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Cardiovascular reflex tests remain the investigational cornerstone for the assessment of patients in the clinical autonomic laboratory. Three cardiovagal tests have been found suitable for testing: the instantaneous heart rate responses induced by deep breathing, Valsalva's manoeuvre and standing up. Suitable laboratory indices of adrenergic function include continuous monitoring of blood pressure responses induced by Valsalva's manoeuvre and standing up, which is now possible through tracking of beat-to-beat blood pressure changes at the finger. Spectral analysis of heart rate and blood pressure and pulse wave analysis for stroke volume changes are promising approaches to evaluate abnormalities in arterial baroreflex regulatory mechanisms in diabetic patients

Head-down tilted bedrest is a ground-based microgravity simulation model. Since in this position the influence of chief external determinants of circadian blood pressure variation, i.e. activity and posture, are reduced, it may reveal endogenous oscillatory factors. The effects of 42 days of 6 degrees head-down tilt on the circadian profiles of continuous finger blood pressure, heart rate, stroke volume, cardiac output and total peripheral resistance were analysed. In seven healthy volunteers (25-31 years) twelve 22 h Portapres registrations were performed: two in an ambulatory baseline period, eight during 42 days of head-down tilt, and two during recovery. Stroke volume was estimated by a pulse contour method ('Modelflow') from the finger arterial blood pressure tracing. Head-down tilt rapidly reduced circadian BP variation, especially for diastolic blood pressure. No effect of long-term head-down tilt on blood pressure level was observed. The day-night difference in heart rate was essentially unaffected. Cardiac output was maintained through an increase of heart rate and simultaneous decline of stroke volume. Our observations confirm the overriding importance of physical activity and orthostatic load on the diurnal variation of BP. The time-frame of the changes in stroke volume and heart rate during head-down tilt might point to a contribution of other factors besides a reduction of circulating blood volume affecting cardiovascular performance under these conditions.

1. Disorders of the autonomic nervous system are frequently diagnosed by measuring heart rate changes in response to deep-breathing and lying-to-standing manoeuvres. The heart rate changes in these manoeuvres are quantified in measures using various units, like beats per minute, seconds and dimensionless ratios. 2. In the present study we mathematically derived relationships between the measures which quantify heart rate changes in beats per minute, seconds and dimensionless ratios. The theoretical outcomes were experimentally confirmed by the results of the deep-breathing and the lying-to-standing test in 525 healthy and diabetic subjects. The measures were found to be non-equivalent, because the mean RR interval duration influenced the measures in different ways. 3. It is argued that measures in seconds are preferable to measures in beats per minute or ratios, because the physiological interpretation of this measure is easier, and the sensitivity of measures in seconds is expected to be greater. 4. Finally, we recommend that measures of heart rate variation in the deep-breathing and lying-to-standing manoeuvre are accompanied by information on the mean RR interval duration or mean heart rate to allow correct interpretation of the measures.

The delay τ between rising systolic blood pressure (SBP) and baroreflex bradycardia has been found to increase when vagal tone is low. The α2-agonist clonidine increases cardiac vagal tone, and this study tested how it affects τ. In eight conscious supine human volunteers clonidine (6 μg/kg po) reduced τ, assessed both by cross correlation baroreflex sensitivity and sequence methods (both P < 0.05). Experiments on urethane-anaesthetized rats reproduced the phenomenon and investigated the underlying mechanism. Heart rate (HR) responses to increasing SBP produced with an arterial balloon catheter showed reduced τ ( P < 0.05) after clonidine (100 μg/kg iv). The central latency of the reflex was unaltered, however, as shown by the unchanged timing with which antidromically identified cardiac vagal motoneurons (CVM) responded to the arterial pulse. Testing the latency of the HR response to brief electrical stimuli to the right vagus showed that this was also unchanged by clonidine. Nevertheless, vagal stimuli delivered at a fixed time in the cardiac cycle (triggered from the ECG R-wave) slowed HR with a 1-beat delay in the baseline state but a 0-beat delay after clonidine ( n = 5, P < 0.05). This was because clonidine lengthened the diastolic period, allowing the vagal volleys to arrive at the heart just in time to postpone the next beat. Calculations indicate that naturally generated CVM volleys in both humans and rats arrive around this critical time. Clonidine thus reduces τ not by changing central or efferent latencies but simply by slowing the heart.

The enhanced heart rate and blood pressure soon after awaking increases cardiac oxygen demand, and has been associated with the high incidence of acute myocardial infarction in the morning. The behavior of cardiac oxygen supply is unknown. We hypothesized that oxygen supply decreases in the morning and to that purpose investigated cardiac oxygen demand and oxygen supply at night and after awaking. We compared hypertensive to normotensive subjects and furthermore assessed whether pressures measured non-invasively and intra-arterially give similar results. Aortic pressure was reconstructed from 24-h intra-brachial and simultaneously obtained non-invasive finger pressure in 14 hypertensives and 8 normotensives. Supply was assessed by Diastolic Time Fraction (DTF, ratio of diastolic and heart period), demand by Rate-Pressure Product (RPP, systolic pressure times heart rate, HR) and supply/demand ratio by A(dia)/A(sys), with A(dia) and A(sys) diastolic and systolic areas under the aortic pressure curve. Hypertensives had lower supply by DTF and higher demand by RPP than normotensives during the night. DTF decreased and RPP increased in both groups after awaking. The DTF of hypertensives decreased less becoming similar to the DTF of normotensives in the morning; the RPP remained higher. A(dia)/A(sys) followed the pattern of DTF. Findings from invasively and non-invasively determined pressure were similar. The cardiac oxygen supply/demand ratio in hypertensive patients is lower than in normotensives at night. With a smaller night-day differences, the hypertensives' risk for cardiovascular events may be more evenly spread over the 24 h. This information can be obtained noninvasively.

Skin sympathetic vasomotor control can be examined in the extremities by the skin vasomotor test. In this test the change in skin blood flow and skin temperature in the hand and foot in response to a cold stimulus is utilized as an index of distal sympathetic nerve fibre integrity. This is of importance in conditions such as diabetes mellitus as peripheral autonomic neuropathy is associated with orthostatic hypotension and diabetic foot complications. The validity and reproducibility of the test as a marker of distal sympathetic nerve function has been studied. The test was performed in nine healthy control subjects and in nine subjects (undergoing minor surgery) after a sympathetic nerve conduction block (L2–L3) was achieved in the lower extremities by spinal analgesia. Changes in skin temperature (p < 0.001) and skin blood flow (p < 0.005) in responses to cooling were significantly larger in the control group than in the group with spinal analgesia. Repeated skin temperature measurements on 42 occasions (test—retest period of 4 weeks) in eight healthy and 34 diabetic subjects indicated a reliability coefficient of 80%. We conclude, therefore, that the skin vasomotor test provides a valid and reproducible quantitative assessment of skin sympathetic nerve function in upper and lower extremities.

