Clinical Aspects of the Control of Plasma Volume at Microgravity and During Return to One Gravity

Plasma volume is reduced by 10%-20% within 24 to 48 h of exposure to simulated or actual microgravity. The clinical importance of microgravity-induced hypovolemia is manifested by its relationship with orthostatic intolerance and reduced VO2max after return to one gravity (1G). Since there is no evidence to suggest plasma volume reduction during microgravity is associated with thirst or renal dysfunctions, a diuresis induced by an immediate blood volume shift to the central circulation appears responsible for microgravity-induced hypovolemia. Since most astronauts choose to restrict their fluid intake before a space mission, absence of increased urine output during actual spaceflight may be explained by low central venous pressure (CVP) which accompanies dehydration. Compelling evidence suggests that prolonged reduction in CVP during exposure to microgravity reflects a 'resetting' to a lower operating point which acts to limit plasma volume expansion during attempts to increase fluid intake. In groudbase and spaceflight experiments, successful restoration and maintenance of plasma volume prior to returning to an upright posture may depend upon development of treatments that can return CVP to its baseline 10 operating point. Fluid-loading and LBNP have not proved completely effective in restoring plasma volume, suggesting that they may not provide the stimulus to elevate the CVP operating point. On the other, exercise, which can chronically increase CVP, has been effective in expanding plasma volume when combined with adequate dietary intake of fluid and electrolytes. The success of designing experiments to understand the physiological mechanisms of and development of effective countermeasures for the control of plasma volume in microgravity and during return to one gravity will depend upon testing that can be conducted under standardized controlled baseline cond

Elevated central venous pressure: A consequence of exercise training-induced hypervolemia

Resting plasma volumes, and arterial and central venous pressures (CVP) were measured in 16 men before and after exercise training to determine if training-induced hypervolemia could be explained by a change in total vascular capacitance. In addition, resting levels of plasma vasopressin (AVP), atrial natriuretic peptide (ANP), aldosterone (ALD), and norepinephrine (NE) were measured before and after training. The same measurements of vacular volume, pressures, and plasma hormones were measured in 8 subjects who did not undergo exercise and acted as controls. The exercise training program consisted of 10 weeks of controlled cycle exercise for 30 min/d, 4 d/wk at 75 to 80 percent of maximal oxygen uptake (VO2max). A training effect was verified by a 20 percent increase in VO2max, a resting bradycardia, and a 370 ml (9 percent) increase in blood volume. Mean arterial blood pressure was unaltered by exercise training, but resting CVP increased. The percent change in blood volume from before to after training was linearly related to the percent change in CVP. As a consequence of elevations in both blood volume and CVP, the volume-to-pressure ratio was essentially unchanged following exercise training. Plasma AVP, ANP, ALD, and NE were unaltered. Results indicate that elevated CVP is a consequence of training-induced hypervolemia without alteration in total effective venous capacitance. This may represent a resetting of the pressure-volume stimulus-response relation for regulation of blood volume

Leg Vascular Responsiveness During Acute Orthostasis Following Simulated Weightlessness

Ten men (35-49 years old) underwent lower body negative pressure (LBNP) exposures before and offer 10 d of continuous 6 degrees head-down bedrest in order to predict the effect of weightlessness on the responsiveness of leg vasculature to an orthostatic stress. Heart rate (HR), mean arterial blood pressure (MAP), and Impedance rheographic indices of arterial pulse volume (APV) of the legs were measured during rest and at 1 min at -30 mm Hg LBNP. Bedrest-induced deconditioning was manifested by decreases (p less than 0.06) in plasma volume (17%), peak oxygen uptake (16%), and LBNP tolerance (17%). Resting HR was unchanged after bedrest, but HR was higher (p less than 0.05) at 1 min of -30 mm Hg LBNP after, compared with before bedrest. Responses of MAP to -30 mm Hg LBNP were not altered by bodrest. Resting APV was decreased (p less than 0.05) by simulated weightlessness. However, APV was reduced (p less than 0.05) from rest to 1 min -30 mm Hg LBNP by the same relative magnitude before and after bodrest (-21.4 +/- 3.4% and -20.5 +/- 2.7%, respectively). We conclude that peripheral arterial vasoconstriction, as indicated by reductions in APV during LBNP, was not affected by bedrest. These results suggest that there was no apparent alteration in responsiveness of the leg vasculature following simulated weightlessness. Therefore, it appears unlikely that control mechanisms of peripheral resistance contribute significantly to reduced orthostatic tolerance following space-flight

An Occupational Performance Test Validation Program for Fire Fighters at the Kennedy Space Center

We evaluated performance of a modified Combat Task Test (CTT) and of standard fitness tests in 20 male subjects to assess the prediction of occupational performance standards for Kennedy Space Center fire fighters. The CTT consisted of stair-climbing, a chopping simulation, and a victim rescue simulation. Average CTT performance time was 3.61 +/- 0.25 min (SEM) and all CTT tasks required 93% to 97% maximal heart rate. By using scores from the standard fitness tests, a multiple linear regression model was fitted to each parameter: the stairclimb (r(exp 2) = .905, P less than .05), the chopping performance time (r(exp 2) = .582, P less than .05), the victim rescue time (r(exp 2) = .218, P = not significant), and the total performance time (r(exp 2) = .769, P less than .05). Treadmill time was the predominant variable, being the major predictor in two of four models. These results indicated that standardized fitness tests can predict performance on some CTT tasks and that test predictors were amenable to exercise training

