Space sickness and fluid shifts: a hypothesis.

In a sample of 64 first-time Space Shuttle crew members, 9 preflight variables related to fluid, electrolyte, and cardiovascular status were previously found to be significantly related to space sickness. The nine variables are serum uric acid, red cell count, environmental temperature at the launch site, serum phosphate, urine osmolality, serum thyroxine, sitting systolic blood pressure, calculated blood volume, and serum chloride. Using discriminant analysis, these preflight variables were used to correctly classify the 64 astronauts according to their space sickness incidence (NOTSICK or SICK) with 80% success, using two methods of pseudo-crossvalidation. Symptoms of motion sickness may be induced on Earth, either with a sufficiently high level of vestibular stimulation or with less vestibular stimulation after reducing the threshold for motion sickness induction. Some of the nine predictor variables support a fluid shift hypothesis of space sickness etiology by which central volume expansion in weightlessness may lower the threshold required for novel vestibular stimulation to cause space sickness. According to this hypothesis, some astronauts suffer a greater central volume expansion than do others, causing them to have greater physiologic responses to fluid shifts, which, in turn, proportionally reduces their threshold for induction of space sickness. The hypothesis is supported by preflight and postflight echocardiographic comparisons of heart volumes in 19 shuttle astronauts. The postflight left ventricular diastolic volume index was decreased by 34 +/- 3% in the astronauts with MODERATE or SEVERE space sickness, but only 9 +/- 5% (P < .05) in the NONE or MILD group, indicating that an exaggerated physiologic adaptation to fluid shifts is associated with space sickness.

A comprehensive Guyton model analysis of physiologic responses to preadapting the blood volume as a countermeasure to fluid shifts.

The Guyton model of fluid, electrolyte, and circulatory regulation is an extensive mathematical model capable of simulating a variety of experimental conditions. It has been modified for use at NASA to simulate head-down tilt, a frequently used analog of weightlessness. Weightlessness causes a headward shift of body fluids that is believed to expand central blood volume, triggering a series of physiologic responses resulting in large losses of body fluids. We used the modified Guyton model to test the hypothesis that preadaptation of the blood volume before weightless exposure could counteract the central volume expansion caused by fluid shifts, and thereby attenuate the circulatory and renal responses that result in body fluid losses. Simulation results show that circulatory preadaptation, by a procedure resembling blood donation immediately before head-down bedrest, is effective in damping the physiologic responses to fluid shifts and reducing body fluid losses. After 10 hours of head-down tilt, preadaptation also produces higher blood volume, extracellular volume, and total body water for 20 to 30 days of bedrest, compared with non-preadapted control. These results indicate that circulatory preadaptation before current Space Shuttle missions may be beneficial for the maintenance of reentry and postflight orthostatic tolerance in astronauts. This paper presents a comprehensive examination of the simulation results pertaining to changes in relevant physiologic variables produced by blood volume reduction before a prolonged head-down tilt. The objectives were to study and develop the countermeasure theoretically, to aid in planning experimental studies of the countermeasure, and to identify potentially disadvantageous physiologic responses that may be caused by the countermeasure.

The effect of dDAVP with saline loading on fluid balance during LBNP and standing after 24-hr head-down bedrest.

Shuttle astronauts currently drink approximately a quart of water with eight salt tablets before reentry to restore lost body fluid and thereby reduce the likelihood of cardiovascular instability and syncope during reentry and after landing. However, the saline loading countermeasure is not entirely effective in restoring orthostatic tolerance to preflight levels. We tested the hypothesis that the effectiveness of this countermeasure could be improved with the use of a vasopressin analog, 1-deamino-8-D-arginine vasopressin (dDAVP). The rationale for this approach is that reducing urine formation with exogenous vasopressin should increase the magnitude and duration of the vascular volume expansion produced by the saline load, and in so doing improve orthostatic tolerance during reentry and postflight.

Computer simulation of the effect of dDAVP with saline loading on fluid balance after 24-hour head-down tilt.