Summary Analysis of beat-to-beat fluctuations of heart rate and blood pressure is a promising new approach to the clinical diagnosis and management of alterations in cardiovascular regulation. We investigated the effects of three induction agents on beat-to-beat heart rate and blood pressure fluctuations in man. Beat-to-beat fluctuations were analysed by spectral analysis. Two spectral areas are of main interest. One area is centred on the respiratory frequency and shifts with changes in respiratory rate (High Frequency area). These high frequency flucuations in heart rate are caused by respiratory-induced blood pressure fluctuations, mediated by the vagus nerve through the baroreflex mechanism. Variability in the Low Frequency area, which occurs between 0.06 and 0.12 Hz is considered to be related to haemodynamic fluctuations due to the sympathetic baroreflex control loop of vasomotor activity and heart rate. Results from our study indicate that thiopentone, etomidate and propofol show considerable differences in their effects on beat-to-beat variability of heart rate and blood pressure. These differences can be explained by their specific effects on the cardiovascular system.

The vasovagal response is the development of inappropriate cardiac slowing and arteriolar dilatation. Vasovagal responses reflect autonomic neural changes: bradycardia results from sudden augmentation of efferent vagal activity, and hypotension results from sudden reduction or cessation of sympathetic activity and relaxation of arterial resistance vessels. Two different neural pathways are thought to be involved, one originating in the hypothalamus, the other in the heart. Direct hypothalamic activation of the medullary cardiovascular centres triggered by emotional stress or pain causes a vasovagal response (central type). The combination of a reduced central blood volume secondary to venous pooling or blood loss, and an increased inotropic state of the heart, may stimulate ventricular mechanoreceptors and provoke vasodilatation and bradycardia (peripheral type). Cardiovascular afferents originating from stretch receptors in various parts of the vascular tree sometimes induce opposite reflexes when compared with those from ventricular afferents. The depressor reflex involved in the peripheral type of vasovagal response originates in the heart itself and overrides normal baroreflex circulatory control; an antagonism between the control of volume and pressure on the filling side of the heart and the control system of arterial pressure becomes apparent. Vasovagal responses are not necessarily abnormal; the neural pathways involved in the vasovagal response are probably present in all healthy subjects who individually mainly differ in susceptibility.

Respiratory sinus arrhythmia (RSA) has received much attention in recent years due to the large body of evidence indicating that variations in this phenomenon represent alterations in parasympathetic cardiac control. Although it appears that respiratory sinus arrhythmia is mediated by vagal mechanisms, the extent to which the well-known respiratory influences (i.e., rate and tidal volume) on respiratory sinus arrhythmia (in altering its magnitude) may moderate the relationship between RSA and cardiac vagal tone has never been systematically studied. We addressed this issue by examining intraindividual relationships among RSA magnitude, respiration (rate and tidal volume), and heart period among six healthy male adults after intravenous administration of 10 mg propranolol, a beta-adrenergic blocker. Subjects were exposed to various behavioral tasks which altered all physiological variables measured. Variations in heart period after beta blockade were assumed to be predominantly vagally mediated. Within-subject regression analyses consistently showed that respiratory parameters influenced RSA magnitude, but not tonic variations in beta-blocked heart period, suggesting that respiratory-mediated RSA alterations are not associated with changes in cardiac vagal tone. Only when respiratory variables were statistically controlled was there evidence of a reasonable correspondence between beta-blocked heart period and RSA amplitude, providing support for the idea that respiratory parameters need to be controlled when using RSA amplitude as an index of cardiac vagal tone. Repeated-measures analyses of variance of mean levels of heart period and respiratory sinus arrhythmia across subjects supplemented and supported the intraindividual results. These findings point to the importance of controlling for respiratory parameters when using respiratory sinus arrhythmia as a cardiac vagal index.

In 2 ESA-cosmonauts we compared the 24-hr profiles in blood pressure (BP) and heart rate (HR) to those that we had observed in an earlier head-down tilted (HDT) bed rest study. In view of the lack of gravitational stress, an attenuated profile was expected, as in HDT. To obtain a full profile we measured automatic upper-arm cuff measurements in 2 cosmonauts, combined with PortapresTM recordings in one. Unlike HDT, actual microgravity did not result in attenuated circadian profiles. The levels of systolic and diastolic pressures tended to be slightly lower in flight. Only nighttime heart rate was significantly lower in Space.

OBJECTIVE. The goal was to investigate cardiovascular responses to a psychosocial stressor in school-aged, formerly premature boys and girls who had been treated neonatally with dexamethasone or hydrocortisone because of chronic lung disease.METHODS. We compared corticosteroid-treated, formerly preterm infants with formerly preterm infants who had not been treated neonatally with corticosteroids (reference group). Children performed the Trier Social Stress Test for Children, which includes a public speaking task and a mental arithmetic task. Blood pressure was recorded continuously before, during, and after the stress test. Plasma norepinephrine levels were determined before the test, directly after the stress task, and after recovery.RESULTS. Overall, in response to stress, girls had significantly larger changes in systolic blood pressure and mean arterial pressure and in stroke volume and cardiac output, compared with boys. Boys exhibited larger total peripheral resistance responses, compared with girls. The hydrocortisone group did not differ significantly from the reference group in any of the outcome measures. However, dexamethasone-treated children had smaller stress-induced increases in systolic and mean arterial blood pressure than did hydrocortisone-treated children. In addition, the dexamethasone group showed smaller increases in stroke volume and blunted norepinephrine responses to stress, compared with children in the reference group. Correction for gender did not affect these results.CONCLUSIONS. The differences in cardiovascular stress responses between girls and boys are consistent with known gender differences in adult cardiovascular stress responses. Our data demonstrate that neonatal treatment with dexamethasone has long-term consequences for the cardiovascular and noradrenergic stress responses; at school age, the cardiovascular stress response was blunted in dexamethasone-treated children. Hydrocortisone-treated children did not differ from the reference group, which suggests that hydrocortisone might be a safe alternative to dexamethasone for treating chronic lung disease of prematurity.

Although blood pressure control is often viewed as a paradigmatic example of a "homeostatic" biological control system, blood pressure levels can fluctuate considerably over shorter and longer time scales. In modern signal analysis, coherence between heart rate and blood pressure variability is used to estimate baroreflex gain. However, the shorter the measurement period, the more variability this gain factor reveals. We review evidence that this variability is not due to the technique used for the estimation, but may be an intrinsic property of the circulatory control mechanisms. The baroreflex is reviewed from its evolutionary origin, starting in fishes as a reflex mechanism to protect the gills from excessively high pressures by slowing the heart via the (parasympathetic) vagus nerve. Baroreflex inhibition of cardiovascular sympathetic nervous outflow is a later development; the maximally possible extent of sympathetic activity probably being set in the central nervous system by mechanisms other than blood pressure per se. In the sympathetic outflow tract not only baroreflex inhibition but also as yet unidentified, stochastic mechanisms decide to pass or not pass on the sympathetic activity to the periphery. In this short essay, the "noisiness" of the baroreflex as nervous control system is stressed. This property is observed in all elements of the reflex, even at the--supposedly--most basic relation between afferent receptor nerve input and efferent--vagus--nerve output signal.

