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The approach introduced by Network Physiology intends to find and quantify connectedness between close- and far related aspects of a person’s Physiome. In this study I applied a Network-inspired analysis to a set of measurement data that had been assembled to detect prospective orthostatic intolerant subjects among people who were destined to go into Space for a two weeks mission. The advantage of this approach being that it is essentially model-free: no complex physiological model is required to interpret the data. This type of analysis is essentially applicable to many datasets where individuals must be found that “stand out from the crowd”. The dataset consists of physiological variables measured in 22 participants (4f/18 m; 12 prospective astronauts/cosmonauts, 10 healthy controls), in supine, + 30° and + 70° upright tilted positions. Steady state values of finger blood pressure and derived thereof: mean arterial pressure, heart rate, stroke volume, cardiac output, systemic vascular resistance; middle cerebral artery blood flow velocity and end-tidal pCO2 in tilted position were (%)-normalized for each participant to the supine position. This yielded averaged responses for each variable, with statistical spread. All variables i.e., the “average person’s response” and a set of %-values defining each participant are presented as radar plots to make each ensemble transparent. Multivariate analysis for all values resulted in obvious dependencies and some unexpected ones. Most interesting is how individual participants maintained their blood pressure and brain blood flow. In fact, 13/22 participants had all normalized Δ-values (i.e., the deviation from the group average, normalized for the standard deviation), both for +30° and +70°, within the 95% range. The remaining group demonstrated miscellaneous response patterns, with one or more larger Δ-values, however of no consequence for orthostasis. The values from one prospective cosmonaut stood out as suspect. However, early morning standing blood pressure within 12 h after return to Earth (without volume repletion) demonstrated no syncope. This study demonstrates an integrative way to model-free assess a large dataset, applying multivariate analysis and common sense derived from textbook physiology.

BACKGROUND: Glomerular hyperfiltration resulting from an elevated intraglomerular pressure (Pglom) is an important cause of CKD, but there is no feasible method to directly assess Pglom in humans. We developed a model to estimate Pglom in patients from combined renal arterial pressure and flow measurements. METHODS: We performed hemodynamic measurements in 34 patients undergoing renal or cardiac angiography under baseline conditions and during hyperemia induced by intrarenal dopamine infusion (30 μg/kg). For each participant during baseline and hyperemia, we fitted an adapted three-element Windkessel model that consisted of characteristic impedance, compliance, afferent resistance, and Pglom. RESULTS: We successfully analyzed data from 28 (82%) patients. Median age was 58 years (IQR, 52–65), median eGFR was 95 ml/min per 1.73 m(2) (IQR, 74–100) using the CKD-EPI formula, 30% had microalbuminuria, and 32% had diabetes. The model showed a mean Pglom of 48.0 mm Hg (SD=10.1) at baseline. Under hyperemia, flow increased by 88% (95% CI, 68% to 111%). This resulted in a 165% (95% CI, 79% to 294%) increase in afferent compliance and a 13.1-mm Hg (95% CI, 10.0 to 16.3) decrease in Pglom. In multiple linear regression analysis, diabetes (coefficient, 10.1; 95% CI, 5.1 to 15.1), BMI (0.99 per kg/m(2); 95% CI, 0.38 to 1.59), and renal perfusion pressure (0.42 per mm Hg; 95% CI, 0.25 to 0.59) were significantly positively associated with baseline Pglom. CONCLUSIONS: We constructed a model on the basis of proximal renal arterial pressure and flow velocity measurements that provides an overall estimate of glomerular pressure and afferent and efferent resistance in humans. The model provides a novel research technique to evaluate the hemodynamics of CKD on the basis of direct pressure and flow measurements. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Functional HEmodynamics in patients with and without Renal Artery stenosis (HERA), NL40795.018.12 at the Dutch national trial registry (toetsingonline.nl).

Background: A recently discovered sudden cardiac arrest (SCA) syndrome is linked to a risk haplotype that harbors the dipeptidyl-peptidase 6 (DPP6) gene as a plausible culprit. Objective: Because DPP6 impacts both cardiomyocyte and neuronal function, we hypothesized that ventricular fibrillation (VF) in risk haplotype carriers arises from functional changes in both the heart and autonomic nervous system. Methods: We studied 6 risk haplotype carriers with previous VF (symptomatic), 8 carriers without VF (asymptomatic), and 7 noncarriers (controls). We analyzed supine and standing heart rate variability, baroreflex sensitivity, pre-VF heart rate changes, and myocardial 123I-meta-iodobenzylguanide (123I-mIBG) scintigraphy. Results: Carriers had longer interbeat intervals than controls (1.03 ± 0.11 seconds vs 0.81 ± 0.07 seconds; P

This paper reviews the many functions of the vagus nerve, to understand how they interact in daily life and what might be accomplished by therapeutical electrical stimulation. A short historical introduction on the discovery and name-giving of the cranial nerves numbers 9-12 is followed by an overview of the functions that are under lower brain stem control: heart (rate, contractility), intestine (swallowing, peristalsis and glands secretions, feeling of satiety), lungs (bronchoconstriction, lung-irritant and stretch receptor signaling), blood pressure (by vascular wall stress sensing) and blood gases by specialized receptors. Key in the review is the physiology behind beat-by-beat heart rate variations, how everyday life is reflected in its variability, from exciting moments to quiet sleep, with the 'common faint' or vasovagal collapse as extreme example. Next, the recently proposed role of the vagus nerve in limiting inflammation is discussed. This has led to adoption of an earlier developed technique for epilepsy treatment, i.e., electrical stimulation of one vagus nerve bundle in the neck, but now for immune diseases like rheumatoid arthritis and the scope is even widening to depression and cluster headache. However, the problem in application of whole vagus nerve stimulation is the lack of specificity: there is no way to titrate the stimulation to an observable effect variable. All nerves in the bundle, incoming and outgoing, can be 'hit', leading to side-effects which limit the intended application.

