Engineering topics

Stenger, Michael B.

Publications and source records attributed to Stenger, Michael B..

51 records · Page 3

NASA NTRS2011

Compression Stockings May Ameliorate Orthostatic Intolerance in Astronauts After Short-Duration Space Flight

Orthostatic intolerance following spaceflight has been observed since the early days of manned spaceflight, and no countermeasure has been 100% effective. During re-entry NASA astronauts currently wear an inflatable anti-gravity suit (AGS) which compresses the legs and abdomen, but this device is uncomfortable and loses effectiveness upon egress from the Space Shuttle. We previously reported that foot-to-thigh, gradient compression stockings were comfortable and effective during standing after Shuttle missions. More recently we showed in a ground-based model of spaceflight that the addition of splanchnic compression to the foot-to-thigh compression stockings, creating foot-to-breast high compression, improved orthostatic tolerance in hypovolemic subjects to a level similar to the AGS. Purpose: To evaluate a new three-piece, foot-to-breast high gradient compression garment as a countermeasure to post-spaceflight orthostatic intolerance. Methods: Fourteen astronauts completed this experiment (7 control, 7 treatment) following Space Shuttle missions lasting 12-16 days. Treatment subjects were custom-fitted for a three-piece, foot-to-breast high compression garment consisting of shorts and foot-to-thigh stockings. The garments were constructed to provide 55 mmHg compression at the ankle and decreased gradually to 15 mmHg over the abdomen. Orthostatic testing occurred ~30 days before flight (without garments) and ~2 hours after flight (with garments for treatment group only) on landing day. Blood pressure (BP) and heart rate (HR) were acquired for 2 minutes while the subject lay prone and then for 3.5 minutes after the subject stood. Data are reported as mean +/- SE. Results: The compression garment successfully prevented the tachycardia and hypotension typically seen post-spaceflight. On landing day, treatment subjects had a smaller change in HR (11+/-1 vs. 21+/-4 beats/min, p< or =0.05) and no decrease in systolic BP (2+/-4 vs. -9+/-2 mmHg, p< or =0.05). Garments also received good comfort ratings and were relatively easy to don. Conclusion: In this small group of astronauts, foot-to-breast high gradient compression garments seem to have prevented these negative effects of spaceflight on the cardiovascular responses to standing.

Platts, Steven H.↗

NASA NTRS2011

Gradient Compression Stockings may Prevent Recovery after Bed Rest Deconditioning

Introduction: Astronauts continue to wear a compression garment during and immediately after landing to prevent orthostatic intolerance (OI). We recently developed a custom-fitted, 3-piece garment that consists of thigh-high stockings with biker-style shorts that provides continuous, gradient compression: 55 mmHg at the ankle that decreases to approximately 20 mmHg at the top of the leg and 15 mmHg over the abdomen. This garment has been shown to be effective in preventing symptoms of OI during a short stand test after Space Shuttle missions, but symptoms may persist for several days after a long-duration mission in some astronauts. The purpose of this study was to confirm the effectiveness of wearing these elastic, gradient compression garments during orthostatic testing after 2 weeks of 6 degree head-down tilt bed rest as a model of spaceflight and to determine whether they would impact recovery after bed rest. Methods: Eight (5 treatment, 3 control) of 16 subjects have completed this study to-date. All subjects wore the 3-piece garment from waking until tilt testing (~3 h) as a simulation of the timeline for astronauts on landing day (BR+0). Control subjects removed the garment after the tilt test. Treatment subjects wore the garment for the remainder of the day and wore lower compression thigh-high only garments on the day after bed rest (BR+1). Blood pressure, heart rate, and stroke volume responses to a 15-min 80 degree head-up tilt test were determined before 2 weeks of 6 degree head-down tilt, and on BR+0 and BR+1. Plasma volume (PV) was measured before each of these test sessions. Data are mean SE. Results: Compression garments prevented signs of OI on BR+0; all subjects in both groups completed the full 15-min test. Heart rate responses to tilt were lower on BR+0 than all other test days. Control subjects demonstrated a marginal PV decrease after bed rest, but showed typical recovery the day after bed rest (BR+0: 2.32 plus or minus 0.15 L to BR+1: 2.79 plus or minus 0.15 L). Treatment subjects did not recover PV the day after bed rest (BR+0: 2.61 plus or minus 0.23 L to BR+1: 2.61 plus or minus 0.23 L). Conclusion: Abdomen-high compression garments, which are effective in preventing post-bed rest orthostatic intolerance, may slow recovery of PV. Modified garments with reduced compression may be necessary to prevent prolonging recovery.

