Arterial structure and function during and after long-duration spaceflight.

Spaceflight missions expose astronauts to increased risk of oxidative stress and inflammatory damage that might accelerate the development of asymptomatic cardiovascular disease. The purpose of this investigation was to determine whether long-duration spaceflight (>4 mo) results in structural and functional changes in the carotid and brachial arteries. Common carotid artery (CCA) intima-media thickness (cIMT), CCA distensibility and stiffness, and brachial artery endothelium-dependent and -independent vasodilation were measured in 13 astronauts (10 men, 3 women) ~180 and 60 days before launch, during the mission on ~15, 60, and 160 days of spaceflight, and within 1 wk after landing. Biomarkers of oxidative stress and inflammation were measured at corresponding times in fasting blood samples and urine samples from 24- or 48-h pools. Biomarkers of oxidative stress and inflammation increased during spaceflight, but most returned to preflight levels within 1 wk of landing. Mean cIMT, CCA stiffness, and distensibility were not significantly different from preflight at any time. As a group, neither mean endothelium-dependent nor -independent vasodilation changed from preflight to postflight, but changes within individuals in endothelial function related to some biomarkers of oxidative stress. Whereas biomarkers of oxidative stress and inflammation are elevated during spaceflight, CCA and brachial artery structure and function were not changed by spaceflight. It is unclear whether future exploration missions, with an extended duration in altered gravity fields and higher radiation exposure, may be problematic.NEW & NOTEWORTHY Carotid artery structure and stiffness did not change on average in astronauts during long-duration spaceflight (<12 mo), despite increased oxidative stress and inflammation. Most oxidative stress and inflammation biomarkers returned to preflight levels soon after landing. Brachial artery structure and function also were unchanged by spaceflight. In this group of healthy middle-aged male and female astronauts, spaceflight in low Earth orbit does not appear to increase long-term cardiovascular health risk.

Impact of Prolonged Spaceflight on Orthostatic Tolerance During Ambulation and Blood Pressure Profiles in Astronauts.

BACKGROUND: Astronauts returning to earth usually demonstrate reduced orthostatic tolerance when assessed on a tilt table or quiet standing, but no studies have evaluated postflight orthostatic tolerance during activities of daily living, when it is most clinically relevant. Ambulatory blood pressure (BP) variability also is associated with orthostatic intolerance in certain patient populations and can capture clinically significant orthostatic hypotension during activities of daily living, especially when measured on a beat-to-beat basis. We evaluated the impact of prolonged spaceflight on orthostatic tolerance and BP profiles in astronauts. METHODS: Ambulatory beat-to-beat BP was recorded using a portable device for multiple 24-hour time periods before, during, and after 6 months of spaceflight in 12 astronauts (4 women; age 48±5 [mean±SD] years). BP variability in the time domain was calculated as the SD. Systolic BP distribution during activities of daily living was characterized by skewness and kurtosis. RESULTS: In contrast with results from previous studies that used tilt tables or stand tests, no astronaut experienced orthostatic intolerance/hypotension during activities of daily living before or after spaceflight. Also, 24-hour systolic BP decreased in space (120±10 mm Hg before spaceflight versus 106±9 mm Hg during spaceflight; P<0.01), but it returned to normal upon landing (122±13 mm Hg). Diastolic BP was unchanged during and after spaceflight. Systolic and diastolic BP variability remained the same before, during, and after spaceflight (both P>0.05). The skewness of systolic BP increased in space (0.74±0.51 versus 1.43±1.00; P=0.001), indicating that signal fluctuations became asymmetrical; however, it returned to preflight levels after landing (0.51±0.42). The kurtosis increased in space (5.01±7.67 versus 11.10±11.79; P=0.010), suggesting that fluctuations concentrated around the mean with a narrow distribution; however, it also returned to preflight levels (2.21±2.56) after return to earth. CONCLUSIONS: Given current countermeasures including in-flight exercise training and volume resuscitation on return, no astronauts experienced orthostatic hypotension or intolerance during routine (for landing day) activities in the initial 24 hours after landing following 6 months in space. Prolonged exposure to spaceflight had little impact on systolic BP variability and its distribution, although the latter showed a transient change in space (accompanied by mild relative hypotension), all of which returned to preflight values after return to earth.

