Automated analysis of finger blood pressure recordings provides insight in determinants of baroreflex sensitivity and heart rate variability-the HELIUS study.

Sympathovagal balance is important in the pathogenesis of hypertension and independently associated with mortality. We evaluated the value of automated analysis of cross-correlation baroreflex sensitivity (xBRS) and heart rate variability (HRV) and its relationship with clinical covariates in 13,326 participants from the multi-ethnic HELIUS study. Finger blood pressure (BP) was continuously recorded, from which xBRS, standard deviation of normal-to-normal intervals (SDNN), and squared root of mean squared successive difference between normal-to-normal intervals (RMSDD) were determined. A subset of 3356 recordings > 300 s was used to derive the minimally required duration by comparing shortened to complete recordings, defined as intraclass correlation (ICC) > 0.90. For xBRS and SDNN, 120 s and 180 s were required (ICC 0.93); for RMSDD, 60 s (ICC 0.94) was sufficient. We included 10,252 participants (median age 46 years, 54% women) with a recording > 180 s for the regression. xBRS, SDNN, and RMSDD decreased linearly up to 50 years of age. For xBRS, there was a signification interaction with sex, with for every 10 years a decrease of 4.3 ms/mmHg (95%CI 4.0-4.6) for men and 5.9 ms/mmHg (95%CI 5.6-6.1) for women. Using splines, we observed sex-dependent nonlinearities in the relation with BP, waist-to-hip-ratio, and body mass index. Future studies can help unravel the dynamics of these relations and assess their predictive value. Panel 1 depicts automatic analysis and filtering of finger BP recordings, panel 2 depicts computation of xBRS from interpolated beat to beat data of systolic BP and interbeat interval, and (IBI) SDNN and RMSDD are computed directly from the filtered IBI dataset. Panel 3 depicts the results of large-scale analysis and relation of xBRS with age, sex, blood pressure and body mass index.

Autonomic Dysfunction Precedes Development of Rheumatoid Arthritis: A Prospective Cohort Study.

BACKGROUND: Heart rate variability (HRV) is a validated method to establish autonomic nervous system (ANS) activity. Rheumatoid arthritis (RA) is accompanied by ANS imbalance. We hypothesized that ANS dysfunction may precede the development of RA, which would suggest that it plays a role in its etiopathogenesis. METHODS: First, we assessed HRV parameters in supine (resting) and upright (active) position in healthy subjects (HS, n=20), individuals at risk of developing arthritis (AR subjects, n=50) and RA patients (RA, n=20). Next, we measured resting heart rate (RHR), a parasympathetic HRV parameter, in an independent prospective cohort of AR subjects (n=45). We also evaluated expression levels of the parasympathetic nicotinic acetylcholine receptor type 7 (α7nAChR) on circulating monocytes. FINDINGS: Both AR subjects (68 beats per minute (bpm), interquartile range (IQR) 68-73) and RA patients (68bpm, IQR 62-76) had a significantly higher RHR compared to HS (60bpm, IQR 56-63). RHR was significantly higher at baseline in individuals who subsequently developed arthritis. Expression levels of α7nAChR were lower in AR subjects with RHR ≥70bpm compared to those with RHR <70bpm, consistent with reduced activity of the parasympathetic cholinergic anti-inflammatory pathway. INTERPRETATION: These data support the notion that autonomic dysfunction precedes the development of RA.

Prolonged post-faint hypotension can be reversed by dynamic tension.

A severe variant of vasovagal syncope, observed during tilt tests and blood donation has recently been termed "prolonged post-faint hypotension" (PPFH). A 49-year-old male with a life-long history of severe fainting attacks underwent head-up tilt for 20 min, and developed syncope 2 min after nitroglycerine spray. He was unconscious for 40 s and asystolic for 22 s. For the first 2 min of recovery, BP and HR remained low (65/45 mmHg and 40 beats/min) despite passive leg-raising. Blood pressure (and symptoms) only improved following active bilateral leg flexion and extension ("dynamic tension"). During PPFH, when vagal activity is extreme, patients may require central stimulation as well as correction of venous return.

Dynamic adaptation of cardiac baroreflex sensitivity to prolonged exposure to microgravity: data from a 16-day spaceflight.