Stenger, Michael B.↗

NASA NTRS2011

Orthostatic Hypotension After Long-Duration Space Flight: NASA's Experiences from the International Space Station

Our laboratory previously reported that the incidence of orthostatic hypotension (OH) was greater after long- than short-duration spaceflight in astronauts who participated in Mir Space Station and Space Shuttle missions. To confirm and extend these findings, we retrospectively examined tilt test data from International Space Station (ISS) and Shuttle astronauts. We anticipated that the proportion of ISS astronauts experiencing OH would be high on landing day and the number of days to recover greater after long- than short-duration missions. Methods: Twenty ISS and 66 Shuttle astronauts participated in 10-min 80? head-up tilt tests 10 d before launch (L-10), on landing day (R+0) or 1 d after landing (R+1). Data from 5 ISS astronauts tested on R+0 or R+1 who used non-standard countermeasures were excluded. Many astronauts repeated the test 3 d (R+3) after landing. Fisher?s Exact Test was used to compare the ability of ISS and Shuttle astronauts to complete the tilt test on R+0. Cox regression was used to identify cardiovascular parameters that were associated with test completion across all tests, and mixed model analysis was used to compare the change and recovery rates between ISS and Shuttle astronauts. In these analyses, ISS data from R+0 and R+1 were pooled to provide sufficient statistical power. Results: The proportion of astronauts who completed the tilt test on R+0 without OH was less in ISS than in Shuttle astronauts (p=0.03). On R+0, only 2 of 6 ISS astronauts completed the test compared to 53 of 66 (80%) Shuttle astronauts. However, 8 of 9 ISS astronauts completed the test on R+1. On R+3, 13 of 15 (87%) of the ISS and 19 of 19 (100%) of the Shuttle astronauts completed the 10-min test. An index comprised of stroke volume and diastolic blood pressure provided a very good prediction of overall tilt survival. This index was altered by spaceflight similarly for both groups soon after landing (pooled R+0 and R+ 1), but ISS astronauts did not recover at the same rate as Shuttle astronauts (p=0.007). Conclusions: The proportion of ISS astronauts who could not complete the tilt test on R+0 due to OH (4 of 6) is similar to that reported in astronauts who flew on Mir (5 of 6). Further, cardiovascular parameters most closely associated with OH recover more slowly after long- compared to short-duration spaceflight.

Lee, Stuart M. C.↗

NASA NTRS2011

Defining the Relationship Between Biomarkers of Oxidative and Inflammatory Stress and the Risk for Atherosclerosis in Astronauts During and After Long-Duration Spaceflight

Future human space travel will primarily consist of long-duration missions aboard the International Space Station (ISS) or exploration class missions to Mars, its moons, or nearby asteroids. These missions will expose astronauts to increased risk of oxidative and inflammatory damage primarily from radiation, but also from psychological stress, reduced physical activity, diminished nutritional status, and, in the case of extravehicular activity, hyperoxic exposure. There is evidence that increased oxidative damage and inflammation can accelerate the development of atherosclerosis. PURPOSE The purpose of this proposal is to identify biomarkers of oxidative and inflammatory stress and to correlate them to indices of atherosclerosis risk before, during, and after long-duration spaceflight. METHODS To meet the objectives of the study, we will study astronauts before, during, and up to 5 years after long-duration missions aboard ISS. Biomarkers of oxidative and inflammatory stress, some of which we have previously shown to be elevated with spaceflight, will be measured before, during, and after spaceflight. Arterial structure will be monitored using ultrasound to measure carotid intima-medial thickness before, during, and after weightlessness. Carotid intima-medial thickness has been shown to be a better indicator than Framingham Risk scores for prediction of atherosclerosis. Arterial function will be monitored using brachial flow-mediated dilation before flight and after landing. Brachial flow-mediated dilation is a good index of endothelium-dependent vasodilation, which is a sensitive predictor of atherosclerotic risk. This is the first study to propose assessing atherosclerotic risk using biochemical, structural, and functional measures before, during, and immediately after spaceflight and structural functional measures for up to 5 years after landing. EXPECTED RESULTS We hypothesize that these biomarkers of oxidative and inflammatory stress will be increased with spaceflight and will correlate with increased carotid intima-medial thickness in- and postflight and with decreased flow-mediated dilation after the mission. Furthermore, we hypothesize that measures of oxidative stress will return to baseline after flight, but that biomarkers of inflammatory stress and vascular indices of atherosclerosis risk will remain elevated.

