Engineering topics

Platts, Steven H.

Publications and source records attributed to Platts, Steven H..

53 records · Page 3

NASA NTRS2009

Efficacy of Compression Garments to Simulate Fluid Shifts during Lunar Bedrest

The effectiveness of JOBST(Registered TradeMark) compression stockings for fluid redistribution was examined in the lunar bed rest analog based on Digital Astronaut computer model predictions. NASA's future goals include missions to the moon which will require extended exposure to the lunar gravity environment. To prepare for these missions, physiological adaptations in various systems must be resolved. A bed rest at a 10 degree head-up tilt was used to simulate lunar gravity. Plasma volume (PV) loss may cause some of the cardiovascular adaptations which occur during space flight so PV is measured in the bed rest analog to evaluate fluid loss. PV varies from individual to individual so PV index (PVI) is used to determine the magnitude and time course of fluid shift and cardiovascular adaptation to 1/6 g. The Digital Astronaut, a computer simulation tool, predicts a 6% PV loss during an extended simulated lunar mission for a male with a body surface area of 1.95 m(exp 2). Simple geometry calculations suggest that 10 degree head-up tilt is most useful for simulated measurement of deconditioning in bone and muscle, however, 2 degree head-up tilt may best imitate cardiovascular fluid shifts. In order to reconcile these different models, compression stocking must be used in the 10 degree paradigm to better approximate expected cardiovascular changes.

Brinley, Alaina↗

NASA NTRS2009

Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias

Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias (Integrated Cardiovascular) will quantify the extent of long-duration space flightassociated cardiac atrophy (deterioration) on the International Space Station crewmembers.

Levine, Benjamin D.↗

NASA NTRS2009

Splanchnic Compression Improves the Efficacy of Compression Stockings to Prevent Orthostatic Intolerance

Purpose: Post-spaceflight orthostatic intolerance (OI) is observed in 20-30% of astronauts. Previous data from our laboratory suggests that this is largely a result of decreased venous return. Currently, NASA astronauts wear an anti-gravity suit (AGS) which consists of inflatable air bladders over the calves, thighs and abdomen, typically pressurized from 26 to 78 mmHg. We recently determined that, thigh-high graded compression stockings (JOBST , 55 mmHg at ankle, 6 mmHg at top of thigh) were effective, though to a lesser degree than the AGS. The purpose of this study was to evaluate the addition of splanchnic compression to prevent orthostatic intolerance. Methods: Ten healthy volunteers (6M, 4F) participated in three 80 head-up tilts on separate days while (1) normovolemic (2) hypovolemic w/ breast-high compression stockings (BS)(JOBST(R), 55 mmHg at the ankle, 6 mmHg at top of thigh, 12 mmHg over abdomen) (3) hypovolemic w/o stockings. Hypovolemia was induced by IV infusion of furosemide (0.5 mg/kg) and 48 hrs of a low salt diet to simulate plasma volume loss following space flight. Hypovolemic testing occurred 24 and 48 hrs after furosemide. One-way repeated measures ANOVA, with Bonferroni corrections, was used to test for differences in blood pressure and heart rate responses to head-up tilt, stand times were compared using a Kaplan-Meyer survival analysis. Results: BS were effective in preventing OI and presyncope in hypovolemic test subjects ( p = 0.015). BS prevented the decrease in systolic blood pressure seen during tilt in normovolemia (p < 0.001) and hypovolemia w/o countermeasure (p = 0.005). BS also prevented the decrease in diastolic blood pressure seen during tilt in normovolemia (p = 0.006) and hypovolemia w/o countermeasure (p = 0.041). Hypovolemia w/o countermeasure showed a higher tilt-induced heart rate increase (p = 0.022) than seen in normovolemia; heart rate while wearing BS was not different than normovolemia (p = 0.353). Conclusion: BS may be an effective countermeasure to post-space flight OI. The addition of splanchnic compression is more effective than the previous thigh-high garments. These stockings are readily available, inexpensive, and can be worn for days following landing as astronauts re-adapt to Earth gravity.

