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Comparative aspects of hematological responses in animal and human models in simulations of weightlessness and space flight

This paper reviews some human and animal responses to space flight as well as in control models in simulations of weightlessness. Astronauts after space flight have been found to have a decreased red blood cell mass and plasma volume. The reason for these changes is unknown but appears to be caused primarily by a decrease in the need of red blood cells in the weightless condition. Similar though more moderate changes have been found in human subjects subjected to prolonged bed rest or water immersion. What happens to the red cell mass of laboratory rats flown in microgravity is not known but rats have shown an increase in the rate of random red cell loss in flight suggesting a probable decrease. Rat models subjected to either head-down suspension or restraint alone have shown a decrease in red blood cell masses and a decrease in their plasma volume.

Lange, R. D.↗

Fluid-electrolyte shifts and thermoregulation - Rest and work in heat with head cooling

The effects of head cooling on thermoregulation and associated plasma fluid and electrolyte shifts during rest and submaximal exercise in the heat are investigated. Thermoregulatory responses and plasma volume were measured in four male subjects fitted with liquid-cooled neoprene headgear during 60 min of rest, 60 min of ergometer exercise at 45% maximal oxygen uptake and 30 min of recovery in the supine position at 40.1 C and 40% relative humidity. It is found that, compared to control responses, head cooling decreased thigh sweating and increased mean skin temperature at rest and attenuated increases in thigh sweating, heart rate, rectal temperature and ventilation during exercise. During recovery, cooling is observed to facilitate decreases in sweat rate, heart rate, rectal temperature and forearm blood flow and enhance the increase in average temperature. Cooling had no effect on plasma protein, osmotic or electrolyte shifts, and decreased plasma volume losses. The findings indicate the effectiveness of moderate head cooling for the improvement of human performance during exercise in heat.

Greenleaf, J. E.↗

Effect of physical training in cool and hot environments on +Gz acceleration tolerance in women

Acceleration tolerance, plasma volume, and maximal oxygen uptake were measured in 15 healthy women before and after submaximal isotonic exercise training periods in cool and hot environments. The women were divided on the basis of age, maximal oxygen uptake, and +Gz tolerance into three groups: a group that exercised in heat (40.6 C), a group that exercised at a lower temperature (18.7 C), and a sedentary control group that functioned in the cool environment. There was no significant change in the +Gz tolerance in any group after training, and terminal heart rates were similar within each group. It is concluded that induction of moderate acclimation responses without increases in sweat rate or resting plasma volume has no influence on +Gz acceleration tolerance in women.

Brock, P. J.↗

Body water compartments during bed rest: Evaluation of analytical methods

Nine healthy young men were studied to determine the reproducibility and interchangeability of the use of radio-iodinated human serum albumin and Evans Blue dye for estimating plasma volume, sodium bromide for extracellular fluid volume, and deuterium oxide for total body water volume. All subjects were tested in a semibasal condition and allowed to rest for at least 30 min. after arriving at the laboratory. The results indicate that there was uniform distribution of I131 and Evans Blue dye 10 min. after injection and of NaBr and D2O 3 hours after oral ingestion; the buildup of residual tracer did not interfere appreciably with the measurement of either or Evans Blue spaces when they are administered at equal intervals, and the buildup of background tracer after ingestion of NaBr and D2O once per week for three consecutive weeks did not affect the accuracy of the measurement. It was found that I131 and Evans Blue may be used interchangeably for estimating plasma volume; for estimating bromide and D2O spaces, one 3-hour equilibrium blood sample gives results similar to the extrapolation of multiple samples.

Young, H. L.↗

Increased renal tubular sodium reabsorption during exercise-induced hypervolemia in humans

We tested the hypothesis that renal tubular Na(+) reabsorption increased during the first 24 h of exercise-induced plasma volume expansion. Renal function was assessed 1 day after no-exercise control (C) or intermittent cycle ergometer exercise (Ex, 85% of peak O(2) uptake) for 2 h before and 3 h after saline loading (12.5 ml/kg over 30 min) in seven subjects. Ex reduced renal blood flow (p-aminohippurate clearance) compared with C (0.83 +/- 0.12 vs. 1.49 +/- 0.24 l/min, P < 0.05) but did not influence glomerular filtration rates (97 +/- 10 ml/min, inulin clearance). Fractional tubular reabsorption of Na(+) in the proximal tubules was higher in Ex than in C (P < 0.05). Saline loading decreased fractional tubular reabsorption of Na(+) from 99.1 +/- 0.1 to 98.7 +/- 0.1% (P < 0.05) in C but not in Ex (99.3 +/- 0.1 to 99.4 +/- 0.1%). Saline loading reduced plasma renin activity and plasma arginine vasopressin levels in C and Ex, although the magnitude of decrease was greater in C (P < 0.05). These results indicate that, during the acute phase of exercise-induced plasma volume expansion, increased tubular Na(+) reabsorption is directed primarily to the proximal tubules and is associated with a decrease in renal blood flow. In addition, saline infusion caused a smaller reduction in fluid-regulating hormones in Ex. The attenuated volume-regulatory response acts to preserve distal tubular Na(+) reabsorption during saline infusion 24 h after exercise.