Lee, Stuart M. C.↗

NASA NTRS2011

Use of Minute-by-Minute Cardiovascular Measurements During Tilt Tests to Strengthen Inference on the Effect of Long-Duration Space Flight on Orthostatic Hypotension

Typical methodology for evaluating the effects of spaceflight on orthostatic hypotension (OH) has been survival analysis of tolerance times from 80 head-up tilt tests. However when scheduled test durations are short, there may not be enough failures to allow survival analysis to adequately estimate and compare the effects of flight phase (e.g. pre-flight, number of days post-flight), flight duration, and their interaction, as well as interactions with effects of interventions or countermeasures. The problem is exacerbated in the presence of a repeated measures design, in which subjects participate in tilt tests during various flight phases. Here we show how it is possible to dramatically improve the efficiency of statistical inference in this setting by making use of the additional information contained in minute-by-minute observations of cardiovascular parameters thought to be reflective of progression towards presyncope during tilt testing. Methods: We retrospectively examined operational tilt test (OTT; 10 -min 80 head-up tilt) data from 20 International Space Station (ISS) and 66 Shuttle astronauts 10 d before launch (L-10), on landing day (R+0) and during recovery (R+1, R+3, R+6-10) depending on the level of participation. Data from 5 ISS astronauts tested on R+0 or R+1 who used non-standard countermeasures were excluded. In addition to OTT survival time, 8 cardiovascular parameters (CP: heart rate, systolic, diastolic, and mean arterial blood pressure, pulse pressure, stroke volume, cardiac output, and total peripheral resistance) that might be predictive of progression towards presyncope were measured every minute of each OTT. Statistical analysis was predicated on a two ]stage model of causation. In the first stage, flight duration and time from landing affect the astronauts' degree of OH, which is manifested in the time trends and variation of the above CPs during OTTs. In the second stage, the behavior of these parameters directly affects OTT survival time. Actual analysis proceeded in the opposite direction. First we identified those CPs or linear combinations that best predicted OTT survival regardless of what spaceflight conditions led to OTT completion or presyncope. From these, we calculated a summary statistic (one per OTT) that best predicted survival. We then used mixed ]model regression analysis to relate changes in the summary statistic to flight phase and duration. Inference on the effects of phase, duration, and their interaction on OH follows directly from this second analysis. Results: A linear combination (W) of diastolic blood pressure (DBP) and stroke volume (SV) was found to be the best predictor of OTT survival using the complete data set of minute-by-minute observations of CPs for each OTT. Furthermore, the log-transformed standard deviation of W (Z = log SW) was found to be a strong predictor of survival in the reduced data set consisting of one observation per OTT. In other words, this measure of variability of W during an OTT was the best indicator of whether or not the subject could complete the 10-min test, with higher variability (i.e. higher values of Z) being associated with greater probability of failure. In the mixed-model regression analysis where Z was now treated as a outcome with flight phase and duration groups (ISS and STS) as predictors, we found that there was a significantly more variability in W (higher values of Z) for both groups at R+0, but with no evidence of an interaction until R+3, when the ISS group still had inflated variability, but not the STS group. Conclusions: Variability of the cardiovascular index W recovers more slowly after long-compared to short-duration spaceflight. Since high variability of W has also been shown to be predictive of OTT failure, a primary manifestation of OH, a logical conclusion is that recovery from OH also is slower after long-duration compared to short-duration spaceflights.

