Blunted cutaneous vasoconstriction and increased frequency of presyncope during an orthostatic challenge under moderate heat stress in the morning

Purpose

In normothermia, the tolerance time to presyncope during an orthostatic challenge is shortened during the early morning. Heat stress reduces tolerance to presyncope and the degree of cutaneous vasoconstriction prior to presyncope. However, whether these changes show diurnal variations remains unknown. Therefore, we examined diurnal changes in orthostatic tolerance and cutaneous vascular conductance (CVC) during an orthostatic challenge under moderate heat stress.

Methods

Each lower body negative pressure (LBNP) under normothermia and whole body heat stress was applied for 7 min or until the appearance of presyncopal symptoms in 16 males at both 08:00 (a.m.) and 17:00 hours (p.m.). Measurements included internal and skin temperatures, forearm skin blood flow, arterial pressure, and heart rate. CVC was calculated as skin blood flow/mean arterial pressure, normalized to CVC prior to LBNP and expressed as %CVC.

Results

The average tolerance time in eight subjects exhibiting presyncopal symptoms due to LBNP and moderate heat stress was significantly shorter in the a.m. than in the p.m. (3.7 ± 0.8 versus 6.7 ± 0.3 min, respectively; P = 0.005). Neither %CVC during LBNP in these subjects under moderate heat stress nor normothermia were significantly decreased in the a.m. (P > 0.05, respectively).

Conclusions

These findings indicate an orthostatic challenge even during moderate heat stress that led to an increase in the frequency of presyncope, especially in the morning. The reduction in tolerance was accompanied by blunted cutaneous vasoconstriction prior to presyncope. Hence, diurnal changes in cutaneous vascular responses during combined orthostatic and heat stresses should contribute, at least partly, to heat-induced orthostatic intolerance in the morning.     

Modulation of the control of muscle sympathetic nerve activity during severe orthostatic stress

We tested the hypothesis that arterial baroreflex (ABR)-mediated beat-to-beat control over muscle sympathetic nerve activity (MSNA) is progressively modulated as orthostatic stress increases in humans, but that this control becomes impaired just before the onset of orthostatic syncope. In 17 healthy subjects, the ABR control over MSNA (burst incidence, burst strength and total MSNA) was evaluated by analysing the relationship between beat-to-beat spontaneous variations in diastolic blood pressure (DAP) and MSNA during supine rest (control) and during progressive, stepwise increases in lower body negative pressure (LBNP) that were incremented by −10 mmHg every 5 min until presyncope (nine subjects) or −60 mmHg was reached. (1) The linear relationships between DAP and burst strength and between DAP and total MSNA were shifted progressively upward as LBNP increased until the level at which syncope occurred. The relationship between DAP and burst incidence, however, gradually shifted upward from control only to LBNP =−30 mmHg; there was no further upward shift at higher LBNPs. (2) Although the slope of the relationship between DAP and burst strength and between DAP and total MSNA remained constant at all LBNPs tested, except at the level where syncope occurred, the slope of the relationship between DAP and burst incidence was reduced at LBNPs of −40 mmHg and higher ( versus control). (3) In syncopal subjects, the slopes of the relationships between DAP and burst incidence, burst strength, and total MSNA were all substantially reduced during the 1–2 min period prior to the onset of syncope. Taken together, these results suggest baroreflex control over MSNA is progressively modulated as orthostatic stress increases, so that its sensitivity is substantially reduced during the period immediately preceding the severe hypotension associated with orthostatic syncope.     

