Effects of repeated long duration +2Gz load on man's cardiovascular function

Usefulness of a short-arm human centrifuge is expected when it is used in space as a countermeasure against cardiovascular deconditioning, problem of bone-calcium metabolism, etc. However, nothing is solidly established regarding the most desirable program for artificial G application. Accordingly, this study was designed to analytically evaluate the effects of repeated long duration +Gz load on human cardiovascular function. Recently heart rate spectral analysis has been recognized as a powerful tool for quantitatively evaluating parasympathetic and sympathetic activity separately in human. It is reported that power of the high frequency component (HF-p) is mediated selectively by parasympathetic activity and the power ratio of low to high frequency components(LF/HF) is indicative of cardiac sympathetic activity or cardiac sympathovagal balance. Sequence method is developed to examine spontaneous baroreceptor reflex sensitivity (BRS). We studied cardiovascular control function by using these methods in 9 healthy men before and after 7 days of daily repeated 1hour +2Gz load. When compared with the data of pre-G load period, post-G load period, decrease of HR, increases of HF-p and BRS were statistically significant. SBP, DBP and LF/HF tended to decrease, however, these changes were not statistically significant. This results indicate that repeated +2Gz load increases parasympathetic activity and arterial baroreceptor-cardiac reflex sensitivity. In recent years, many investigators suggest that space flight and head-down bedrest leads to impaired baroreceptor-cardiac reflex responses and decrease of parasympathetic activity, which may contribute to orthostatic intolerance. So our results suggest that daily repeated 1hour +2Gz load would be useful in preventing post-flight orthostatic intolerance.     

Exercise response to simulated weightlessness

Two bed rest analog studies of space flight were performed; one 14 d and the other 28 d in duration. Exercise response was studied in detail during the 28 d study and following both the 14 d and 28 d studies. This paper relates the results of these studies to physiologic changes noted during and following space flight. The most consistent change noted after both bed rest and space flight is an elevated heart rate during exercise. A second consistent finding is a postflight or postbed rest reduction in cardiac stroke volume. Cardiac output changes were variable. The inability to simulate inflight activity levels and personal exercise makes a direct comparison between bed rest and the results from specific space flights difficult.     

Changes in mood status and neurotic levels during a 20-day bed rest

This study evaluated changes of mood status and depressive and neurotic levels in nine young male subjects during a 20-day 6 degrees head-down tilting bed rest and examined whether exercise training modified these changes. Participants were asked to complete psychometrical inventories on before, during, and after the bed rest experiment. Depressive and neurotic levels were enhanced during bed rest period according to the Japanese version of Zung's Self-rating Depression Scale and the Japanese version of the General Health Questionnaire. Mood state "vigor" was impaired and "confusion" was increased during bed rest and recumbent control periods compared to pre-bed rest and ambulatory control periods according to the Japanese version of Profiles of Mood State, whereas the mood "tension-anxiety", "depression-dejection", "anger-hostility" and "fatigue" were relatively stable during experiment. Isometric exercise training did not modify these results. Microgravity, along with confinement to bed and isolation from familiar environments, induced impairment of mental status.     

Comparison of gradual and rapid onset runs in a short-arm centrifugation

A gradual onset run (GOR) in a short-arm centrifugation was performed on ten healthy students. The centrifuge had a 1.8 m radius, and the subjects sat on a chair in a cabin. The Gz force increased to 2.2 Gz at 0.1 °/sec² for 32 min. and the same Gz-level was maintained for 20 min. Three out of ten subjects completed the whole protocol; the load on the others was terminated because of symptoms or increased heart rate. There were few symptoms such as vertigo, that was a common problem with a rapid onset run (ROR) in former experiments, due to the short-arm centrifugation. The changes of the flicker test after the load were much less in the GOR protocol than in the ROR protocol, even in the terminated group. GOR seemed preferable to ROR in preventing vertigo even though it took longer to reach the necessary G load.     