Platts, Steven H.↗

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

Validation of Cardiovascular Parameters During NASA's Functional Task Test

Microgravity-induced physiological changes, including cardiovascular deconditioning may impair crewmembers f capabilities during exploration missions on the Moon and Mars. The Functional Task Test (FTT), which will be used to assess task performance in short and long duration astronauts, consists of 7 functional tests to evaluate crewmembers f ability to perform activities to be conducted in a partial-gravity environment or following an emergency landing on Earth. The Recovery from Fall/Stand Test (RFST) tests both the subject fs ability to get up from a prone position and orthostatic intolerance. PURPOSE: Crewmembers have never become presyncopal in the first 3 min of quiet stand, yet it is unknown whether 3 min is long enough to cause similar heart rate fluctuations to a 5-min stand. The purpose of this study was to validate and test the reliability of heart rate variability (HRV) analysis of a 3-min quiet stand. METHODS: To determine the validity of using 3 vs. 5-min of standing to assess HRV, 7 healthy subjects remained in a prone position for 2 min, stood up quickly and stood quietly for 6 min. ECG and continuous blood pressure data were recorded. Mean R-R interval and spectral HRV were measured in minutes 0-3 and 0-5 following the heart rate transient due to standing. Significant differences between the segments were determined by a paired t-test. To determine the reliability of the 3-min stand test, 13 healthy subjects completed 3 trials of the complete FTT on separate days, including the RFST with a 3-min stand test. Analysis of variance (ANOVA) was performed on the HRV measures. RESULTS: Spectral HRV measures reflecting autonomic activity were not different (p>0.05) during the 0-3 and 0-5 min segment (mean R-R interval: 738+/-74 ms, 728+/-69 ms; low frequency to high frequency ratio: 6.5+/-2.2, 7.7+/-2.7; normalized high frequency: 0.19+/-0.03, 0.18+/-0.04). The average coefficient of variation for mean R-R interval, systolic and diastolic blood pressures in the prone position and stand test were less than 8% for the test sessions. ANOVA results yielded a greater inter-subject variability (p.0.006) than inter-session variability (p>0.05) for HRV in the stand test. CONCLUSION: These studies show that a 3 minute stand delivers repeatable cardiovascular heart rate and BP data in the context of this larger series of tests such as the FTT.

Arzeno, N. M.↗

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

Midodrine as a Countermeasure for Post-spaceflight Orthostatic Hypotension

Up to 30 % of astronauts exhibit post-spaceflight orthostatic hypotension due to inadequate norepinephrine release during upright posture following short duration spaceflight. We hypothesize that the (alpha)1-adrenergic agonist midodrine will be an effective countermeasure. This study is being conducted in 2 phases. The first phase is complete and consisted testing six short duration crew members. All of these subjects participated in preflight and postflight tilt testing on a control flight as well as on the test flights, where midodrine was administered after landing, 1 hour before testing. Hemodynamic variables were compared between the 2 flights. Midodrine improved stroke volume, cardiac output, systolic pressure and heart rate, without increasing vascular resistance. None of these subjects experienced orthostatic hypotension on landing day. Phase II is similar to phase I, except that midodrine is ingested in flight (near TIG) and the tilt test is performed immediately after landing on the CTV. One crewmember has completed phase II testing. This crewmember had no evidence of orthostatic hypotension or presyncope, four additional crewmembers have volunteered for this study. To date, midodrine has been shown to be a safe and effective countermeasure to post-spaceflight orthostatic hypotension.

Platts, Steven H.↗

NASA NTRS2007

Cardiovascular Adaptations to Long Duration Head Down Tilt Bed Rest

Orthostatic hypotension is a recognized risk for crewmembers returning from space. Numerous cardiovascular mechanisms have been proposed to account for this problem including vascular and cardiac dysfunction. We studied arterial and cardiac function in 6-degree head-down tilt bed rest, which is the most widely accepted ground-based analog of spaceflight. Eleven subjects are included in this study (8 men and 3 women). Data analysis was limited to the first 49 days, and compared to pre-bed rest baseline data. Using ultrasound, data was collected on arterial diameters and flows at baseline and during reactive hyperemia and following administration of nitroglycerin. Echocardiography was used to acquire information regarding systolic and diastolic function as well as ventricular mass and diameter. Plasma volumes were significantly decreased by 7 days of bed rest and stayed down through 49 days. There were no differences in reactive hyperemic response in the arm at any time point. However, the hyperemic response in the leg was significantly increased at day 49. Arterial responses to nitroglycerin did not change over the duration of bed rest (day effect) in either the arm or leg, but there was a significant difference between the arm and the leg responses. There was a marked decrease in anterior tibial intimal-medial thickness at days 21, 35 and 49. Several cardiac functional parameters including IVRT, Mitral e-wave, ejection time, velocity of circumferential shortening and myocardial performance index were significantly changed following 49 days of bed rest. These data show that some cardiovascular measures change during bed rest, while others do not. Further study is needed to determine if these measures can provide any insight into the effects of bed rest, or spaceflight, on human cardiovascular performance.

