Spaceflight Associated Neuro-ocular Syndrome (SANS)

No abstract availabl

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

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

Impact of +Gz TO -Gz Induced Fluid Shifts on Ocular and Cerebral Parameters During Simulated Orion Re-Entry

No abstract availabl

Lower Limb Venous Compliance is Different Between Men and Women Following 60 Days of Head-Down Bedrest but Is Not Associated with Venoconstriction Dysfunction

Space flight-induced orthostatic intolerance (OI) is more prevalent in female (F) than male (M) astronauts. The mechanisms explaining the higher incidence of OI in F are unclear. We tested the hypothesis that venous compliance would be higher in F more than M following 6 deg head-down bed rest (BR) and would be associated with constrictor dysfunction. Using 2-D ultrasound, dorsal hand (DHV) and dorsal foot (DFV) vein compliances were determined in 24 subjects (10 F, 14 M; 35 +/- 1 yr) by measuring mean diameter response to increasing congestion pressure (0, 20, 30, and 40 mmHg) before and after 60 d of BR. Constrictor function was assessed by intravenous infusions of Ketorolac (KE; 1.5 ig/min) Phenylephrine (PE; 3160 ng/min), and L-NMMA (50 ig/min). The effects of BR between F vs. M and hand vs. foot were determined using mixed-effects linear regression. DFV but not DHV compliance changed in response to BR (p=0.012). Mean DFV increased significantly (0.903 mm to 1.191mm) in F but decreased in M (1.353 mm to 1.154 mm). DFV constrictor response was not different between sexes in response to BR (KE; p=0.647, PE; p=0.717, and L-NMMA; p=0.825). These BR data suggest that the higher incidence of OI in F astronauts may be related to increased lower limb venous compliance, contributing to blood pooling upon standing. Notably, changes to DFV compliance was not accompanied by impaired constrictor function

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

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

Future human space travel will consist primarily of long-duration missions onboard 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 from a variety of sources, including radiation, psychological stress, reduced physical activity, diminished nutritional status, and hyperoxic exposure during extravehicular activity. Evidence exists that increased oxidative damage and inflammation can accelerate the development of atherosclerosis

Analysis of Arterial Mechanics During Head-down Tilt Bed Rest

Arterial health may be affected by microgravity or ground based analogs of spaceflight, as shown by an increase in thoracic aorta stiffness1. Head-down tilt bed rest (HDTBR) is often used as a ground-based simulation of spaceflight because it induces physiological changes similar to those that occur in space2, 3. This abstract details an analysis of arterial stiffness (a subclinical measure of atherosclerosis), the distensibility coefficient (DC), and the pressure-strain elastic modulus (PSE) of the arterial walls during HDTBR. This project may help determine how spaceflight differentially affects arterial function in the upper vs. lower body

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.

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