Effectiveness of centrifuge-induced artificial gravity with ergometric exercise as a countermeasure during simulated microgravity exposure in humans

To test the effectiveness of centrifuge-induced artificial gravity with ergometric exercise, 12 healthy young men (20.7 +/- 1.9 yr) were exposed to simulated microgravity for 14 days of -6 degrees head-down bedrest. Half the subjects were randomly selected and loaded 1.2 G artificial gravity with 60 W (four out of six subjects) or 40 W (two out of six subjects) of ergometric workload on days 1, 2, 3, 5, 7, 9, 11, 12, 13, 14 (CM group). The rest of the subjects served as the control. Anti-G score, defined as the G-load x running time to the endpoint, was significantly elongated by the load of the centrifuge-ergometer. Plasma volume loss was suppressed (-5.0 +/- 2.4 vs. -16.4 +/- 1.9%), and fluid volume shift was prevented by the countermeasure load. Elevated heart rate and muscle sympathetic nerve activity after bedrest were counteracted, and exaggerated response to head-up tilt was also suppressed. Centrifuge-induced artificial gravity with exercise is effective in preventing cardiovascular deconditioning due to microgravity exposure, however, an effective and appropriate regimen (magnitude of G-load and exercise workload) should be determined in future studies.     

Biochemical and hormonal changes in endurance trained volunteers during and after exposure to bed rest and chronic hyperhydration.

The objective of this investigation was to assess the effect of a daily intake of fluid and salt supplementation on biochemical and hormonal changes in endurance trained volunteers aged 19-24 yrs during 30-day bed rest and during 15 days of post bed rest period. The studies were performed on 30 long distance runners aged 19-24 yrs who had a peak oxygen uptake of 66 ml/kg/min and had taken 14.5 km/day on average prior to their participation in the study. The volunteers were divided into three groups: the volunteers in the first group were under normal ambulatory conditions (control subjects); the second group subjected to bed rest alone unsupplemented (bed rested volunteers); the third group was submitted to bed rest and consumed daily 30 ml water/kg bodyweight and 0.1 g of sodium chloride (NaCl)/kg body weight (supplemented bed rested volunteers). The second and third groups of volunteers were kept under a rigorous bed rest regime for 30 days. During the pre bed rest period of 15 days, during the bed rest period of 30 days and during the post bed rest period of 15 days cyclic adenosine monophosphate, cyclic guanosine monophosphate, prostaglandins of pressor, prostaglandins depressor groups, renin activity in plasma and aldosterone in plasma and in urine were determined. We found that in bed rested volunteers without fluid and salt supplementation intake plasma renin activity and aldosterone in plasma and urine continued to increase during the bed rest period as plasma volume decreased. Moreover, in this group, cyclic nucleotides measured as an indicator of adrenosympathetic system activity increased and prostaglandins as local vasoactive substances decreased during the bed rest period. These variables returned toward the baselines in the post bed rest period as plasma volume deficit was restituted. On the other hand, the hormonal levels in the other two groups remained rather constant during the experimental period. We concluded that daily intake of fluid and salt supplementation may minimize the biochemical and hormonal changes in endurance trained volunteers dorm their exposure to bed rest conditions.     

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.     

Lower body negative pressure (LBNP) as a countermeasure for long term spaceflight

The article presents the current status of lower body negative pressure (LBNP) as a countermeasure for preventing orthostatic intolerance after space flight or bed rest. Devices discussed include the Chibis vacuum suit, the Anthrorack device, a collapsible device, and an inflatable device. Two bed rest studies examined the effect of LBNP and exercise on orthostatic tolerance; plasma volume; vasopressin, plasma renin activity, and catecholamines; and side effects.     