Since the now classical experiments by Brown and Eccles in 1934, the effect of a stimulation of the vagus nerve on the heart has been derived from changes in the length of cardiac periods. Based on a simple model for the genesis of heartbeats, it is shown that the procedure employed by Brown and Eccles gives a distorted picture of the actual vagal effect. A corrected procedure for inferring the vagal effect from changes in heart period lenght is proposed. This new procedure is applied to empirical data from animal experiments with direct stimulation of the vagus nerve. It is shown that, if the vagal effect depends on time of stimulation within the cardiac cycle (cycle time-dependency), single vagal effects curves for each time of stimulation within the cycle have to be constructed. Other data reduction procedures are reviewed with respect to their appropriateness for demonstrating cycle time-dependency.

OBJECTIVE--To determine the long term effects of relaxation therapy on 24 hour ambulatory intra-arterial blood pressure in patients with mild untreated and uncomplicated hypertension. DESIGN--Four week screening period followed by randomisation to receive either relaxation therapy or non-specific counselling for one year. Ambulatory intra-arterial blood pressure was measured before and after treatment. SETTING--Outpatient clinic in Amsterdam's university hospital. SUBJECTS--35 Subjects aged 20-60 who were being treated by general practitioners for hypertension but were referred to take part in the study. At three consecutive screening visits all subjects had a diastolic blood pressure without treatment of 95-110 mm Hg. Subjects were excluded if they had damaged target organs, secondary hypertension, diabetes mellitus, a cholesterol concentration greater than 8 mmol/l, or a history of malignant hypertension. INTERVENTIONS--The group allocated to relaxation therapy was trained for eight weeks (one hour a week) in muscle relaxation, yoga exercises, and stress management and continued exercising twice daily for one year with monthly visits to the clinic. The control group had the same attendance schedule but had no training and were requested just to sit and relax twice a day. All subjects were asked not to change their diet or physical activity. MAIN OUTCOME MEASURE--Changes in ambulatory intra-arterial blood pressure after one year of relaxation therapy or non-specific counselling. RESULTS--Mean urinary sodium excretion, serum concentration of cholesterol, and body weight did not change in either group. Diastolic pressures measured by sphygmomanometry were 2 and 3 mm Hg lower in subjects in the relaxation group and control group respectively at the one year follow up compared with initial readings. The mean diastolic ambulatory intra-arterial pressure during the daytime had not changed after one year in either group, but small treatment effects could not be excluded: the mean change for the relaxation group was -1 mm Hg (95% confidence interval -6 to 3.9 mm Hg) and for the control group -0.4 mm Hg (-5.3 to 4.6 mm Hg). Mean ambulatory pressure in the evening also had not changed over the year, and in both groups nighttime pressure was 5 mm Hg higher. The variability in blood pressure was the same at both measurements. CONCLUSIONS--Relaxation therapy was an ineffective method of lowering 24 hour blood pressure, being no more beneficial than non-specific advice, support, and reassurance--themselves ineffective as a treatment for hypertension.

Objective Sympathetic baroreflex sensitivity (symBRS) can be defined as the maximum sensitivity of muscle sympathetic nerve activity (MSNA) to changes in arterial blood pressure. This sensitivity is the slope of the linear middle part of the sigmoid curve that relates blood pressure to MSNA. SymBRS is known to vary with conditions, for instance during cold pressor testing. We investigated whether symBRS is affected by infusions of phenylephrine and nitroprusside. Methods In 10 healthy subjects, vasoactive infusions were varied in slow steps, as customary in protocols to determine ‘graded infusion symBRS' (symBRS inf ). During each step, symBRS was estimated from spontaneous beat-to-beat fluctuations (symBRS sp ). As a secondary goal, symBRS inf was compared to the symBRS sp without infusions. Results The symBRS sp for MSNA burst area varied with infusions, augmenting with decreasing blood pressure, however the symBRS sp for burst occurrence was not affected. There were large differences between symBRS inf and symBRS sp at rest. Conclusions symBRS sp varies systematically with infusions during a symBRS inf protocol. This denotes a fundamental difference between these methods. Significance The relationship between ‘slow' infusion effects (symBRS inf ) and changes in symBRS sp is elucidated. The mathematical model that describes this relationship can also explain the increase of symBRS found with other sympathoexcitatory stimuli.

Wave reflections affect the proximal aortic pressure and flow waves and play a role in systolic hypertension. A measure of wave reflection, receiving much attention, is the augmentation index (AI), the ratio of the secondary rise in pressure and pulse pressure. AI can be limiting, because it depends not only on the magnitude of wave reflection but also on wave shapes and timing of incident and reflected waves. More accurate measures are obtainable after separation of pressure in its forward (P f ) and reflected (P b ) components. However, this calculation requires measurement of aortic flow. We explore the possibility of replacing the unknown flow by a triangular wave, with duration equal to ejection time, and peak flow at the inflection point of pressure (F tIP ) and, for a second analysis, at 30% of ejection time (F t30 ). Wave form analysis gave forward and backward pressure waves. Reflection magnitude (RM) and reflection index (RI) were defined as RM=P b /P f and RI=P b /(P f +P b ), respectively. Healthy subjects, including interventions such as exercise and Valsalva maneuvers, and patients with ischemic heart disease and failure were analyzed. RMs and RIs using F tIP and F t30 were compared with those using measured flow (F m ). Pressure and flow were recorded with high fidelity pressure and velocity sensors. Relations are: RM tIP =0.82RM mf +0.06 ( R 2 =0.79; n=24), RM t30 =0.79RM mf +0.08 ( R 2 =0.85; n=29) and RI tIP =0.89RI mf +0.02 ( R 2 =0.81; n=24), RI t30 =0.83RI mf +0.05 ( R 2 =0.88; n=29). We suggest that wave reflection can be derived from uncalibrated aortic pressure alone, even when no clear inflection point is distinguishable and AI cannot be obtained. Epidemiological studies should establish its clinical value.