Fluid loading (FL) before Shuttle reentry is a countermeasure currently in use by NASA to improve the orthostatic tolerance of astronauts during reentry and postflight. The fluid load consists of water and salt tablets equivalent to 32 oz (946 ml) of isotonic saline. However, the effectiveness of this countermeasure has been observed to decrease with the duration of spaceflight. The countermeasure's effectiveness may be improved by enhancing fluid retention using analogs of vasopressin such as lypressin (LVP) and desmopressin (dDAVP). In a computer simulation study reported previously, we attempted to assess the improvement in fluid retention obtained by the use of LVP administered before FL. The present study is concerned with the use of dDAVP. In a recent 24-hour, 6 degree head-down tilt (HDT) study involving seven men, dDAVP was found to improve orthostatic tolerance as assessed by both lower body negative pressure (LBNP) and stand tests. The treatment restored Luft's cumulative stress index (cumulative product of magnitude and duration of LBNP) to nearly pre-bedrest level. The heart rate was lower and stroke volume was marginally higher at the same LBNP levels with administration of dDAVP compared to placebo. Lower heart rates were also observed with dDAVP during stand test, despite the lower level of cardiovascular stress. These improvements were seen with only a small but significant increase in plasma volume of approximately 3 percent. This paper presents a computer simulation analysis of some of the results of this HDT study.

Blood volume reduction counteracts fluid shifts in water immersion.

Six healthy men were bled by 15% of their total blood volume (TBV) before 7 h of seated water immersion to test the hypothesis that some of the major physiological responses to an expansion of central blood volume can be counteracted by prior reduction of TBV. Subjects were their own controls under two conditions: seated dry in air and seated immersed to the suprasternal notch in water. Immersion without prior reduction of TBV (WC = Wet Control) caused a statistically significant 22% increase in cardiac output (CO), 368% increase in urine production, and 200% increase in sodium excretion relative to dry control (DC) sessions. When TBV was reduced before immersion, CO was the same as during DC sessions; however there were significant increases above DC in urine flow (+73%) and sodium excretion (+120%), although they were significantly reduced from WC values. Potassium excretion was similar during DC and WC sessions, but was significantly increased (+75%) when subjects were immersed after 15% reduction of TBV.

Physiologic mechanisms effecting circulatory and body fluid losses in weightlessness as shown by mathematical modeling.

The mechanisms causing large body water losses in weightlessness are not clear. It has long been considered that a central volume expansion drives the physiologic adaptation to a reduced total blood volume, with normal blood composition eventually regained. However, inflight venous pressure measures suggest that central volume expansion in weightlessness may be very transient, or that considerable cardiovascular adaptation to fluid shifts occurs on the ground while astronauts wait in the semi-supine pre-launch position. If a central volume stimulus does not persist, other mechanisms must drive the adaptation of circulation to a reduced blood volume and account for body fluid losses. Recent results from the SLS-1 mission suggest that body fluid volumes do not simply decline to new equilibria but that they decrease to a low point, then undergo some recovery. Similar "under-shoots" of body fluid volumes have also been shown in computer simulations, providing confidence in the validity of the model. The purpose of this study was to examine the mechanisms which could explain the loss of body fluids in weightlessness and how a cardiovascular preadaptation countermeasure we previously tested ameliorated body fluid losses. It is assumed that the physiology of head down tilt (HDT) provides a reasonably accurate analog of weightless exposure.

Simulation of the fluid retention effects of a vasopressin analog using the Guyton model of circulation.

Fluid-loading (FL) consisting of water and salt tablets equivalent of 32 oz of isotonic saline is a countermeasure currently in use by NASA to improve the orthostatic tolerance of astronauts during Shuttle reentry. However, the effectiveness of this countermeasure has been observed to decrease with the duration of space flight. Possible ways to improve fluid retention and thus the effectiveness of FL include use of analogs of vasopressin such as lypressin (LVP). This study used a computer simulation approach to analyze the potential benefits on fluid retention with LVP administered before FL.

The relationship between space sickness and preflight diet.

