Individual stability of orthostatic tolerance response.

We studied individual stability of orthostatic tolerance as well as presyncopal signs and symptoms across four runs in subjects undergoing combined head-up tilt (HUT) and lower body negative pressure (LBNP). Ten healthy young males were subjected to HUT+ LBNP, to achieve a presyncopal end-point. Four test runs were separated by two week intervals. Hemodynamic variables and orthostatic tolerance were measured. From supine control to presyncope, heart rate increased while mean arterial blood pressure and stroke index decreased significantly. Individual orthostatic tolerance ranged from 7.2 to 30.0 min. Repetitions from the 1st to the 4th trial increased orthostatic tolerance by about 3 min, from 15+/-6 (trial 1) to 18+/-7 min (trial 4) but not significantly (p>0.05). Additionally, specific signs and symptoms as subjects approached presyncope were not always identical in the same persons. While considerable difference existed in tolerance times between healthy young men, orthostatic tolerance within subjects was similar, with little individual variability. However, as the reasons for termination of the tests were not always identical in the same subjects, and many subjects showed presyncopal symptoms rather than signs, close attention must be given to monitoring not only the signs but also the symptoms in subjects reaching presyncope.

Postural changes associated with public speech tests lead to mild and selective activation of stress hormone release.

We tested whether simulation of postural changes, which occur during public speech test procedures, activates cardiovascular system and stress hormone release that could interfere with the effect of psychosocial stress load. Young healthy male volunteers (n=8) underwent procedure imitating exactly all postural changes present in the psychosocial stress model based on public speech used in this laboratory (namely changes from sitting to standing and repeated sitting). Postural changes were associated with increases in heart rate, blood pressure, plasma concentrations of noradrenaline and aldosterone and elevation in plasma renin activity. In contrast to cardiovascular parameters, adrenocorticotropic hormone, cortisol and adrenaline, the main characteristics of hormonal response during mental stress, were not significantly influenced. The overall magnitude of all observed alterations was much smaller than that seen following mental stress procedures in our previous studies. This study provides evidence that changes in body posture during public speech test procedure influence hemodynamics and endocrine responses in a mild manner. Though this influence may represent a source of unspecific variance, substantial confounding effects on responses to the psychosocial component of the procedure are unlikely. In any case, models combining mental stressors and changes in body posture must be interpreted as complex stress stimuli.

Renal adrenomedullin and high altitude diuresis.

Previous investigations revealed that most of the fluid regulating hormones showed no consistent relationship to the hypoxic diuretic response (HDR). In this study we examined if adrenomedullin (AM), a hypoxia-mediated diuretic/natriuretic peptide is connected to HDR. Thirty-three persons were examined at low altitude (LA), on the third exposure day at 3440 m (medium altitude, MA) and on the fourteenth day at 5050 m (high altitude, HA). Nocturnal diuresis rose from 460 ml [interquartile range 302 ml] at LA to 560 [660] ml at MA to 1015 [750] ml at HA (p<0.005). Sodium excretion was similar at LA and MA (41.8 [27.0] vs. 41.4 [28.4] mM) and increased to 80.2 [29.1] mM at HA (p<0.005). Urinary AM excretion was 7.9 [3.9] at LA, 7.5 [5.7] pM at MA, and increased to 10.5 [5.1] pM (p<0.05) at HA. Urinary AM excretion was correlated to diuresis (r=0.72, p<0.005) and sodium excretion (r=0.57, p<0.005). Plasma AM concentration rose from 16.4 [3.1] to 18.8 [4.9] pM/l at MA (p<0.005) and to 18.3 [4.3] pM/l at HA (p<0.005). Plasma AM concentration and urinary AM excretion were not correlated, neither were plasma AM concentration and diuresis or natriuresis. Our data suggest the involvement of increased renal AM production in the pathophysiology of high altitude fluid and sodium loss.

Post-exercise decrease of plasma hyaluronan: increased clearance or diminished production?