Background and Purpose— We addressed whether dynamic cerebral autoregulation (dCA) is affected in middle cerebral artery (MCA) territory (MCAS) and lacunar ischemic stroke (LS). Methods— Blood pressure (MAP) and MCA velocity (V) were measured in 10 patients with large MCAS (National Institutes of Health Stroke score, 17±2; mean±SEM), in 10 with LS (score, 9±1), and in 10 reference subjects. dCA was evaluated in time (delay of the MCA V mean counter-regulation during changes in MAP) and frequency domains (cross-spectral MCA V mean -to-MAP phase lead). Results— In reference subjects, latencies for MAP increments (5.3±0.5 seconds) and decrements (5.6±0.5 seconds) were comparable, and low frequency MCA V mean -to-MAP phase lead was 56±5 and 59±5° (left and right hemisphere). In MCAS, these latencies were 4.6±0.7 and 5.6±0.5 seconds in the nonischemic hemisphere and not detectable in the ischemic hemisphere. In the unaffected hemisphere, phase lead was 61±6° versus 26±6° on the ischemic side ( P Conclusions— In large MCAS infarcts, dynamic cerebral autoregulation was impaired in the affected hemisphere. In LS, dynamic cerebral autoregulation was impaired bilaterally, a finding consistent with the hypothesis of bilateral small vessel disease in patients with lacunar infarcts.

Reduction in plasma volume is a major contributor to orthostatic tachycardia and hypotension after spaceflight. We set out to determine time- and frequency-domain baroreflex (BRS) function during preflight baseline and venous occlusion and postflight orthostatic stress, testing the hypothesis that a reduction in central blood volume could mimic the postflight orthostatic response. In five cosmonauts, we measured finger arterial pressure noninvasively in supine and upright positions. Preflight measurements were repeated using venous occlusion thigh cuffs to impede venous return and “trap” an increased blood volume in the lower extremities; postflight sessions were between 1 and 3 days after return from 10- to 11-day spaceflight. BRS was determined by spectral analysis and by PRVXBRS, a time-domain BRS computation method. Although all completed the stand tests, two of five cosmonauts had drastically reduced pulse pressures and an increase in heart rate of ∼30 beats/min or more during standing after spaceflight. Averaged for all five subjects in standing position, high-frequency interbeat interval spectral power or transfer gain did not decrease postflight. Low-frequency gain decreased from 8.1 (SD 4.0) preflight baseline to 6.8 (SD 3.4) postflight ( P = 0.033); preflight with thigh cuffs inflated, low-frequency gain was 9.4 (SD 4.3) ms/mmHg. There was a shift in time-domain-determined pulse interval-to-pressure lag, Tau, toward higher values ( P < 0.001). None of the postflight results were mimicked during preflight venous occlusion. In conclusion, two of five cosmonauts showed abnormal orthostatic response 1 and 2 days after spaceflight. Overall, there were indications of increased sympathetic response to standing, even though we can expect (partial) restoration of plasma volume to have taken place. Preflight venous occlusion did not mimic the postflight orthostatic response.

Cardiovascular response to fast posture change can be used to model individual orthostatic response under normal circumstances and after spaceflight. We set out to construct a computer-controlled tilt table suitable for repeated sinusoidal tilt motion as well as fast, single head-up tilt (HUT). The movement profile of the table was designed to prevent muscle tensing and limit vestibular stimulation.On the new table, 20 healthy subjects underwent a protocol of fast HUT and sinusoidal tilt motion at 2.5 tilts per minute. BP was measured non-invasively (Finapres). Time domain dynamic response to HUT and frequency domain response to sinusoidal tilts were derived from the beat-to-beat BP and from interbeat-interval (IBI) series.Tilt motion did not induce dizziness and was experienced by all subjects as smooth. The systolic BP response to fast HUT correlated mildly with the systolic BP spectral power at the sinusoidal tilt frequency (R = 0.47). The IBI response to fast HUT correlated well with the IBI power at the sinusoidal tilt frequency (R = 0.74).In this study we presented a computer controlled tilt table capable of fast posture change and sinusoidal tilts. An exploratory protocol demonstrated that the table is suitable for obtaining cardiovascular response to posture change for modeling purposes.

Contains fulltext : 58704.pdf (Publisher’s version ) (Closed access) Iatrogenic bilateral denervation of carotid sinus baroreceptors may occur as a complication of carotid body tumor resection and radiation therapy of the neck. The acute phase of the resulting syndrome of baroreflex failure is characterized by a limited blood pressure buffering capacity against excessive rise or fall in response to emotional and physical stimuli like sexual arousal and cold. Paroxysms of severe hypertension and tachycardia, accompanied by excessive increments in sympathetic tone and catecholamine plasma levels, were ascribed to loss of tonic inhibitory influence of baroreceptors on sympathetic tone. Bilateral anesthetic blockade of baroreceptor afferent nerves was shown to result in a strong increase in muscle sympathetic nerve activity and disruption of its normal patterning. This chapter reviews our findings on the long-term effects of iatrogenic baroreflex trauma on the hemodynamic responses to pharmacological, physical, and emotional stress in the autonomic function laboratory as well as under daily life conditions. Chronic attenuation of baroreflex sensitivity after carotid body tumor resection and neck irradiation results in an increased blood pressure variability. However, unopposed sympathetic activation in response to physical and emotional stress appears to be limited to the acute phase of baroreflex failure.

Contains fulltext : 59280.pdf (Publisher’s version ) (Open Access) The direct vasodilatory and negative chronotropic effects of adenosine in humans are counterbalanced by a reflex increase in sympathetic nerve traffic. A suggested mechanism for this reflex includes peripheral chemoreceptor activation. We, therefore, assessed the contribution of carotid chemoreceptors to sympatho-excitation by adenosine. Muscle sympathetic nerve activity was recorded during adenosine infusion (140 microg.kg(-1).min(-1) for 5 min) in five patients lacking carotid chemoreceptors after bilateral carotid body tumour resection (one male and four female, mean age 51 +/- 11 years) and in six healthy controls (two male and four female, mean age 50 +/- 7 years). Sympathetic responses to sodium nitroprusside injections were assessed to measure baroreceptor-mediated sympathetic activation. In response to adenosine, controls showed no change in blood pressure, an increase in heart rate (+48.2 +/- 13.2%; P

In man assuming the upright position, end-tidal P(CO(2)) (P(ETCO(2))) decreases. With the rising interest in cerebral autoregulation during posture change, which is known to be affected by P(ETCO(2)), we sought to determine the factors leading to hypocapnia during standing up from the supine position. To study the contribution of an increase in tidal volume (V(T)) and breathing frequency, a decrease in stroke volume (SV), a ventilation-perfusion (V/Q) gradient and an increase in functional residual capacity (FRC) to hypocapnia in the standing position, we developed a mathematical model of the lung to follow breath-to-breath variations in P(ETCO(2)). A gravity-induced apical-to-basal V/Q gradient in the lung was modelled using nine lung segments. We tested the model using an eight-subject data set with measurements of V(T), pulmonary O(2) uptake and breath-to-breath lumped SV. On average, the P(ETCO(2)) decreased from 40 mmHg to 36 mmHg after 150 s standing. Results show that the model is able to track breath-to-breath P(ETCO(2)) variations (r(2)= 0.74, P P 0.05). Model parameter sensitivity analysis demonstrates that the decrease in P(ETCO(2)) during standing is due primarily to increased V(T), and transiently to decreased SV and increased FRC; a slight gravity-induced V/Q mismatch also contributes to the hypocapnia. The influence of cardiac output on hypocapnia in the standing position was verified in experiments on human subjects, where first breathing alone, and then breathing, FRC and V/Q were controlled.

