Biomedical subjects

C E Wade

Publications and source records attributed to C E Wade.

At least 19 recordsLinked to original sources

PubMed2005

Intensive exercise training suppresses testosterone during bed rest.

Spaceflight and prolonged bed rest (BR) alter plasma hormone levels inconsistently. This may be due, in part, to prescription of heavy exercise as a countermeasure for ameliorating the adverse effects of disuse. The initial project was to assess exercise programs to maintain aerobic performance and leg strength during BR. The present study evaluates the effect of BR and the performance of the prescribed exercise countermeasures on plasma steroid levels. In a 30-day BR study of male subjects, the efficacy of isotonic (ITE, n = 7) or isokinetic exercise (IKE, n = 7) training was evaluated in contrast to no exercise (n = 5). These exercise countermeasures protected aerobic performance and leg strength successfully. BR alone (no-exercise group) did not change steroidogenesis, as assessed by the plasma concentrations of cortisol, progesterone, aldosterone, and free (FT) and total testosterone (TT). In the exercise groups, both FT and TT were decreased (P < 0.05): FT during IKE from 24 +/- 1.7 to 18 +/- 2.0 pg/ml and during ITE from 21 +/- 1.5 to 18 +/- 1 pg/ml, and TT during IKE from 748 +/- 68 to 534 +/- 46 ng/dl and during ITE from 565 +/- 36 to 496 +/- 38 ng/dl. The effect of intensive exercise countermeasures on plasma testosterone was not associated with indexes of overtraining. The reduction in plasma testosterone associated with both the IKE and ITE countermeasures during BR supports our hypothesis that intensive exercise countermeasures may, in part, contribute to changes in plasma steroid concentrations during spaceflight.

Adaptation, Physiological↗

PubMed2005

Metabolic consequences of muscle disuse atrophy.

In response to decreased usage, skeletal muscle undergoes an adaptive reductive remodeling. This adaptive response has been found with disuse during human spaceflight, rat spaceflight, rat hind-limb unloading, bed rest, and aging. The reductive remodeling of skeletal muscle with disuse is largely independent of the reason for the disuse. The process involves more than a transition from slow to fast myosin fiber types. There are associated metabolic changes including a fuel shift toward glycolysis, decreased capacity for fat oxidation, and energy substrate accumulation in the atrophied muscles. Glycolysis is very effective for high-intensity short-duration acute activities, but if sustained output is needed, an energy profile where fat use is favored rather than compromised is desirable. For astronauts, there is a need to maintain as much functional capacity as possible during spaceflight for extravehicular activities. The shift toward increased activity of the glycolytic enzymes in atrophied muscle is accommodated by an increase in gluconeogenic capacity in the liver.

Animals↗

PubMed2004

Effects of disrupted beta1-integrin function on the skeletal response to short-term hindlimb unloading in mice.

The study was designed to determine whether beta1-integrin plays a role in mediating the acute skeletal response to mechanical unloading. Transgenic (TG) mice were generated to express a dominant negative form of beta1-integrin under the control of the osteocalcin promoter, which targets expression of the transgene to mature osteoblasts. At 63 days of age, wild-type (WT) and TG mice were subjected to hindlimb unloading by tail suspension for 1 wk. Pair-fed, normally loaded WT and TG mice served as age-matched controls. Bone samples from each mouse were processed for quantitative bone histomorphometry and biomechanical testing. The skeletal phenotype of TG mice was characterized by lower cancellous bone mass in the distal femoral metaphysis (-52%) and lumbar vertebral body (-20%), reduced curvature of the proximal tibia (-20%), and decreased bone strength (-20%) and stiffness (-23%) of the femoral diaphysis with relatively normal indexes of cancellous bone turnover. Hindlimb unloading for only 1 wk induced a 10% decline in tibial curvature and a 30% loss of cancellous bone in the distal femur due to a combination of increased bone resorption and decreased bone formation in both WT and TG mice. However, the strength and stiffness of the femoral diaphysis were unaffected by short-term hindlimb unloading in both genotypes. The observed increase in osteoclast surface was greater in unloaded TG mice (92%) than in unloaded WT mice (52%). Cancellous bone formation rate was decreased in unloaded WT (-29%) and TG (-15%) mice, but, in contrast to osteoclast surface, the genotype by loading interaction was not statistically significant. The results indicate that altered integrin function in mature osteoblasts may enhance the osteoclastic response to mechanical unloading but that it does not have a major effect on the development of cancellous osteopenia in mice during the early stages of hindlimb unloading.