The exercise-induced increase and post-exercise decrease of plasma hyaluronan concentration were studied in human subjects. Six well trained men performed incremental exercise until exhaustion (MAX), intensive (submaximal, SUB) and extensive exercise (moderate, MOD) on a bicycle ergometer, defined as work at 100, 77 and 50% of maximal oxygen consumption. Hyaluronan was analyzed using a high-sensitivity, proteoglycan-dependent time-resolved immunoassay and hemoglobin, hematocrit and plasma protein levels were assessed using standard laboratory procedures. Compared to resting control levels, the plasma hyaluronan concentration (pHA) increased (p < 0.05) by 76% (65.0 +/- 6.1 vs. 37.0 +/- 1.0 microg/l) during 15 min MAX, by 44% (56.4 +/- 2.6 vs. 39.2 +/- 3.8 microg/l) during 30 min SUB and by 27% (46.3 +/- 7.8 vs. 36.4 +/- 4.3 microg/l) during 90 min MOD. The increase with time averaged 4.03%.min(-1) during MAX, 1.35%.min(-1) during SUB and 0.35%.min during MOD. After exercise (15 and 30 min), pHA decreased by 43% below resting levels after MAX (p < 0.05) and by 36% after SUB, respectively. In conclusion, pHA steadily rose with time during physical exertion, with a non-linear increase of concentration/time slope with exercise intensity; second, the magnitude of the post-exercise pHA decrease was proportional to the exercise-induced pHA increase, suggesting elevated hyaluronan clearance with rising plasma levels after physical exertion.

Cardiovascular and hormonal changes with different angles of head-up tilt in men.

The purpose of this study was to assess the endocrine status, thoracic impedance, blood concentration, and hemodynamic dose-responses using different angles of passive head-up tilt (HUT) ranging from 12 degrees to 70 degrees in the same subjects. Measurements were performed during 20 min supine position (pre-HUT), 30 min upright (HUT12, HUT30, HUT53, or HUT70), and 20 min supine (post-HUT); subjects 70 min in the supine position only (HUT0) served as resting controls. Norepinephrine increased above resting control values by 19, 44, 80, and 102%; epinephrine by 30, 41, 64, and 68%; aldosterone by 29, 62, 139, and 165%; plasma renin activity n. s., 41, 91, and 89%; vasopressin n.s., 27, 47, and 59%; thoracic bioimpedance n. s., 8, 13, and 16%; heart rate n. s., 5, 26, and 45%, and mean arterial pressure n. s., 5, 7, and 10%; at min 27 of HUT12, HUT30, HUT53, and HUT70, respectively. Pulse pressure decreased with HUT53 and HUT70 by 4 and 10%. Hematocrit increased by 0.2, 1.7, 6.3, and 7.2%, respectively. Blood density increased by 2.3 and 3.0 g/l, plasma density by 1.7 and 1.8 g/l with HUT53 and HUT70. After finishing HUT, heart rate fell to values which stayed below pre-HUT, and also below resting control levels for > or = 5 min ("post-orthostatic bradycardia") even after the lowest orthostatic load (HUT12). Thoracic impedance and arterial pressure remained increased after terminating HUT30, HUT53, and HUT70. In conclusion, passive orthostatic loading of different extent produces specific dose-responses of different magnitude in the endocrine system, blood composition, thoracic impedance, and hemodynamic variables. The heart rate is depressed even after HUT12, while arterial blood pressure and thoracic impedance exceed pre-stimulus levels after greater head-up tilt, indicating altered cardiovascular response after passive orthostasis.

Permanent depression of plasma cGMP during long-term space flight.