Internal jugular pressure increases during parabolic flight.

One hypothesized contributor to vision changes experienced by >75% of International Space Station astronauts is elevated intracranial pressure (ICP). While no definitive data yet exist, elevated ICP might be secondary to the microgravity-induced cephalad fluid shift, resulting in venous congestion (overfilling and distension) and inhibition of cerebrospinal and lymphatic fluid drainage from the skull. The objective of this study was to measure internal jugular venous pressure (IJVP) during normo- and hypo-gravity as an index of venous congestion. IJVP was measured noninvasively using compression sonography at rest during end-expiration in 11 normal, healthy subjects (3 M, 8 F) during normal gravity (1G; supine) and weightlessness (0G; seated) produced by parabolic flight. IJVP also was measured in two subjects during parabolas approximating Lunar (1/6G) and Martian gravity (1/3G). Finally, IJVP was measured during increased intrathoracic pressure produced using controlled Valsalva maneuvers. IJVP was higher in 0G than 1G (23.9 ± 5.6 vs. 9.9 ± 5.1 mmHg, mean ± SD P < 0.001) in all subjects, and IJVP increased as gravity levels decreased in two subjects. Finally, IJVP was greater in 0G than 1G at all expiration pressures (P < 0.01). Taken together, these data suggest that IJVP is elevated during acute exposure to reduced gravity and may be elevated further by conditions that increase intrathoracic pressure, a strong modulator of central venous pressure and IJVP However, whether elevated IJVP, and perhaps consequent venous congestion, observed during acute microgravity exposure contribute to vision changes during long-duration spaceflight is yet to be determined.

Left ventricular remodeling during and after 60 days of sedentary head-down bed rest.

Short periods of weightlessness are associated with reduced stroke volume and left ventricular (LV) mass that appear rapidly and are thought to be largely dependent on plasma volume. The magnitude of these cardiac adaptations are even greater after prolonged periods of simulated weightlessness, but the time course during and the recovery from bed rest has not been previously described. We collected serial measures of plasma volume (PV, carbon monoxide rebreathing) and LV structure and function [tissue Doppler imaging, three-dimensional (3-D) and 2-D echocardiography] before, during, and up to 2 wk after 60 days of 6° head down tilt bed rest (HDTBR) in seven healthy subjects (four men, three women). By 60 days of HDTBR, PV was markedly reduced (2.7 ± 0.3 vs. 2.3 ± 0.3 liters,P< 0.001). Resting measures of LV volume and mass were ∼15% (P< 0.001) and ∼14% lower (P< 0.001), respectively, compared with pre-HDTBR values. After 3 days of reambulation, both PV and LV volumes were not different than pre-HDTBR values. However, LV mass did not recover with normalization of PV and remained 12 ± 4% lower than pre-bed rest values (P< 0.001). As previously reported, decreased PV and LV volume precede and likely contribute to cardiac atrophy during prolonged LV unloading. Although PV and LV volume recover rapidly after HDTBR, there is no concomitant normalization of LV mass. These results demonstrate that reduced LV mass in response to prolonged simulated weightlessness is not a simple effect of tissue dehydration, but rather true LV muscle atrophy that persists well into recovery.

Orthostatic Intolerance After ISS and Space Shuttle Missions.