Animals↗

PubMed2003

Effects of hypergravity on mammary metabolic function: gravity acts as a continuum.

Mammary metabolic activity in pregnant rats is significantly increased in response to spaceflight. To determine whether changes in mammary metabolism are related to gravity load, we exposed pregnant rats to hypergravity and measured mammary metabolic activity. From days 11-20 of gestation (G), animals were centrifuged (20 rpm; 1.5, 1.75, or 2.0 x gravity) or were maintained at 1 G. On G20, five rats from each group were removed from the centrifuge and euthanized. The remaining dams (n = 5/treatment) were housed at 1 G until parturition. After 2 h of nursing by the pups, the postpartum dams were euthanized (G22). Glucose oxidation to CO2 and incorporation into lipids was measured. Mammary glands from dams euthanized on G20 revealed a strong negative correlation between metabolic rate and increased G load. Approximately 98% of the variation in glucose oxidation and 94% of the variation in glucose incorporation into lipids can be accounted for by differences in G load. Differences in metabolic activity disappeared in the postpartum dams. When we combined previous data from the microgravity with hypergravity environments and plotted the ratio of mammary metabolic rate vs. G load, there was a significant exponential relationship (r2 = 0.99). These data demonstrate a remarkable continuum of response across the microgravity and hypergravity environments and support the concept that gravitational load influences mammary tissue metabolism.

Animals↗

PubMed2003

Chronic centrifugation (hypergravity) disrupts the circadian system of the rat.

The present study was conducted to evaluate the response of rat deep body temperature (DBT) and gross locomotor activity (LMA) circadian rhythms to acute hypergravity onset and adaptation to chronic (14 day) hypergravity exposure over three gravity intensities (1.25, 1.5, and 2 G). Centrifugation of unanesthetized naive animals resulted in a dramatic acute decrease in DBT (-1.45, -2.40, and -3.09 degrees C for the 1.25, 1.5, and 2.0 G groups, respectively). LMA was suppressed for the duration of centrifugation (vs. control period); the percent decrease for each group on days 12-14, respectively, was 1.0 G, -15.2%, P = not significant; 1.25 G, -26.9%, P < 0.02; 1.5 G, -44.5%, P < 0.01; and 2.0 G, -63.1%, P < 0.002. The time required for DBT and LMA circadian rhythmic adaptation and stabilization to hypergravity onset increased from 1.25 to 2.0 G in all circadian metrics except daily means. Periodicity analysis detected the phenomenon of circadian rhythm splitting, which has not been reported previously in response to chronic hypergravity exposure. Our analysis documents the disruptive and dose-dependent effects of hypergravity on circadian rhythmicity and the time course of adaptation to 14-day chronic centrifugation exposure.

Adaptation, Physiological↗

PubMed2002

Renal effects of fresh water-induced hypo-osmolality in a marine adapted seal.

With few exceptions, marine mammals are not exposed to fresh water; however quantifying the endocrine and renal responses of a marine-adapted mammal to the infusion of fresh water could provide insight on the evolutionary adaptation of kidney function and on the renal capabilities of these mammals. Therefore, renal function and hormonal changes associated with fresh water-induced diuresis were examined in four, fasting northern elephant seal ( Mirounga angustirostris) (NES) pups. A series of plasma samples and 24-h urine voids were collected prior to (control) and after the infusion of water. Water infusion resulted in an osmotic diuresis associated with an increase in glomerular filtration rate (GFR), but not an increase in free water clearance. The increase in excreted urea accounted for 96% of the increase in osmotic excretion. Following infusion of fresh water, plasma osmolality and renin activity decreased, while plasma aldosterone increased. Although primary regulators of aldosterone release (Na(+), K(+) and angiotensin II) were not significantly altered in the appropriate directions to individually stimulate aldosterone secretion, increased aldosterone may have resulted from multiple, non-significant changes acting in concert. Aldosterone release may also be hypersensitive to slight reductions in plasma Na(+), which may be an adaptive mechanism in a species not known to drink seawater. Excreted aldosterone and urea were correlated suggesting aldosterone may regulate urea excretion during hypo-osmotic conditions in NES pups. Urea excretion appears to be a significant mechanism by which NES pups sustain electrolyte resorption during conditions that can negatively affect ionic homeostasis such as prolonged fasting.

Adaptation, Physiological↗

PubMed2002

Body mass, energy intake, and water consumption of rats and humans during space flight.