Feiveson, Alan H.↗

NASA NTRS2010

Midodrine as a Countermeasure to Orthostatic Hypotension Immediately After Space Shuttle Landing

Midodrine prevents post-space flight orthostatic intolerance when testing is conducted in a controlled laboratory setting within 2-4 hours after Space Shuttle landing. It is unknown if midodrine is as effective during re-entry and immediately following landing. METHODS: Cardiovascular responses to 10 minutes of 80 head-up tilt in five male astronauts were compared before and immediately after Space Shuttle missions. Preflight tests were conducted in the Johnson Space Center Cardiovascular Laboratory without midodrine. Post-flight testing was performed in the Crew Transport Vehicle on the Space Shuttle runway within 60 minutes of landing; midodrine was self-administered before re-entry. Survival analysis was performed (Gehan-Breslow test) to compare presyncope rates pre- to post-flight. Cardiovascular responses (last minute standing minus supine) to tilt before and after space flight were compared using paired t-tests. RESULTS: Midodrine did not prevent post-flight orthostatic hypotension in two of the five astronauts, but the rate of presyncope across the group did not increase (p=0.17) from pre- to post-flight. Also, although the change in heart rate from supine to the last minute of standing was not affected by space flight, systolic blood pressure decreased more (p=0.05) and diastolic blood pressure tended to decrease (p=0.08) after space flight. CONCLUSIONS: Accurate interpretation of the current results requires that similar data be collected in control subjects (without midodrine) on the CTV. However, drug interaction concerns with commonly used anti-emetics and potentiation of prolonged QTc intervals observed in long duration astronauts make the routine use of midodrine for immediate post-flight orthostatic hypotension unlikely. 2

Platts, Steven H.↗

NASA NTRS2010

Custom Gradient Compression Stockings May Prevent Orthostatic Intolerance in Astronauts After Space Flight

Orthostatic intolerance after space flight is still an issue for astronauts as no in-flight countermeasure has been 100% effective. NASA astronauts currently wear an inflatable anti-gravity suit (AGS) during re-entry, but this device is uncomfortable and loses effectiveness upon egress from the Shuttle. We recently determined that thigh-high, gradient compression stockings were comfortable and effective after space flight, though to a lesser degree than the AGS. We also recently showed that addition of splanchnic compression to this thigh-high compression stocking paradigm improved orthostatic tolerance to a level similar to the AGS, in a ground based model. Purpose: The purpose of this study was to evaluate a new, three-piece breast-high gradient compression garment as a countermeasure to post-space flight orthostatic intolerance. Methods: Eight U.S. astronauts have volunteered for this experiment and were individually fitted for a three-piece, breast-high compression garment to provide 55 mmHg compression at the ankle which decreased to approximately 20 mmHg at the top of the leg and provides ~15 mmHg over the abdomen. Orthostatic testing occurred 30 days pre-flight (w/o garment) and ~2 hours after flight (w/ garment) on landing day. Blood pressure (BP), Heart Rate (HR) and Stroke Volume (SV) were acquired for 2 minutes while the subject lay prone and then for 3.5 minutes after the subject stands up. To date, two astronauts have completed pre- and post-space flight testing. Data are mean SD. Results: BP [pre (prone to stand): 137+/-1.6 to 129+/-2.5; post: 130+/-2.4 to 122+/-1.6 mmHg] and SV [pre (prone to stand): 61+/-1.6 to 38+/-0.2; post: 58+/-6.4 to 37+/-6.0 ml] decreased with standing, but no differences were seen post-flight w/ compression garments compared to pre-flight w/o garments. HR [pre (prone to stand): 66+/-1.6 to 74+/-3.0, post: 67+/-5.6 to 78+/-6.8 bpm] increased with standing, but no differences were seen pre- to post-flight. Conclusion: After space flight, blood pressure and stroke volume are normally decreased and heart rate is usually elevated to compensate. In this small group of subjects, breast-high gradient compression stockings seem to have prevented these negative effects of spaceflight.