NASA Discipline Cardiopulmonary↗

Cardiovascular Adaptations to Long Duration Head-Down Tilt Bed Rest

INTRODUCTION: Orthostatic hypotension is a serious risk for crewmembers returning from spaceflight. Numerous cardiovascular mechanisms have been proposed to account for this problem, including vascular and cardiac dysfunction, which we studied during bed rest. METHODS: Thirteen subjects were studied before and during bed rest. Statistical analysis was limited to the first 49-60 days of bed rest, and compared to pre-bed rest data. Ultrasound data were collected on vascular and cardiac structure and function. Tilt testing was conducted for 30 minutes or until presyncopal symptoms intervened. RESULTS: Plasma volume was significantly reduced by day 7 of bed rest. Flow-mediated dilation in the leg was significantly increased at bed rest day 49. Arterial responses to nitroglycerin differed in the arm and leg, but did not change as a result of bed rest. Intimal-medial thickness markedly decreased at bed rest days 21, 35 and 49. Several cardiac functional parameters including isovolumic relaxation time, ejection time and myocardial performance index were significantly increased (indicating a decrease in cardiac function) during bed rest. There was a trend for decreased orthostatic tolerance following 60 days of bed rest. DISCUSSION: These data suggest that 6 head-down tilt bed rest alters cardiovascular structure and function in a pattern similar to short duration spaceflight. Additionally, the vascular alterations are primarily seen in the lower body, while vessels of the upper body are unaffected. KEY WORDS: spaceflight, orthostatic intolerance, hypotension, fluid-shift, plasma volume

Platts, Steven H.↗

Cardiovascular Session Summary

It was apparent that the bed-rest and spaceflight data indicated that decreases in plasma volume and cardiac atrophy along with cardiac remodeling were fundamental changes which predisposed many astronauts to post flight orthostatic intolerance. Despite the recently acquired in-flight and post-flight muscle sympathetic nerve activity findings suggesting that the sympathetic nerve responses were appropriate there remains significant contrary data from bed-rest studies, post- flight stand tests and hind-limb unweighted rat studies that suggest that the vasoconstrictive responses were compromised at least insufficient in susceptible individuals. The key issues raised is whether a diminished increase in sympathetic activity from baseline without changes in 254 First Biennial Space Biomedical Investigators'Workshop Cardiovascular peak response or receptor adaptations is an abnormal response or is an individual variance of response to the accentuated decrease in stroke volume. Data relating autonomic neural control of heart rate were presented to suggest that the vagal and sympathetic control of heart rate was attenuated. Also, bed-rest and space flight induced attenuated baroreflex control of heart rate was shown to be restored to pre-bedrest function by one bout of maximal dynamic exercise. However, these data were confounded by relying on the use of R-R interval as a measure of efferent responses of the baroreflex during a condition in which the baseline heart rate was changed. Clearly the idea that the autonomic control of heart rate may be changed by microgravity needs further investigation. This direction is suggested despite the fact that in the triple product (HR x SV x TPR = MAP) assessment of the regulation of arterial blood pressure during orthostasis the role of the HR reflex may be less influential than that associated. with cardiac atrophy (SV changes) and aberrant sympathetic vasoconstriction (resistance) changes. Although sympathetic nerve activity responses in-flight and post-flight on neurolab appeared appropriate, enough bed-rest and post-flight stand test data, along with animal model data suggest that vasoconstriction was compromised. The mechanism of this compromised vasoconstriction needs to be delineated. Other major findings concerning microgravity and physiological regulatory systems are that: I . Thermoregulatory adaptation appear to suggest some decrements in the control of cutaneous vasodilation and sweating; 2. Calcium resorption and dietary calcium need to be defined for differing durations of spaceflight, especially as the effects of excess calcium on vasomotor function appears to be detrimental; 3. Neurohumoral mechanisms of microgravity induced changes in neural function and the regulation of plasma volume and total body water, bone resorption and autonomic neural control of the circulation need further delineation; 4. As performance of work tasks become prolonged, the mechanisms of blood pressure regulation in microgravity needs to be used in the recovery period from prolonged work tasks.

Raven, Peter↗

Red blood cell and iron metabolism during space flight

Space flight anemia is a widely recognized phenomenon in astronauts. Reduction in circulating red blood cells and plasma volume results in a 10% to 15% decrement in circulatory volume. This effect appears to be a normal physiologic adaptation to weightlessness and results from the removal of newly released blood cells from the circulation. Iron availability increases, and (in the few subjects studied) iron stores increase during long-duration space flight. The consequences of these changes are not fully understood.

