Fluid volume control during short-term space flight and implications for human performance
Department of Integrative Physiology, and Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USA
*Present address: Naval Submarine Medical Research Laboratory, Box 900, Groton, CT 06349-5900, USA (e-mail: watenpaugh{at}nsmrl.navy.mil)
Accepted July 5, 2001
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Summary |
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Key words: microgravity, human, central venous pressure, plasma volume, extracellular fluid volume, intracellular fluid volume, antidiuretic hormone, thirst.
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Introduction |
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The hypothetical foundation |
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Recent developments |
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In a subsequent study, Videbaek and Norsk (Videbaek and Norsk, 1997) discovered how simultaneous cardiac expansion and Pcv reduction occur in microgravity. They measured atrial diameter, Pcv and pressure outside the heart (esophageal pressure, a measure of intrathoracic pressure) in supine subjects during parabolic flight, which produces short periods of micro- and hypergravity. They confirmed that Pcv decreases in microgravity relative to supine 1g conditions, and they further found that intrathoracic pressure decreases with reduced Gx substantially more than Pcv, such that cardiac transmural pressure increases in microgravity (Gx is ventral to dorsal acceleration; Fig.1). Increased cardiac transmural pressure in 0g corresponded to increased atrial diameter. It appears that removal of gravitational compression expands the thorax and thereby decreases pressure inside it (and inside the abdomen)(Estenne et al., 1992) such that effective cardiac filling pressure increases in acute microgravity (Watenpaugh and Smith, 1998; White and Blomqvist, 1998).
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Fluid volume acclimation to and homeostasis in chronic microgravity
Leach, Alfrey and co-workers (Leach et al., 1996; Alfrey et al., 1996b) recently provided the most comprehensive and best-controlled description to date of fluid regulatory acclimation to space flight. Their data from seven Spacelab Life Sciences (SLS) astronaut subjects yielded key new findings and confirmed some older results that had been tentative (Leach et al., 1983). They collected pre- and post-flight data with subjects in the supine position.
They found a 9% increase in plasma protein concentration on flight day 1, and a 17% reduction in plasma volume by 22h of flight. This agrees with the early in-flight hemoconcentration seen by others (Kirsch et al., 1984) and establishes that plasma volume contraction occurs quickly in microgravity. This hemoconcentration probably results from increased upper-body vascular pressures in microgravity (Parazynski et al., 1991) and perhaps reduced interstitial pressures (Estenne et al., 1992); both factors would encourage transcapillary fluid filtration into upper-body interstitial spaces, and substantial filtration can occur in minutes (Watenpaugh et al., 1992). The early hemoconcentration is all the more notable given the probable concomitant tissue fluid reabsorption from the legs into the circulation (Thornton et al., 1992). Although some protein may leave the circulation early in flight, the increased plasma protein concentration on flight day 1 does not support extravasation of protein as a primary mechanism for early in-flight net capillary filtration and plasma volume contraction. Increased plasma protein concentration increases plasma colloid osmotic pressure and, therefore, opposes capillary filtration.
In agreement with earlier reports (Drummer et al., 1993; Leach, 1987; Leach et al., 1983), the SLS results revealed no natriuresis or diuresis in microgravity, so diuresis cannot explain microgravity-induced hypovolemia. Leach and co-workers (Leach et al., 1996) confirmed that both fluid intake and urine output decrease significantly on the first day in flight and remain relatively low during space flight (Fig.2). The reductions in thirst and fluid intake occur regardless of space motion sickness. For example, none of the four studied SLS-2 crew members experienced motion sickness.