The purpose of this study was to investigate plasma concentrations of cyclic guanosine monophosphate (cGMP) and atrial natriuretic peptide (ANP) during and after real and simulated space flight. Venous blood was obtained 3 min after the beginning and 2 min after the lower body negative pressure maneuver in two cosmonauts preflight (supine), inflight, and postflight (supine) and in five other subjects before, at the end, and 4 days after a 5-day head-down tilt (-6 degrees) bed rest. In cosmonaut 1 (10 days in space), plasma cGMP fell from preflight 4.3 to 1.4 nM on flight day 6, and was 3.0 nM on the fourth day after landing. In cosmonaut 2 (438 days in space), it fell from preflight 4.9 to 0.5 nM on on flight day 3, and stayed <0.1 nM with 5, 9, and 14 months in space, as well as on the fourth day after landing. Three months after the flight his plasma cGMP was back to normal (6.3 nM). Cosmonaut 2 also displayed relatively low inflight ANP values but returned to preflight level immediately after landing. In a ground-based simulation on five other persons, supine plasma cGMP was reduced by an average of 30% within 5 days of 6 degrees head-down tilt bed rest. The data consistently demonstrate lowered plasma cGMP with real and simulated weightlessness, and a complete disappearance of cGMP from plasma during, and shortly after long-duration space flight.

Cardiovascular and humoral readjustment after different levels of head-up tilt in humans.

PURPOSE: To get a more complete picture of cardiovascular regulation after postural changes, this investigation directly monitored volume-related, hemodynamic, and endocrine variables during and after 30 min of passive head-up tilt (HUT) of various degrees. It was hypothesized that the return of variables to pre-tilt control level is of system-specific duration and different from what is found after lower body negative pressure (LBNP). DESIGN: We tested 7 persons on 5 different days using, in random order, no (HUT0) or different intensity (12 degrees , 30 degrees , 53 degrees , and 70 degrees ) of passive orthostasis (HUT12, HUT30, HUT53, HUT70). Data were collected before (supine), during, and after (supine) HUT and compared with synchronous data from HUT0. RESULTS: There was graded alteration with the sine of tilt angle for all hormones and directly volume-related variables. The effects of HUT70 were of the same magnitude as previously documented by others. After HUT, hemodynamic variables and catecholamines returned to control levels most rapidly. Heart rate depression, as observed in a companion LBNP study in the same subjects, did not occur. Vasopressin, PRA, plasma volume and Z0 returned to nominal values more slowly. Plasma aldosterone was still elevated 50 min after reassuming supine posture. CONCLUSION: Besides specific dose-responses within hemodynamic, volume-dependent, and hormonal variables after orthostatic loading of different degree, the return to control levels after HUT occurs with distinctly different time-courses, which are not identical with those seen after LBNP-simulated orthostasis.

Orthostatic stimuli rapidly change plasma adrenomedullin in humans.

The aim of this study was to evaluate the effect of orthostasis on the time course of plasma adrenomedullin concentration. On 5 different days, normotensive subjects were randomized to undergo for 30 minutes either 12 degrees, 30 degrees, 53 degrees, or 70 degrees passive head-up tilt or to remain supine. Venous blood was collected from each subject in the supine position before tilting, at 3 and 27 minutes during tilting, and at 2 and 50 minutes after orthostasis. Plasma adrenomedullin increased significantly with tilt of >/=30 degrees in a stimulus-dependent manner. Approximately half of the increase seen at 27 minutes occurred during the first 2 minutes of upright positioning; the maximum effect with 70 degrees tilt was +70%. Elevations in norepinephrine, epinephrine, aldosterone, plasma renin activity, vasopressin, heart rate, and mean arterial pressure were also significant. Hematocrit, blood density, plasma density, and plasma volume loss rose (P<0.05) at 53 degrees and 70 degrees tilt. Our results indicate that adrenomedullin may play an important role in stabilization of hemodynamics during passive orthostasis. In conclusion, plasma adrenomedullin rapidly increases with orthostatic challenge in a stimulus-dependent manner and also swiftly returns to baseline levels after the subject resumes the supine position.

Endocrine status and LBNP-induced hormone changes during a 438-day spaceflight: a case study.