Acute volume expansion preserves orthostatic tolerance during whole-body heat stress in humans

Whole-body heat stress reduces orthostatic tolerance via a yet to be identified mechanism(s). The reduction in central blood volume that accompanies heat stress may contribute to this phenomenon. The purpose of this study was to test the hypothesis that acute volume expansion prior to the application of an orthostatic challenge attenuates heat stress-induced reductions in orthostatic tolerance. In seven normotensive subjects (age, 40 ± 10 years: mean ± s.d. ), orthostatic tolerance was assessed using graded lower-body negative pressure (LBNP) until the onset of symptoms associated with ensuing syncope. Orthostatic tolerance (expressed in cumulative stress index units, CSI) was determined on each of 3 days, with each day having a unique experimental condition: normothermia, whole-body heating, and whole-body heating + acute volume expansion. For the whole-body heating + acute volume expansion experimental day, dextran 40 was rapidly infused prior to LBNP sufficient to return central venous pressure to pre-heat stress values. Whole-body heat stress alone reduced orthostatic tolerance by ∼80% compared to normothermia (938 ± 152 versus 182 ± 57 CSI; mean ± s.e.m. , P < 0.001). Acute volume expansion during whole-body heating completely ameliorated the heat stress-induced reduction in orthostatic tolerance (1110 ± 69 CSI, P < 0.001). Although heat stress results in many cardiovascular and neural responses that directionally challenge blood pressure regulation, reduced central blood volume appears to be an underlying mechanism responsible for impaired orthostatic tolerance in the heat-stressed human.     

Sympathetic nerve activity in hypotension and orthostatic intolerance

AIM: The present paper reviews how changes in sympathetic nerve activity are related to hypotensive episodes and orthostatic intolerance in humans. RESULTS: It has been well documented that sympathetic neural traffic to skeletal muscles (muscle sympathetic nerve activity; MSNA) plays an essential role in maintaining blood pressure homeostasis mainly through baroreflex. The MSNA responded to gravitational loading from the head to the leg (+Gz) during passive head-up tilt (HUT). Patients who suffered from orthostatic hypotension with or without syncope were classified into at least two groups; low and high responders of MSNA to orthostatic loading. The typical examples belonging to the former group were patients of multiple system atrophy who had very low basal sympathetic outflow to muscle which responded extremely poorly to HUT. Patients of multiple system atrophy presented also postprandial hypotension in which muscle sympathetic response to oral glucose administration was absent. The latter group was represented by subjects who manifested vasovagal syncope with normal or even higher muscle sympathetic response to HUT, which was suddenly withdrawn concomitantly with bradycardia and hypotension. Similar withdrawal of sympathetic nerve traffic to muscle was encountered in a rare case of idiopathic non-orthostatic episodic hypotension which accompanied bradycardia. The MSNA was suppressed by short-term exposure to microgravity but was enhanced after long-term exposure to microgravity. Orthostatic intolerance after long-term exposure to microgravity was related to progressive reduction of muscle sympathetic response to orthostatic loading with impaired arterial baroreflex. CONCLUSION: It is concluded that hypotensive episodes are closely related to poor or lack of muscle sympathetic outflow, but may depend on various neural mechanisms to induce it.     

R-R interval-blood pressure interaction in subjects with different tolerances to orthostatic stress

In addition to the gain, the time delay in the input-output response in a feedback system is crucial for the maintenance of its stability. Patients with posturally related (vasovagal) syncope have inadequate control of blood pressure and one possible explanation for this could be prolonged latency of the baroreflex. We studied 14 patients with histories of syncope and poor orthostatic tolerance (assessed by a progressive orthostatic stress test) and 16 healthy controls. We performed spontaneous sequence analysis of the fluctuations of R-R period (ECG) and systolic arterial pressure (SAP, Finapres) recorded during a 20 min supine period and during 20 min 60 deg head-up tilt (HUT). The baroreflex latency was determined by identifying the lag between the changes in SAP and in R-R interval from which the highest correlation coefficient was obtained. During the supine period, 74% of sequences in control subjects and 54% in patients occurred with zero beats of delay (i.e. R-R interval changed within the same R-R interval). The remaining sequences occurred with delays of up to four beats. HUT shifted the baroreflex delay to be approximately one heartbeat slower and again patients showed more sequences with prolonged response. The delay in heartbeats was transformed into delay in time. In control subjects, 75% of baroreflex responses occurred within 1 s. In patients, 75% of baroreflex responses took more than 2 s to occur. The results showed that syncopal patients with poor orthostatic tolerance have increased baroreflex latency. This may lead to instability and inadequate blood pressure control and may predispose to vasovagal syncope.     