The results of many medical measurements are directly or indirectly influenced by the autonomic nervous system (ANS). For example pupil size or heart rate may demonstrate striking moment-to-moment variability. This review intends to elucidate the physiology behind this seemingly unpredictable system. The review is split up into: 1. The peripheral ANS, parallel innervation by the sympathetic and parasympathetic branches, their transmitters and co-transmitters. It treats questions like the supposed sympatho/vagal balance, organization in plexuses and the 'little brains' that are active like in the enteric system or around the heart. Part 2 treats ANS-function in some (example-) organs in more detail: the eye, the heart, blood vessels, lungs, respiration and cardiorespiratory coupling. Part 3 poses the question of who is directing what? Is the ANS a strictly top-down directed system or is its organization bottom-up? Finally, it is concluded that the 'noisy numbers' in medical measurements, caused by ANS variability, are part and parcel of how the system works. This topical review is a one-man's undertaking and may possibly give a biased view. The author has explicitly indicated in the text where his views are not (yet) supported by facts, hoping to provoke discussion and instigate new research.

Introduction Baroreflex sensitivity (BRS) is often presented as a single number, but it is actually a frequency-dependent phenomenon whose value changes constantly due to internal and external stimuli. The standing posture, for instance, necessitates a changeover from vagal to sympathetic predominance for cardiovascular control. We present a wavelet cross-spectral analysis of blood pressure (BP) and interbeat interval (IBI) recordings in the search for variations in gain and phase between these signals. Additionally, we show how the lag in sympathetic response dictates BP-to-IBI phase relations. Methods Recordings in supine and head-up tilted (HUT) position, obtained earlier in 10 healthy subjects (4f/6m, aged 27-47 years) were used. BP and IBI were measured from the continuous finger pressure (by Finometer). The cross-wavelet analysis produced time- and frequency dependent gain (wBRS, wavelet derived BRS) and phase, using the MATLAB® wavelet toolbox. We also applied the wBRS method to model-generated BP- and IBI-data with known interrelations to test the results of this analysis technique. Finally, wBRS values were compared with the xBRS-approach, which is a time domain method for continuous BRS estimation in a sliding 10-s window. Results In resting supine conditions, wBRS fluctuates; more at respiratory frequencies than in the 0.1 Hz band. After HUT, wBRS at the respiratory frequency decreases from average 22.7 to 8.5 ms/mmHg, phase between BP and IBI increases from -30° to -54°; in the sympathetic 0.1 Hz range these numbers are 13.3→6.3 ms/mmHg and -54°→-59°. The values found by xBRS are intermediate between wBRS-resp and wBRS-0.1 Hz. The Appendix shows that for the simulated data the BRS and phase values as found by the wavelet technique can be explained from vector additions of vagal and sympathetic BRS contributions. Discussion During supine rest parasympathetic control of heart rate dominates BRS; after HUT this is diminished and less effective. Due to the reaction times of the autonomic effectors, the phase relations between the signals depend on the relative contribution of the sympathetics, which explains the larger phase shift. Conclusion Cross wavelet analysis allows to follow fast BRS changes in time and frequency, while the computed phase relations help understand sympathetic participation.

karel hendrik wesseling ([Fig. 1][1]), emeritus professor of biomedical instrumentation, was born in The Hague, The Netherlands, on April 23, 1935. He studied electrical engineering, in his words, from 1950 on, and since 1953 at the Delft University of Technology (DUT) from which he graduated with

Spontaneous oscillations of blood pressure (BP) and interbeat interval (IBI) may reveal important information on the underlying baroreflex control and regulation of BP. We evaluated the method of continuously measured instantaneous baroreflex sensitivity by cross correlation (xBRS) validating its mean value against the gold standard of phenylephrine (Phe) and nitroprusside (SNP) bolus injections, and focusing on its spontaneous changes quantified as variability around the mean. For this purpose, we analyzed data from an earlier study of eight healthy males (aged 25–46 years) who had received Phe and SNP in conditions of baseline and autonomic blocking agents: atropine, propranolol, and clonidine. Average xBRS corresponds well to Phe/SNP‐BRS, with xBRS levels ranging from 1.2 (atropine) to 102 msec/mmHg (subject asleep under clonidine). Time shifts from BP‐ to IBI‐signal increased from ≤1 sec (maximum correlations within the current heartbeat) to 3–5 sec (under atropine). Plotted on a logarithmic vertical scale, xBRS values show 40% variability (defined as SD/mean) over the whole range in the various conditions, except twice when the subjects had fallen asleep and it dropped to 20%. The xBRS oscillates at frequencies of 0.1 Hz and lower, dominant between 0.02–0.05 Hz. Although xBRS is the result of IBI/BP‐changes, no linear coherence was found in the cross‐spectra of the xBRS‐signal and IBI or BP. We speculate that the level of variability in the xBRS‐signal may act as a probe into the central nervous condition, as evidenced in the two subjects who fell asleep with high xBRS and only 20% of relative variation.