Stenger, Michael B.↗

NASA NTRS2009

Functional Task Test (FTT)

This slide presentation reviews the Functional Task Test (FTT), an interdisciplinary testing regimen that has been developed to evaluate astronaut postflight functional performance and related physiological changes. The objectives of the project are: (1) to develop a set of functional tasks that represent critical mission tasks for the Constellation Program, (2) determine the ability to perform these tasks after space flight, (3) Identify the key physiological factors that contribute to functional decrements and (4) Use this information to develop targeted countermeasures.

Bloomberg, Jacob J.↗

NASA NTRS2009

Gender-related Changes in Dorsal Hand and Foot Vein Function Following 60 Days of Head Down Bed Rest

It is well known that female astronauts are more likely to experience post-flight orthostatic hypotension and presyncope compared to male astronauts. It has been suggested that the disproportionally higher incidence of presyncope (83% of female vs. 20% male crewmembers) may be due to sex-related differences in vascular function between the upper and lower limbs. However, much of this evidence is specific to changes in resistance vessels. Given that more than 70% of the circulating blood volume resides in compliance vessels, it is conceivable that even small changes in venous function may contribute to post-flight orthostatic hypotension. In spite of this, little is currently known regarding the influence of microgravity exposure on venous function between males and females. PURPOSE: To determine the influence of 60 days of HDBR on dorsal foot and hand vein function between healthy males (M) and females (F). METHODS: Using 2-D ultrasound, dorsal hand and foot vein diameter responses to intravenous infusions phenylephrine (PE), acetylcholine (ACh), and nitroglycerine (NTG) were determined in 26 adults; 10 females (age:37 +/- 2 yr ) and 16 males (age:34 +/- 2 yr ). Changes in venous function were calculated as the difference between diameter at baseline and following each venoactive drug. Differences in venous function between limb and sexes across HDBR were determined using mixed-effects linear regression. RESULTS: In response to 60 days of HDBR, the change in venousconstrictor response to PE in the dorsal hand veins was not significantly different between M and F. Interestingly, the change in constrictor response in the dorsal foot veins (compared to pre HDBR) was approximately 30% greater in the F, whereas the constrictor response was approximately 45% less in the M (p=0.026). HDBR had no influence on the change in dilator response to ACh, or NTG between M and F and between vascular beds. CONCLUSION: These results demonstrate that 60 days of HDBR contributes to sex-related differences in venous function. Importantly, the changes are specific to dorsal foot veins and do not appear to be related to changes in endothelial or smooth muscle function. Previous data from our laboratory indicate that females have an impaired sympathetic response following HDBR. However, the results from the current investigation imply that F maintain the ability to respond to sympathetic stimulation but may not be able to adequately activate a proper response following HDBR.

Westby, Christian M.↗

NASA NTRS2009

Evidence Based Review: Risk of Cardiac Rhythm Problems During Spaceflight

Very little research has systematically evaluated the prevalence (or potential risk) of cardiac arrhythmias during space flight. There are several observational reports of non life-threatening but potentially concerning arrhythmias. At least two potential risk factors for arrhythmias have been reported either during or immediately after space flight: cardiac atrophy and a prolonged QTc interval. The potential severity of the mission impact of a serious arrhythmia requires that a systematic evaluation be conducted of the risk of arrhythmia due to space flight.

Platts, Steven H.↗

NASA NTRS2008

Midodrine as a Countermeasure for Post-Spaceflight Orthostatic Hypotension

One possible mechanism for post-spaceflight orthostatic hypotension, which affects approximately 30% of astronauts after short duration shuttle missions, is inadequate norepinephrine release during upright posture. We performed a two phased study to determine the effectiveness of an alpha1-adrenergic agonist, midodrine, as a countermeasure to post-spaceflight orthostatic hypotension. The first phase of the study examined the landing day orthostatic responses of six veteran astronauts after oral midodrine (10 mg) administered on the ground within approximately two hours of wheel stop. One female crewmember exhibited orthostatic hypotension in a previous flight but not after midodrine. Five male crewmembers, who did not exhibit orthostatic hypotension during previous flights, also did not show signs of orthostatic hypotension after midodrine. Additionally, phase one showed that midodrine did not cause hypertension in these crewmembers. In the second phase of this study, midodrine is ingested inflight (near time of ignition, TIG) and orthostatic responses are determined immediately upon landing via an 80 degree head-up tilt test performed on the crew transport vehicle (CTV). Four of ten crewmembers have completed phase two of this study. Two crewmembers completed the landing day tilt tests, while two tests were ended early due to presyncopal symptoms. All subjects had decreased landing day stroke volumes and increased heart rates compared to preflight. Midodrine appears to have increased total peripheral resistance in one crewmember who was able to complete the landing day tilt test. The effectiveness of midodrine as a countermeasure to immediate post-spaceflight orthostatic hypotension has yet to be determined; interpretation is made more difficult due to low subject number and the lack of control subjects on the CTV.