Comparison of Two Methods for Noninvasive Determination of Stroke Volume During Orthostatic Challenge

Background: The real time, beat-by-beat, non-invasive determination of stroke volume (SV) is an important parameter in many aerospace related physiologic protocols. In this study, we compared simultaneous estimates of SV calculated from peripheral pulse waveforms with a more conventional non-invasive technique. Methods: Using a prospective, randomized blinded protocol, ten males and nine females completed 12-mm tilt table protocols. The relative change (%(Delta)) in beat-to-beat SV was estimated non-invasively from changes in pulse waveforms measured by application of infrared finger photoplethysmography (IFP) with a Portapres(Registered TradeMark) blood pressure monitoring device and by thoracic impedance cardiography (TIC). The %(Delta) SV values were calculated from continuous SV measurements in the supine posture and over the first 10 s (T1), second 10 s (T2), and 3.5 minutes (T3) of 80deg head-up tilt (HUT). Results: The average %(Delta) SV measured by IFP at T1 (-11.7 +/- 3.7 %) was statistically less (P or = 0.322) than the average %(Delta) SV measured by TIC at T2 (-21.8 +/- 2.5 %), and T3 (-22.6 +/- 2.9 %). Correlation coefficients (r(sup 2)) between IFP and TIC were 0.117 (T1), 0.387 (T2), and 0.7 18 (T3). Conclusion: IFP provides beat-to-beat (real time) assessment of %(Delta) SV after 20 sec of transition to an orthostatic challenge that is comparable to the commonly accepted TIC. Our data support the notion that IFP technology which has flown during space missions can be used to accurately assess physiological status and countermeasure effectiveness for orth static problems that may arise in astronauts after space flight. While the peripherally measured IFP response is slightly delayed, the ease of implementing this monitor in the field is advantageous

Resting sympathetic baroreflex sensitivity in subjects with low and high tolerance to central hypovolemia induced by lower body negative pressure

Central hypovolemia elicited by orthostasis or hemorrhage triggers sympathetically-mediated baroreflex responses to maintain organ perfusion; these reflexes are less sensitive in patients with orthostatic intolerance, and during conditions of severe blood loss, may result in cardiovascular collapse (decompensatory or circulatory shock). The ability to tolerate central hypovolemia is variable and physiological factors contributing to tolerance are emerging. We tested the hypothesis that resting muscle sympathetic nerve activity (MSNA) and sympathetic baroreflex sensitivity (BRS) are attenuated in male and female subjects who have low tolerance (LT) to central hypovolemia induced by lower body negative pressure (LBNP). MSNA and diastolic arterial pressure (DAP) were recorded in 47 human subjects who subsequently underwent LBNP to tolerance (onset of presyncopal symptoms). LT subjects experienced presyncopal symptoms prior to completing LBNP of -60 mm Hg, and subjects with high tolerance (HT) experienced presyncopal symptoms after completing LBNP after -60 mmHg. Contrary to our hypothesis, resting MSNA burst incidence was not different between LT and HT subjects, and was not related to time to presyncope. BRS was assessed as the slope of the relationship between spontaneous fluctuations in DAP and MSNA during 5 min of supine rest. MSNA burst incidence/DAP correlations were greater than or equal to 0.5 in 37 subjects (LT: n= 9; HT: n=28), and BRS was not different between LT and HT (-1.8 ± 0.3 vs. -2.2 ± 0.2 bursts•(100 beats)-1•mmHg-1, p=0.29). We conclude that tolerance to central hypovolemia is not related to either resting MSNA or sympathetic BRS

Heart Rate Variability during Simulated Hemorrhage with Lower Body Negative Pressure in High and Low Tolerant Subjects

Heart rate variability (HRV) decreases during hemorrhage, and has been proposed as a new vital sign to assess cardiovascular stability in trauma patients. The purpose of this study was to determine if any of the HRV metrics could accurately distinguish between individuals with different tolerance to simulated hemorrhage. Specifically, we hypothesized that (1) HRV would be similar in low tolerant (LT) and high tolerant (HT) subjects at presyncope when both groups are on the verge of hemodynamic collapse; and (2) HRV could distinguish LT subjects at presyncope from hemodynamically stable HT subjects (i.e., at a submaximal level of hypovolemia). Lower body negative pressure (LBNP) was used as a model of hemorrhage in healthy human subjects, eliciting central hypovolemia to the point of presyncopal symptoms (onset of hemodynamic collapse). Subjects were classified as LT if presyncopal symptoms occurred during the −15 to −60 mmHg levels of LBNP, and HT if symptoms occurred after LBNP of −60 mmHg. A total of 20 HRV metrics were derived from R–R interval measurements at the time of presyncope, and at one level prior to presyncope (submax) in LT and HT groups. Only four HRV metrics (Long-range Detrended Fluctuation Analysis, Forbidden Words, Poincaré Plot Descriptor Ratio, and Fractal Dimensions by Curve Length) supported both hypotheses. These four HRV metrics were evaluated further for their ability to identify individual LT subjects at presyncope when compared to HT subjects at submax. Variability in individual LT and HT responses was so high that LT responses overlapped with HT responses by 85–97%. The sensitivity of these HRV metrics to distinguish between individual LT from HT subjects was 6–33%, and positive predictive values were 40–73%. These results indicate that while a small number of HRV metrics can accurately distinguish between LT and HT subjects using group mean data, individual HRV values are poor indicators of tolerance to hypovolemia