Standing up elicits a host of cardiovascular changes which all affect the cerebral circulation. Lowered mean arterial blood pressure (ABP) at brain level, change in the cerebral venous outflow path, lowered end‐tidal PCO 2 (PETCO 2), and intracranial pressure (ICP) modify cerebral blood flow (CBF). The question we undertook to answer is whether gravity‐induced blood pressure (BP) changes are compensated in CBF with the same dynamics as are spontaneous or induced ABP changes in a stable position. Twenty‐two healthy subjects (18/4 m/f, 40 ± 8 years) were subjected to 30° and 70° head‐up tilt (HUT) and sinusoidal tilts (SinTilt, 0°↨60° around 30° at 2.5–10 tilts/min). Additionally, at those three tilt levels, they performed paced breathing at 6–15 breaths/min to induce larger than spontaneous cardiovascular oscillations. We measured continuous finger BP and cerebral blood flow velocity (CBFv) in the middle cerebral artery by transcranial Doppler to compute transfer functions (TFs) from ABP‐ to CBFv oscillations. SinTilt induces the largest ABP oscillations at brain level with CBFv gains strikingly lower than for paced breathing or spontaneous variations. This would imply better autoregulation for dynamic gravitational changes. We demonstrate in a mathematical model that this difference is explained by ICP changes due to movement of cerebrospinal fluid (CSF) into and out of the spinal dural sack. Dynamic cerebrovascular autoregulation seems insensitive to how BP oscillations originate if the effect of ICP is factored in. CSF‐movement in‐and‐out of the spinal dural space contributes importantly to orthostatic tolerance by its effect on cerebral perfusion pressure.

Aim Glucocorticoids impair glucose tolerance by inducing insulin resistance. We investigated the dose-dependent effects of glucocorticoid treatment on islet-cell function in healthy males and studied the role of the autonomic nervous system. Design and Methods A randomized, placebo-controlled, double-blind, dose–response intervention study was conducted in 32 healthy males (age: 21 ± 2 years; BMI: 21.9 ± 1.7 kg/m 2 ). Participants were allocated to prednisolone 7.5 mg once daily (n = 12), prednisolone 30 mg once daily (n = 12), or placebo (n = 8) for two weeks. Beta-cell function was measured by hyperglycemic clamp with arginine stimulation, glucagon levels were measured following a standardized meal test. Results We found that prednisolone treatment dose-dependently reduced C-peptide secretion following arginine stimulation on top of hyperglycemia (ASI-iAUC CP ): − 2.8 (− 5.2;0.2) and − 3.1 (− 8.8; − 1.0) nmol L − 1 min − 1 for prednisolone 7.5 mg and prednisolone 30 mg, respectively ( P = 0.035 vs. placebo). Fasting glucagon levels increased dose-dependently (vs. placebo; P = 0.001), whereas postprandial glucagon levels were only increased by prednisolone 30 mg. Changes in parasympathetic activity related with changes in fasting glucose levels (r = − 0.407; P = 0.03) and showed a trend towards correlation with fasting glucagon concentrations (r = − 0.337; P = 0.07). The change in sympathovagal balance was inversely related to ASI-iAUC CP (r = − 0.365; P = 0.05). Conclusion We conclude that in addition to inducing insulin resistance, prednisolone treatment dose-dependently impaired islet-cell function. Altered sympathovagal balance may be related to these effects.

Objectives: Early-life adversity has been shown to be associated with cardiovascular disease and mortality in later life, but little is known about the mechanisms that underlie this association. Prenatal undernutrition, a severe early-life stressor, is associated with double the risk of coronary heart disease and increased blood pressure responses to psychological stress. In the present study, we tested the hypothesis that prenatal undernutrition induces alterations in the autonomic nervous system, which may increase the risk of developing heart disease.Methods: We studied autonomic function in 740 men and women (mean [SD] age, 58 [0.9] years) who were members of the Dutch famine birth cohort. We compared those exposed to famine during early (n = 64), mid (n = 107), or late gestation (n = 127) to those unexposed to famine in utero (n = 442). Participants underwent a series of 3 psychological stressors (Stroop, mirror tracing, and speech) while their blood pressure and heart rate were recorded continuously.Results: Data had sufficient quality in 602 participants for derivation of autonomic function indices by spectral analysis. The stress protocol led to significant sample-level changes in systolic blood pressure, heart rate, and all cardiovascular control measures (all p values < .001). None of the autonomic function parameters, at rest or in response to stress, differed significantly (all p values > .050) according to prenatal famine exposure.Conclusions: Prenatal undernutrition was not associated with autonomic function in late adulthood. We conclude that altered autonomic function does not seem to explain our previous findings of increased coronary heart disease risk among those exposed to famine prenatally.

The external pumping action in CPR should generate sufficient flow and pressure, but the pump must also be 'primed' by ongoing venous return. Different additions to standard CPR are in use just for this purpose. Active decompression of the thorax (ACD-CPR) to 'suck in' venous blood has proven successful, but, theoretically, compression of venous reservoirs in the abdomen should be even more effective. We compared different techniques for improved CPR with specific attention to the pulmonary circulation. We did our comparisons 'in silico' rather than 'in vivo' in a well-evaluated computer model. Methods: We used an adapted version of Babb's computer model for CPR, reprogrammed in Matlab (R). (1) We compared standard chest compression-only CPR (CO-CPR) and ACD-CPR to CPR with interposed abdominal compression (IAC-CPR). (2) Since the thorax/heart configuration differs between patients, and consequently the way blood is propelled by the chest compressions, we checked the influence of the ratio thoracic/cardiac pump effectiveness. Results: (1) Only IAC-CPR leads to physiological values for mean aortic pressure and cardiac output. (2) However, since the whole heart is in the pressure chamber of the compressed thorax, pulmonary artery pressure rises to about the same level as aortic pressure. In practice, this might lead to pulmonary edema during and after CPR, unless (3) intra-abdominal compression pressure is strictly limited; simulations indicate that intra-abdominal pressure should not exceed 30-40mmHg. Conclusions: IAC-CPR outperforms the other techniques in achieving good aortic pressure and cardiac output. However, abdominal pressure should be limited. (C) 2012 Elsevier Ireland Ltd. All rights reserved