Alteration of metabolism has been suggested as a major limiting factor to long-term space flight. In humans and primates, a negative energy balance has been reported. The metabolic response of rats to space flight has been suggested to result in a negative energy balance. We hypothesized that rats flown in space would maintain energy balance as indicated by maintenance of caloric intake and body mass gain. Further, the metabolism of the rat would be similar to that of laboratory-reared animals. We studied the results from 15 space flights lasting 4 to 19 d. There was no difference in average body weight (206 +/- 13.9 versus 206 +/- 14.8 g), body weight gain (5.8 +/- 0.48 versus 5.9 +/- 0.56 g/d), caloric intake (309 +/- 21.0 versus 309 +/- 20.1 kcal/kg of body mass per day), or water intake (200 +/- 8.6 versus 199 +/- 9.3 mL/kg of body mass per day) between flight and ground control animals. Compared with standard laboratory animals of similar body mass, no differences were noted. The observations suggested that the negative balance observed in humans and non-human primates may be due to other factors in the space-flight environment.

Adaptation, Physiological↗

PubMed2002

Rate controlling steps in fatty acid oxidation by unloaded rodent soleus muscle.

In response to decreased usage skeletal muscle undergoes an adaptive reductive remodeling due to the decrease in tension on the weight bearing components of the musculo-skeletal system. Accompanying a shift in fiber type is an increased reliance of carbohydrate metabolism and decreased reliance on fat for energy. These responses have been found with both space flight and ground based models of disuse atrophy including the chronically adapted rodent hind limb suspended (HLS) rat (1, 4-7, 10, 11). In addition, after space flight, the ability of soleus muscle homogenates to oxidize palmitate is decreased. We have previously shown that expression of the mRNA of enzymes involved in beta-oxidation is reduced in the soleus muscle of HLS rats. At the same time mRNA expression of enzymes involved in glycolysis was increased. This study extends these observations to address the question of whether the decrease in beta-oxidation is caused by a reduction in the capacity of the pathway to oxidize fat or the regulation is effected before fatty acids enter the mitochondria, i.e. the reduced capacity of the fatty acid oxidation pathway is because less fat is available for oxidation. The two key steps involved in fatty acid uptake into the cells are lipoprotein lipase and the transport of the free fatty acids produced by lipoprotein lipase into the cell via the carnitine acyltransferase system.

NASA Discipline Regulatory Physiology↗

PubMed2001

Maternal reproductive experience enhances early postnatal outcome following gestation and birth of rats in hypergravity.

A major goal of space life sciences research is to broaden scientific knowledge of the influence of gravity on living systems. Recent spaceflight and centrifugation studies demonstrate that reproduction and ontogenesis in mammals are amenable to study under gravitational conditions that deviate considerably from those typically experienced on Earth (1 x g). In the present study, we tested the hypothesis that maternal reproductive experience determines neonatal outcome following gestation and birth under increased (hyper) gravity. Primigravid and bigravid female rats and their offspring were exposed to 1.5 x g centrifugation from Gestational Day 11 either through birth or through the first postnatal week. On the day of birth, litter sizes were identical across gravity and parity conditions, although significantly fewer live neonates were observed among hypergravity-reared litters born to primigravid dams than among those born to bigravid dams (82% and 94%, respectively; 1.0 x g controls, 99%). Within the hypergravity groups, neonatal mortality was comparable across parity conditions from Postnatal Day 1 through Day 7, at which time litter sizes stabilized. Maternal reproductive experience ameliorated neonatal losses during the first 24 h after birth but not on subsequent days, and neonatal mortality was associated with changes in maternal care patterns. These results indicate that repeated maternal reproductive experience affords protection against neonatal losses during exposure to increased gravity. Differential mortality of neonates born to primigravid versus bigravid dams denotes gravitational load as one environmental mechanism enabling the expression of parity-related variations in birth outcome.

Animals↗

PubMed2001

The catecholamine response to spaceflight: role of diet and gender.