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It is striking that fluid intake decreases by 41% on flight day 1 while ADH levels are so markedly elevated. Normally, ADH secretion and thirst correlate strongly, which is logical (Guyton, 1991). The same stimuli (hyperosmolarity, reduced blood volume and blood pressure) and hypothalamic regions regulate ADH secretion and thirst, and they each act to preserve or increase fluid volume and decrease osmolarity (Jurzak and Schmid, 1998; McKinley et al., 1999). Serum osmolarity remained unchanged by space flight (Leach et al., 1996), so hypo-osmolarity does not reduce thirst in space. Central volume expansion reduces thirst, even in subjects made hyperosmotic by dehydration (Wada et al., 1995), so central volume expansion probably contributes to the reduction in thirst in microgravity. If stress-induced ADH elevation and central blood volume expansion compete in central nervous control of thirst and in control of diuresis, then central blood volume expansion clearly wins control of thirst, whereas ADH wins control of renal water excretion, at least in the circumstances of early acclimation to microgravity.
Reduced angiotensin II levels early in flight may also decrease fluid intake at that time. Angiotensin II is a physiologically important mediator of thirst and drinking (Guyton and Hall, 1997). On flight day 1, Leach and co-workers (Leach et al., 1996) reported that plasma renin activity declined to half the value seen pre-flight. A decline in plasma renin levels would lead to a reduced level of plasma angiotensin. Evaporative (insensible) loss of fluid decreases somewhat in microgravity (Leach et al., 1978) which, in turn, reduces the need to drink.
ADH decreases back to pre-flight levels by the second day in flight, so persistent in-flight antidiuresis must result from mechanisms other than ADH. Reninangiotensin may contribute because plasma renin activity is commonly elevated after a few days in space (Smith et al., 1997). However, aldosterone levels usually remain stable or decrease in microgravity (Leach et al., 1996), and such uncoupling between reninangiotensin and aldosterone also occurs during bed rest (Fortney et al., 1996). Atrial natriuretic peptide (ANP) levels usually tend to decrease during space flight (Leach et al., 1996; Smith et al., 1997), and reduced ANP levels could decrease urine production. Reduced urine flow in space may simply result from the decreased thirst and fluid intake; the mechanism for the latter may be the indirect cause of the former.
Leach and colleagues (Leach et al., 1996) found that extracellular fluid volume decreased in microgravity (by approximately 10% by flight day 2 and approximately 14% by flight day 7/8), yet they also found that total body water content remained unchanged in flight, such that calculated intracellular fluid volume tended to increase (Fig.3, Fig.4). Given that K+ is the primary intracellular cation, upregulation of intracellular volume in flight agrees with the trend towards reduced K+ excretion observed during the first 2 days in flight. Na+ excretion did not change in microgravity. By the second day in flight, plasma protein concentration decreased back to pre-flight levels, probably as a result of hepatic catabolism of plasma albumin in response to elevated flight day 1 plasma protein levels.
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In-flight response to isotonic volume expansion
In the first in-flight study of fluid volume regulation employing an experimental intervention, Norsk and co-workers (Norsk et al., 1995) investigated how endocrine and renal responses to an acute isotonic volume stimulus in microgravity compared with those responses in 1g. They assessed the responses of four astronauts to 2%bodymass of isotonic saline (approximately 1.8l) infused intravenously over 2022min in supine and seated postures before flight and in microgravity on flight days 46 of the Spacelab D-2 mission.
Norsk and co-workers (Norsk et al., 1995) found that in-flight Na+ and volume excretory responses to saline infusion were approximately half of those seen in pre-flight supine conditions (Fig.5), and in-flight responses were somewhat delayed relative to pre-flight supine responses. In-flight responses slightly exceeded those seen in pre-flight seated conditions. They noted that their flight results differed from findings in a ground-based flight simulation employing head-down bed rest: after 6 days of bed rest, Drummer and colleagues (Drummer et al., 1992) observed responses to saline infusion that were similar to pre-bed-rest supine responses.
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Norsk and co-workers (Norsk et al., 1995) stated that microgravity-induced extracellular fluid volume contraction probably led to attenuation of in-flight renal responses to infusion relative to pre-flight supine responses. With the extracellular fluid compartment 1015% less than full in microgravity, an infused volume challenge may be temporarily stored more easily in that compartment, thereby allaying renal responses. They further postulated that early in-flight reduction of fluid and Na+ intake contributes to the extracellular hypovolemia. Finally, their data confirm that fluid volume acclimation to microgravity sets the central circulation to homeostatic conditions similar to those found in an upright sitting posture on Earth (Watenpaugh and Hargens, 1996).