During standing, both the position of the cerebral circulation and the reductions in mean arterial pressure (MAP) and cardiac output challenge cerebral autoregulatory (CA) mechanisms. Syncope is most often associated with the upright position and can be provoked by any condition that jeopardizes cerebral blood flow (CBF) and regional cerebral tissue oxygenation (cO2Hb). Reflex (vasovagal) responses, cardiac arrhythmias, and autonomic failure are common causes. An important defense against a critical reduction in the central blood volume is that of muscle activity (“the muscle pump”), and if it is not applied even normal humans faint. Continuous tracking of CBF by transcranial Doppler-determined cerebral blood velocity ( Vmean) and near-infrared spectroscopy-determined cO2Hb contribute to understanding the cerebrovascular adjustments to postural stress; e.g., MAP does not necessarily reflect the cerebrovascular phenomena associated with (pre)syncope. CA may be interpreted as a frequency-dependent phenomenon with attenuated transfer of oscillations in MAP to Vmeanat low frequencies. The clinical implication is that CA does not respond to rapid changes in MAP; e.g., there is a transient fall in Vmeanon standing up and therefore a feeling of lightheadedness that even healthy humans sometimes experience. In subjects with recurrent vasovagal syncope, dynamic CA seems not different from that of healthy controls even during the last minutes before the syncope. Redistribution of cardiac output may affect cerebral perfusion by increased cerebral vascular resistance, supporting the view that cerebral perfusion depends on arterial inflow pressure provided that there is a sufficient cardiac output.

Objective To investigate whether bilateral carotid body tumor resection invariably and chronically affects arterial baroreflex or peripheral chemoreflex function. Methods We studied eight consecutive patients (two men and six women; ages 48.1 +/- 11.8 years), a median time of 3.4 years (range 1.3-20.6 years) after bilateral carotid body tumor resection, and 12 healthy control individuals (eight men and four women; ages 53.7 +/- 10.1 years). Baroreflex sensitivity (phenylephrine), blood pressure and its variability (24 h Spacelabs and 5 h Portapres recordings), responses to standard cardiovascular reflex tests and the ventilatory responses to normocapnic and hypercapnic hypoxia were assessed. Results Baroreflex sensitivity was lower in patients (6.4 +/- 7.2 ms/mmHg) than in controls (14.7 +/- 6.6 ms/mmHg; P +/- 0.011). Mean office blood pressure and heart rate were normal in patients (1123.3 +/- 11.9/79.0 +/- 7.3 mmHg and 67.5 +/- 9.4 beats/min, respectively) and controls (117.8 +/- 10.6/74.0 +/- 6.8 mmHg and 61.1 +/- 9.2 beats/min, respectively). Blood pressure variability was increased during ambulatory measurements. Three patients exhibited orthostatic hypotension. The Valsalva ratio, an index of baroreflex-mediated cardiovagal innervation, was lower in patients (1.4 +/- 0.2) than in controls (1.8 +/- 0.5; P +/- 0.008). The normocapnic ventilatory response to hypoxia was absent in all patients, whereas a small residual response to hypoxia was observed under hypercapnic conditions in two patients. Conclusions Bilateral carotid body tumor resection results in heterogeneous expression of arterial baroreflex dysfunction, whereas the normocapnic hypoxic drive is invariably abolished as a result of peripheral chemoreflex failure. (C) 2003 Lippincott Williams Wilkins

Item does not contain fulltext Experimental denervation in animals has shown that carotid baro- and chemoreceptors play an eminent role in maintaining blood pressure and blood gas homeostasis. Denervation of carotid sinus baro- and chemoreceptors in humans may occur as a complication of invasive interventions on the neck or after experimental surgical treatment in asthma. In this topical review, the short- and long-term effects of carotid baro- and chemoreceptor denervation on the control of circulation and ventilation in humans are discussed. Carotid baroreceptor denervation in humans causes a persistent decrease in vagal and sympathetic baroreflex sensitivity and an increase in blood pressure variability; however, carotid denervation does not lead to chronic hypertension. Therefore, although carotid baroreceptors contribute to short-term blood pressure control, other receptors are able to maintain normal chronic blood pressure levels in the absence of carotid baroreceptors. Conversely, carotid chemoreceptor denervation leads to permanent abolition of normocapnic ventilatory responses to hypoxia and reduced ventilatory responses to hypercapnia.

Bilateral carotid body tumor resection causes a permanent attenuation of vagal baroreflex sensitivity. We retrospectively examined the effects of bilateral carotid body tumor resection on the baroreflex control of sympathetic nerve traffic. Muscle sympathetic nerve activity was recorded in 5 patients after bilateral carotid body tumor resection (1 man and 4 women, 51±11 years) and 6 healthy control subjects (2 men and 4 women, 50±7 years). Baroreflex sensitivity was calculated from changes in R-R interval and muscle sympathetic nerve activity in response to bolus injections of phenylephrine and nitroprusside. In addition, sympathetic responses to the Valsalva maneuver and cold pressor test were measured. The integrated neurogram of patients and control subjects contained a similar pattern of pulse synchronous burst of nerve activity. Baroreflex control of both heart rate and sympathetic nerve activity were attenuated in patients as compared with control subjects [heart rate baroreflex sensitivity: 3.68±0.93 versus 11.61±4.72 ms/mm Hg (phenylephrine, P =0.011) and 2.53±1.36 versus 5.82±1.94 ms/mm Hg (nitroprusside, P =0.05); sympathetic baroreflex sensitivity: 3.70±2.90 versus 7.53±4.12 activity/100 beats/mm Hg (phenylephrine, P =0.10) and 3.93±4.43 versus 15.27±10.03 activity/100 beats/mm Hg (nitroprusside, P =0.028)]. The Valsalva maneuver elicited normal reflex changes in muscle sympathetic nerve activity, whereas heart rate responses were blunted in the patients with bilateral carotid body tumor resection. Maximal sympathetic responses to the cold pressor test did not differ between the two groups. Denervation of carotid sinus baroreceptors as the result of bilateral carotid body tumor resection produces chronic impairment of baroreflex control of both heart rate and sympathetic nerve activity. During the Valsalva maneuver, loss of carotid baroreflex control of heart rate is less well compensated for by the extra carotid baroreceptors than the control of muscle sympathetic nerve activity.