INTRODUCTION: Cardiovascular deconditioning apparently progresses with flight duration, resulting in a greater incidence of orthostatic intolerance following long-duration missions. Therefore, we anticipated that the proportion of astronauts who could not complete an orthostatic tilt test (OTT) would be higher on landing day and the number of days to recover greater after International Space Station (ISS) than after Space Shuttle missions. METHODS: There were 20 ISS and 65 Shuttle astronauts who participated in 10-min 80° head-up tilt tests 10 d before launch, on landing day (R+0), and 3 d after landing (R+3). Fisher's Exact Test was used to compare the ability of ISS and Shuttle astronauts to complete the OTT. Cox regression was used to identify cardiovascular parameters associated with OTT completion and mixed model analysis was used to compare the change and recovery rates between groups. RESULTS: The proportion of astronauts who completed the OTT on R+0 (2 of 6) was less in ISS than in Shuttle astronauts (52 of 65). On R+3, 13 of 15 and 19 of 19 of the ISS and Shuttle astronauts, respectively, completed the OTT. An index comprised of stroke volume and diastolic blood pressure provided a good prediction of OTT completion and was altered by spaceflight similarly for both astronaut groups, but recovery was slower in ISS than in Shuttle astronauts. CONCLUSIONS: The proportion of ISS astronauts who could not complete the OTT on R+0 was greater and the recovery rate slower after ISS compared to Shuttle missions. Thus, mission planners and crew surgeons should anticipate the need to tailor scheduled activities and level of medical support to accommodate protracted recovery after long-duration microgravity exposures.

Understanding stress in the healthy animal - potential paths for progress.

Although stress is usually associated with disease, the physiological and behavioral responses to stressors are critical mechanisms of resilience for healthy organisms. A recent workshop comprised of researchers who study healthy humans and both free-living and captive non-human animals identified a number of key roadblocks that are impeding progress in understanding how stress responses integrate into the normal physiology of an animal. These include the lack of: (1) an unambiguous definition of a stress phenotype; (2) a robust biomarker, or suite of biomarkers, to indicate that phenotype; (3) theoretical and quantitative models to predict how humans and other animals will react to stressors; (4) a comprehensive understanding of how individual variability in stress responses arise and (5) an understanding of the transitions between acute and chronic stress responses. Collectively, these deficiencies impair our ability to both assess the physiological status of individuals and develop procedures and techniques to reverse the effects elicited by chronic stress before they become pathological. Workshop participants also identified a number of potential approaches to facilitate progress on these problems. They include: (1) increased use of mathematical models to provide quantitative predictions; (2) use of network theory to expose emergent properties not predicted from traditional approaches; (3) development and deployment of improved sensor technology that will allow long-term, dynamic, non-invasive, multi-factor measurements of suites of stress mediators and (4) the recruitment of scientists with diverse skill sets, such as engineers, bioinformaticians, etc.; and (5) the training of young scientists in the multidisciplinary study of stress. Incorporating these approaches in new research should reinvigorate the study of stress and stimulate progress in understanding both how healthy humans cope with stressors and how other animals, including free-living animals, cope with stressors in a rapidly changing environment.

Effects of sex and gender on adaptation to space: cardiovascular alterations.

Sex and gender differences in the cardiovascular adaptation to spaceflight were examined with the goal of optimizing the health and safety of male and female astronauts at the forefront of space exploration. Female astronauts are more susceptible to orthostatic intolerance after space flight; the visual impairment intracranial pressure syndrome predominates slightly in males. Since spaceflight simulates vascular aging, sex-specific effects on vascular endothelium and thrombotic risk warrant examination as predisposing factors to atherosclerosis, important as the current cohort of astronauts ages. Currently, 20% of astronauts are women, and the recently selected astronaut recruits are 50% women. Thus there should be expectation that future research will reflect the composition of the overall population to determine potential benefits or risks. This should apply both to clinical studies and to basic science research.

Gradient compression garments protect against orthostatic intolerance during recovery from bed rest.