The objective of the present study was to test the hypothesis that controlled, adequately compensated, central hypovolemia in subjects with intact autoregulation would be associated with decreased peripheral microcirculatory diffusion and convection properties and, consequently, decreased tissue oxygen carrying capacity and tissue oxygenation. Furthermore, we evaluated the impact of hypovolemia-induced microcirculatory alterations on resting tissue oxygen consumption. To this end, 24 subjects were subjected to a progressive lower body negative pressure (LBNP) protocol of which 14 reached the end of the protocol. At baseline and at LBNP = − 60 mm Hg, sidestream dark field (SDF) images of the sublingual microcirculation were acquired to measure microvascular density and perfusion; thenar and forearm tissue hemoglobin content (THI) and tissue oxygenation (StO2) were recorded using near-infrared spectroscopy (NIRS); and a vascular occlusion test (VOT) was performed to assess resting tissue oxygen consumption rate. SDF images were analyzed for total vessel density (TVD), perfused vessel density (PVD), the microvascular flow index (MFI), and flow heterogeneity (MFIhetero). We found that application of LBNP resulted in: 1) a significantly decreased microvascular density (PVD) and perfusion (MFI and MFIhetero); 2) a significantly decreased THI and StO2; and 3) an unaltered resting tissue oxygen consumption rate. In conclusion, using SDF imaging in combination with NIRS we showed that controlled, adequately compensated, central hypovolemia in subjects with intact autoregulation is associated with decreased microcirculatory diffusion (PVD) and convection (MFI and MFIhetero) properties and, consequently, decreased tissue oxygen carrying capacity (THI) and tissue oxygenation (StO2). Furthermore, using a VOT we found that resting tissue oxygen consumption was maintained under conditions of adequately compensated central hypovolemia.

Exercise testing is often used to assess cardiac function during physical exertion to obtain diagnostic information. However, this procedure is limited to measuring the electrical activity of the heart using electrocardiography and intermittent blood pressure (BP) measurements and does not involve the continuous assessment of heart functioning. In this study, we compared continuous beat-to-beat pulse contour analysis to monitor noninvasive cardiac output (CO) during exercise with inert gas rebreathing and respired gas analysis. Nineteen healthy male volunteers were subjected to bicycle ergometry testing with increasing workloads. Cardiac output was deter- mined noninvasively by continuous beat-to-beat pulse contour analysis (Nexfin) and by inert gas rebreathing, and estimated using the respired gas analysis method. The effects of the rebreathing maneuver on heart rate (HR), stroke volume (SV), and CO were evaluated. The CO values derived from the Nexfin- and inert gas rebreathing methods were well correlated (r = 0.88, P < 0.01) and the limits of agreement were 30.3% with a measurement bias of 0.4 ± 1.8 L/min. Nexfin- and respired gas analysis-derived CO values correlated even better (r = 0.94, P < 0.01) and the limits of agreement were 21.5% with a measurement bias of -0.70 ± 1.6 L/min. At rest, the rebreathing maneuver increased HR by 13 beats/min (P < 0.01), SV remained unaffected (P = 0.7), while CO increased by 1.0 L/min (P < 0.01). Rebreathing did not affect these parameters during exercise. Nexfin continuous beat-to-beat pulse contour analysis is an appropriate method for noninvasive assessment of CO during exercise

Objective During hypotension induced by tilt-table testing, low presyncopal blood pressure (BP) usually recovers within 1 min after tilt back. However, in some patients prolonged post faint hypotension (PPFH) is observed. We assessed the hemodynamics underlying PPFH in a retrospective study. Methods Seven patients (2 females, aged 31–72 years) experiencing PPFH were studied. PPFH was defined as a systolic BP below 85 mmHg for at least 2 min after tilt back. In 6 out of 7 presyncope was provoked by 0.4 mg sublingual NTG, administered in the 60° head-up tilt position following head-up tilt for 20 min. Continuous BP was monitored and stroke volume (SV) was computed from pressure pulsations. Cardiac output (CO) was calculated from SV × heart rate (HR); and total peripheral resistance (TPR) from mean BP/CO. Left ventricular contractility was estimated by dP/dtmax of finger pressure pulse. Results Systolic BP (SYS), diastolic BP (DIAS) and HR during PPFH were lower compared to baseline: SYS 75 ± 14 versus 121 ± 18 mmHg, DIAS 49 ± 9 versus 71 ± 9 mmHg and HR 52 ± 14 versus 67 ± 12 beats/min (p

Acute psychological stress challenges the cardiovascular system with an increase in BP (blood pressure), HR (heart rate) and reduced BRS (baroreflex sensitivity). β-adrenergic blockade enhances BRS during rest, but its effect on BRS during acute psychological stress is unknown. This study tested the hypothesis that BRS is higher during acute psychological stress in healthy subjects under β-adrenergic blockade. Twenty healthy novice male bungee jumpers were randomized and studied with (PROP, n=10) or without (CTRL, n=10) propranolol. BP and HR responses and BRS [cross-correlation time-domain (BRSTD) and cross-spectral frequency-domain (BRSFD) analysis] were evaluated from 30 min prior up to 2 h after the jump. HR, cardiac output and pulse pressure were lower in the PROP group throughout the study. Prior to the bungee jump, BRS was higher in the PROP group compared with the CTRL group [BRSTD: 28 (24–42) compared with 17 (16–28) ms·mmHg−1, P

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.