Item does not contain fulltext The literature on the involvement of the autonomic nervous system (ANS) in amyotrophic lateral sclerosis (ALS) is conflicting. We therefore investigated several aspects of autonomic function, namely muscle sympathetic nerve activity (MSNA), blood pressure, cardiac function (electrocardiogram; ECG), and respiration in 16 patients with sporadic ALS and in 12 age-matched healthy volunteers, both at rest and during sympathoexcitatory stimulation. We measured MSNA by provoking venous pooling during short-lasting lower body negative pressure (LBNP) and during the cold pressor test (CPT). To assess the vagal (baroreflex) control of heart rate (HR), we measured spontaneous baroreflex sensitivity (BRS). To assess the involvement of the ANS beyond the cardiovascular system, we measured the sympathetic skin response (SSR). The stand-up test showed that none of the subjects had orthostatic intolerance. In comparison with the control group, the ALS patients had an increased HR and a decreased BRS at rest, and a reduced MSNA response to LBNP. The CPT response was normal and the total MSNA at rest did not differ significantly from that of controls. The latencies of the palmar and plantar SSR were prolonged, and in 3 ALS patients there was no plantar SSR. The results indicate that the sympathetic nervous system shows subtle abnormalities in ALS, predominantly sympathetic overactivity. They also point to the involvement of the preganglionic sympathetic column as the cause of the higher sympathetic activity and the absence of SSR. The higher sympathetic activity is postulated to be due to changes in modulation of the sympathetic system, whereas the absence of the SSR is probably caused by disruption of the reflex pathway.

Item does not contain fulltext PURPOSE: Denervation of the carotid sinus causes baroreflex and chemoreflex failure, resulting in labile hypertension and loss of hypoxic responsiveness. We investigated whether radiation therapy for laryngeal or pharyngeal cancer affects baroreflex and chemoreflex function. METHODS AND MATERIALS: Twelve patients were studied after radiation therapy for locally advanced laryngeal or pharyngeal cancer (11 male, 1 female, age: 56.0 +/- 7.9 years), 3.3 years (median; range 1.0-4.7) after radiotherapy and 15 healthy controls (11 male, 4 female, 53.4 +/- 9.2 years). We measured baroreflex sensitivity (phenylephrine), blood pressure level and variability (24-h Spacelabs and 5-h Portapres recordings), responses to cardiovascular reflex tests, and the ventilatory responses to normocapnic and hypercapnic hypoxia. RESULTS: Baroreflex sensitivity was lower in patients (9.7 +/- 7.8 ms/mm Hg) than in controls (17.5 +/- 10.3 ms/mm Hg, p = 0.011). Mean office blood pressure was significantly higher in patients (141.5 +/- 27.8/89.2 +/- 10.6 mm Hg, 63.3 +/- 12.3 bpm) than in controls (117.3 +/- 10.1/75.1 +/- 6.8 mm Hg, 61.8 +/- 10.8 bpm). Blood pressure variability was not different between groups, nor were the responses to reflex tests. The normo/hypercapnic ventilatory response to hypoxia was similar in patients (0.21 +/- 0.10/1.37 +/- 0.60 L/min/%) and controls (0.22 +/- 0.16/1.19 +/- 0.78 L/min/%). CONCLUSIONS: Radiation therapy for laryngeal or pharyngeal carcinoma does not affect chemoreflex function, but results in an attenuated baroreflex sensitivity. Clinically relevant blood pressure lability is absent however.

Orthostatic intolerance is common when astronauts return to Earth: after brief spaceflight, up to two-thirds are unable to remain standing for 10 min. Previous research suggests that susceptible individuals are unable to increase their systemic vascular resistance and plasma noradrenaline concentrations above pre-flight upright levels. In this study, we tested the hypothesis that adaptation to the microgravity of space impairs sympathetic neural responses to upright posture on Earth. We studied six astronauts ∼72 and 23 days before and on landing day after the 16 day Neurolab space shuttle mission. We measured heart rate, arterial pressure and cardiac output, and calculated stroke volume and total peripheral resistance, during supine rest and 10 min of 60 deg upright tilt. Muscle sympathetic nerve activity was recorded in five subjects, as a direct measure of sympathetic nervous system responses. As in previous studies, mean (± s.e.m.) stroke volume was lower (46 ± 5 vs. 76 ± 3 ml, P = 0.017) and heart rate was higher (93 ± 1 vs. 74 ± 4 beats min−1, P = 0.002) during tilt after spaceflight than before spaceflight. Total peripheral resistance during tilt post flight was higher in some, but not all astronauts (1674 ± 256 vs. 1372 ± 62 dynes s cm−5, P = 0.32). No crew member exhibited orthostatic hypotension or presyncopal symptoms during the 10 min of postflight tilting. Muscle sympathetic nerve activity was higher post flight in all subjects, in supine (27 ± 4 vs. 17 ± 2 bursts min−1, P = 0.04) and tilted (46 ± 4 vs. 38 ± 3 bursts min−1, P = 0.01) positions. A strong (r2 = 0.91–1.00) linear correlation between left ventricular stroke volume and muscle sympathetic nerve activity suggested that sympathetic responses were appropriate for the haemodynamic challenge of upright tilt and were unaffected by spaceflight. We conclude that after 16 days of spaceflight, muscle sympathetic nerve responses to upright tilt are normal.

In healthy humans blood pressure and heart periods fluctuate at respiratory and other frequencies. The extent of these fluctuations is situation and age dependent. Although literature concurs that most of these fluctuations are reflex driven, some insist on an exemption for the respiratory