UNLABELLED: Compared with men, women appear to have a decreased sympathetic nervous system (SNS) response to stress. The two manifestations where the sexual dimorphism has been the most pronounced involve the response of the SNS to fluid shifts and fuel metabolism during exercise. The objectives of this study were to investigate whether a similar sexual dimorphism was found in the response to spaceflight. To do so, we compared catecholamine excretion by male and female astronauts from two similar shuttle missions, Spacelab Life Sciences 1 (SLS1, 1991) and 2 (SLS2, 1993) for evidence of sexual dimorphism. To evaluate the variability of the catecholamine response in men, we compared catecholamine excretion from the two SLS missions against the 1996 Life and Microgravity Sciences Mission (LMS) and the 1973 Skylab missions. RESULTS: No gender- or mission-dependent changes were found with epinephrine. Separating out the SLS1/2 data by gender shows that norepinephrine excretion was essentially unchanged with spaceflight in women (98 +/- 10%; n = 3) and substantially decreased with the men (41 +/- 9%; n = 4, P < 0.05). Data are a percentage of mean preflight value +/- SE. Comparisons among males demonstrated significant mission effects on norepinephrine excretion. After flight, there was a transient increase in norepinephrine but no evidence of any gender-specific effects. We conclude that norepinephrine excretion during spaceflight is both mission and gender dependent. Men show the greater response, with at least three factors being involved, a response to microgravity, energy balance, and the ratio of carbohydrate to fat in the diet.

Diet↗

PubMed2001

Effects of prolonged fasting on plasma cortisol and TH in postweaned northern elephant seal pups.

Northern elephant seal (Mirounga angustirostris) pups rely on the oxidation of fat stores as their primary source of energy during their 8- to 12-wk postweaning fast; however, potential endocrine mechanisms involved with this increased fat metabolism have yet to be examined. Therefore, 15 pups were serially blood sampled in the field during the first 7 wk of their postweaning fast to examine the changes in plasma concentrations of cortisol and thyroid hormones (TH), which are involved in fat metabolism in other mammals. Cortisol increased, indicating that it contributed to an increase in lipolysis. Increased total triiodothyronine (tT(3)) and thyroxine (tT(4)) may not reflect increased thyroid gland activity, but rather alterations in hormone metabolism. tT(3)-to-tT(4) ratio decreased, suggesting a decrease in thyroxine (T(4)) deiodination, whereas the negative correlation between total proteins and free T(4) suggests that the increase in free hormone is attributed to a decrease in binding globulins. Changes in TH are most similar to those observed during hibernation than starvation in mammals, suggesting that the metabolic adaptations to natural fasting are more similar to hibernation despite the fact these animals remain active throughout the fasting period.

Animals↗

PubMed2001

Evidence for central venous pressure resetting during initial exposure to microgravity.

We measured central venous pressure (CVP); plasma volume (PV); urine volume rate (UVR); renal excretion of sodium (UNa); and renal clearances of creatinine, sodium, and osmolality before and after acute volume infusion to test the hypothesis that exposure to microgravity causes resetting of the CVP operating point. Six rhesus monkeys underwent two experimental conditions in a crossover counterbalance design: 1) continuous exposure to 10 degrees head-down tilt (HDT) and 2) a control, defined as 16 h/day of 80 degrees head-up tilt and 8 h prone. After 48 h of exposure to either test condition, a 120-min course of continuous infusion of isotonic saline (0.4 ml. kg(-1). min(-1) iv) was administered. Baseline CVP was lower (P = 0.011) in HDT (2.3 +/- 0.3 mmHg) compared with the control (4.5 +/- 1.4 mmHg) condition. After 2 h of saline infusion, CVP was elevated (P = 0.002) to a similar magnitude (P = 0.485) in HDT (DeltaCVP = 2.7 +/- 0.8 mmHg) and control (DeltaCVP = 2.3 +/- 0.8 mmHg) conditions and returned to preinfusion levels 18 h postinfusion in both treatments. PV followed the same pattern as CVP. The response relationships between CVP and UVR and between CVP and UNa shifted to the left with HDT. The restoration of CVP and PV to lower preinfusion levels after volume loading in HDT compared with control supports the notion that lower CVP during HDT may reflect a new operating point about which vascular volume is regulated. These results may explain the ineffective fluid intake procedures currently employed to treat patients and astronauts.

Animals↗

PubMed2001

Hormonal modulation of food intake in response to low leptin levels induced by hypergravity.