STS Shuttle Project↗

Evidence for increased cardiac compliance during exposure to simulated microgravity

We measured hemodynamic responses during 4 days of head-down tilt (HDT) and during graded lower body negative pressure (LBNP) in invasively instrumented rhesus monkeys to test the hypotheses that exposure to simulated microgravity increases cardiac compliance and that decreased stroke volume, cardiac output, and orthostatic tolerance are associated with reduced left ventricular peak dP/dt. Six monkeys underwent two 4-day (96 h) experimental conditions separated by 9 days of ambulatory activities in a crossover counterbalance design: 1) continuous exposure to 10 degrees HDT and 2) approximately 12-14 h per day of 80 degrees head-up tilt and 10-12 h supine (control condition). Each animal underwent measurements of central venous pressure (CVP), left ventricular and aortic pressures, stroke volume, esophageal pressure (EsP), plasma volume, alpha1- and beta1-adrenergic responsiveness, and tolerance to LBNP. HDT induced a hypovolemic and hypoadrenergic state with reduced LBNP tolerance compared with the control condition. Decreased LBNP tolerance with HDT was associated with reduced stroke volume, cardiac output, and peak dP/dt. Compared with the control condition, a 34% reduction in CVP (P = 0.010) and no change in left ventricular end-diastolic area during HDT was associated with increased ventricular compliance (P = 0.0053). Increased cardiac compliance could not be explained by reduced intrathoracic pressure since EsP was unaltered by HDT. Our data provide the first direct evidence that increased cardiac compliance was associated with headward fluid shifts similar to those induced by exposure to spaceflight and that reduced orthostatic tolerance was associated with lower cardiac contractility.

Non-NASA Center↗

Spacelab Life Sciences flight experiments: an integrated approach to the study of cardiovascular deconditioning and orthostatic hypotension

The microgravity environment of spaceflight produces rapid cardiovascular changes which are adaptive and appropriate in that setting, but are associated with significant deconditioning and orthostatic hypotension on return to Earth's gravity. The rapidity with which these space flight induced changes appear and disappear provides an ideal model for studying the underlying pathophysiological mechanisms of deconditioning and orthostatic hypotension, regardless of etiology. Since significant deconditioning is seen after flights of very short duration, muscle atrophy due to inactivity plays, at most, a small role. These changes in circulatory control associated with cephalad fluid shifts, rather than inactivity per se, are probably more important factors. In order to test this hypothesis in a systematic way, a multidisciplinary approach which defines and integrates inputs and responses from a wide variety of circulatory sub-systems is required. The cardiovascular experiments selected for Spacelab Life Sciences flights 1 and 2 provide such an approach. Both human and animal models will be utilized. Pre- and post-flight characterization of the payload crew includes determination of maximal exercise capacity (bicycle ergometry), orthostatic tolerance (lower body negative pressure), alpha and beta adrenergic sensitivity (isoproterenol and phenylephrine infusions), baroreflex sensitivity (ECG-gated, stepwise changes in carotid artery transmural pressure with a pneumatic neck collar), and responses to a 24 h period of 5 deg head-down tilt. Measurements of cardiac output (CO2 and C2H2 rebreathing), cardiac chamber dimensions (phased-array 2-dimensional echocardiography), direct central venous pressure, leg volume (Thornton sock), limb blood flow and venous compliance (occlusion plethysmography), blood and plasma volumes, renal plasma flow and glomerular filtration rates, and various hormonal levels including catecholamines and atrial natriuretic factor will also be obtained. The central venous catheter will be inserted immediately pre-launch and monitored with heart rate and blood pressure in-flight until cardiac output, respiratory gas exchange and quantitative 2D echocardiography measurements can be performed. In-flight hemodynamic measurements will be repeated at rest and during submaximal exercise daily and also during maximal exercise midway through the flight to document the timecourse and extent of cardiovascular changes in the payload crew. Parallel studies are planned for the animals. In addition to measurements of right atrial and aortic pressures and cardiac output, a dorsal micro-circulatory chamber will allow determinations of changes in capillary and venular architecture and function in six of the rats. The techniques and findings from many of the SLS-1 and 2 supporting studies have already yielded significant information about circulatory regulation in patients with both hypo- and hypertension. The flight experiments themselves will provide new data to test the validity of both animal and human models currently used for simulating the fluid shifts of a micro-gravity environment. The development of effective countermeasures, not only for short and long duration space travellers, but also for Earth-bound medical patients can then be physiologically based on experimental data rather than anecdote.

Non-NASA Center↗

Passenger fluid volumes measured before and after a prolonged commercial jet flight.

