self-rating were not noticeably altered. +Gz loads in the course of descent from orbit instigated a syndrome characteristic of return to Earth from prolonged microgravity, i.e. a sensation of fierce pressure on the body, difficult breathing and speech, sine tachycardia, tachypnea, singular arrhythmias, petechial hemorrhage in the back integument, and vestibular/autonomous reactions. However, no evidence of any unusual physiological reactions that had never been seen in the other cosmonauts donned in the anti-g suits on earlier and less extended (from 65- to 366-day) missions were found. Extra systoles were registered on the phase of return to Earth after the 438-day but not previous 241-day mission of the space physician; they were probably associated with aging as he made his maiden flight at 47, and the second, at 53. The results speak in favor of the countermeasures against the adverse effects of microgravity applied during the mission, and the anti-g suits worn on the stage of return to Earth.
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