The effects of breathing 5% CO2 on human cardiovascular responses and tolerance to orthostatic stress

Breathing carbon dioxide (CO2) is known to induce hypercapnic acidosis and to affect chemoreceptor regulation of the cardiovascular system. However, there is limited information in the literature regarding the effects of breathing CO2 upon tolerance to orthostatic stress where cardiovascular regulation is challenged. The purpose of this study was to investigate the effect of breathing 5% CO2 on presyncopal tolerance to lower body negative pressure (LBNP). Nine subjects (five males and four females; average +/-s.d. age 21.9 +/- 0.9 years, height 172.4 +/- 9.7 cm, mass 70.3 +/- 7.1 kg) volunteered to participate in this study. Orthostatic tolerance was determined by exposing subjects to LBNP until the onset of presyncopal signs and symptoms on two occasions each separated by approximately 1 week. On one occasion investigations were carried out while subjects were breathing room air and on the other while subjects were breathing air containing 5% CO2, inducing hypercapnia and stimulating systemic chemoreceptors. During hypercapnic conditions, as compared with normocapnia, there were significant increases (P < 0.05) in minute ventilation, end-tidal CO2 and estimated arterial P(CO2). Furthermore, under hypercapnic conditions there was an increase in orthostatic tolerance, peak heart rate and time to peak heart rate during LBNP. The LBNP-induced increase in calf circumference was significantly attenuated at -50 mmHg of LBNP in addition to a further 22.3% reduction in stroke volume under hypercapnic conditions. In conclusion, these results suggest that the possible protective element of presyncope was delayed during hypercapnia at the expense of further reductions in stroke volume. This delayed presyncopal response may have been associated with increases in cerebral blood flow (CBF) induced by the increased arterial P(CO2).     

Increased hypoxic ventilatory response during hypovolemic stress imposed through head-up-tilt and lower-body negative pressure

The aim of this study was to quantify the influence of head-up-tilt (HUT) on the isocapnic hypoxic ventilatory response (HVR) in man, and to investigate the effect of orthostatic blood shifts separately from other gravitational effects by the application of lower-body negative pressure (LBNP) with subjects in a horizontal position. HVR was measured in 15 subjects during passive HUT from 0° to 85° as well as during −7° head-down-tilt and while they were in a sitting position. In a subgroup of eight subjects the effect of 85° HUT was compared to a corresponding LBNP of −70 mbar on HVR. Moreover, by imposing graded HUT (7°, 15°, 30°, 50°) and LBNP (−15, −30 mbar) we studied the effect of low-level orthostatic stress on HVR. Ventilation, end-tidal partial pressure of CO₂, heart rate and blood pressure were recorded continuously for 1 min before, and during HVR. HVR was significantly increased by ≅50% through both 85° HUT and −70 mbar LBNP as compared to 0° and 0 mbar, respectively, at unchanged mean arterial pressure. Low-level HUT and LBNP had no effect on HVR. It was concluded that the orthostatic HVR increase may be attributable to caudal blood shifts (i.e., central hypovolemia). This HVR increase requires a pronounced hypovolemic stress but no decrease in arterial blood pressure. It is suggested that a central interaction of arterial and cardiopulmonary baroreceptors is underlying this response. Their separate contribution remains to be assessed. Accepted: 14 October 1999     

Cardiovascular responses during arm exercise and orthostatic challenge in individuals with paraplegia