INTRODUCTION: Abdomen-high, lower body graded compression garments (GCGs) may represent the next-generation of orthostatic intolerance protection with applications for exploration missions and commercial space flight. PURPOSE: To evaluate the efficacy of the GCG to prevent orthostatic intolerance after a 14-day 6° head-down tilt bed rest (BR) and to determine whether wearing thigh-high compression garments impairs recovery from BR. METHODS: Sixteen (12 M, 4 F) subjects participated in a 15-min 80° head-up tilt test 5 day before BR (BR-5), on the last morning of BR (BR+0), and on day 1 (BR+1) and 3 after BR (BR+3). No subjects wore the GCG on BR-5, and all subjects wore the GCG during testing on BR+0. Control subjects (n = 8) wore the GCG only through testing on BR+0. Treatment subjects (n = 8) wore the GCG on BR+0 and thigh-high garments on BR+1 and BR+2. RESULTS: No subjects were presyncopal during tilt on BR+0 while wearing the GCG. Despite lower plasma volume index (BR-5: 1.52 ± 0.06, BR+0: 1.32 ± 0.05 l/m(2)), the tilt-induced increase in heart rate (ΔHR, 17 ± 2 bpm) and decrease in stroke volume (ΔSV, -28 ± 3 ml) on BR+0 were less than on BR-5 (24 ± 2 bpm, -43 ± 4 ml). On BR+1 ΔHR in the control group (33 ± 4 bpm) was higher than in the treatment group (23 ± 2 bpm) but there were no group differences on BR+3. CONCLUSIONS: Wearing the GCG prevented the orthostatic intolerance that is normally present after BR. Thigh-high garments provided protection after BR, and wearing these garments did not impair recovery.

Abdomen-high elastic gradient compression garments during post-spaceflight stand tests.

UNLABELLED: Space Shuttle astronauts wore an inflatable antigravity suit during reentry and landing, and astronauts and cosmonauts wear an elastic-compression garment (with lacing) during Soyuz re-entry and landings and in the first few days of recovery. However, neither garment is an ideal countermeasure to spaceflight-induced orthostatic intolerance. Our laboratory has been investigating an elastic graded compression garment (GCG) that applies graduated pressures from the feet to the abdomen for use following International Space Station missions and possibly during exploration missions. METHODS: Before and after Shuttle missions, 14 astronauts participated in a 3.5-min stand test. The stand test was conducted without garments preflight. On landing day, 7 astronauts wore the GCG while 7 astronauts did not (controls). Heart rate and blood pressure were measured in all astronauts during prone rest and standing. Stroke volume and cardiac output were measured only in GCG subjects. RESULTS: No astronauts in either group became presyncopal during the stand test preflight or postflight. The change in heart rate from prone to standing was lower in the GCG subjects on landing day than in the control subjects. Within the GCG subjects only, the increase in total peripheral resistance from prone to standing was higher after spaceflight. CONCLUSIONS: The GCG prevented tachycardia and increased total peripheral resistance with standing after spaceflight. The GCG shows promise as a countermeasure against post-spaceflight orthostatic intolerance, can be easily donned, and is relatively comfortable to wear, but has not been validated after long-duration spaceflight.

Sex differences in blood pressure control during 6° head-down tilt bed rest.

Spaceflight-induced orthostatic intolerance has been studied for decades. Although ∼22% of the astronaut corps are women, most mechanistic studies use mostly male subjects, despite known sex differences in autonomic control and postflight orthostatic intolerance. We studied adrenergic, baroreflex, and autonomic indexes during continuous infusions of vasoactive drugs in men and women during a 60-day head-down bed rest. Volunteers were tested before bed rest (20 men and 10 women) and around day 30 (20 men and 10 women) and day 60 (16 men and 8 women) of bed rest. Three increasing doses of phenylephrine (PE) and sodium nitroprusside were infused for 10 min after an infusion of normal saline. A 20-min rest period separated the phenylephrine and sodium nitroprusside infusions. Autonomic activity was approximated by spectral indexes of heart rate and blood pressure variability, and baroreflex sensitivity was measured by the spontaneous baroreflex slope. Parasympathetic modulation and baroreflex sensitivity decreased with bed rest, with women experiencing a larger decrease in baroreflex sensitivity by day 30 than men. The sympathetic activation of men and parasympathetic responsiveness of women in blood pressure control during physiological stress were preserved throughout bed rest. During PE infusions, women experienced saturation of the R-R interval at high frequency, whereas men did not, revealing a sex difference in the parabolic relationship between high-frequency R-R interval, a measurement of respiratory sinus arrhythmia, and R-R interval. These sex differences in blood pressure control during simulated microgravity reveal the need to study sex differences in long-duration spaceflight to ensure the health and safety of the entire astronaut corps.