Stenger, Michael B.↗

NASA NTRS2008

Gender Differences in Bed Rest: Preliminary Analysis of Vascular Function

Orthostatic intolerance is a recognized consequence of spaceflight. Numerous studies have shown that women are more susceptible to orthostatic intolerance following spaceflight as well as bed rest, the most commonly used ground-based analog for spaceflight. One of the possible mechanisms proposed to account for this is a difference in vascular responsiveness between genders. We hypothesized that women and men would have differing vascular responses to 90 days of 6-degree head down tilt bed rest. Additionally, we hypothesized that vessels in the upper and lower body would respond differently, as has been shown in the animal literature. Thirteen subjects were placed in bedrest for 90 days (8 men, 5 women) at the Flight Analogs Unit, UTMB. Direct arterial and venous measurements were made with ultrasound to evaluate changes in vascular structure and function. Arterial function was assessed, in the arm and leg, during a reactive hyperemia protocol and during sublingual nitroglycerin administration to gauge the contributions of endothelial dependent and independent dilator function respectively. Venous function was assessed in dorsal hand and foot veins during the administration of pharmaceuticals to assess constrictor and dilator function. Both gender and day effects are seen in arterial dilator function to reactive hyperemia, but none are seen with nitroglycerin. There are also differences in the wall thickness in the arm vs the leg during bed rest, which return toward pre-bed rest levels by day 90. More subjects are required, especially females as there is not sufficient power to properly analyze venous function. Day 90 data are most underpowered.

Platts, Steven H.↗

NASA NTRS2008

Cardiovascular Adaptations to Long Duration Head-Down Tilt 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 days 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 minutes or until presyncopal symptoms intervened. RESULTS: Plasma volume was significantly reduced by day 7 of bed rest. Flow-mediated dilation in the leg was significantly increased at bed rest day 49. Arterial responses to nitroglycerin differed in the arm and leg, but did not change as a result of bed rest. Intimal-medial thickness markedly decreased at bed rest days 21, 35 and 49. Several cardiac functional parameters including isovolumic relaxation time, ejection time and myocardial performance index were significantly increased (indicating a decrease in cardiac function) during bed rest. There was a trend for decreased orthostatic tolerance following 60 days of bed rest. DISCUSSION: These data suggest that 6 head-down tilt bed rest alters cardiovascular structure and function in a pattern similar to short duration spaceflight. Additionally, the vascular alterations are primarily seen in the lower body, while vessels of the upper body are unaffected. KEY WORDS: spaceflight, orthostatic intolerance, hypotension, fluid-shift, plasma volume

Platts, Steven H.↗

NASA NTRS2008

Arterial Structure and Function in Women and Men Following Long Duration Bed Rest