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Predictable post-flight fluid regulatory events |
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The context of limits to human performance |
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Fluid loss in space most definitely contributes to reduced performance upon return to 1g. Post-flight hypovolemia and relative anemia constitute probably the most important mechanisms for post-flight reduction of orthostatic tolerance and upright exercise capacity (Buckey et al., 1996b; Levine et al., 1996; Michel et al., 1977; Watenpaugh and Hargens, 1996). Compromised cerebral perfusion in upright posture after flight may also reduce mental performance. The hypovolemia results in a reduced stroke volume during orthostasis and exercise which, in turn, decreases cardiac output at a given heart rate and, therefore, decreases the heart rate reserve and peak cardiac output available to compensate for these stresses. Reduced red cell mass decreases exercise performance by decreasing the capacity for oxygen delivery.
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Fluid volume regulation and countermeasures to deconditioning in microgravity |
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As noted above, exercise training expands blood volume (Sawka et al., 2000). Therefore, some have postulated that in-flight exercise training may help prevent microgravity-induced losses of fluid and thereby protect orthostatic tolerance and upright exercise capacity (Convertino, 1987; Watenpaugh, 2000). The strategy seems to work for protection of blood volume and exercise capacity during simulated space flight (bed rest), but not necessarily for orthostatic tolerance (Fortney et al., 1997; Watenpaugh et al., 1994). Protection of orthostatic tolerance during space flight probably requires stimulation of orthostatic blood pressure control systems in addition to fluid maintenance or replacement. Exercise may solve the fluid problem, but does not challenge the circulation to maintain cerebral perfusion, as does orthostasis.
However, from a broader perspective, a collection of separate countermeasures against specific single components of microgravity-induced deconditioning (fluid loss, vascular atrophy, cardiac remodeling, skeletal muscle atrophy, bone demineralization, vestibular dysfunction, etc.) is probably not the most efficient way to protect overall astronaut 1g performance. The body functions as an integrated system so, to be most time- and energy-efficient, countermeasures against 0g should exploit and stimulate integrated functional adaptations to gravity as much as possible.
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Possible future research directions |
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Interesting discrepancies exist between microgravity and its ground-based simulations such as bed rest and water immersion. The simulations elicit the expected natriuresis and diuresis (Fortney et al., 1996; Norsk and Epstein, 1991), whereas space flight does not. Confounding complications surrounding the early phase of space flight (pre-launch posture, acceleration of launch, stress, space motion sickness, etc.) may partly explain this discrepancy, but other more fundamental differences may also be important.
The effects of microgravity on cell volume and its regulation deserve further attention. It is probable that gravitational force exerts tissue- and cellular-level effects, such that removal of gravitational force leads to reduced tissue pressures (Estenne et al., 1992; Videbaek and Norsk, 1997) and cytoskeletal effects (Guignandon et al., 1995; Skagen, 1998), which could increase cell volumes, for example. The effects of microgravity on cell volume may be linked to neuroendocrine responses to microgravity (Hussy et al., 2000). Given that K+ is the primary intracellular cation and given the trend for early in-flight reduction of K+ excretion (Leach et al., 1996), regulation of K+ levels may prove interesting to study in space.
A recumbent posture during waking hours shifts fluid centrally and thereby activates HenryGauer and related reflexes to increase urine flow (Vagnucci et al., 1969). However, at night, renal responses to such fluid shifts are suppressed (Krishna and Danovitch, 1983; Shiraki et al., 1986). No postural fluid shifts occur in space, yet circadian rhythmicity in renal function may or may not persist. The implications of such rhythmicity for fluid metabolism in microgravity remain unknown.
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Acknowledgments |
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