A loss in fat mass is a common response to centrifugation and it results in low circulating leptin concentrations. However, rats adapted to hypergravity are euphagic. The focus of this study was to examine leptin and other peripheral signals of energy balance in the presence of a hypergravity-induced loss of fat mass and euphagia. Male Sprague-Dawley rats were centrifuged for 14 days at gravity levels of 1.25, 1.5, or 2 G, or they remained stationary at 1 G. Urinary catecholamines, urinary corticosterone, food intake, and body mass were measured on Days 11 to 14. Plasma hormones and epididymal fat pad mass were measured on Day 14. Mean body mass of the 1.25, 1.5, and 2 G groups were significantly (P < 0.05) lower than controls, and no differences were found in food intake (g/day/100 g body mass) between the hypergravity groups and controls. Epididymal fat mass was 14%, 14%, and 21% lower than controls in the 1.25, 1.5, and 2.0 G groups, respectively. Plasma leptin was significantly reduced from controls by 46%, 45%, and 65% in the 1.25, 1.5, and 2 G groups, respectively. Plasma insulin was significantly lower in the 1.25, 1.5, and 2.0 G groups than controls by 35%, 38%, and 33%. No differences were found between controls and hypergravity groups in urinary corticosterone. Mean urinary epinephrine was significantly higher in the 1.5 and 2.0 G groups than in controls. Mean urinary norepinephrine was significantly higher in the 1.25, 1.5 and 2.0 G groups than in controls. Significant correlations were found between G load and body mass, fat mass, leptin, urinary epinephrine, and norepinephrine. During hypergravity exposure, maintenance of food intake is the result of a complex relationship between multiple pathways, which abates the importance of leptin as a primary signal.

Animals↗

PubMed2001

Effects of hypergravity exposure on the developing central nervous system: possible involvement of thyroid hormone.

The present study examined the effects of hypergravity exposure on the developing brain and specifically explored the possibility that these effects are mediated by altered thyroid status. Thirty-four timed-pregnant Sprague-Dawley rats were exposed to continuous centrifugation at 1.5 G (HG) from gestational Day 11 until one of three key developmental points: postnatal Day (P) 6, P15, or P21 (10 pups/dam: 5 males/5 females). During the 32-day centrifugation, stationary controls (SC, n = 25 dams) were housed in the same room as HG animals. Neonatal body, forebrain, and cerebellum mass and neonatal and maternal thyroid status were assessed at each time point. The body mass of centrifuged neonates was comparatively lower at each time point. The mass of the forebrain and the mass of the cerebellum were maximally reduced in hypergravity-exposed neonates at P6 by 15.9% and 25.6%, respectively. Analysis of neonatal plasma suggested a transient hypothyroid status, as indicated by increased thyroid stimulating hormone (TSH) level (38.6%) at P6, while maternal plasma TSH levels were maximally elevated at P15 (38.9%). Neither neonatal nor maternal plasma TH levels were altered, suggesting a moderate hypothyroid condition. Thus, continuous exposure of the developing rats to hypergravity during the embryonic and neonatal periods has a highly significant effect on the developing forebrain and cerebellum and neonatal thyroid status (P < 0.05, Bonferroni corrected). These data are consistent with the hypothesized role of the thyroid hormone in mediating the effect of hypergravity in the developing central nervous system and begin to define the role of TH in the overall response of the developing organism to altered gravity.

Animals↗

PubMed2001

Blood pressure changes during orthostatic stress: evidence of gender differences in neuroeffector distribution.

BACKGROUND: Research has demonstrated that exogenous adrenergic agonists produce dose-related vasoconstriction in men but not women. This suggests that the distribution of adrenergic receptor sites differ with gender. Women may have a higher density of receptor sites in the arterioles (fast acting with low gain) while men may have higher density in the larger vessels (slow acting with high gain). METHODS: To partially test this hypothesis, the time course in beat-to-beat responses in systolic and diastolic BP, and heart rate was compared between six men and six women during the transition from a supine to an upright posture and during prolonged standing. RESULTS: The transient change in systolic and diastolic BP was very rapid in women, but completed within 15 to 30 s after assuming an upright position. Men increased BP at a much slower rate, but continued to produce higher BPs over the complete testing session (up to 15 min). The rate of change for men (15 mm Hg systolic and 10 mm Hg diastolic) was approximately half that for women (30 mm Hg systolic and 15 mm Hg diastolic) during the first 30 s of upright posture. However, after 60 s of standing, absolute change in systolic BP for the men exceeded that of the women by approximately 5 mm Hg for both systolic and diastolic BP. While men's heart rate remained relatively constant during standing, women compensated for the lower change in BP by a continual increase in heart rate throughout the duration of the test. Although both men and women demonstrated increases in norepinephrine at 5 and 15 min during standing, no difference between genders was observed. Similarly, there were no differences in dominant periodicity of heart rate during standing, although women demonstrated slightly higher beat-to-beat variation (RMS) than men. CONCLUSION: The results support the hypothesis of distributional differences in neuroeffector responses between men and women and have implications for how men and women respond to orthostatic stress across a variety of environmental conditions.