In this study the cardiorespiratory responses during arm crank ergometry (ACE) performed at two submaximal intensities (30% and 50% of heart rate reserve) and moderate orthostatic challenge were investigated in individuals with paraplegia (PARA). The effect of concurrent electrical stimulation (ES)-induced leg muscle contractions on the responses to ACE during orthostatic challenge was also investigated. Eight PARA (T5–T12) and eight able-bodied (AB) individuals participated in this study, however only seven subjects from each group completed all tests and were used in subsequent data analyses. Oxygen uptake ( ), heart rate (f _c), stroke volume (SV) and cardiac output ( ) were assessed during (1) ACE alone, (2) ACE and lower body negative pressure (ACE+LBNP), and, in PARA only, (3) ACE+LBNP with ES (ACE+LBNP+ES). In both PARA and AB, ACE+LBNP decreased SV (by 13–18% and 20–23%, respectively) and increased f _c (by 13–15% and 16%, respectively) compared to ACE alone. The decrease in SV was greater in AB than in PARA (significant group × trial interaction; both ACE intensities pooled), but there was no difference in the magnitude of increase in f _c between groups. ES-induced leg muscle contractions increased SV (up to 16%) but did not change or . The smaller reduction in SV from ACE to ACE+LBNP in PARA may indicate a mechanism by which adequate central blood volume can be maintained in the face of orthostatic challenge, despite the absence of supraspinal control below the spinal cord lesion. With ES-induced leg muscle contractions, the decrease in SV, which occurred during ACE+LBNP, was reversed via reactivation of the lower limb muscle pump and augmented venous return. Electronic Publication     

Aortic,cerebral and lower limb arterial and venous response to orthostatic stress after a 60-day bedrest

The objective of this study is to assess by echography and Doppler the Cerebral (Vmca), Aortic (Vao) and Femoral (Vfem) arterial flow velocity and calf vein (Tibial, Gastrocnemius) section (Tib, Gast) during orthostatic intolerance (OI) test after a 60-day, head down tilt bed rest (HDBR). Twenty-four women (25–40 years) underwent a 60-day HDBR at −6°: eight as control (Con), eight with exercise against lower body negative pressure (Ex-Lb) and eight with nutrition supplement (Nut). Before and after (R0) HDBR, all subjects underwent a 10-min, 80° tilt followed by progressive LBNP until presyncope. After the post-HDBR Tilt + LBNP test, two groups were identified: finishers (F, n = 11) who completed the Tilt and non-finishers (NF, n = 13). A higher percentage decrease in Vao flow, higher percentage distension of Tib vein and a lack of increase in Vmca/Vfem ratio during the post-HDBR Tilt + LBNP compared to pre-HDBR were correlated to OI, but not all of these abnormal responses were present in each of the NF subjects. Abnormal responses were more frequent in Con and Nut than in Ex-Lb subjects. (1) HDBR did not affect the cardiac, arterial and venous responses to the orthostatic test to the same extent in each subject. (2) Exercise within LBNP partially preserved the cardiovascular response to Tilt, while Nutrition supplementation had no efficacy. (3) Cerebral/femoral flow ratio and aortic flow were the parameters most closely related to OI. (4) Reduction in aortic flow was not the major hemodynamic change preceding syncope.     

The effects of isometric exercise training on resting blood pressure and orthostatic tolerance in humans