Virtual guidance as a tool to obtain diagnostic ultrasound for spaceflight and remote environments.

INTRODUCTION: With missions planned to travel greater distances from Earth at ranges that make real-time two-way communication impractical, astronauts will be required to perform autonomous medical diagnostic procedures during future exploration missions. Virtual guidance is a form of just-in-time training developed to allow novice ultrasound operators to acquire diagnostically-adequate images of clinically relevant anatomical structures using a prerecorded audio/visual tutorial viewed in real-time. METHODS: Individuals without previous experience in ultrasound were recruited to perform carotid artery (N = 10) and ophthalmic (N = 9) ultrasound examinations using virtual guidance as their only training tool. In the carotid group, each untrained operator acquired two-dimensional, pulsed and color Doppler of the carotid artery. In the ophthalmic group, operators acquired representative images of the anterior chamber of the eye, retina, optic nerve, and nerve sheath. Ultrasound image quality was evaluated by independent imaging experts. RESULTS: Of the studies, 8 of the 10 carotid and 17 of 18 of the ophthalmic images (2 images collected per study) were judged to be diagnostically adequate. The quality of all but one of the ophthalmic images ranged from adequate to excellent. DISCUSSION: Diagnostically-adequate carotid and ophthalmic ultrasound examinations can be obtained by previously untrained operators with assistance from only an audio/video tutorial viewed in real time while scanning. This form of just-in-time training, which can be applied to other examinations, represents an opportunity to acquire important information for NASA flight surgeons and researchers when trained medical personnel are not available or when remote guidance is impractical.

Artificial gravity training reduces bed rest-induced cardiovascular deconditioning.

We studied 15 men (8 treatment, 7 control) before and after 21 days of 6º head-down tilt to determine whether daily, 1-h exposures to 1.0 G(z) (at the heart) artificial gravity (AG) would prevent bed rest-induced cardiovascular deconditioning. Testing included echocardiographic analysis of cardiac function, plasma volume (PV), aerobic power (VO(2)pk) and cardiovascular and neuroendocrine responses to 80º head-up tilt (HUT). Data collected during HUT were ECG, stroke volume (SV), blood pressure (BP) and blood for catecholamines and vasoactive hormones. Heart rate (HR), cardiac output (CO), total peripheral resistance, and spectral power of BP and HR were calculated. Bed rest decreased PV, supine and HUT SV, and indices of cardiac function in both groups. Although PV was decreased in control and AG after bed rest, AG attenuated the decrease in orthostatic tolerance [pre- to post-bed rest change; control: -11.8 ± 2.0, AG: -6.0 ± 2.8 min (p = 0.012)] and VO(2)pk [pre- to post-bed rest change; control: -0.39 ± 0.11, AG: -0.17 ± 0.06 L/min (p = 0.041)]. AG prevented increases in pre-tilt levels of plasma renin activity [pre- to post-bed rest change; control: 1.53 ± 0.23, AG: -0.07 ± 0.34 ng/mL/h (p = 0.001)] and angiotensin II [pre- to post-bed rest change; control: 3.00 ± 1.04, AG: -0.63 ± 0.81 pg/mL (p = 0.009)] and increased HUT aldosterone [post-bed rest; control: 107 ± 30 pg/mL, AG: 229 ± 68 pg/mL (p = 0.045)] and norepinephrine [post-bed rest; control: 453 ± 107, AG: 732 ± 131 pg/mL (p = 0.003)]. We conclude that AG can mitigate some aspects of bed rest-induced cardiovascular deconditioning, including orthostatic intolerance and aerobic power. Mechanisms of improvement were not cardiac-mediated, but likely through improved sympathetic responsiveness to orthostatic stress.

Metabolic consequences of garments worn to protect against post-spaceflight orthostatic intolerance.