Sympathetic Responses to Central Hypovolemia: New Insights from Microneurographic Recordings

Hemorrhage remains a major cause of mortality following traumatic injury in both military and civilian settings. Lower body negative pressure (LBNP) has been used as an experimental model to study the compensatory phase of hemorrhage in conscious humans, as it elicits central hypovolemia like that induced by hemorrhage. One physiological compensatory mechanism that changes during the course of central hypovolemia induced by both LBNP and hemorrhage is a baroreflex-mediated increase in muscle sympathetic nerve activity (MSNA), as assessed with microneurography. The purpose of this review is to describe recent results obtained using microneurography in our laboratory as well as those of others that have revealed new insights into mechanisms underlying compensatory increases in MSNA during progressive reductions in central blood volume and how MSNA is altered at the point of hemodynamic decompensation. We will also review recent work that has compared direct MSNA recordings with non-invasive surrogates of MSNA to determine the appropriateness of using such surrogates in assessing the clinical status of hemorrhaging patients

Evidence for Increased Beta-Adrenoreceptor Responsiveness Induced by 14 Days of Simulated Microgravity in Humans

We studied hemodynamic responses to alpha and beta receptor agonists in 8 healthy men ( 38+- 2 yrs) before and after 14 days of 6 degree head-down tilt (HDT) to test the hypothesis that increased adrenergic responsiveness is induced by prolonged exposure to microgravity. Immediately following a 30-min baseline period, a steady-state infusion of isoproterenol (ISO) was used to assess beta 1- and beta 2-adrenergic responsiveness. ISO was infused at three graded constant rates of 0.005, 0.01 and 0.02 ug/kg/min. After heart rate and blood pressure had been allowed to return to baseline levels following ISO infusion graded infusion of phenylephrine (PE) was used to assess responsiveness of alpha I-vascular receptors. PE was infused at three graded constant rates of 0.25, 0.50 and 1.00 ug/kg/min. Each infusion interval for both drugs was 9 min. During the infusions, constant monitoring of beat-to-beat blood pressure and heart rate was performed and leg blood flow was measured with occlusion plethysmography at each infusion level. The slopes calculated from linear regressions between ISO and PE doses and changes in heart rate, blood pressure, and leg vascular resistance for each subject were used to represent alpha- and beta- adrenoreceptor responsiveness. Fourteen days HDT increased the slopes of heart rate (1056 +- 107 to 1553 +- 83 beats/ug/kg/min; P= 0.014) and vasodilation (-469ft +- 111 to -l446 +- 309 PRU/ug/kg/min; P =0.0224) to ISO infusion. There was no alteration in blood pressure or vascular resistance responses to PE infusion after HDT. Our results provide evidence that microgravity causes selective increases in beta 1- and beta 2-adrenergic responsiveness without affecting alpha 1-vascular responses

Responses to LBNP in men with varying profiles of strength and aerobic capacity: Implications for flight crews

Hemodynamic and hormonal responses to lower-body negative pressure (LBNP) were examined in 24 healthy men to test the hypothesis that responsiveness of reflex control of blood pressure during orthostatic stress is associated with strength and/or aerobic capacity. Subjects underwent treadmill tests to determine peak oxygen uptake (peak VO2) and isokinetic dynamo meter tests to determine leg strength. Based on predetermined criteria, the subjects were classified into one of four fitness profiles of six subjects each matched for age, height, and weight: (1) low strength/low aerobic fitness; (2) low strength/high aerobic fitness; (3) high strength/low aerobic fitness; and (4) high strength/high aerobic fitness. Following 90 min of 6 degree head-down tilt (HDT), each subject underwent graded LBNP through -50 mmHg or presyncope, with maximal duration 15 min. All groups exhibited typical hemodynamic, hormonal, and fluid shift responses during LBNP, with no intergroup differences except for catecholamines. Seven subjects, distributed among the four fitness profiles, became presyncopal. Subjects who showed greatest reduction in mean arterial pressure (MAP) during LBNP had greater elevations in vasopressin and lesser increases in heart rate and peripheral resistance. Peak VO2 nor leg strength were correlated with fall in MAP or with syncopal episodes. We conclude that neither aerobic nor strength fitness characteristics are good predictors of responses to LBNP stress