The nine astronauts who flew three Skylab missions during 1973 and 1974 were on carefully planned diets. Each astronaut selected his preferences from a list of approximately 70 food items, from which dietitians developed a rotating sequence of six daily menus. In addition to strict control of the inflight diet, each crewman consumed his planned diet for 21 days preflight and for 18 days postflight. While the amount consumed at each particular meal was largely discretionary, all deviations from the planned meals (which were few) were fully documented. Diets were controlled to provide adequate calcium, phosphorus, and protein because of bone and muscle losses observed on previous flights. Each day's menu had a similar elemental composition; if any particular item was not consumed, supplements in the form of capsules or tablets were prescribed the next day to make up for the shortfall. However, the dieticians did not so carefully control the relative proportions of carbohydrate, fat, and protein (though meticulous records were kept), which were instead selected somewhat incidentally as menus were constructed around each astronaut's food preferences. There are several possible physiologic determinants for food preferences and the regulation of dietary macro-nutrients. Monozygotic twins chose more similar intakes of total energy, protein, fat, and carbohydrate than did dizygotic twins, suggesting a genetic component of dietary regulation. The biosynthesis of neurotransmitters is directly influenced by the availability of their precursor nutrients, such as tryptophan for serotonin and choline for acetylcholine. Diet affects behavior, and it has been suggested that dietary self-selection by rats is regulated by effects of the diet on brain neurotransmitters. Some preflight variables relating to fluid, electrolyte and cardiovascular status, and to environmental exposures, have previously been found to have significant relationships to space sickness. The purpose of this study was to determine if diet could be another factor contributing to space sickness, since diet determines so much of physiology and behavior.

Tissue-specific effects of physiological ANP infusion on blood-tissue albumin transport.

Blood-tissue transport of 131I-labeled bovine serum albumin (BSA) during intravenous infusion of synthetic atrial natriuretic peptide (ANP) was examined in anesthetized male Wistar rats. Plasma volumes were maintained at pre-ANP levels by infusion of 2% BSA in lactated Ringer solution (LR) to minimize compensatory responses to ANP-induced hypovolemia. 131I-BSA clearance was measured over 30 min, and 125I-BSA was injected terminally to correct for intravascular volume. Thirty-minute infusion of 20 ng.kg-1.min-1 ANP resulted in a tissue-selective increase in 131I-BSA clearance in jejunum and colon compared with controls given LR only. Smaller but significant increases in tracer clearance also were observed in fat, kidney, left ventricle, and skeletal muscle exposed to 400 ng.kg-1.min-1 ANP. The observed elevation in tracer albumin extravasation was not associated with any measurable increase in tissue extravascular water content. Furthermore, it was shown that coupling of 131I-BSA transport to filtration induced by hindlimb venous congestion was similar in control and ANP-treated rats. In a second series of experiments, plasma ANP levels were determined after 30-min ANP infusions from 0 to 180 ng.kg-1.min-1. Significant linear associations between physiological ANP levels (62-578 pg/ml) and 131I-BSA clearance were demonstrable for small intestine, colon, fat, kidney, and skeletal muscle but not for skin, heart, diaphragm, and lung. We conclude that raising plasma ANP by infusion of the synthetic peptide results in a filtration-independent, tissue-selective increase in albumin transport. Tissue uptake of albumin is a potential mechanism for extrarenal fluid shift during circulatory volume overload.

Computer simulation analysis of the effects of countermeasures for reentry orthostatic intolerance.

Fluid loading is a countermeasure currently in routine use to improve the g-tolerance of crewmembers during reentry and return of Shuttle flights. However, its effectiveness diminishes with mission duration. Countermeasures that will be effective on long-duration flights are needed and are presently under development. This paper discusses the application of computer simulation in the analysis of the effects of countermeasures for reentry orthostatic intolerance. The results suggest improvements upon the fluid loading countermeasure currently in use.

Elastooptic photon signal modulation in collagenic fiber optics of tendon.

In a test of a hypothesis of cell-to-cell communication via their endogeneous photon emissions, the nearly pure collagen fibers in tendon were found to exhibit the fiber optic property of axially conducting light, providing a mechanism for photon exchange between nonadjacent cells. Further, it was found that light penetrates farther along the tendon fibers when tension is applied to an end-illuminated tendon, establishing that an elastooptic mechanism exists for the modulation of photon signals in transit between cells, in the hypothesized system of cell-to-cell photon communication.