INTRODUCTION: Astronauts have worn an inflatable antigravity suit (AGS) during Space Shuttle re-entry and landing to protect against hypotension and syncope, but ambulation with an inflated AGS requires significant effort and may prevent successful completion of an unaided emergency egress from the vehicle. NASA is considering the use of alternative garments to provide protection against post-spaceflight orthostatic intolerance. The purpose of this study was to compare the metabolic cost of walking in NASA's current AGS with that of walking in a commercially available elastic compression garment (thigh-high stockings), a candidate garment for use after exploration missions. METHODS: There were 10 volunteers (5 men, 5 women) who walked on a treadmill at 5.6 km x h(-1) for 5 min, a simulation of unaided egress previously used in our laboratory, in 3 different conditions presented in random order: wearing exercise clothes, wearing elastic compression garments, and wearing the AGS. Oxygen consumption (Vo2), carbon dioxide production (Vco2), and ventilation (V(E)) were compared using repeated-measures ANOVA and Tukey's Honestly Significant Difference test. RESULTS: Vo2 while wearing the AGS was 12% greater than when wearing the elastic compression garments and 15% greater than while wearing exercise clothes. There were no differences between the elastic compression garments and exercise clothes only conditions. Vco2 and VE also were greater while walking in the AGS than walking in the elastic compression garments or exercise clothes. CONCLUSIONS: Wearing elastic compression garments as a countermeasure to post-spaceflight orthostatic intolerance may not impair unaided egress from a space vehicle.

Effects of promethazine and midodrine on orthostatic tolerance.

INTRODUCTION: Astronauts experience both orthostatic hypotension and space motion sickness during re-entry. Midodrine, an alpha1-adrenergic agonist, is used to treat orthostatic hypotension. Promethazine, a histamine H1-receptor antagonist, is prescribed for space motion sickness. Many astronauts need both midodrine and promethazine. This study evaluated the interactive effects of midodrine and promethazine on hemodynamic responses to upright tilt. METHODS: Subjects (5 men; 3 women) were studied four times: control (no drug); midodrine only; promethazine only; or midodrine plus promethazine. Hemodynamic parameters, plasma norepinephrine, renin activity, and aldosterone were measured supine and upright. RESULTS: Rates of presyncope were 38% with no drug; 0% with midodrine alone; 100% with promethazine alone; and 63% with both drugs. Supine to upright decreases in systolic pressure were greater with promethazine alone than control (P < 0.01); midodrine (P < 0.05) or both drugs (P < 0.05). Supine to upright increases in plasma norepinephrine, renin activity, and aldosterone all were significantly reduced with promethazine alone compared to control (P < 0.05, P < 0.05, P < 0.05) and midodrine alone (P < 0.05, P < 0.01, P < 0.01). Cardiac output fell more with promethazine alone than with no drug (P < 0.05) or with midodrine plus promethazine (P < 0.05). DISCUSSION: Promethazine significantly increased the incidence of orthostatic hypotension in subjects, even when combined with midodrine. Inhibition of sympathetic responses, likely via enhancement of the inhibitive effects of GABA, by promethazine may underlie the increased orthostatic hypotension. Promethazine also appears to inhibit responses of the renin angiotensisn system during orthostatic challenge.

Gradient compression garments as a countermeasure to post-spaceflight orthostatic intolerance.