Blood pressure (BP) and heart rate (HR) are continually varying. The nervous mechanisms behind this variability have been studied extensively in non-human animal models (for reviews, see Eckberg & Sleight, 1992). Since the 1980s, the combined availability of non-invasive blood pressure measurement by the Penaz-Wesseling Finapres, and more and more powerful computers in the laboratory, have revived research into prevalence and physiological meaning of this variability in humans. When Fourier analysis was applied to analysis of BP variability (BPV) and HR variability (HRV), two frequency peaks stood out: one around the respiratory frequency and one around 0.1 Hz, or one oscillation in 10 s. These frequencies had been observed in blood pressure recordings before, actually over 130 years ago: Traube-Hering waves (coupled to respiration) and Mayer waves, the 0.1 Hz and slower oscillations. In the earlier research it had been established that oscillating sympathetic activity causes the Mayer waves in blood pressure. The respiration-coupled blood pressure oscillations were partly explained by mechanical effects of respiration and possibly by the vagally induced heart period oscillations coupled to respiration, known as respiratory sinus arrhythmia (RSA) (Eckberg & Sleight, 1992). Due to the easy availability of ECG recordings, heart rate oscillations have extensively been studied, much more so than blood pressure oscillations. In this field of research the idea was put forward that the 0.1 Hz oscillation in HRV, also called low frequency or LF, might be used as indicator of sympathetic activity. The respiratory (high frequency or HF) frequency in HR must be due to vagal activity, the vagus nerve being the only one that can make HRV follow at the respiratory rate; atropine also completely blocks RSA. It was but one step to suggest that the relative amounts of LF and HF HRV gave an impression of the balance between sympathetic and parasympathetic (vagal) outflow to the heart. Indeed, on many occasions where one would expect the balance to shift either way, the LF/HF ratio shifted similarly, even though it is common knowledge that atropine not only blocks HF but most of LF as well, demonstrating that both peaks in HRV are due to (mainly) vagal activity. A review of this theory and the arguments is given by Camm et al. (1996). This leaves a discrepancy: why would the LF/HF HRV ratio have a relation to the sympathetic/vagal outflow at all? The answer lies in the baroreflex: LF HRV is riding on a blood pressure oscillation. That, too, explains the phase relationship: blood pressure is leading the HR wave. The basis of this particular oscillation is, still, an unsettled matter. In this issue of The Journal of Physiology, Cooke et al. (1999) have very carefully investigated the prevalence of LF oscillations in healthy test humans who were subjected to graded passive orthostatic tilt on a tilt table. Efferent sympathetic activity, measured directly from the peroneal nerve, increased in proportion to the orthostatic load. However, in spite of large changes in baroreceptor loading and accompanying nerve traffic, the frequency of the LF band did not change at all. In the view of the authors, this pleads against the current theory for the origin of LF: up until now, many shared the view that this oscillation found its origin in the slowness of the baroreflex feedback to changes in peripheral resistance (resonance theory). This was supported by computer simulations of the cardiovascular control system and by other supporting evidence (DeBoer et al. 1987). Cooke et al. (1999) are inclined to put the origin of LF oscillations in some pacemaker, possibly in the CNS, rather than in the baroreflex. A comparable, unsettled matter is the origin of RSA. One explanation has been to see it as a baroreflex phenomenon: BP changing mechanically by the respiratory act, and HR following at the speed of vagal control, within the same beat (DeBoer et al. 1987). Another explanation would place the origin of RSA in the CNS, where co-activity of the vagus nerve with respiratory activity would drive HR in the same frequency as respiration (Taylor & Eckberg, 1996). Careful analysis of the phase relationships between respiratory oscillations in HR and BP should give the answer: is HR leading, or is BP?Cooke et al. (1999) have dealt with this issue as well: their analysis yields a phase advance for HR compared with BP changes. A comparable phase advance had been found earlier, by slightly different (Fourier) analysis methods (DeBoer et al. 1987). However, this had led those authors to give the advantage to BP, favouring the baroreflex hypothesis. The basic problem here is how one turns essentially discontinuous signals (systolic pressure values, heart period durations) into continuous ones that are input into the Fourier analysis. This calls for a meta-analysis of methods and results, rather than more experiments. The study by Cooke et al. (1999) has been one of the most carefully executed experimental studies in literature to date, so the final answer should be at hand. Where does this leave the LF/HF ratio as a measure for sympatho-vagal balance? From the Cooke et al. (1999) paper we learn how LF BP increases at increasing orthostatic stress. At the same time respiration-related vagal activity decreases, resulting in less HF HRV and almost unchanged LF HRV. The net effect is that LF/HF HRV, indeed, would shift as predicted. But then, so what? One may wonder if we should put much more effort in to what is clearly an epiphenomenon of basic processes in central cardiovascular control. The paper by Cooke et al. (1999) has probably not put an end to LF/HF HRV computations, but sends a clear warning sign to all who take its physiology seriously.

The occurrence of vasovagal fainting is common in young subjects, but the origin of the precipitating hemodynamic mechanisms involved remain a subject of considerable speculation. Vasovagal fainting is not a sudden onset phenomenon, early failure of vascular resistance responses occurs in faint-prone young subjects. The variability of hemodynamic responses during the actual faint is large, but the main mechanism operative during, is withdrawal of sympathetic outflow to blood vessels in skeletal muscle with impairment of ability to maintain vasomotor tone.

In the present experiments it was decided to have each test-subject serve as his own control by fitting the test-subjects with a G-suit and comparing the condition of inflated G-suit to the normal situation. G-suit inflation was intended to only displace blood on the venous side of the circulation, not to increase total peripheral resistance. Therefore, a very modest inflation of 50 mmHg was applied. This was considered sufficient to expel most of the blood from the venous pool in abdomen and legs, even under the condition of increased G-loading in the pull-up phase. The parabolas were to be undergone in three body positions: standing upright, sitting and supine. The prediction of the experimental outcome was that we would find no difference between transients with and without G-suit inflation in the supine position, that an initial overshoot in pressure and stroke volume in the upright position would be very much damped by the G-suit, even more in the standing than in the sitting position. Studies were performed in 5 flights of NASA's KC-135, in January 1993. Per flight 40 parabolas were flown in an adapted 'roller coaster profile', i.e. 0-G phases were followed by a 2-G pull-out phase, after a very brief 1-G phase again followed by the next 2-G pull-up phase. This sequence was flown for 10 parabolas, then a 1-G horizontal flight period was inserted. The first 3 parabolas of each set of 10 the subjects were sitting upright, seat belt fastened. The next three they were standing, feet stuck under a load strap on the floor, stabilizing themselves by a grip on the ceiling. Then three parabolas were flown with the test-subject supine, loosely attached to the floor by a load strap and further aided by a grip to another strap on the floor. The last parabola of a set was used as 'spare' to repeat any failed maneuver.

The objective of this study was to determine the effect of aging on beat-to-beat blood pressure and pulse interval variability in resting conditions and to determine the effect of aging on the sympathetic and vagal influence on the cardiovascular system by power spectral analysis of blood pressure and pulse interval. We studied three groups of healthy, normotensive subjects: young (10 to 15 years, n = 16), adult (20 to 40 years, n = 16), and elderly (70 to 90 years, n = 25). Beat-to-beat blood pressure was measured by Finapres during 20 minutes supine and 10 minutes standing. Overall systolic and diastolic blood pressures and pulse interval variability were determined as SD and as coefficient of variation. Also, relative powers of the mid-frequency (0.08 to 0.12 Hz) and high-frequency bands (0.15 to 0.40 Hz) were determined by spectral analysis. In these subjects no differences in blood pressure variability (either as SD or coefficient of variation) were found between age groups, except for the coefficient of variation of standing diastolic blood pressure, which decreased with aging. Pulse interval variability decreased with aging. Power of the mid-frequency band of systolic and diastolic blood pressures was markedly decreased in the elderly, especially in the standing position. Power of the high-frequency band of pulse interval was also decreased in the elderly. Baroreflex sensitivity calculated by fast Fourier transformation spectral analysis was decreased in the elderly subjects compared with the younger groups. In conclusion, we found no change in the overall variability of blood pressure with aging. Mid-frequency spectral power of blood pressure and mid- and high-frequency spectral powers of pulse interval variability were decreased in the elderly. These results suggest that aging does not merely influence the magnitude of blood pressure and pulse interval variability but causes a complex rearrangement of the variability pattern by changes in neurocardiovascular regulation.