Orthostatic intolerance is a well-recognized consequence of space flight and bed rest (BR), with a greater incidence reported in women. We hypothesized that leg, but not arm, arterial structure and function would be altered following prolonged BR, as a model of space flight, and that women would be more susceptible to BR-induced deconditioning than men. METHODS: Ten volunteers (5 males, 5 females) completed 90 d of 6 head-down BR. Subjects participated in tests of brachial (BA) and anterior tibial (AT) artery endothelium-dependent (flow mediated dilation [FMD] following 5-7 min of arterial occlusion) and endothelium-independent (0.4 mg sublingual nitroglycerin [SN]) vasodilation before BR (PRE) and on days 7 (BR7), 21 (BR21), and 90 (BR90) of BR. Vessel diameter and intimal medial thickness (IMT) were measured by ultrasound. IMT, baseline diameter, and percent change in diameter from baseline during FMD and SN tests were compared across BR and between genders using repeated measures two-way ANOVA with Bonferroni post-hoc tests in which PRE and women were control conditions. RESULTS: Baseline vessel diameter was lower in women than in men in both the BA (p=0.005) and AT (p=0.01) across all days. Baseline AT diameter decreased during BR (p=0.01) and tended to be more profound in women (interaction, p=0.06). AT diameter was reduced in women at BR21 and BR90 (p<0.01) but not in men. In contrast, there was no BR effect on baseline BA diameter. IMT also decreased in the AT (p<0.001) but not in the BA during BR; AT IMT was reduced by BR21 (p<0.05). As a group, there was no effect of BR on AT FMD, BA FMD, and AT SN-dilation, although BA SN-dilation was significantly reduced on BR21 (p=0.01). Across all BR days, women exhibited higher AT FMD (p=0.03), BA FMD (p=0.02), and BA SN-dilation (p=0.01) and tended to demonstrate greater AT SN-dilation (p=0.11). CONCLUSIONS: These preliminary results suggest that arterial remodeling occurs during BR in the leg (decreased diameter and IMT), but not in the arm, and that women appear to be more responsive to BR than men. These changes in the leg, coupled with larger responses to direct and indirect stimulation of the arterial smooth muscle, may be related to the greater incidence of orthostatic intolerance in women after BR and space flight.

Lee, Stuart M. C.↗

NASA NTRS2007

Hypovolemia Induced Orthostatic Hypotension in Presyncopal Astronauts and Normal Subjects Relates to Hypo-Sympathetic Responsiveness

Circulating blood volume is reduced during spaceflight, leaving astronauts hemodynamically compromised after landing. Because of this hypovolemia, crew members are able to withstand a postflight 10 minute upright tilt test only if they are able to mount a hyper-sympathetic response. Previous work from this laboratory has shown that about 30% of astronauts, primarily female, have postflight sympathetic responses to tilt that are equal to or less than their preflight responses and thus, they become presyncopal. Part of the mission of the cardiovascular lab at the Johnson Space Center is to identify susceptible crewmembers before flight so that individualized countermeasures can be prescribed. The goal of this study was to develop a ground based model of hypovolemia that could be used for this purpose We tested the hypothesis that hypovolemia alone, in the absence of spaceflight, would reproduce the landing day rate of presyncope during upright tilt in normal volunteers. Further, we hypothesized that, during hypovolemia, subjects who had sympathetic responses that were equal to or less than their normovolemic responses would become presyncopal during upright tilt tests. We studied 20 subjects, 13 male and 7 female, on two separate occasions: during normovolemia and hypovolemia. We induced hypovolemia with intravenous furosemide 40 hours prior to the experiment day, followed by a 10MEq Na diet. On the normovolemia and hypovolemia test days, plasma volume, tilt tolerance and supine and standing arterial pressure, heart rate and plasma norepinephrine levels were measured. A two factor, repeated measures analysis of variance was performed to examine the differences between group (presyncopal vs. non-presyncopal) and day (normovolemia vs. hypovolemia) effects. There were no differences in baseline arterial pressure between normovolemia and hypovolemia or between presyncopal and non-presyncopal groups, but heart rates were higher with hypovolemia in both groups (presyncopal: 70 5 bpm vs. 63 3 bpm, P = 0.003, non-presyncopal: 59 2 bpm vs. 52 2 bpm, P = 0.003). Similar to patterns reported after flight, non-presyncopal subjects had greater norepinephrine responses to tilt during hypovolemia compared to normovolemia (580 79 vs. 298 37 pg/ml, P < 0.05), but presyncopal subjects did not (180 44 vs. 145 32 pg/ml, P = NS). This new model has the potential to accelerate the development of countermeasures and save flight resources. It can be used to identify astronauts who will become presyncopal on landing day, so that prospective, individualized countermeasures can be developed. In addition, it can also be used to screen candidate countermeasures prior to requests for bed rest or inflight resources.

Meck, Janice V.↗