CCISS,Vascular and BP Reg: Canadian space life science research on ISS

A comprehensive goal of the Canadian Space Agency studies (CCISS, Vascular and BP Reg) has been to investigate the efficacy of current exercise countermeasures to maintain cardiovascular and cerebrovascular health on return to Earth after up to 6-months in space. Results from the CCISS experiments revealed no significant change of in-flight heart rate during daily activities or sleep, and small, but variable between astronauts, post-flight elevation. The between astronaut differences were exaggerated during measurement of spontaneous baroreflex slope, which was reduced post-flight (P<0.05) during paced breathing with 3 astronauts having significant correlations between reduced baroreflex and reduced RR-interval (consistent with reduced fitness). Cerebrovascular autoregulation and CO₂ response were mildly impaired after flight. Some loss of in-flight fitness of astronauts in Vascular was reflected by the increase in HR at a work rate of 161±46 W of 12.3±10.5 bpm, 10.4±5.9 bpm and 13.4±5.7 bpm for early-flight, late-flight and R+1, respectively. On return to gravity, changes in resting heart rate for supine (5.9±3.5 bpm), sit (8.1±3.3 bpm) and stand (10.3±10.0 bpm) were small but variable between individuals (from −5 bpm to +20 bpm in post-flight standing) and not related to the change in exercise heart rate. In Vascular astronauts, pulse wave transit time measured to the finger tended to be reduced post-flight and carotid artery distensibility was significantly reduced (P=0.03, and n=6). The heart rate and baroreflex data suggest that some astronauts return with cardiovascular deconditioning in spite of the exercise regimes. However, greater arterial stiffness is common among all astronauts studied to date. The new CSA project, BP Reg, will monitor inflight blood pressure in an attempt to identify astronauts in greater need for countermeasures. Future research should focus on whether Vascular changes in astronauts might make them an appropriate model to study the mechanisms of arterial aging on Earth.     

Physiological effects of acute and ordinary bed rest conditions on endurance trained volunteers.

The aim of this study was to carry out a comparative study of water balance and water protein composition of the blood during exposure to acute (abrupt restriction of motor activity) and ordinary rigorous bed rest of 7 days. The studies were performed on 30 long distance runners aged 22-25 years old who had a VO2, max of 66 ml kg-1 min-1 on the average. The volunteers were divided into three equal groups: the volunteers in the 1st group were under a normal ambulatory life conditions (control subjects), the volunteers of the 2nd group subjected to an acute bed rest (abrupt restriction of motor activity) regime (acute bed rested subjects) and the volunteers of the 3rd group were submitted to ordinary and rigorous bed rest (rigorous bed rested subjects). All volunteers were on an average of 13.8 km day before taking part in this investigation. The 2nd and 3rd groups of volunteers were kept under a rigorous bed rest regime for 7 days. During the prebed rest period and actual bed rest period plasma volume (PV), total protein and protein fractions (albumins and globulins) and hematocrit were measured. Exposure to acute bed rest conditions induced a significant increase in hematocrit, hemoglobin concentration, protein fractions and marked decrease in (PV) and water balance which were significantly more pronounced than during exposure to ordinary rigorous bed rest. It was concluded that exposure to acute bed rest conditions induces significantly greater changes in water balance and water protein concentration of the blood of endurance trained volunteers than exposure to ordinary rigorous bed rest conditions.     