We investigated basal levels and lower body negative pressure (LBNP)-induced changes of volume regulating (PRA, aldosterone, AVP, ANP99-126) and other stress-sensitive hormones (catecholamines, cortisol, ACTH) in venous plasma from one cosmonaut before (-45 d), during (3, 170, 287, 430 d) and after (+4, +90 d) a record-breaking long-term (438 d) spaceflight. Blood was taken at the beginning and immediately after ending LBNP (-15/-30/-35 mm Hg for 15/15/10 min, respectively) preflight supine, inflight, and postflight supine. PRA, aldosterone, and vasopressin levels stayed within normal boundaries during the entire flight and after landing. Catecholamines exceeded reference limits (epinephrine > 140 pg x ml(-1), norepinephrine >1000 pg x ml(-1) 5 and 9 mo inflight, and 4 d postflight. ANP and cGMP were lower inflight (p<0.04) than pre- or postflight. Cortisol and ACTH were not consistently altered. LBNP-induced hormonal changes were not different (p>0.05) in microgravity and 1-G. Based on data from one cosmonaut, we conclude that long-term spaceflight up to 430 d duration appeared to lower plasma ANP and cGMP during flight and occasionally elevate catecholamine levels, without significantly altering LBNP-induced relative hormone changes as compared with those observed on the ground.

Plasma hyaluronan concentration: no circadian rhythm but large effect of food intake in humans.

This study was designed to determine if a circadian rhythm in plasma hyaluronan concentration [HA] exists in the absence of physical activity, and if plasma [HA] is associated with feeding in human subjects. Five persons were studied under standardized conditions, blood samples being taken between 0600 and 2200 hours at 30-min intervals. Any orthostatic challenge and muscle activity was abolished by immobilization by a 6 degrees head-down bed-rest, and the effect of a quasi-continuous ingestion of energy compared a normal, three-portion diet of equivalent energy content or to fasting. Reproducibility of HA profiles on two consecutive half-days was also studied. A highly sensitive immunoassay was used to determine plasma [HA]. The data indicated that without physical activity and without food ingestion, [HA] was unchanged and displayed no diurnal rhythm. In addition, we observed that [HA] increased after the first food intake, peaking after 60 min, and concluded from our results that without ingestion of a larger meal, and sessions of postural or muscle activity, no circadian plasma [HA] rhythm exists.

Cardiovascular changes during and after different LBNP levels in men.

BACKGROUND: This study quantifies hemodynamic and thoracic impedance (TI) changes with four levels of lower body negative pressure (LBNP) from -15 to -65 mm Hg in seven healthy men in supine position 20 min before (pre-LBNP), 30 min during, and 20 min after suction (post-LBNP) as well as without suction (LBNP-0, rest control). RESULTS: LBNP > 15 mm Hg increased basic TI by up to 2.2 omega (+9.5%). TI-computed stroke volume index (SVI) continuously decreased with time up to -12%, -28%, -36%, and -40% at the end of LBNP-15, -35, -55, and -65. TI-computed cardiac index decreased most (-14%) at LBNP-15 and -35, resulting in a 19% increase of calculated total peripheral resistance index at those intensities. Mean arterial pressure (MAP) did not change in any systematic way with lower LBNP levels, but increased +4.7% and +7.4% at the end of LBNP-55 and -65, respectively. Heart rate remained unchanged at LBNP-15, but continuously increased to reach +22%, +42%, and +55% at the end of LBNP-35, -55, and -65. After finishing LBNP, heart rate fell to values below both pre-LBNP and rest control for > or = 5 min (post-LBNP bradycardia). SVI transiently returned to, and MAP increased above, pre-LBNP levels after suction. CONCLUSION: In conclusion, different levels of lower body subatmospheric pressure produced quantitatively different time course and dose-response patterns and remained non-hypotensive up to -65 mm Hg suction. Further, heart rate was depressed after LBNP, while arterial BP and TI-computed total peripheral resistance exceeded pre-stimulus levels, indicating an altered cardiovascular state after 30 min of simulated orthostasis.

Head-up tilt and lower body suction: comparison of hormone responses in healthy men.