Isometric exercise training has been shown to reduce resting blood pressure, but the effect that this might have on orthostatic tolerance is poorly understood. Changes in orthostatic tolerance may also be dependent on whether the upper or lower limbs of the body are trained using isometric exercise. Twenty-seven subjects were allocated to either a training or control group. A training group first undertook 5 weeks of isometric exercise training of the legs, and after an 8 week intervening period, a second training group containing six subjects from the initial training group, undertook 5 weeks of isometric arm-training. The control group were asked to continue their normal daily activities throughout the 18 weeks of the study. In all subjects orthostatic tolerance, assessed using lower body negative pressure (LBNP), and resting blood pressure were measured before and after each of the 5 week training or control periods. Estimated lean leg volume was determined before and after leg-training. During all LBNP tests, heart rate and blood pressure were recorded each minute, and the time taken to reach the highest heart rate was derived (time to peak HR). Resting systolic blood pressure (mean +/- S.D.), when measured during the last week of training, was significantly reduced after both leg (-10 +/- 8.7 mmHg) and arm (-12.4 +/- 9.3 mmHg; P < 0.05) isometric exercise training, compared to controls. This reduction disappeared when blood pressure was measured immediately before the LBNP tests, which followed training. Orthostatic tolerance only increased after leg-training (20.8 +/- 16.4 LTI; P < 0.05) and was accompanied by an increased time to peak HR (119.8 +/- 106.3 beats min(-1); P < 0.05) in this group. Blood pressure responses to LBNP did not change after arm-training, leg-training or in controls (P > 0.05). There was a small but significant increase in estimated lean leg volume after leg-training (0.1 +/- 0.1 1; P < 0.05). These results suggest that lower resting blood pressure is probably not responsible for the increased orthostatic tolerance after isometric exercise training of the legs. Rather, it is possible that the training altered some other aspect of cardiovascular control during orthostatic stress that was apparent in the changes in heart rate. Leg-training was accompanied by increases in estimated lean leg volume. The effects of isometric training on orthostatic tolerance appear to be specific to limbs that are directly involved in LBNP testing.     

Training mode does not affect orthostatic tolerance in chronically exercising subjects

This study tested the hypotheses that trained swimmers would have greater orthostatic tolerance than runners and, if present, it would be due to differences in their autonomic and hemodynamic responses to graded central hypovolemia. Twenty intercollegiate male athletes [11 runners and 9 swimmers; V˙O_2max =70.0 (1.6) vs 69.5 (2.6) ml·kg⁻¹·min⁻¹, respectively] underwent graded lower body negative pressure (LBNP) to presyncope. The swimmers were heavier [80.5 (1.9) vs 70.3 (1.9) kg, P<0.05], with larger resting cardiac [4.44 (0.29) vs 3.68 (0.18) l·min⁻¹·m⁻²] and total peripheral conductance [0.056 (0.04) vs 0.044 (0.02) units·m⁻²] indices. Neither spontaneous cardiac baroreflex sensitivity (sequence method) nor heart rate variability (spectral analysis) differed significantly between groups at rest. LBNP tolerance did not differ between groups, with an index value of 51 (2) kPa·min for the runners and 54 (4) kPa·min for the swimmers [383 (16) vs 402 (32) mmHg·min] , although the swimmers had larger declines in pulse pressure and tended (P=0.078) to have larger declines in total peripheral conductance index in the last completed stage of LBNP. These responses did not differ between groups in the last 2 min of LBNP. Neither the heart rate, mean arterial pressure nor forearm vascular conductance responses differed between groups throughout. Changes in heart rate variability indices did not differ significantly between groups, with similar declines in the high frequency component and increases in the low frequency/high frequency ratio. These data suggest that swim training does not lead to greater orthostatic tolerance than run training, and responses to maximal LBNP do not differ between swimmers and runners. Moreover, neither heart rate nor the autonomic modulation of the heart rate response to LBNP are affected by training modality. Electronic Publication     

Hypotension induced by central hypovolaemia and hypoxaemia

Our question was whether the reduced orthostatic tolerance that accompanies hypoxaemia in some (not all) subjects might be associated with an abnormally large release of adrenaline. Eight normal young men were exposed to lower body negative pressure (LBNP) at -30 to -40 mmHg while breathing air or 10% O2 in N2. Four subjects developed hypotension and bradycardia whenever LBNP was applied during hypoxaemia; four showed a rise in heart rate and stable blood pressure. During normoxia plasma adrenaline concentration did not rise during LBNP in any subject, nor during hypoxaemia plus LBNP in the subjects who remained normotensive. In the four men whose heart rates and blood pressures fell during LBNP with hypoxaemia, adrenaline rose markedly, reaching 200-1600 pg ml-1. All subjects showed similar elevations in noradrenaline concentration during LBNP in both normoxia and hypoxaemia. The results suggest that reduced tolerance to central hypovolaemia during hypoxaemia could stem from known vasomotor and cardiac effects attending high plasma concentrations of adrenaline.     