Adult↗

PubMed2001

No effect of hypergravity on adult rat ventral horn neuron size or SDH activity.

BACKGROUND: Spaceflights of short duration (approximately 2 wk) result in adaptations in the size and/or metabolic properties of a select population of motoneurons located in the lumbosacral region of the rat spinal cord. A decrease in succinate dehydrogenase (SDH, an oxidative marker enzyme) activity of moderately sized (500-800 microm2) motoneurons in the retrodorsolateral region of the spinal cord (L6) has been observed after a 14-d flight. HYPOTHESIS: Our hypothesis was that exposure to short-term hypergravity would result in adaptations in the opposite direction, reflecting a continuum of morphological and biochemical responses in the spinal motoneurons from zero gravity to hypergravity. METHODS: Young, male rats were centrifuged at either 1.5 or 2.0 G for 2 wk. The size and SDH activity of a population of motoneurons in the retrodorsolateral region of the spinal cord (L5) were determined and compared with age-matched rats maintained at 1.0 G. The absolute and relative (to body weight) masses of the soleus, gastrocnemius, adductor longus and tibialis anterior muscles were compared among the three groups. RESULTS: There were no effects of either hypergravity intervention on the motoneuron properties. Rats maintained under hypergravity conditions gained less body mass than rats kept at 1.0 G. For the 1.5 and 2.0 G groups, the muscle absolute mass was smaller and relative mass similar to that observed in the 1.0 G rats, except for the adductor longus. The adductor longus absolute mass was similar to and the relative mass larger in both hypergravity groups than in the 1.0 G group. CONCLUSIONS: Our hypothesis was rejected. The findings suggest that rat motoneurons are more responsive to short-term chronic exposure to spaceflight than to hypergravity conditions.

Adaptation, Physiological↗

PubMed2001

Renal function of rats in response to 37 days of head-down tilt.

Spaceflight induces changes in human renal function, suggesting similar changes may occur in rats. Since rats continue to be the prime mammalian model for study in space, the effects of chronic microgravity on rat renal function should be clarified. Acute studies in rats using the ground-based microgravity simulation model, head-down tilt (HDT), have shown increases in glomerular filtration rate (GFR), electrolyte excretion, and a diuresis. However, long term effects of HDT have not been studied extensively. This study was performed to elucidate rat renal function following long-term simulated microgravity. Chronic exposure to HDT will cause an increase in GFR and electrolyte excretion in rats, similar to acute exposures, and lead to a decrease in the fractional excretion of filtered electrolytes. Experimental animals (HDT, n=10) were tail-suspended for 37 days and renal function compared to ambulatory controls (AMB, n=10). On day 37 of HDT, GFR, osmolal clearance, and electrolyte excretion were decreased, while plasma osmolality and free water clearance were increased. Urine output remained similar between groups. The fractional excretion of the filtered electrolytes was unchanged except for a decrease in the percentage of filtered calcium excreted. Chronic exposure to HDT results in decreased GFR and electrolyte excretion, but the fractional excretion of filtered electrolytes remained primarily unaffected.

Animals↗

PubMed2001

Is there resetting of central venous pressure in microgravity?

In the early phase of the Space Shuttle program, NASA flight surgeons implemented a fluid-loading countermeasure in which astronauts were instructed to ingest eight 1-g salt tablets with 960 ml of water approximately 2 hours prior to reentry from space. This fluid loading regimen was intended to enhance orthostatic tolerance by replacing circulating plasma volume reduced during the space mission. Unfortunately, fluid loading failed to replace plasma volume in groundbased experiments and has proven minimally effective as a countermeasure against post-spaceflight orthostatic intolerance. In addition to the reduction of plasma volume, central venous pressure (CVP) is reduced during exposure to actual and groundbased analogs of microgravity. In the present study, we hypothesized that the reduction in CVP due to exposure to microgravity represents a resetting of the CVP operating point to a lower threshold. A lower CVP 'setpoint' might explain the failure of fluid loading to restore plasma volume. In order to test this hypothesis, we conducted an investigation in which we administered an acute volume load (stimulus) and measured responses in CVP, plasma volume and renal functions. If our hypothesis is true, we would expect the elevation in CVP induced by saline infusion to return to its pre-infusion levels in both HDT and upright control conditions despite lower vascular volume during HDT. In contrast to previous experiments, our approach is novel in that it provides information on alterations in CVP and vascular volume during HDT that are necessary for interpretation of the proposed CVP operating point resetting hypothesis.

Aerospace Medicine↗