The purpose of this study was to compare, in the same subjects, hormonal responses to 30-min head-up tilt (HUT) and lower body suction (LBNP) of different intensity (24 degrees and 70 degrees, and 15 and 35 mm Hg, respectively). Basal pooled individual data from -10 min (n = 32) were within normal reference limits: norepinephrine (NE) averaged 318 +/- 23 pg/ml; epinephrine, 34.0 +/- 5.5 pg/ml; plasma renin activity (PRA), 0.72 +/- 0.08 ng ATII/ml/h; aldosterone, 164 +/- 20 pg/ml; atrial natriuretic peptide (ANP), 29.9 +/- 2.0 pg/ml; cGMP, 6.29 +/- 0.59 mmol/l; cortisol, 95.7 +/- 5.8 ng/ml; and ACTH, 50.3 +/- 2.6 pg/ml. The low-level stimuli failed to induce consistent changes in hormone levels. From the onset of the stimulus (minute 0) to its termination (minute 30), norepinephrine (NE) increased by 101% with LBNP-35, and by 70% with HUT70, respectively. The NE increase with LBNP-35 was higher (p < 0.05) than with HUT70. Epinephrine rose with HUT70 (by 162%) only. PRA increased by 157% with LBNP-35, and by 119% with HUT70, respectively; these responses were not significantly different. Aldosterone rose equally (by 85 and 89%) with LBNP-35 and HUT70 but not with the low-level stimuli. No consistent changes were observed in ANP, c-GMP or ACTH concentrations. Cortisol values fell during the LBNP and HUT24 situations but rose transiently after HUT70. We conclude that the hormones investigated respond differently to head-up posture and lower body suction and in a specific manner. Greater effects of high-level stimuli (HUT70, LBNP-35) were noted as compared to low-level stimuli (HUT24, LBNP-15). The application of combined sets of models stimulating the cardiovascular system may aid in the analysis of responses of hormonal systems in man.

Plasma volume with alternative tilting: effect of fluid ingestion.

The present study determines the effect of repeated 70 degrees head-up tilt (HUT) on plasma volume (PV) shifts by measuring blood density (BD), plasma density (PD), and hematocrit (Hct). Eight men (18-26 yr) underwent a predrink period with two supine (P1 and P3) and two HUT (P2 and P4) phases of 45 min each. At the end of P4 they drank 10 ml/kg body wt of isotonic (290 mosmol/kg) sodium chloride (Iso) or hypotonic (< 10 mosmol/kg) unsweetened tea (Hypo) or nothing [control (Con)]. The following periods continued the supine (P5, P7)/upright (P6) sequence. BD and PD were measured from ear lobe blood; they were different (P < 0.05) between Con, Hypo, and Iso P6 and P7. The density of fluid that moved between intra- and extravascular compartments was 1,008.2 +/- 0.4 g/l and did not differ with test situations. In Con (P3, P5, P7), supine PV steadily decreased compared with P1 (P < 0.05). PV in P1, P2, and P3 of all treatments averaged 120 +/- 1, 101 +/- 1, and 115 +/- 1%, respectively, of PV in P4. Tilt-induced PV shifts ranged from -9.7 to -16.7% compared with PV during the respective previous phases. After drinking, PV increased (P < 0.05) above Con values at the end of P7 by 12.9% with Iso and by 6.6% with Hypo. Progressive hemoconcentration occurred in the nondrink supine periods; isotonic saline ingestion increased supine PV to Con level but did not stop or reverse the decrease of upright hemoconcentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Orthostasis and transcapillary fluid shifts.

Postural blood volume changes aggravate the regulation of arterial blood pressure and perfusion vis-a-vis the hydrostatic effects of orthostasis, ie, blood pooling below the hydrostatic indifferent points and reduced cardiac preload. Corresponding problems surface with extended passive standing, particularly in highly trained, dehydrated, or otherwise compromised subjects, or after long-lasting immobilization, as with space flight.

Is there "cardiovascular drift" during and after simulated orthostasis in humans?