Purpose To test the hypothesis that the sensitivity of near-infrared spectroscopy (NIRS) in reflecting the degree of (compensated) hypovolemia would be affected by the application site and probing depth. We simultaneously applied multi-site (thenar and forearm) and multi-depth (15–2.5 and 25–2.5 mm probe distance) NIRS in a model of simulated hypovolemia: lower body negative pressure (LBNP). Methods The study group comprised 24 healthy male volunteers who were subjected to an LBNP protocol in which a baseline period of 30 min was followed by a step-wise manipulation of negative pressure in the following steps: 0, −20, −40, −60, −80 and −100 mmHg. Stroke volume and heart rate were measured using volume-clamp finger plethysmography. Two multi-depth NIRS devices were used to measure tissue oxygen saturation (StO2) and tissue hemoglobin index (THI) continuously in the thenar and the forearm. To monitor the shift of blood volume towards the lower extremities, calf THI was measured by single-depth NIRS. Results The main findings were that the application of LBNP resulted in a significant reduction in stroke volume which was accompanied by a reduction in forearm StO2 and THI. Conclusions NIRS can be used to detect changes in StO2 and THI consequent upon central hypovolemia. Forearm NIRS measurements reflect hypovolemia more sensitively than thenar NIRS measurements. The sensitivity of these NIRS measurements does not depend on NIRS probing depth. The LBNP-induced shift in blood volume is reflected by a decreased THI in the forearm and an increased THI in the calf. Electronic supplementary material The online version of this article (doi:10.1007/s00134-010-2128-6) contains supplementary material, which is available to authorized users.

Objective Medical communication is goal oriented behavior. As such, it can be modeled as a chain of decisions, resulting from cognitive and emotional processes each potentially associated with psychophysiological reactions. Psychophysiological may be helpful to detect small changes in affect or arousal in the course of a consultation that would be difficult to detect by other evaluations of the process, like self-reports. The question is how psychophysiological communication research should be modeled for unraveling in more detail the cognitive, emotional and interpersonal processes which underlie physician and patient behavior. Methods In the world of medical communication research the six-function model of medical communication reveals a number of fundamental perceptual, cognitive and emotional processes which may evoke psychophysiological responses. The world of psychophysiological research encompasses domains of perception, mental imagery, anticipation and action which all have close connections with fundamental tasks in communication. Conclusion This paper discusses ten methodological issues in linking continuous psychophysiological data to verbal and nonverbal events in a medical consultation observed with the Verona coding system. Practice implications When linking the two worlds of research, the methodological challenges discussed need to be solved to obtain a valid and reliable application of psychophysiological measures in medical communication research.

Introduction: Medical communication can be a stressful experience for both doctors and patients. In particular, inexperienced doctors facing the demanding task of a bad news consultation may experience high levels of distress. The aim of this exploratory study is to test students' differential cardiovascular reactivity to history taking and bad news consultations with a simulated patient, and to test the relation between the students' self-reported stressfulness of the consultation and their cardiovascular response: Methods: Fourth and fifth year medical students (n = 20) conducted a history taking (HT) and a bad news (BN) consultation in a randomized order with a standardized patient. Heart rate (HR), mean arterial pressure (MAP), cardiac output (CO) and systemic vascular resistance (SVR) were assessed by way of the Finapres-technique in four conditions: rest, reading aloud, and during both consultations. Self-reported stress was assessed before and after each interview using the State and Trait Anxiety Inventory (STAI), and a visual analogue scale (VAS). Results: Both HT and BN provoked more cardiovascular stress than reading. Bad-news provoked the highest HR and CO responses compared to all other conditions, and had a greater impact when it was the student's first consultation. The STAI and VAS data showed some correlations with the cardiovascular stress measures and a comparable but less significant pattern in stress response. Discussion: The effect of order of the HT and BN consultations on the students' stress levels suggests an additional impact of novelty and habituation. Unfamiliarity with the patient may enhance the stressfulness of the task of breaking bad news. (C) 2010 Elsevier B.V. All rights reserved

Inflight 24-h profiles of blood pressure (BP) and heart rate (HR) were recorded in 2 ESA-astronauts by automatic upper arm cuff measurements. In one astronaut this was combined with Portapres (TM) continuous finger blood pressure recordings. It was the intention to contrast the latter to 24-h recordings in an earlier Head-Down-Tilted (HDT) bed rest study [Voogel, A.J., Stok, W.J., Pretorius, P.J., Van Montfrans, G.A., Langewouters, G.J., Karemaker, J.M., 1997. Circadian blood pressure and systemic haemodynamics during 42 days of 6 degrees head-down tilt. Acta Physiol. Scand. 161, pp. 71-80]. BP-levels in Space were not very Much changed from preflight; the circadian BP-rhythm seemed dampened. Only daytime diastolic pressures (both subjects) and nighttime HR (one subject) were significantly lower in Space. However, compared to the effect of a control tilt marroeuvre on the ground, even lower BP values might have been expected. Striking were the BP- and HR-surges during the working days in Space, often related to stressful moments like live appearances on public TV. Systemic vascular resistance (SVR) dropped during the night, unlike HDT. Thus, actual spaceflight refuted our earlier findings in HDT both for BP-levels and for daytime to nighttime changes. The combined observations lead to the hypothesis that short-lasting spaceflight may induce strong psychological stress in astronauts. When interpreting space-physiological observations this must be taken into account. (C) 2009 Elsevier B.V. All rights reserved

Di Rienzo M, Castiglioni P, Iellamo F, Volterrani M, Pagani M, Mancia G, Karemaker JM, Parati G. Dynamic adaptation of cardiac baroreflex sensitivity to prolonged exposure to microgravity: data from a 16-day spaceflight. J Appl Physiol 105: 1569-1575, 2008. First published August 28, 2008; doi:10.1152/japplphysiol.90625.2008.-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