Platts, Steven H.↗

NASA NTRS2007

Role for Lower Extremity Interstitial Fluid Volume Changes in the Development of Orthostasis after Simulated Microgravity

Reentry orthostasis after exposure to the conditions of spaceflight is a persistent problem among astronauts. In a previous study, a computer model systems analysis was used to examine the physiologic mechanisms involved in this phenomenon. In this analysis, it was determined that an augmented capacitance of lower extremity veins due to a fluid volume contracture of the surrounding interstitial spaces during spaceflight results in an increase in sequestered blood volume upon standing and appears to be the initiating mechanism responsible for reentry orthostasis. In this study, we attempt to validate the central premise of this hypothesis using a ground-based spaceflight analog. 10 healthy subjects were placed at bed rest in a 6 head down tilt position for 60 days of bed rest. The impact of adaptations in interstitial fluid volume and venous capacitance in the lower extremities were then observed during a standard tilt test protocol performed before and after the confinement period. The interstitial thickness superficial to the calcaneous immediately below the lateral malleolus was measured using ultrasound with a 17-5 MHz linear array transducer. Measurements of the changes in anterior tibial vein diameter during tilt were obtained by similar methods. The measurements were taken while the subjects were supine and then during upright tilt (80') for thirty minutes, or until the subject had signs of presyncope. Additional measurements of the superficial left tibia interstitial thickness and stroke volume by standard echocardiographic methods were also recorded. In addition, calf compliance was measured over a pressure range of 10-60 mmHg, using plethysmography, in a subset of these subjects (n = 5). There was a average of 6% diminution in the size of the lower extremity interstitial space as compared to measurements acquired prior to bed rest. This contracture of the interstitial space coincided with a subsequent relative increase in the percentage change in tibial vein diameter and stroke volume upon tilting in contrast to the observations made before bed rest (54 vs 23% respectively). Compliance in the calf increased by an average of 36% by day 27 of bedrest. A systems analysis using a computer model of cardiovascular physiology suggests that microgravity induced interstitial volume depletion results in an accentuation of venous blood volume sequestration and is the initiating event in reentry orthostasis. This hypothesis was tested in volunteer subjects using a ground-based spaceflight analog model that simulated the body fluid redistribution induced by microgravity exposure. Measurements of changes in the interstitial spaces and observed responses of the anterior tibial vein with tilt, together with the increase in calf compliance, were consistent with our proposed mechanism for the initiation of postflight orthostasis often seen in astronauts.

Platts, Steven H.↗

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.↗

NASA NTRS2006

Hypovolemia Induced Orthostatic Hypotension in Presyncopal Astronauts and Normal Subjects Related to Hypoadrenergic Responsiveness

Circulating blood volume is reduced during spaceflight, making astronauts hemodynamically compromised. After landing, astronauts separate into two groups. One group compensates for the hypovolemia with a hyper-sympathetic response during upright tilt testing and can complete a tilt test with few symptoms. The other group is unable to mount a hyper-sympathetic response and experiences orthostatic hypotension and presyncope during upright tilt tests. We tested the hypothesis that hypovolemia alone, in the absence of spaceflight, also would cause subjects to separate into presyncopal and non-presyncopal groups according to their sympathetic responses during tilt. We studied 20 subjects, including 10 veteran astronauts, on three occasions. On Days 1 (normovolemia) and 3 (hypovolemia), plasma volume, tilt tolerance and supine and standing plasma norepinephrine levels were measured. Forty hours prior to Day 3, subjects were given intravenous furosemide, followed by 36 hours of a 10MEq Na diet. Statistical comparisons were made between normovolemia and hypovolemia responses. This protocol reproduced landing day tilt test outcomes with 100% fidelity in the astronauts. Similarly to patterns reported after flight, non-presyncopal subjects had greater norepinephrine responses to tilt during hypovolemia compared to normovolemia (580 plus or minus 79 vs. 298 plus or minus 37 pg/ml, P less than 0.05), but presyncopal subjects had no increase (180 plus or minus 44 vs. 145 plus or minus 32 pg/ml, P=NS). This model can be used to predict astronauts who will become presyncopal on landing day, so that prospective, individualized countermeasures can be developed. Within patient populations, it can be used to study the interaction of volemic state and the sympathetic nervous system.

Meck, Janice V.↗

NASA NTRS2006

Hemodynamic Effects of Midodrine After Space Flight in Astronauts Without Orthostatic Hypotension

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 -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. Five male astronauts participated in preflight and postflight tilt testing on a control flight as well as on the test flights, where midodrine (10 mg, orally) was administered after landing, approximately 1 hour before testing. 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). 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.

Platts, Steven H.↗

NASA NTRS2006

Midodrine Exacerbates Promethazine-induced Akathisia

The study of physiological changes during spaceflight, and the pursuit of remedies to counteract those changes, often requires unique research protocols that lead to unexpected findings; some with important clinical implications. In our research into the development of treatments to counteract the detrimental cardiovascular effects of spaceflight, we have discovered an important drug interaction between promethazine and midodrine.

Platts, Steven H.↗