Cardiorespiratory responses to exercise after bed rest in men and women

The purpose of this study was to compare cardiorespiratory responses of men and women to submaximal and maximal workloads before and after bed rest (BR). Fifteen male college students (19-23 yr) and 8 female nurses (23-34 yr) underwent 14 d and 17 d, respectively of bed rest. The maximal work capacity test was performed in the supine position on a bicycle ergometer just before and immediately after bed rest. The women's maximal O2 uptake (maximal VO2) was 41% lower (P<0.05) than the men's before bed rest and 42% lower (P<0.05) after bed rest. During bed rest the women's maximal VO2 decreased from 2.06 to 1.86 liter/min (-9.7%, P<0.05), and that of the men decreased from 3.52 to 3.20 liter/min (-9.1%, P<0.05). Compared with pre-BR values, after bed rest the maximal ventilatory volume was essentially unchanged in the men (+1.8%) and women (+ 2.3%), but maximal heart rate was elevated from 185 to 193 b/min (+ 4.3%, P<0.05) in the men and from 181 to 187 b/min (3.3%, P<0.05) in the women. Submaximal VO2 was unchanged after bed rest in the men but was significantly reduced in the women; the women's Hct and RBC levels were lower (P<0.05) than comparable male data. Mean corpuscular volume was unchanged in both groups pre- and post-bed rest. It is concluded that the proportional deterioration in maximal VO2 following prolonged bed rest was essentially the same in young men and women.     

Evaluation of spontaneous baroreflex response after 28 days head down tilt bedrest

The spontaneous baroreflex response was evaluated during supine rest and head up tilt (60 degrees) before and immediately after a 28 day 6 degrees HDT bedrest in 6 healthy adult men (age 30-42 years). Sequences of 3 or more beats where RR-interval and systolic blood pressure changed in the same direction were used to evaluate baroreflex response slope (BRS). Prior to bedrest, the mean BRS and RR-interval were 18.0 +/- 3.9 ms/mm Hg and 926 +/- 61 ms at rest and 10.5 +/- 2.5 ms/mm Hg and 772 +/- 63 ms during the first 10 min of 60 degrees tilt. Following bedrest, these values changed to 15.6 +/- 2.7 ms/mm Hg and 780 +/- 53 ms at rest, and to 6.5 +/- 1.2 ms/mm Hg and 636 +/- 44 ms during tilt. Thus, (1) the spontaneous baroreflex can be evaluated in human subjects during experiments of orthostatic stress; (2) the baroreflex slope was reduced on going from supine to the head up tilt position; and (3) 28 days of bedrest reduced the spontaneous baroreflex slope.     

Cardiac and vascular adaptation to 0g with and without thigh cuffs (Antares 14 and Altair 21 day Mir spaceflights)

Cardiovascular Actaptation was evaluated on 2 astronauts: one wearing thigh cuffs from flight day 1 to 8 (14d flight), the second without cuffs (21d flight). Ultrasound investigations were performed at rest and during LBNP. Results: Without thigh cuffs the cardiovascular Actaptation consists in (1) the development of a hypovolemia with an increase of the heart rate and the cardiac output, (2) the decrease of the vascular tone in the deep (mesenteric and splanchnic) and peripheral (Lower limbs) vascular areas. The use of thigh cuffs maintains the volemia and the cardiac output at the preflight level (without heart rate increase) and prevents the loss of vascular tone in the deep and peripheral areas. Moreover the adaptative process changes since the cuffs are removed and even the volemia seems to be unaffected at this stage the vascular tone decreases to a comparable extend as during the flight without cuffs. Nevertheless during the flight without cuffs or 3 days after removing the cuffs hemodynamic signs of decreased orthostatic tolerance are present during the inflight and the 3 days post flight LBNP. Presently the possible contribution of the thigh cuffs to the reduction of the vascular deconditioning has not been tested yet.     

Plasma volume and biochemical changes in athletes during bed rest chronic hyperhydration