NTG (nitroglycerine) is used in routine tilt testing to elicit a vasovagal response. In the present study we hypothesized that with increasing age NTG triggers a more gradual BP (blood pressure) decline due to a diminished baroreflex-buffering capacity. The purpose of the present study was to examine the effect of NTG on baroreflex control of BP in patients with distinct age-related vasovagal collapse patterns. The study groups consisted of 29 patients (16–71 years old, 17 females) with clinically suspected VVS (vasovagal syncope) and a positive tilt test. Mean FAP (finger arterial pressure) was monitored continuously (Finapres). Left ventricular SV (stroke volume), CO (cardiac output) and SVR (systemic vascular resistance) were computed from the pressure pulsations (Modelflow). BRS (baroreflex sensitivity) was estimated in the time domain. In the first 3 min after NTG administration, BP was well-maintained in all patients. This implied an adequate arterial resistance response to compensate for steeper reductions in SV and CO with increasing age. HR (heart rate) increased and the BRS decreased after NTG administration. The rate of mean FAP fall leading to presyncope was inversely related to age (r=0.51, P=0.005). Accordingly, patients with a mean FAP fall >1.44 mmHg/s (median) were generally younger compared with patients with a slower mean FAP-fall (30±10 years compared with 51±17 years; P=0.001). The main determinant of the rate of BP fall on approach of presyncope was the rate of fall in HR (r=0.75, P

Postural stress requires immediate autonomic nervous action to maintain blood pressure. We determined time-domain cardiac baroreflex sensitivity (BRS) and time delay (tau) between systolic blood pressure and interbeat interval variations during stepwise changes in the angle of vertical body axis (alpha). The assumption was that with increasing postural stress, BRS becomes attenuated, accompanied by a shift in tau toward higher values. In 10 healthy young volunteers, alpha included 20 degrees head-down tilt (-20 degrees), supine (0 degree), 30 and 70 degrees head-up tilt (30 degrees, 70 degrees), and free standing (90 degrees). Noninvasive blood pressures were analyzed over 6-min periods before and after each change in alpha. The BRS was determined by frequency-domain analysis and with xBRS, a cross-correlation time-domain method. On average, between 28 (-20 degrees) to 45 (90 degrees) xBRS estimates per minute became available. Following a change in alpha, xBRS reached a different mean level in the first minute in 78% of the cases and in 93% after 6 min. With increasing alpha, BRS decreased: BRS = -10.1.sin(alpha) + 18.7 (r(2) = 0.99) with tight correlation between xBRS and cross-spectral gain (r(2) approximately 0.97). Delay tau shifted toward higher values. In conclusion, in healthy subjects the sensitivity of the cardiac baroreflex obtained from time domain decreases linearly with sin(alpha), and the start of baroreflex adaptation to a physiological perturbation like postural stress occurs rapidly. The decreases of BRS and reduction of short tau may be the result of reduced vagal activity with increasing alpha.

Noninvasive finger blood pressure has become a surrogate for central blood pressure under widely varying circumstances. We tested the validity of finger-aorta transfer functions (TF) to reconstruct aortic pressure in seven cardiac patients before, during, and after incremental bicycle exercise. The autoregressive exogenous model method was used for calculating finger-aorta TFs. Finger pressure was measured noninvasively using Finapres and aortic pressure using a catheter-tip manometer. When applying the individual TFs found during rest for reconstruction of aortic pressure during all workloads, systolic pressure was increasingly underestimated, with large variation between subjects: +4.0 to −18.1 mmHg. In most subjects, diastolic pressure was overestimated: −3.9 to +5.5 mmHg. Pulse pressure estimation varied between +4.5 and −21.9 mmHg. In all cases, wave distortion was present. Postexercise, error in reconstructed aortic systolic pressure slowly declined, and diastolic pressure was overestimated. During rest, the TF gain had a minimum between 3.65 and 4.85 Hz (Fmin). During exercise, Fmin shifted to frequencies between 4.95 and 7.15 Hz at the maximum workload, with no change in gain. Postexercise, gain in most subjects shifted to values closer to unity, whereas Fmin did not return to resting values. Within each subject, aorta-Finapres travel time was linearly related to mean pressure. During exercise, Fmin was linearly related to both delay and heart rate. We conclude that, during increasing exercise, rest TFs give an increasingly unreliable reconstruction of aortic pressure, especially at higher heart rates.

OBJECTIVE: To evaluate whether sympathetic activity is increased in early-onset hypertensive pregnancy and whether this can be influenced by management with plasma volume expansion. METHODS: The study group consisted of 74 subjects, of which 37 had early-onset hypertensive disorders of pregnancy (preeclampsia or gestational hypertension with fetal growth restriction), who were included at 24 to 34 weeks in a randomized controlled trial of management with (n = 18) or without (n = 19) plasma volume expansion. Heart rate and blood pressure variabilities, LF/HF ratio for heart rate, baroreflex sensitivity, and phase difference at low frequency (LF approximately 0.1 Hz) were calculated by spectral analysis from continuous heart rate and blood pressure recordings of the finger pulse wave (Portaprestrade mark, TNO). Measurements were performed at inclusion, after 20 to 40 hours and after 65 to 100 hours. The control group consisted of 29 women with a normal pregnancy and 8 women who had late-onset preeclampsia after 34 weeks. Controls were measured at 32 weeks. All controls had a normal blood pressures at that time. RESULTS: LF variability of heart rate and blood pressure were significantly higher and baroreflex sensitivity was significantly lower in early-onset patients compared with normal controls. A significant trend towards higher LF variability of blood pressure and lower baroreflex sensitivity was found from normal controls to late-onset controls to early-onset patients. Parameters of sympathetic activity were not influenced by plasma volume expansion. CONCLUSION: Sympathetic activity was increased in early-onset hypertensive pregnancy. However, this was not affected by management with plasma volume expansion, suggesting that hypovolaemia in preeclampsia is a secondary phenomenon

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 ∼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.