This study explored the process of arterial baroreflex adaptation to microgravity, starting from the first day of flight, during the 16-day STS-107 Columbia Space Shuttle mission. Continuous blood pressure (BP), ECG, and respiratory frequency were collected in four astronauts on ground (baseline) and during flight at days 0-1, 6-7, and 12-13, both at rest and during moderate exercise (75 W) on a cycle ergometer. Sensitivity of the baroreflex heart rate control (BRS) was assessed by sequence and spectral alpha methods. Baroreflex effectiveness index (BEI); low-frequency (LF) power and high-frequency (HF) power of systolic BP (SBP), diastolic BP (DBP), and R-R interval (RRI); the RRI LF/HF ratio; and the RRI root mean square of successive differences (RMSSD) index were also estimated. We found that, at rest, BRS increased in early flight phase, compared with baseline (means +/- SE: 18.3 +/- 3.4 vs. 10.4 +/- 1.2 ms/mmHg; P < 0.05), and it tended to return to baseline in subsequent days. During exercise, BRS was lower than at rest, without differences between preflight and in-flight values. At rest, in the early flight phase, RMSSD and RRI HF power increased (P < 0.05) compared with baseline, whereas LF powers of SBP and DBP decreased. No statistical difference was found in these parameters during exercise before vs. during flight. These findings demonstrate that heart rate baroreflex sensitivity and markers of cardiac vagal modulation are enhanced during early exposure to microgravity, likely because of the blood centralization, and return to baseline values in subsequent flight phases, possibly because of the fluid loss. No deconditioning seems to occur in the baroreflex control of the heart.

Mathematical modeling of gravitational effects on the circulation: importance of the time course of venous pooling and blood volume changes in the lungs.

A dip in blood pressure (BP) in response to head-up tilt (HUT) or active standing might be due to rapid pooling in the veins below the heart (preload) or muscle activation-induced drop in systemic vascular resistance (afterload). We hypothesized that, in the cardiovascular response to passive HUT, where, in contrast to active standing, little BP dip is observed, features affecting the preload play a key role. We developed a baroreflex model combined with a lumped-parameter model of the circulation, including viscoelastic stress-relaxation of the systemic veins. Cardiac contraction is modeled using the varying-elastance concept. Gravity affects not only the systemic, but also the pulmonary, circulation. In accordance with the experimental results, model simulations do not show a BP dip on HUT; the tilt-back response is also realistic. If it is assumed that venous capacities are steady-state values, the introduction of stress-relaxation initially reduces venous pooling. The resulting time course of venous pooling is comparable to measured impedance changes. When venous pressure-volume dynamics are neglected, rapid (completed within 30 s) venous pooling leads to a drop in BP. The direct effect of gravity on the pulmonary circulation influences the BP response in the first approximately 5 s after HUT and tilt back. In conclusion, the initial BP response to HUT is mainly determined by the response of the venous system. The time course of lower body pooling is essential in understanding the response to passive HUT.

Orthostatic blood pressure control before and after spaceflight, determined by time-domain baroreflex method.

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 approximately 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.

Baroreflex failure: a neglected type of secondary hypertension.

The arterial baroreflex buffers abrupt transients of blood pressure and prevents pressure from rising or falling excessively. In experimental animals, baroreceptor denervation results in temporary or permanent increases in blood pressure level and variability, depending on the extent of denervation. In humans, the clinical syndrome of baroreflex failure may arise from denervation of carotid baroreceptors following carotid body tumour resection, carotid artery surgery, neck irradiation and neck trauma. The syndrome is characterised by acute malignant hypertension and tachycardia followed by labile hypertension and hypotension. Baroreflex failure can be a cause of hypertension and should also be considered in the differential diagnosis of pheochromocytoma. Patients with suspected baroreflex failure should be referred to specialised centres for diagnostic testing and treatment.

Human cerebral venous outflow pathway depends on posture and central venous pressure.