Daily fluid and salt supplements (FSS) may be used to reduce plasma biochemical changes during bed rest (BR). The aim of this study was to evaluate the effect of a daily intake of FSS on plasma volume (PV) and biochemical changes during BR. Studies were done during a pre BR period of 15 days and during a BR period of 30 days. Thirty male athletes aged 22-26 years were chosen as subjects. They were divided into three groups: unsupplemented ambulatory control subjects (UACS), unsupplemented bed rested subjects (UBRS) and supplemented bed rested subjects (SBRS). The UBRS and SBRS were kept under a rigorous bed rest regime for 30 days. The SBRS took 26 ml water/kg body weight and 0.1 g sodium chloride/kg body weight daily. PV, protein, albumin, sodium (Na), Chloride (Cl), potassium (K), osmolality, creatinine, glucose, and whole blood haematocrit (Hct) and haemoglobin (Hb) concentrations were measured. PV increased significantly (P < or = 0.01) while plasma protein, albumin. Na, Cl, K, glucose, creatinine, osmolality, and whole blood Hb and Hct concentration decreased significantly (P < or = 0.01) in the SBRS group when compared with the UBRS group. By contrast, PV decreased significantly (P < or = 0.01), while plasma protein, albumin, Na, Cl, K, glucose, creatinine, osmolality and whole blood Hct and Hb concentration increased significantly (P < or = 0.01) in the UBRS group when compared with the SBRS and UACS groups. The measured parameters did not change significantly in the UACS group when compared with the baseline control values. It was concluded that a daily intake of FSS may be used to attenuate PV losses and biochemical changes in endurance trained athletes during bed rest.     

Ion regulatory function of the human kidney in prolonged space flights.

Ten cosmonauts, who performed 30-175-day space flights aboard Salyut-4 and Salyut-6, and over 60 test subjects who were exposed to bed rest of up to 182 days and immersion of up to 56 days, were examined. The renal excretion of potassium and calcium increased, reaching a maximum by the 4-6th weeks in prolonged space flights and simulation studies. During the load tests with potassium and calcium salt, excretion postflight was much higher than preflight. During potassium chloride load tests a positive correlation between the blood content of aldosterone and potassium excretion existed, whereas during calcium lactate load tests an increased calcium excretion was accompanied by a decrease in blood parathyroid hormone concentration. The most probable cause of the negative ion balance in weightlessness is the reduced capacity of tissues to retain electrolytes due to the decreased ion pool capacity. Different exercises have been shown to exert a beneficial effect on electrolyte metabolism.     

Fluid and salt supplementation effect on body hydration and electrolyte homeostasis during bed rest and ambulation

Bed rest (BR) induces significant urinary and blood electrolyte changes, but little is known about the effect of fluid and salt supplements (FSS) on catabolism, hydration and electrolytes. The aim was to measure the effect of FSS on catabolism, body hydration and electrolytes during BR.

Studies were done during 7 days of a pre-bed rest period and during 30 days of a rigorous bed rest period. Thirty male athletes aged, 24.6±7.6 years were chosen as subjects. They were divided into three groups: unsupplemented ambulatory control subjects (UACS), unsupplemented bed rested subjects (UBRS) and supplemented bed rested subjects (SBRS). The UBRS and SBRS groups were kept under a rigorous bed rest regime for 30 days. The SBRS daily took 30 ml water per kg body weight and 0.1 sodium chloride per kg body weight.

Plasma sodium (Na), potassium (K), calcium (Ca) and magnesium (Mg) levels, urinary Na, K, Ca and Mg excretion, plasma osmolality, plasma protein level, whole blood hemoglobin (Hb) and hematocrit (Hct) level increased significantly (p≤0.05), while plasma volume (PV), body weight, body fat, peak oxygen uptake, food and fluid intake decreased significantly (p≤0.05) in the UBRS group when compared with the SBRS and UACS groups. In contrast, plasma and urinary electrolytes, osmolality, protein level, whole blood Hct and Hb level decreased significantly (p≤0.05), while PV, fluid intake, body weight and peak oxygen uptake increased significantly (p≤0.05) in the SBRS group when compared with the UBRS group. The measured parameters did not change significantly in the UACS group when compared with their baseline control values.

The data indicate that FSS stabilizes electrolytes and body hydration during BR, while BR alone induces significant changes in electrolytes and body hydration. We conclude that FSS may be used to prevent catabolism and normalize body hydration status and electrolyte values during BR.     