This study investigates the time course of hemodynamic variables during and after simulated orthostasis (lower body suction at 55mmHg for 30 mins: LBNP-55). Individual strategies of blood pressure defense could be observed; LBNP-55 increased heart rate and reduced stroke volume, but was non-hypotensive. During 20 minutes post-LBNP, heart rate was decreased as well as stroke volume index below pre-LBNP values. The reduced cardiac index together with unchanged mean arterial pressure gave a highly significant increase of peripheral resistance after LBNP. The validity of stroke volume results under the experimental conditions given needs to be clarified.

Changes in blood and plasma composition with lower body negative pressure on the ground and in space in one subject.

In one cosmonaut, we investigated lower body negative pressure (LBNP)-induced capillary fluid shifts which we hypothesized would be changed by microgravity (micrograms) adaptation. Sound pulse velocity (SV) was determined in whole blood and plasma samples, using a new method that could detect 0.1% protein concentration changes. Experiments were performed 3 months preflight (supine), during space flight (6th day in orbit), and postflight (supine; 4th day after landing). Antecubital blood was taken at the beginning (3 min: time a) and after shut-down (+2 min: time b) of 40 min LBNP (-15/-30/-35 mm Hg for 15/15/10 min, respectively), since in control experiments with multiple sampling on Earth, the largest difference (increase) between blood and plasma SV was observed between a and b. Our cosmonaut had a 1.6 m/s increase in blood sound pulse velocity (BSV) preflight and a 4.0 m/s increase postflight, whereas BSV stayed unchanged in flight. Plasma sound pulse velocity (PSV) increased 1.2 m/s preflight and 1.7 m/s postflight, whereas PSV did not rise (-0.4 m/s) in flight. This would indicate profoundly altered LBNP-induced fluid dynamics in flight, compared to control (1-g) conditions. On the 4th day postflight, blood and plasma sound velocity increased more with LBNP than preflight, indicating greater hemoconcentration than under control conditions. In summary, the data suggest: 1) altered fluid shifts between blood and interstitial compartments during LBNP with 6 d adaptation to microgravity; and 2) increased hemoconcentration during LBNP early after a 10-d spaceflight.(ABSTRACT TRUNCATED AT 250 WORDS)

Hormonal changes with lower body negative pressure on the 6th day in microgravity in one cosmonaut.

We measured volume regulating and stress hormones (AVP, aldosterone, ANP, c-GMP, angiotensin II, PRA, epinephrine, norepinephrine, ACTH, cortisol) in venous blood twice during a lower body negative pressure (LBNP) maneuver in one cosmonaut (31 years, 75 kg, 180 cm) preflight (supine), inflight (6th d in orbit), and on the 4th d (supine) after a 10-d flight. Antecubital blood was taken at the beginning (3 min: "a") and after ceasing (2 min: "b") 40 min LBNP (-15/-30/-35 mm Hg for 15/15/10 min). At the beginning of LBNP, no big changes of resting hormone levels are to be expected. Comparison of "a" values: Inflight, there was a 4-5-fold increase in vasopressin and epinephrine, a slight increase in aldosterone, ANP, norepinephrine, cortisol and ACTH, and a decrease in PRA levels. Postflight, vasopressin was almost as much increased as inflight, and aldosterone and ANP levels were higher than pre- or inflight. PRA, epinephrine, norepinephrine, and cortisol were moderately increased, whereas ACTH and angiotensin II were diminished. Comparison of "b" to "a" values (2 min after LBNP to 3 min intra-LBNP): Preflight, ANP, PRA, and epinephrine rose more than 100%. The inflight response was higher for aldosterone but lower for all other volume active hormones. Postflight, the increase in PRA was pronounced, whereas little change occurred in other hormones. Cortisol and ACTH fell similarly during LBNP under all conditions. In summary, the data provide evidence that not only the endocrine status but also the neuroendocrine responsiveness to stimulation; i.e., the hormone response during cardiovascular load, are altered by the stay in microgravity and readaptation to normal conditions.