INTRODUCTION: Post-spaceflight orthostatic intolerance affects approximately 30% of short-duration and 80% of long-duration crewmembers. While the current NASA antigravity suit is effective during Space Shuttle re-entry, it is not designed to be worn postflight and has several drawbacks. The purpose of this study was to evaluate the use of commercially available, thigh-high, gradient compression garments to prevent post-spaceflight orthostatic intolerance. METHODS: Before spaceflight, five male Shuttle astronauts were fitted for compression garments. Postflight stand time, blood pressure, heart rate, stroke volume, cardiac output, and peripheral resistance during 10-min, 80 degrees head-up tilt test within 4 h of landing in these astronauts were retrospectively compared to a group of nine male astronauts not wearing the compression garments. RESULTS: On landing day, three of nine non-countermeasure astronauts developed presyncopal symptoms and could not complete the test, while no countermeasure subjects became presyncopal. Compared to the non-countermeasure subjects, the countermeasure subjects had higher systolic blood pressure (116 +/- 3 vs. 134 +/- 2 mmHg), stroke volume (42 +/- 5 vs. 57 +/- 6 ml), and cardiac output (3.1 +/- 0.3 vs. 4.6 +/- 0.4 L). Heart rate was not different between groups. CONCLUSIONS: In this small pilot study, the rate of presyncope in the non-countermeasure group was similar to that reported previously in subjects without a compression garment. In contrast, thigh-high graded compression garments mitigated the symptoms of orthostatic intolerance by improving stroke volume, cardiac output, and systolic blood pressure responses to standing.

Ventricular chamber sphericity during spaceflight and parabolic flight intervals of less than 1 G.

INTRODUCTION: Pathology driven alterations in the geometric shape of the heart have been found to result in regional changes in ventricular wall stress and a remodeling of the myocardium. If reductions in the gravitational forces acting on the heart produce similar changes in the overall contour of the ventricles, this modification might also induce adaptations in the cardiac structure during long-term spaceflight. In this study we examined the changes in left ventricle (LV) shape in spaceflight and during parabolic flights. METHODS: The diastole dimensions of the human LV were assessed with echocardiography during spaceflight and in parabolic flights which replicated the gravity of the Moon, Mars, and spaceflight and were compared to findings in Earth's gravity. LV dimensions were translated into circularity indices and geometric aspect ratios and correlated with their corresponding gravitational conditions. RESULTS: During parabolic flight, a linear relationship (r = 0.99) was found between both the circularity index and geometric aspect ratio values and the respective gravitational fields in which they were measured. During spaceflight (N = 4) and parabolic flights (N = 3), there was an average 4.1 and 4.4% higher circularity index and a 5.3 and 8.1% lower geometric aspect ratio, respectively. CONCLUSIONS: A correlative trend was found between the degree of LV sphericity and the amount of gravitational force directed caudal to the longitudinal orientation of the body. The importance of this finding is uncertain, but may have implications regarding physiologic adaptations in the myocardial structure secondary to changes in LV wall stress upon prolonged exposure to microgravity.

Aerobic exercise deconditioning and countermeasures during bed rest.

Bed rest is a well-accepted model for spaceflight in which the physiologic adaptations, particularly in the cardiovascular system, are studied and potential countermeasures can be tested. Bed rest without countermeasures results in reduced aerobic capacity and altered submaximal exercise responses. Aerobic endurance and factors which may impact prolonged exercise, however, have not been well studied. The initial loss of aerobic capacity is rapid, occurring in parallel with the loss of plasma volume. Thereafter, the reduction in maximal aerobic capacity proceeds more slowly and is influenced by central and peripheral adaptation. Exercise capacity can be maintained during bed rest and may be improved during recovery with appropriate countermeasures. Plasma volume restoration, resistive exercise, orthostatic stress, aerobic exercise, and aerobic exercise plus orthostatic stress all have been tested with varying levels of success. However, the optimal combination of elements-exercise modality, intensity, duration, muscle groups exercised and frequency of aerobic exercise, orthostatic stress, and supplementary resistive or anaerobic exercise training-has not been systematically evaluated. Currently, frequent (at least 3 days per week) bouts of intense exercise (interval-style and near maximal) with orthostatic stress appears to be the most efficacious method to protect aerobic capacity during bed rest. Further refinement of protocols and countermeasure hardware may be necessary to insure the success of countermeasures in the unique environment of space.

Cardiovascular adaptations to long-duration head-down bed rest.