Internal jugular veins are the major cerebral venous outflow pathway in supine humans. In upright humans the positioning of these veins above heart level causes them to collapse. An alternative cerebral outflow pathway is the vertebral venous plexus. We set out to determine the effect of posture and central venous pressure (CVP) on the distribution of cerebral outflow over the internal jugular veins and the vertebral plexus, using a mathematical model. Input to the model was a data set of beat-to-beat cerebral blood flow velocity and CVP measurements in 10 healthy subjects, during baseline rest and a Valsalva manoeuvre in the supine and standing position. The model, consisting of 2 jugular veins, each a chain of 10 units containing nonlinear resistances and capacitors, and a vertebral plexus containing a resistance, showed blood flow mainly through the internal jugular veins in the supine position, but mainly through the vertebral plexus in the upright position. A Valsalva manoeuvre while standing completely re-opened the jugular veins. Results of ultrasound imaging of the right internal jugular vein cross-sectional area at the level of the laryngeal prominence in six healthy subjects, before and during a Valsalva manoeuvre in both body positions, correlate highly with model simulation of the jugular cross-sectional area (R(2) = 0.97). The results suggest that the cerebral venous flow distribution depends on posture and CVP: in supine humans the internal jugular veins are the primary pathway. The internal jugular veins are collapsed in the standing position and blood is shunted to an alternative venous pathway, but a marked increase in CVP while standing completely re-opens the jugular veins.

Serial assessment of cardiovascular control shows early signs of developing pre-eclampsia.

PURPOSE: To evaluate whether differences in autonomic cardiovascular control between normal pregnant women and women who develop pre-eclampsia later in pregnancy can be detected even before or early in pregnancy. DESIGN: We studied 42 women, 21 multigravid with a history of pre-eclampsia and 21 primigravid, before pregnancy, at 6, 8, 12, 16, 20 and 32 weeks gestation and 15 weeks after delivery. METHODS: The outcome of pregnancy was classified after delivery as normal pregnancy (NP group) or pre-eclampsia (PE group). Continuous heart rate and blood pressure were recorded by Portapres (TNO, Amsterdam, The Netherlands) during orthostatic stress, during rest in a supine and sitting position, and during paced breathing for periods of 1 min at breathing frequencies of 6, 10 and 15 breaths/min. Baroreflex gain from heart rate and blood pressure variability and the phase angle between both signals at low (approximately 0.1 Hz) and high frequency (respiratory rate) were analyzed by spectral analysis. RESULTS: Eight women were diagnosed with pre-eclampsia. Subgroups did not differ in age, weight or height. The PE group showed a significantly higher mean arterial pressure before and during pregnancy [analysis of variance (ANOVA), P = 0.001], a significantly larger initial blood pressure drop to orthostatic stress before and in the first half of pregnancy (ANOVA, P = 0.002) and a significantly larger negative phase difference during supine rest at low frequency from 8 weeks onward (ANOVA P = 0.003). CONCLUSIONS: These findings are compatible with increased resting sympathetic activity and decreased circulating volume, already present before and early in pregnancy, in women who will later develop pre-eclampsia.

Dynamic cerebral autoregulation under sinusoidal gravitational loading.

Dynamic cerebral autoregulation (CA) has been studied previously using spectral analysis of oscillations in arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV). The dynamics of the CA can be modeled as a high-pass filter. The purpose of this study is to compare CA of blood pressure oscillations induced by gravitational loading to CA during resting conditions. We subjected twelve healthy subjects to repeated sinusoidal head-up (0 degrees - 60 degrees) tilts at several set frequencies (0.07 to 0.25 Hz) on a computer controlled tilt table while we recorded ABP (Finapres) and CBFV (transcranial Doppler ultrasound). We fitted the data sets to a high-pass filter model and computed an average time constant (T). Our results show similar phase leads of CBFV to ABPbrain in the rest recording and in sinusoidal tilting, in the studied frequency range. The transfer function gain of the resting spectra increased with increasing frequency, the gain of the tilting spectra did not. Fitting the phase responses of both data sets to a high pass filter model yielded similar time constants.

[Labile hypertension due to iatrogenic denervation of the carotid sinus]. / Labiele hypertensie door iatrogene denervatie van de sinus caroticus.