Modulation of arterial baroreflex dynamic response during mild orthostatic stress in humans

We tested the hypothesis that in humans, carotid-baroreflex dynamic responses (evaluated by examining the time course of the carotid-baroreflex-induced alterations in muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP) and heart rate (HR)) would be altered during mild orthostatic stress in ways that serve to limit orthostatic hypotension. In 12 healthy subjects (10 male, 2 female), 5-s periods of neck pressure (NP) (50 mmHg) and neck suction (NS) (− 60 mmHg) were used to evaluate carotid baroreflex function at rest (CON) and during lower body negative pressure (LBNP) (−15 mmHg). During LBNP (as compared with CON) (a) the augmentations in MSNA and MAP elicited by NP were greater, (b) the NS-induced period of MSNA suppression was, if anything, shorter, (c) the peak decrement in MAP elicited by NS, although not different in amplitude, occurred earlier and recovered to its initial level more quickly after NS, and (d) the HR responses to NP and NS were greater. These results suggest that during mild orthostatic stress, carotid-baroreflex dynamic responses are modulated in ways that should help maintain blood pressure and limit orthostatic hypotension.     

Cardiovascular responses to an orthostatic challenge and electrical-stimulation-induced leg muscle contractions in individuals with paraplegia

The purpose of this study was to investigate the cardiovascular and haemodynamic responses that occur during moderate orthostatic challenge in people with paraplegia, and the effect of electrical stimulation (ES)-induced leg muscle contractions on their responses to orthostatic challenge. Eight males with complete spinal lesions between the 5th and 12th thoracic vertebrae (PARA) and eight able-bodied individuals (AB) volunteered for this study. Changes in heart rate (f _c), stroke volume (SV), cardiac output (Q˙ _c), mean arterial pressure (MAP), total peripheral resistance (TPR), limb volumes and indices of neural modulation of f _c, [parasympathetic (PNS) and sympathetic (SNS) nervous system indicators] were assessed during: (1) supine rest (REST), (2) REST with lower-body negative pressure at ?30 torr (LBNP ?30, where 1 torr?=?133.32?N/m²), and (3) for PARA only, LBNP ?30 with ES-induced leg muscle contractions (LBNP?+?ES). LBNP ?30 elicited a decrease in SV (by 23% and 22%), Q˙ _c (by 15% and 18%) and the PNS indicator, but an increase in f _c (by 10% and 9%), TPR (by 23% and 17%) and calf volume (by 1.51% and 4.04%) in both PARA and AB subjects, respectively. The SNS indicator was increased in the AB group only. Compared to LBNP ?30, LBNP?+?ES increased SV (by 20%) and Q˙ _c (by 16%), and decreased TPR (by 12%) in the PARA group. MAP was unchanged from REST during all trials, for both groups. The orthostatic challenge induced by LBNP ?30 elicited similar cardiovascular adaptations in PARA and AB subjects. ES-induced muscle contractions during LBNP ?30 augmented the cardiovascular responses exhibited by the PARA group, probably via reactivation of the skeletal muscle pump and improved venous return.     

Involvement of the paraventricular nucleus (PVN) of hypothalamus in the cardiovascular alterations to head up tilt in conscious rats

We evaluated the involvement of paraventricular nucleus (PVN) in the changes in mean arterial pressure (MAP) and heart rate (HR) during an orthostatic challenge (head up tilt, HUT). Adult male Wistar rats, instrumented with guide cannulas to PVN and artery and vein catheters were submitted to MAP and HR recording in conscious state and induction of HUT. The HUT induced an increase in MAP and HR and the pretreatment with prazosin and atenolol blocked these effects. After inhibition of neurotransmission with cobalt chloride (1 mM/100 nl) into the PVN the HR parameters did not change, however we observed a decrease in MAP during HUT. Our data suggest the involvement of PVN in the brain circuitry involved in cardiovascular adjustment during orthostatic challenges.     