Interstitial and intracellular fluid volumes were calculated from measured plasma volume, extracellular volume and total body water of six subjects before and after a 24-hour commercial overseas flight. No change occurred in these spaces or in peripheral hematocrit or total serum protein concentration. The subjective feeling of dehydration and the actual swelling of the lower extremities characteristically found among passengers at the end of a long trip of this type seems to represent a shift in body fluids to the dependent portions of the body rather than water retention or a decrease in the intravascular water volume.

Johnson, P. C.↗

Changes in total plasma content of electrolytes and proteins with maximal exercise.

To determine to what extent the increases in concentration of plasma proteins and electrolytes with short maximal work were a result of hemoconcentration, the changes in plasma volume and total content of the plasma constituents were simultaneously evaluated. The results obtained from six human subjects indicated that in comparison to preexercise values there was a net decrease in total content of plasma protein, sodium, and chloride in the first 2 min of the postexercise period, due primarily to a significant loss (13-15%) of plasma fluid. The total plasma potassium content was increased immediately after exercise but was significantly below the preexercise plasma content after 2 min of recovery.

Van Beaumont, W.↗

Observational constraints for a theoretical model describing the soft X-ray flare

High-resolution solar flare X-ray spectra have recently been obtained from X-ray spectrometer experiments flown on an Air Force spacecraft (P78-1) launched on 1979 February 24. Interpretation of the spectra has produced new results concerning the physical conditions and time behavior of the thermal soft X-ray emitting plasma at temperatures near 20,000,000 K. It is argued that soft and hard X-ray events are not causally related to each other, but are simply two different manifestations of flare energy release. They probably occur in different plasma volumes. The source of the preflare plasma appears to be in the cooler parts of the solar atmosphere, perhaps transition region loops with initial temperatures of 100,000 K and densities of 10 to the 11th per cu cm. Continuous energy input, rather than sequential activation of loops, is required to explain the observations. Compression coupled with chromospheric ablation may produce the high densities in coronal flare loops.

Feldman, U.↗

Measurement of net whole-body transcapillary fluid transport and effective vascular compliance in humans

BACKGROUND: Net whole-body transcapillary fluid transport (TFT) between the circulation and the interstitial (extravascular) space may be calculated as: IV - deltaPV - UV - IL, where IV=infused or ingested volume (when applicable), deltaPV = change in plasma volume, UV=urine volume, and IL=insensible loss. RESULTS: Infusion of 30 mL/kg isotonic saline over 25 minutes increased supine TFT from a basal capillary reabsorption of -106+/-24 mL/h (mean+/-SE) to a net filtration of 1,229+/-124 mL/h. One hour after infusion, reabsorption of -236+/-102 mL/h was seen, and control reabsorption levels returned by 3 hours. Four hours of 30 mm Hg lower body negative pressure (LBNP) elicited no net TFT, probably because of upper body reabsorptive compensation for lower body capillary filtration. When ingestion of 1 L of isotonic saline accompanied LBNP, filtration of 145+/-10 mL/h occurred. Reabsorption of extravascular fluid into the circulation always followed LBNP. CONCLUSION: Application of this technique could aid understanding of physiologic conditions, experimental interventions, disease states, and therapies that cause or are influenced by fluid shifts between intravascular and interstitial compartments.

NASA Center JSC↗

Cardiac and Vascular Function in Bedrested Volunteers: Effects of Artificial Gravity Training

Cardiovascular effects of an artificial gravity (AG) countermeasure on deconditioned male volunteers were studied. In two groups of men we measured cardiovascular parameters at rest and in response to 30 minutes of 80 deg. head up tilt (HUT) before, at the end of, and four days following 21 days of 6 deg. head down bed rest (HDBR). One group (N=7) underwent no countermeasure while the other (N=8) received a daily, one hour, dose (2.5 gz at the foot, decreasing to 1.0 gz at the heart) of AG training on the Johnson Space Center short radius centrifuge. Cardiovascular parameters measured included heart rate, blood pressure, stroke volume, cardiac output, peripheral vascular resistance, plasma volume shifts, and vasoactive hormones. Untrained subjects exhibited shorter tilt survival (on average 8 minutes shorter) compared to trained subjects. By the end of bed rest, mean heart rate (MHR) was elevated in both groups (both supine and during tilt). In addition, treated subjects demonstrated lower, tilt-induced, increases in MHR four days following HDBR, indicating a more rapid return to pre bed rest conditions. Results from an index of autonomic balance (percentage of MHR spectral power in the respiratory frequency range) in control of heart rate are consistent with the interpretation that parasympathetic nervous system withdrawal was responsible for both tilt- and bed rest-induced increases in MHR. Our data support our pre-study hypothesis that AG treatment would lessen cardiovascular effects of deconditioning in bed rested men and suggest that AG should be further pursued as a space flight countermeasure.

Meng, M.↗