The NASA Performance Assessment Workstation: cognitive performance during head-down bed rest

The NASA Performance Assessment Workstation was used to assess cognitive performance changes in eight males subjected to seventeen days of 6 degrees head-down bed rest. PAWS uses six performance tasks to assess directed and divided attention, spatial, mathematical, and memory skills, and tracking ability. Subjective scales assess overall fatigue and mood state. Subjects completed training trials, practice trials, bed rest trials, and recovery trials. The last eight practice trials and all bed rest trials were performed with subjects lying face-down on a gurney. In general, there was no apparent cumulative effect of bed rest. Following a short period of performance stabilization, a slight but steady trend of performance improvement was observed across all trials. For most tasks, this trend of performance improvement was enhanced during recovery. No statistically significant differences in performance were observed when comparing bed rest with the control period. Additionally, fatigue scores showed little change across all periods.     

Biochemical and hemodynamic changes in normal subjects during acute and rigorous bed rest and ambulation

Rigorous bed rest (RBR) induces significant biochemical and circulatory changes. However, little is known about acute rigorous bed rest (ARBR). Measuring biochemical and circulatory variables during ARBR and RBR the aim of this study was to establish the significance of ARBR effect. Studies were done during 3 days of a pre-bed rest (BR) period and during 7 days of ARBR and RBR period. Thirty normal male individuals aged, 24.1 +/- 6.3 years were chosen as subjects. They were divided equally into three groups: 10 subjects placed under active control conditions served as unrestricted ambulatory control subjects (UACS), 10 subjects submitted to an acute rigorous bed rest served as acute rigorous bed rested subjects (ARBRS) and 10 subjects submitted to a rigorous bed rest served as rigorous bed rested subjects (RBRS). The UACS were maintained under an average running distance of 9.7 km day-1. For the ARBR effect simulation, ARBRS were submitted abruptly to BR for 7 days. They did not have any prior knowledge of the exact date and time when they would be asked to confine to RBR. For the RBR effect simulation, RBRS were subjected to BR for 7 days on a predetermined date and time known to them right away from the start of the study. Plasma renin activity (PRA), plasma cortisol (PC), plasma aldosterone (PA), plasma and urinary sodium (Na) and potassium (K) levels, heart rate (HR), cardiac output (CO), and arterial blood pressure (ABP) increased significantly, and urinary aldosterone (UA), stroke volume (SV) and plasma volume (PV) decreased significantly (p<0.05) in ARBRS and RBRS as compared with their pre-BR values and the values in UACS. Electrolyte, hormonal and hemodynamic responses were significantly (p<0.05) greater and occurred significantly faster (p<0.05) during ARBR than RBR. Parameters change insignificantly (p>0.05) in UACS compared with pre-BR control values. It was concluded that, the more abruptly muscular activity is restricted in experimental subjects while they are very active, the greater hemodynamic and biochemical change there is and probably in individuals whose muscular activity is abruptly terminated after an accident or sudden illness.     

Hemodynamic and neurohormonal responses to extreme orthostatic stress in physically fit young adults

Blood pressure stability may be jeopardized in astronauts experiencing orthostatic stress. There is disagreement about cardiovascular and endocrine stress responses that emerge when a critical (presyncopal) state is reached. We studied hemodynamic and neurohormonal changes as induced by an orthostatic stress paradigm (head-up tilt combined with lower body negative pressure) that leads to a syncopal endpoint. From supine control to presyncope, heart rate increased by 78% and thoracic impedance by 12%. There was a 49% fall in stroke volume index, 19% in mean arterial blood pressure, 14% in total peripheral resistance index and 11% in plasma volume. Plasma norepinephrine rose by 107, epinephrine by 491, plasma renin activity by 167, and cortisol by 25%. Hemodynamic and hormonal changes of clearly different magnitude emerge in presyncope as compared to supine rest. Additional studies are warranted to reveal the exact time course of orthostatic changes up to syncopal levels.