Background— In patients with a malignant hypertension, immediate parenteral treatment with blood pressure–lowering agents such as intravenous sodium nitroprusside (SNP) is indicated. In this study, we evaluated static and dynamic cerebral autoregulation (CA) during acute blood pressure lowering with SNP in these patients. Methods and Results— In 8 patients with mean arterial pressure (MAP) >140 mm Hg and grade III or IV hypertensive retinopathy at hospital admission, middle cerebral artery blood velocity (MCA V) and blood pressure were monitored. Dynamic CA was expressed as the 0.1-Hz MCA V mean to MAP phase lead and static CA as the MCA V mean to MAP relationship during SNP treatment. Eight normotensive subjects served as a reference group. In the patients, the MCA V mean to MAP phase lead was lower (30±8° versus 58±5°, mean±SEM; P mean decrease was 22±4%, along with a 27±3% reduction in MAP (from 166±4 to 121±6 mm Hg; P −1 · % mm Hg −1 ; r =0.70±0.07). Conclusions— In patients with malignant hypertension, dynamic CA is impaired. An MCA V mean plateau was not detected during the whole SNP treatment, indicating loss of static CA as well. This study showed that during the whole rapid reduction in blood pressure with SNP, MCA V mean decreases almost one on one with MAP.

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.

In man assuming the upright position, end-tidal PCO2 (PETCO2) decreases. With the rising interest in cerebral autoregulation during posture change, which is known to be affected by PETCO2, 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 (VT) 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 PETCO2. 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 VT, pulmonary O2 uptake and breath-to-breath lumped SV. On average, the PETCO2 decreased from 40 mmHg to 36 mmHg after 150 s standing. Results show that the model is able to track breath-to-breath PETCO2 variations (r2= 0.74, P < 0.05). Model parameter sensitivity analysis demonstrates that the decrease in PETCO2 during standing is due primarily to increased VT, 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.

OBJECTIVES - We set out to determine the effect of sublingual nitroglycerin (NTG), as used during routine tilt testing in patients with unexplained syncope, on hemodynamic characteristics and baroreflex control of heart rate (HR) and systemic vascular resistance (SVR). BACKGROUND Nitroglycerin is used in tilt testing to elicit a vasovagal response. It is known to induce venous dilation and enhance pooling. Also, NTG is lipophilic and readily passes cell membranes, and animal studies suggest a sympatho-inhibitory effect of NTG on circulatory control. METHODS Routine tilt testing was conducted in 39 patients with suspected vasovagal syncope (age 36 16 years, 18 females). Patients were otherwise healthy and free of medication. Before a loss of consciousness set in, oncoming syncope was cut short by tilt-back or counter-maneuvers. Finger arterial pressure was monitored continuously (Finapres). Left ventricular stroke volume (SV) was computed from the pressure pulsations (Modelflow). Spontaneous baroreflex control of HR was estimated in the time and frequency domains. RESULTS During tilt testing, 22 patients developed presyncope. After NTG administration but before presyncope, SV and cardiac output (CO) decreased (p

Contains fulltext : 57505.pdf (Publisher’s version ) (Closed access) BACKGROUND AND PURPOSE: Carotid endarterectomy (CE) may be complicated by the clinical syndrome of baroreflex failure. Alterations of baroreflex function may also account for the frequently observed blood pressure lability in the first hours following surgery. We investigated the long-term effects of unilateral CE on baroreflex control of function and blood pressure. METHODS: We investigated 14 patients after unilateral CE (13 m:1 f, 64.8 +/- 6.5 years), 9 patients with a surgically untreated uni-/bilateral carotid stenosis (CS, 7 m:2 f, 57.6 +/- 10.7 years) and 12 healthy controls (HC, 11 m:1 f, 60.9 +/- 7.9 years) by means of Valsalva maneuver, active standing, forced breathing, cold face test, cold pressor test and mental arithmetic. Ambulatory blood pressure level and variability were determined from 24-hour Spacelabs and 5-hour beat-to-beat Portapres recordings. RESULTS: Baroreflex sensitivity (derived from phase IV Valsalva maneuver) was significantly lower in CE (1.53 +/- 0.83 ms/mmHg) than in CS (4.39 +/- 2.27, p = 0.002) and HC (5.34 +/- 3.78, p = 0.003). CE patients exhibited a decreased reflex control of heart rate in response to Valsalva's maneuver and active standing without orthostatic hypotension. Office blood pressure levels before and after endarterectomy were similar, as were ambulatory blood pressure levels in the three groups. Ambulatory blood pressure variability was higher in CE and CS than in HC, but not different between CE and CS. CONCLUSIONS: Unilateral CE causes a long-term impairment of baroreflex function, resulting in an attenuated reflex control of heart rate, but no hypertension or blood pressure lability.