Reduced orthostatic tolerance following 4 h head-down tilt

Summary The cardiovascular responses to a 10-min 1.22 rad (70°) head-up tilt orthostatic tolerance test (OST) was observed in eight healthy men following each of a 5-min supine baseline (control), 4 h of 0.1 rad (6°) head-down tilt (HDT), or 4 h 0.52 rad (30°) headup tilt (HUT). An important clinical observation was presyncopal symptoms in six of eight subjects following 4 h HDT, but in no subjects following 4 h HUT. Immediately prior to the OST, there were no differences in heart rate, stroke volume, cardiac output, mean arterial pressure and total peripheral resistance for HDT and HUT. However, stroke volume and cardiac output were greater for the control group. Mean arterial pressure for the control group was less than HDT but not HUT. Over the full 10-min period of OST, the mean arterial pressure was not different between groups. Heart rate increased to the same level for all three treatments. Stroke volume decreased across the full time period for control and HDT, but only at 3 and 9 min for HUT. There was a higher total peripheral resistance in the HDT group than control or HUT. The pre-ejection period to left ventricular ejection time ratio was less in HDT than for control or HUT groups. These data indicate a rapid adaptation of the cardiovascular system to 4 h HDT that appears to be inappropriate on reapplication of a head to foot gravity vector. We speculate that the cause of the impaired orthostatic tolerance is decreased tone in venous capacitance vessels so that venous return is inadequate.     

Hemodynamic and hormonal responses to lower body negative pressure in men with varying profiles of strength and aerobic power

Hemodynamic, cardiac, 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 challenge is associated with interactions between strength and aerobic power. Subjects underwent treadmill tests to determine peak oxygen uptake ( O_2max) and isokinetic dynamometer tests to determine knee extensor strength. Based on predetermined criteria, subjects were classified into one of four fitness profiles of six subjects each, matched for age, height, and body mass: (a) low strength/average aerobic fitness, (b) low strength/high aerobic fitness, (c) high strength/average aerobic fitness, and (d) high strength/high aerobic fitness. Following 90 min of 0.11 rad (6°) head-down tilt (HDT), each subject underwent graded LBNP to –6.7 kPa or presyncope, with maximal duration 15 min, while hemodynamic, cardiac, and hormonal responses were measured. All groups exhibited typical hemodynamic, hormonal, and fluid shift responses during LBNP, with no intergroup differences between high and low strength characteristics. Subjects with high aerobic power exhibited greater (P < 0.05) stroke volume and lower (P < 0.05) heart rate, vascular peripheral resistance, and mean arterial pressure during rest, HDT, and LBNP. Seven subjects, distributed among the four fitness profiles, became presyncopal. These subjects showed greatest reduction in mean arterial pressure during LBNP, had greater elevations in vasopressin, and lesser increases in heart rate and peripheral resistance. Neither O_2max nor leg strength were associated with fall in arterial pressure or with syncopal episodes. We conclude that interactions between aerobic and strength fitness characteristics do not influence responses to LBNP challenge.     

Effects of moderate exercise training on plasma volume, baroreceptor sensitivity and orthostatic tolerance in healthy subjects

The effect of physical training on an individual's ability to withstand an orthostatic stress is unclear. This study was undertaken to determine the effects on orthostatic tolerance in healthy volunteers of training at a level appropriate for unfit subjects and cardiorespiratory patients. In 11 asymptomatic, untrained subjects the following assessments were made: plasma volume by Evans Blue dye dilution and blood volume derived from haematocrit; carotid baroreceptor sensitivity from the slope of the regression of change in cardiac interval against pressure applied to a neck chamber; orthostatic tolerance as time to presyncope in a test of head-up tilting combined with lower body suction; exercise test relating heart rate to oxygen consumption. Subjects were then given a training schedule (5BX/XBX, Royal Canadian Air Force) involving 11-12 min of mixed exercises per day until an age/sex related 'target' was reached. Following training all subjects showed evidence of improved fitness, seen as decreases in heart rate at an oxygen uptake (Vo2) of 1.5 1 min-1 and in the elevation of the regression line between heart rate and Vo2. All also had increases in plasma and blood volumes and decreases in baroreceptor sensitivity. Seven of the subjects showed increases in orthostatic tolerance. Improvement in orthostatic tolerance was related to a low initial tolerance, and was associated with increases in plasma volume and decreases in baroreceptor sensitivity. These results show that moderate exercise training increases orthostatic tolerance in subjects who do not already have a high initial tolerance and suggest that training may be of value in the management of untrained patients with attacks of syncope due to orthostatic intolerance.     

