Engineering topics

Waters, Wendy W.

Publications and source records attributed to Waters, Wendy W..

9 records

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 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 NTRS2004

Mechanisms of postspaceflight orthostatic hypotension: low alpha1-adrenergic receptor responses before flight and central autonomic dysregulation postflight

Although all astronauts experience symptoms of orthostatic intolerance after short-duration spaceflight, only approximately 20% actually experience presyncope during upright posture on landing day. The presyncopal group is characterized by low vascular resistance before and after flight and low norepinephrine release during orthostatic stress on landing day. Our purpose was to determine the mechanisms of the differences between presyncopal and nonpresyncopal groups. We studied 23 astronauts 10 days before launch, on landing day, and 3 days after landing. We measured pressor responses to phenylephrine injections; norepinephrine release with tyramine injections; plasma volumes; resting plasma levels of chromogranin A (a marker of sympathetic nerve terminal release), endothelin, dihydroxyphenylglycol (DHPG, an intracellular metabolite of norepinephrine); and lymphocyte beta(2)-adrenergic receptors. We then measured hemodynamic and neurohumoral responses to upright tilt. Astronauts were separated into two groups according to their ability to complete 10 min of upright tilt on landing day. Compared with astronauts who were not presyncopal on landing day, presyncopal astronauts had 1). significantly smaller pressor responses to phenylephrine both before and after flight; 2). significantly smaller baseline norepinephrine, but significantly greater DHPG levels, on landing day; 3). significantly greater norepinephrine release with tyramine on landing day; and 4). significantly smaller norepinephrine release, but significantly greater epinephrine and arginine vasopressin release, with upright tilt on landing day. These data suggest that the etiology of orthostatic hypotension and presyncope after spaceflight includes low alpha(1)-adrenergic receptor responsiveness before flight and a remodeling of the central nervous system during spaceflight such that sympathetic responses to baroreceptor input become impaired.

Clinical Trial↗

NASA NTRS2003

Pressor response to intravenous tyramine is a marker of cardiac, but not vascular, adrenergic function

Intravenous injections of the indirect sympathetic amine, tyramine, are used as a test of peripheral adrenergic function. The authors measured the time course of increases in ejection fraction, heart rate, systolic and diastolic pressure, popliteal artery flow, and greater saphenous vein diameter before and after an injection of 4.0 mg/m(2) body surface area of tyramine in normal human subjects. The tyramine caused moderate, significant increases in systolic pressure and significant decreases in total peripheral resistance. The earliest changes were a 30% increase in ejection fraction and a 16% increase in systolic pressure, followed by a 60% increase in popliteal artery flow and a later 11% increase in greater saphenous vein diameter. There were no changes in diastolic pressure or heart rate. These results suggest that pressor responses during tyramine injections are primarily due to an inotropic response that increases cardiac output and pressure and causes a reflex decrease in vascular resistance. Thus, tyramine pressor tests are a measure of cardiac, but not vascular, sympathetic function.

NASA Discipline Cardiopulmonary↗

NASA NTRS2002

Postspaceflight orthostatic hypotension occurs mostly in women and is predicted by low vascular resistance

About 20% of astronauts suffer postspaceflight presyncope. We studied pre- to postflight (5- to 16-day missions) cardiovascular responses to standing in 35 astronauts to determine differences between 1) men and women and 2) presyncopal and nonpresyncopal groups. The groups were presyncopal women, presyncopal men, and nonpresyncopal men based on their ability to stand for 10 min postflight. Preflight, women and presyncopal men had low vascular resistance, with the women having the lowest. Postflight, women experienced higher rates of presyncope (100 vs. 20%; P = 0.001) and greater losses of plasma volume (20 vs. 7%; P < 0.05) than men. Also, presyncopal subjects had lower standing mean arterial pressure (P < or = 0.001) and vascular resistance (P < 0.05), smaller increases in norepinephrine (P < or = 0.058) and greater increases in epinephrine (P < or = 0.058) than nonpresyncopal subjects. Presyncopal subjects had a strong dependence on plasma volume to maintain standing stroke volume. These findings suggest that postflight presyncope is greatest in women, and this can be ascribed to a combination of inherently low-resistance responses, a strong dependence on volume status, and relative hypoadrenergic responses. Conversely, high vascular resistance and postflight hyperadrenergic responses prevent presyncope.

Flight Experiment↗

NASA NTRS2001

Post-Spaceflight Orthostatic Hypotension Occurs Mostly in Women and is Predicted by Low Vascular Resistance

About 20% of astronauts suffer post-spaceflight presyncope, but the underlying etiology remains elusive. We studied responses to standing in 36 astronauts before and after spaceflight (5- 16 days). Individuals were separated into presyncopal women, presyncopal men, and non-presyncopal men based on their ability to stand for 10 min postflight. Preflight, presyncopal women and presyncopal men had low vascular resistance, with the women having the lowest. Postflight, women experienced significantly higher rates of presyncope (P<0.01) and significantly greater losses of plasma volume than the men (P<0.05). Both presyncopal women and men had lower standing arterial pressure (P<=0.001) and vascular resistance (P<0.05), smaller increases in norepinephrine (P<=0.058) and greater increases in epinephrine (P<=0.058) than nonpresyncopal men. Both presyncopal groups had a strong dependence (P<=0.05) on plasma volume to maintain standing stroke volume. These findings suggest that postflight presyncope is ascribed to a combination of inherently low resistance responses, a strong dependence on volume status, and spaceflight-induced hypoadrenergic responses. In contrast, high vascular resistance and spaceflight-induced hyperadrenergic responses prevent presyncope.

Waters, Wendy W.↗

NASA NTRS1999

Gender-Related Differences in Cardiovascular Responses to Orthostatic Stress

There is evidence that men and women have different cardiovascular responses to standing, and that women are more susceptible to orthostatic hypotension than men. The present study seeks to determine if decreased orthostatic tolerance in women is caused by diminished vasoconstrictive responses.

Fritsch-Yelle, Janice M.↗