Integrated 1 Year Mission: Investigators Face-to-Face

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Human Research Program

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Effects of Long Duration Spaceflight on Venous and Arterial Compliance in Astronants

1. Project Overview Visual impairment and intracranial pressure (VIIP) is a spaceflight-associated medical condition affecting at least a third of American astronauts who have flown International Space Station (ISS) missions. VIIP is defined primarily by visual acuity deficits and anatomical changes to eye structures. In some astronauts, eye-related changes do not revert back to the preflight state upon return to Earth. Our team will study some of the possible causes for this syndrome. This will be achieved by reviewing previous astronaut data for factors that may predispose astronauts to higher rates of developing this syndrome or greater severity of symptoms. Additionally, we will conduct 3 separate experiments that will characterize vessels in the head and neck and measure the effects of the experimental conditions on ocular structures and function. 2. Technical Summary The primary objective of this study is to determine whether vascular compliance is altered by spaceflight and whether such adaptations are related to the incidence of the VIIP. In particular, we will measure ocular parameters and vascular compliance in vessels of the head and neck in astronauts who have no spaceflight experience (Ground), in astronauts before, during, and after spaceflight (Flight), and in bed rest subjects with conditions similar to spaceflight (Bed Rest). Additionally, we will analyze astronaut data from the Lifetime Surveillance of Astronaut Health (LSAH) archives to determine which factors might be predictive of the development of VIIP (Data Mining). The project will be conducted in four separate, but related parts. Hypothesis The central hypothesis of this proposal is that exposure to the spaceflight environment aboard the ISS may lead to development of the VIIP syndrome (increased intracranial pressure and impaired visual acuity) and that this may be related to alterations in venous and/or arterial compliance in the head and neck. Specific Aims 1. To determine whether noninvasive measures of venous and arterial compliance are altered by long-duration spaceflight exposure in ISS astronauts and whether these changes are related to the development of the VIIP syndrome. (Flight) 2. To determine whether previous spaceflight experience predispose astronauts to lower venous compliance and/or the development of the VIIP syndrome. (Ground + Flight) 3. To use a 14-day, 6deg head-down-tilt bed rest as a model of spaceflight, to evaluate the effect of aging on vascular compliance using a subject population similar to younger (25-35 yr) and older (45-55 yr) astronaut cohorts. (Bed Rest) 4. To determine what factors contribute to lower venous compliance and/or the development of the VIIP syndrome in astronauts. (Data Mining) 3. Earth Applications This research may inform the mechanisms that regulate blood/fluid flow in and out of the brain in the head and neck. This information may help with understanding of the mechanisms behind idiopathic intracranial hypertension. 4. Link to NASA Taskbook Entry Not Yet Availabl

Risk of Reduced Physical Performance Due to Reduced Aerobic Capacity

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Potential Technology Needs

This slide presentation reviews some of the technologies that will be required to maintain crew health. The general principle guiding the technology development is to integrate individual devices into small, flight-ready, reportable units

NASA Flight Research Overview

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A Data Mining Project to Identify Cardiovascular Related Factors That May Contribute to Changes in Visual Acuity Within the US Astronaut Corps

Many of the cardiovascular-related adaptations that occur in the microgravity environment are due, in part, to a well-characterized cephalad-fluid shift that is evidenced by facial edema and decreased lower limb circumference. It is believed that most of these alterations occur as a compensatory response necessary to maintain a "normal" blood pressure and cardiac output while in space. However, data from both flight and analog research suggest that in some instances these microgravity-induced alterations may contribute to cardiovascular-related pathologies. Most concerning is the potential relation between the vision disturbances experienced by some long duration crewmembers and changes in cerebral blood flow and intra-ocular pressure. The purpose of this project was to identify cardiovascular measures that may potentially distinguish individuals at risk for visual disturbances after long duration space flight. Toward this goal, we constructed a dataset from Medical Operation tilt/stand test evaluations pre- (days L-15-L-5) and immediate post-flight (day R+0) on 20 (3 females, 17 males). We restricted our evaluation to only crewmembers who participated in both shuttle and space station missions. Data analysis was performed using both descriptive and analytical methods (Stata 11.2, College Station, TX) and are presented as means +/- 95% CI. Crewmembers averaged 5207 (3447 - 8934) flight hours across both long (MIR-23 through Expedition16) and short (STS-27 through STS-101) duration missions between 1988 and 2008. The mean age of the crew at the time of their most recent shuttle flight was 41 (34-44) compared to 47 (40-54) years during their time on station. In order to focus our analysis (we did not have codes to separate out subjects by symptomotology) , we performed a visual inspection of each cardiovascular measures captured during testing and plotted them against stand time, pre- to post-flight, and between mission duration. It was found that pulse pressure most clearly differentiated the two mission types. Statistical analysis confirmed that pulse pressure was significantly higher before [45.6; (42.1 to 49.1)] and after [50.7; (46.9 to 54.6)] time on station compared with their most recent shuttle flight [31.6 (27.8 to 35.4), and 32.2 (28.3 to 36.0) respectively] even after correcting differences in age and cumulative number of mission hours. Without knowing the identity of which long duration crewmembers demonstrated visual changes, we were limited to examining whether certain crew regulate components of pulse pressure, systolic and diastolic blood pressure, differently due to microgravity exposure. To that end, we stratified crew into tertiles based on either their pre-flight measure of systolic or diastolic blood pressure. Those crew in the highest tertile for both systolic (lower tertile (n=8; 103-111), middle tertile (n=7; 113-121), and upper tertile (n=5; 125-136) and diastolic blood pressure (lower tertile (n=8; 58-64), middle tertile (n=7; 67-73), and upper tertile (n=5; 75-81) demonstrated less variability in pulse pressure between R+0 and L-10 (Figure 2). Interestingly, those crewmembers with the highest resting systolic blood pressure demonstrated either no change or in some instances an increase in total peripheral resistance, where those in the lower tertiles had lower values of total peripheral resistance compared to pre-flight levels. In this study, it was found that crewmembers in the highest tertile for both systolic and diastolic blood pressure demonstrated less variability in pulse pressure and that the decrease in variability was due in part to lower levels of compliance as indicated by similar or higher levels of total peripheral resistance after compared with before flight levels. Whether there is a relation between blood pressure regulation and total peripheral resistance in crew presenting with negative changes in visual acuity remains unknown

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

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

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