Reproducibility of the heart rate variability responses to graded lower body negative pressure

The reproducibility of heart rate variability (HRV) measures during graded lower body negative pressure (LBNP) have not been studied in sufficient detail. Active college age men (n=14) underwent an orientation exposure and two trials of graded LBNP to presyncope or –100 mmHg, separated by 1 week. Heart rate, stroke volume (impedance cardiography), blood pressure (Finapres), and forearm blood flow were assessed, as was HRV in both time and frequency domains. The trial-to-trial responses to LBNP common to all subjects (LBNP–60 mmHg and at test termination) showed parallel changes, suggesting similar responses between both trials. Good reproducibility estimates were found for the resting HRV data (lowest: R=0.62 for low frequency/high frequency ratio; highest: R=0.94 for standard deviation of normal R-R intervals). During LBNP, reproducibility estimates varied but were generally similar to that seen at rest. At test termination, they were unacceptably low (R<0.41) for the HRV data assessed in the frequency domain and expressed in absolute units. LBNP tolerance was lower in the first trial [LBNP tolerance index: 404 (21) versus 437 (15) mmHg min^–1; P<0.05] but the intraclass correlation coefficient was high (R=0.87). These data suggest that (1) HRV responses to submaximal LBNP up to –60 mmHg are consistent across trials, (2) the considerable variability seen in the HRV parameters at maximal LBNP can be reduced by expressing these data in either the time domain or using normalized units in the frequency domain, and (3) cardiovascular responses to sub- and maximal LBNP are reproducible. Data are presented as mean (SEM) unless otherwise stated.     

Melatonin attenuates the sympathetic nerve responses to orthostatic stress in humans

Previous studies have suggested that melatonin alters sympathetic outflow in humans. The purpose of the present study was to determine in humans the effect of melatonin on sympathetic nerve activity and arterial blood pressure during orthostatic stress. Fifty minutes after receiving a 3 mg tablet of melatonin or placebo (different days), muscle sympathetic nerve activity (MSNA), arterial blood pressure, heart rate, forearm blood flow and thoracic impedance were measured for 10 min at rest and during 5 min of lower body negative pressure (LBNP) at -10 and -40 mmHg ( n = 11). During LBNP, MSNA responses were attenuated after melatonin at both -10 and -40 mmHg ( P < 0.03). Specifically, during the placebo trial, MSNA increased by 33 ± 8 and 251 ± 70 % during -10 and -40 mmHg, respectively, but increased by only 8 ± 7 and 111 ± 35 % during -10 and -40 mmHg with melatonin, respectively. However, arterial blood pressure and forearm vascular resistance responses were unchanged by melatonin during LBNP. MSNA responses were not affected by melatonin during an isometric handgrip test (30 % maximum voluntary contraction) and a cold pressor test. Plasma melatonin concentration was measured at 25 min intervals for 125 min in six subjects. Melatonin concentration was 14 ± 11 pg ml⁻¹ before ingestion and was significantly increased at each time point (peaking at 75 min; 1830 ± 848 pg ml⁻¹). These findings indicate that in humans, a high concentration of melatonin can attenuate the reflex sympathetic increases that occur in response to orthostatic stress. These alterations appear to be mediated by melatonin-induced changes to the baroreflexes.