Two patients, a man and a woman aged 36 and 40 years, respectively, were found to have disturbed blood pressure regulation after medical intervention in the jugular area. The man had undergone radiation therapy of the neck due to regional lymph node involvement of a nasopharyngeal carcinoma. Six years later he developed episodic complaints of headache accompanied by labile hypo- and hypertension. Mental and physical stimuli resulted in excessive sympathetic activation. In the woman, a carotid body tumour was resected bilaterally. There was an immediate onset of hypertension after surgery. In both patients, the clinical syndrome was attributed to afferent baroreflex failure due to carotid sinus denervation.

Effects of treatment of obstructive sleep apnea on circadian hemodynamics.

INTRODUCTION: The role of obstructive sleep apnea syndrome (OSAS) in the etiology of daytime hypertension is still an issue of debate, which is fed by the high prevalence of the syndrome in hypertensive patients. In this study the anti-hypertensive effect of short-term treatment of obstructive sleep apnea with nasal continuous positive airway pressure (nCPAP) was assessed. PATIENTS AND METHODS: In eight patients with documented OSAS (mean apnea index 62 apneas/h), two 24-h continuous finger blood pressure registrations (Portapres) were performed. At baseline and after 3 weeks of treatment with nCPAP. Ten hypertensive control subjects were studied. Stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were assessed by pulse contour analysis. RESULTS: Hemodynamics were highly reproducible in the controls. nCPAP therapy improved apnea-activity in all OSAS patients. This was associated with a reduction of nighttime systolic (SBP), mean arterial (MAP) and diastolic blood pressure (DBP). Treatment also reduced daytime MAP by -11 mm Hg (ranging from -27 to 1; P < 0.05), and DBP by -7 mm Hg (-24 to 3; P < 0.05). CO was significantly increased in daytime by 9% (-4 to 25; P < 0.05), whereas TPR was reduced by -15% (-34 to 3; P < 0.05). CONCLUSIONS: Treatment of OSAS caused a reduction in daytime MAP and DBP, associated with a reduction of vascular resistance. These findings are consistent with the hypothesis of a reduced sympathetic outflow at night after therapy of obstructive sleep apnea, carrying over to the day.

Noninvasive cardiac output measurement in orthostasis: pulse contour analysis compared with acetylene rebreathing.

We tested the reliability of noninvasive cardiac output (CO) measurement in different body positions by pulse contour analysis (CO(pc)) by using a transmission line model (K. H. Wesseling, B. De Wit, J. A. P. Weber, and N. T. Smith. Adv. Cardiol. Phys. 5, Suppl. II: 16-52, 1983). Acetylene rebreathing (CO(rebr)) was used as a reference method. Twelve subjects (age 21-34 yr) were studied: 1) six in whom CO(rebr) and CO(pc) were measured in the standing and 6 degrees head-down tilt (HDT) postures and 2) six in whom CO was measured in the 30 degrees HDT, supine, 30 degrees head up-tilt (HUT), and 70 degrees HUT postures on a tilt table. The CO(rebr)-to-CO(pc) ratio in (near) the supine position during rebreathing was used as the calibration factor for CO(pc) measurements. Calibrated CO(pc) (CO(cal sup)) consistently overestimated CO in the upright posture. The drop in CO with upright posture was underestimated by approximately 50%. CO(cal sup) and CO(rebr) values did not differ in the 30 degrees HDT position. Changes in the CO(rebr)-to-CO(pc) ratio are highly variable among subjects in response to a change in posture. Therefore, CO(pc) must be recalibrated for each subject in each posture.

Baroreflex failure following radiation therapy for nasopharyngeal carcinoma.

The authors present a 51-year-old man with right-sided nasopharyngeal carcinoma who was treated for regional lymph node involvement by bilateral radiation therapy of the neck. Six years later he presented with episodic complaints of headache, flushing, and palpitations accompanied by elevations of blood pressure. Examination of arterial baroreflex function indicated selective afferent carotid sinus denervation. Cross spectral analysis of spontaneous heart rate and blood pressure variability showed decreased arterial baroreflex sensitivity (6.5 ms/mm Hg). Twenty-four hour measurements of blood pressure and heart rate variability showed labile hypertension during normal daytime activities. Baroreflex failure in this patient probably represents a late complication of bilateral radiation therapy of the neck.

Circadian blood pressure and systemic haemodynamics during 42 days of 6 degrees head-down tilt.

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.