INTRODUCTION: Orthostatic hypotension is a serious risk for crewmembers returning from spaceflight. Numerous cardiovascular mechanisms have been proposed to account for this problem, including vascular and cardiac dysfunction, which we studied during bed rest. METHODS: Thirteen subjects were studied before and during bed rest. Statistical analysis was limited to the first 49-60 d of bed rest and compared to pre-bed rest data. Ultrasound data were collected on vascular and cardiac structure and function. Tilt testing was conducted for 30 min or until presyncopal symptoms intervened. RESULTS: Plasma volume was significantly reduced (15%) by day 7 of bed rest. Flow-mediated dilation in the leg was significantly increased at bed rest day 49 (6% from pre-bed rest). Arterial responses to nitroglycerin differed in the arm and leg, but did not change as a result of bed rest. Anterior tibial artery intimal-medial thickness markedly decreased at bed rest days 21 (21%), 35 (22%), and 49 (19%). Several cardiac functional parameters, including isovolumic relaxation time (73 ms to 85 ms at day 7) and myocardial performance index, were significantly increased (0.41 to 0.49 by day 7 of bed rest; indicating a decrease in cardiac function) during bed rest. There was a trend for decreased orthostatic tolerance following 60 d of bed rest (P = 0.1). DISCUSSION: Our data suggest that bed rest altered cardiovascular structure and function in a pattern similar to short-duration spaceflight. Additionally, the vascular alterations were primarily seen in the lower body, while vessels of the upper body were unaffected.

Compression garments as countermeasures to orthostatic intolerance.

INTRODUCTION: All astronauts experience some degree of orthostatic intolerance following spaceflight, ranging from tachycardia to orthostatic hypotension and syncope. The purpose of this study was to evaluate the ability of two compression garments, the National Aeronautics and Space Administration's inflatable antigravity suit (AGS) and the Russian Federal Space Agency's non-inflatable compression garment (Kentavr), to prevent hypovolemia-related orthostatic intolerance. METHODS: To mimic the plasma volume loss experienced by astronauts during spaceflight 19 healthy subjects received an intravenous dose of a diuretic, furosemide (0.5 mg x kg(-1)), and then consumed a low-salt diet for 36 h. Thereafter, subjects participated in a 15-min 80 degrees head-up tilt test wearing either the AGS (N = 9) or Kentavr (N = 10). Compression garments were used in the fashion recommended by the respective agencies, delivering approximately 78 mmHg and approximately 30 mmHg of compression in the AGS and Kentavr, respectively. Incidence of presyncope and hemodynamic responses during upright tilt were compared to a separate group of hypovolemic control subjects (N = 16). RESULTS: Subjects wearing the AGS or Kentavr completed the full 15 min of upright tilt without incidence of orthostatic hypotension or presyncope. In contrast, only 9 control subjects (56%) were able to complete the tilt test. In addition, both types of compression garments maintained systolic blood pressure and significantly reduced tilt-induced tachycardia and reductions in stroke volume. CONCLUSIONS: Although both garments successfully countered hypovolemia-induced orthostatic intolerance, the Kentavr provided protection by using lower levels of compression. Determining the optimal compression level required for protection of intolerance may improve crewmember comfort and decrease restrictions on physical activities after spaceflight.

Hemodynamic effects of midodrine after spaceflight in astronauts without orthostatic hypotension.

INTRODUCTION: Orthostatic hypotension and presyncope are common and potentially serious risks for astronauts returning from space. Susceptible subjects fail to generate an adequate adrenergic response to upright posture. The alpha-1 adrenergic agonist, midodrine, may be an effective countermeasure. We tested the hypothesis that midodrine would have no negative hemodynamic effect on healthy astronauts returning from space. METHODS: Five male astronauts participated in preflight and post-flight tilt testing on a control flight as well as on the test flights, where midodrine (10 mg, orally) was administered after landing approximately 1 h before testing. RESULTS: None of these astronauts exhibited orthostatic hypotension or presyncope before or after either flight. Midodrine did not cause any untoward reactions in these subjects before or after flight; in fact, a modest beneficial effect was seen on postflight tachycardia (p = 0.036). DISCUSSION: These data show that midodrine protected against post-spaceflight increases in heart rate without having any adverse hemodynamic effects on non-presyncopal, male astronauts. Among these subjects, midodrine was a safe cardiovascular countermeasure.