to the editor: Science is not decided by democratic vote. If it were, my “Counterpoint” would now probably be counted as outvoted. I thank those who took part in this debate and I will reciprocate below. First, let me add a note on the function and importance of modeling in physiology as I see

Introduction: Hypovolemia and hypovolemic shock are life-threatening conditions that occur in numerous clinical scenarios. Near-infrared spectroscopy (NIRS) has been widely explored, successfully and unsuccessfully, in an attempt to use it as an early detector of hypovolemia by measuring tissue oxygen saturation (StO(2)). In order to investigate the measurement site dependence and probe dependence of NIRS in response to hemodynamic changes, such as hypovolemia, we applied a simple cardiovascular challenge: a posture change from supine to upright, causing a decrease in stroke volume (as in hypovolemia) and a heart rate increase in combination with peripheral vasoconstriction to maintain adequate blood pressure. Methods: Multi-depth NIRS was used in nine healthy volunteers to assess changes in StO(2) in the thenar and forearm in response to the hemodynamic changes associated with a posture change from supine to upright. Results: A posture change from supine to upright resulted in a significant increase (P < 0.001) in heart rate. Thenar StO(2) did not respond to the hemodynamic changes following the posture change, whereas forearm StO(2) did. Forearm StO(2) was significantly lower (P < 0.001) in the upright position compared to supine for all probing depths. Conclusion: The primary findings in this study were that forearm StO(2) is a more sensitive parameter to hemodynamic changes than thenar StO(2) and that the depth at which StO(2) is measured is of minor influence. Our data support the use of forearm StO(2) as a sensitive parameter for the detection of central hypovolemia and hypovolemic shock in (trauma) patients.

Neurocardiovascular control during postural change was investigated in two teenage females with complaints of dizziness almost immediately on standing up. Blood pressure and heart rate were monitored continuously with a FinapresTM device. On standing there was a brief but marked fall in blood pressure between 5–10 s after the onset of the manoeuvre. The maximum fall in systolic and diastolic blood pressure was 65 mmHg and 40 mmHg respectively in the first subject, and 58mmHg and 29 mmHg respectively in the second subject. In both, postural tachycardia was present after 1–2 min of standing with heart rate increasing by up to 39 beats/min in the first subject and 60 beats/min in the second subject. On a follow-up examination 3 years later these changes had disappeared in the first subject while they persisted in the second subject, when she was studied two years later. We conclude that in these patients initial postural dizziness is related to an excessive fall in blood pressure upon standing.

In a patient with tetanus we tested the hypothesis that the hyperadrenergic cardiovascular instability might be due to impairment of the baroreceptor reflex by the tetanus toxin. Baroreflex sensitivity assessed with the phenylephrine method was found to be normal. Changes in arterial pressure correlated inversely with relative changes in plasma volume but not with plasma catecholamine levels. There were both extreme hypo- and hyper-adrenergic episodes. We conclude that sympathetic overactivity in tetanus temporarily overrules a functionally intact baroreflex leading to severe blood pressure instability with episodes of hypertension.

1. The magnitude and time course of circulatory adaptation to active standing were investigated in healthy premenarchic girls and boys (n = 24; 10–14 years old) by non-invasive measurement of heart rate and continuous finger blood pressure (Finapres). 2. Four subjects (two girls, two boys) showed presyncopal symptoms after 4–9 min of free standing. 3. In the 20 non-fainting subjects, changes in blood pressure and heart rate upon standing did not differ between girls (n = 10) and boys (n = 10). In the initial phase of standing (first 30 s) systolic and diastolic blood pressures dropped by 22 ± 14 (mean ± sd) and 16 ± 7 mmHg, respectively, at 8 ± 2 s. Blood pressure subsequently recovered and showed an overshoot in all subjects. The transient drop in blood pressure was accompanied by an increase in heart rate of 40 ± 7 beats/min. These characteristic transient changes were not observed with passive head-up tilt. During the early steady-state phase (2 min), systolic blood pressure was similar to the supine value and diastolic blood pressure rose by 11 ± 5 mmHg. Heart rate increased by 25 ± 11 beats/min. In six of the subjects (three girls, three boys) the increase in heart rate exceeded 30 beats/min (postural tachycardia). Little further changes were observed during prolonged (10 min) standing. 4. Typical findings in the four near-fainting subjects were higher supine heart rates, no blood pressure overshoot in the initial phase (in three out of four subjects), postural tachycardia in the early steady-state phase and progressive decreases in blood pressure and heart rate afterwards. 5. In conclusion, for investigation of orthostatic circulatory adaptation in childhood it is important to pay attention to the dynamics of the circulatory response. No important differences appear to exist in orthostatic circulatory control between premenarchic girls and boys: orthostatic tachycardia and fainting appear to be common in both.

1. Continuous orthostatic responses of blood pressure and heart rate were measured in 40 healthy and active elderly subjects over 70 years of age in order to assess the time course and rapidity of orthostatic cardiovascular adaptation in old age. 2. During the first 30 s (initial phase) the effects of active standing and passive head-up tilt closely resembled those observed earlier in younger age groups. Standing up was accompanied by a drop (mean ± SD) in systolic and diastolic blood pressures of 26 ± 13 mmHg and 12 ± 18 mmHg, respectively, at around 10 s, and a subsequent rise up to 11 ± 17 mmHg and 8 ± 6 mmHg above supine values at around 20 s. The drop in blood pressure upon standing was accompanied by a transient increase in heart rate with a maximum of 13 beats/min, followed by a gradual decrease to 7 beats/min above supine levels. These characteristic transient changes were absent upon a passive head-up tilt. 3. After 1–2 min of standing (early steady-state phase) diastolic blood pressure and heart rate increased significantly after active and passive postural changes. On average, for all subjects systolic blood pressure tended to increase from control during 5–10 min standing, reaching a significant difference at 10 min. During standing, the largest increases in systolic blood pressure were found in subjects with the lowest supine blood pressures. 4. In conclusion, for the investigation of orthostatic circulatory responses in elderly subjects the following factors have to be taken into account: active versus passive changes in posture, the timing of the blood pressure reading, and the level of supine blood pressure.

The following letter is in response to the Point:Counterpoint series “Cardiovascular variability is/is not an index of autonomic control of circulation” that appeared in the August issue (vol. 101: 676-682, 2006; ). To the Editor : The Point