Background and aim Analysis of heart rate variability (HRV) has recently become the playing field of mathematicians and physicists, losing its relation to physiology and the clinic. To set the record straight, a set of animal experiments is presented here, which was designed to test how vagus nerve traffic might produce beat to beat (b-t-b) heart rate (HR) control, like the baroreflex will do in vivo. Methods The response of HR to vagus nerve stimulation was tested after bilateral vagotomy in rabbits under anesthesia. Three protocols were followed: 1. Single burst stimulation at varying moments in one cardiac cycle; 2. B-t-b stimulation in each cycle, coupled to the P-wave with variable delays; in addition, testing the effects of one increased or decreased burst; 3. Tetanic stimulation, shortly interrupted or increased at varying moments in the cardiac cycle. Results and conclusions Sensitivity of the sinoatrial node to the timing of vagal bursts in its cycle from protocol 1 explains most of the observations. A single burst would be most effective when applied in late repolarization or early diastole of the sinoatrial node's action potential. In b-t-b stimulation the longest cardiac cycles occur when bursts are timed just before the end of the 'sensitive period'. Later coming bursts have their (diminished) effect on the next cycle; critically timed bursts induce an unstable HR, alternating between long and short cycles. This ran in synchrony with the respirator, thus producing a large respiratory sinus arrhythmia, even though the vagus nerves had been cut. HR-response to vagal burst activity shows two components: a fast one which is phase-sensitive and a slow one that builds up with longer lasting activity and also disappears slowly. Tetanic stimulation results in prolonged, but variable cycle lengths which are difficult to change by short-lasting manipulation of impulse frequency, be it up or down. Relevance for patients Measurement of heart rate variability (HRV) and baroreflex sensitivity (BRS) have become clinical tools in the cardiology clinic and in hypertension research. This study shows how the underlying vagus nerve to heart rate physiology is responsible for moment-to-moment variability in these numbers at almost unchanged underlying physiology. Programmed stimulation of the vagus nerves in acute animals (rabbits) demonstrates that the optimal mode of fast, beat-to-beat heart rate control by these nerves is by means of bursts of impulses arriving in every heart beat at well-timed moments. In vivo this is how the baroreflex stabilizes blood pressure at the expense of HRV.

PURPOSE: Pre-eclampsia is a major complication of pregnancy. Although the disorder usually becomes apparent only in the third trimester of pregnancy, evidence is available that underlying pathophysiological abnormalities are already present early in pregnancy. The association between alterations in autonomic cardiovascular control and the development of hypertension in pregnancy has been investigated for some time. Non-invasive methods are especially of interest, since they have the advantage of minimal risk for the mother and the conceptus and enable repeated measurements during pregnancy. If non-invasive tests for autonomic cardiovascular control could demonstrate the increased sympathetic activity, as observed by microneurography than this method is a candidate for early identification of pre-eclampsia. Therefore, the literature on non-invasive testing of autonomic cardiovascular control in normal pregnancies and pre-eclampsia was summarized. DATA IDENTIFICATION AND SELECTION: Medline was searched and 36 articles on autonomic cardiovascular control in human pregnancy by non-invasive test methods were reviewed. For each test method, data of different studies were summarized to evaluate if the method could discriminate between healthy pregnancy and pre-eclampsia. CONCLUSION: Although small differences have been observed between normal pregnancy and pre-eclampsia in individual studies using non-invasive methods, the consistency in the available data is insufficient to discriminate between normal pregnancy and pre-eclampsia. The failure to demonstrate the increased sympathetic activity, as observed by direct microneurography, might be due to methodological factors of the non-invasive studies. Alternatively, sympathetic activity to resistance vessels in skeletal muscle may not be a proper reflection of autonomic cardiovascular control in pregnancy. Well-designed longitudinal research could be useful to test these suppositions

Background — After experimental carotid sinus denervation in animals, blood pressure (BP) level and variability increase markedly but normalize to preoperative levels within 10 to 14 days. We investigated the course of arterial BP level and variability after bilateral denervation of the carotid sinus baroreceptors in humans. Methods and Results — We studied 4 women (age 41 to 63 years) who were referred for evaluation of arterial baroreflex function because of clinical suspicion of carotid sinus denervation attributable to bilateral carotid body tumor resection. The course of BP level and variability was assessed from repeated office and 24-hour ambulatory measurements (Spacelabs/Portapres) during 1 to 10 years of (retrospective) follow-up. Rapid cardiovascular reflex adjustments to active standing and Valsalva’s maneuver were assessed. Office BP level increased from 132/86 mm Hg (range, 118 to 148/80 to 92 mm Hg) before bilateral surgery to 160/105 mm Hg (range, 143 to 194/90 to 116 mm Hg) 1 to 10 years after surgery. During continuous 24-hour noninvasive BP recording (Portapres), a marked BP variability was apparent in all 4 patients. Initial symptomatic hypotension on change to the upright posture and abnormal responses to Valsalva’s maneuver were observed. Conclusions — Acute carotid sinus denervation, as a result of bilateral carotid body tumor resection, has a long-term effect on the level, variability, and rapid reflex control of arterial BP. Therefore, in contrast to earlier experimental observations, the compensatory ability of the baroreceptor areas outside the carotid sinus seems to be of limited importance in the regulation of BP in humans.

Endoscopic thoracic sympathectomy at T2-T4 is an effective and safe treatment for primary axillary and palmar hyperhidrosis and facial blushing refractory to conventional treatment. T2 and T4 ganglia however are in the direct pathway of sympathetic innervation of the heart and part of the vasomotor nerves. In this study we investigate possible changes in steady-state hemodynamics as well as in beat-to-beat cardiovascular control after thoracoscopic sympathectomy of T2-T4. In 12 patients we measured continuously heart rate (HR) and blood pressure (BP) (non-invasively with Finapres(TM)) during rest and during deep inspiration, in supine and sitting position as well as during a change from lying to standing. Stroke volume (SV) and total peripheral resistance (TPR) were estimated from the BP recordings by the Modelflow method. Markers for cardiovascular control were obtained from power and cross-spectra of BP and HR. After sympathectomy, only in the sitting position was mean HR decreased, while TPR and BP (diastolic and mean) were lower in the supine as well as sitting positions. SV clearly increased. Low frequency power in HR and BP was significantly decreased, just like the max/min ratio in HR after standing up, indicating a diminished capacity in sympathetic vasomotor control. High frequency power of HR as well as baroreflex sensitivity, both parasympathetic markers, did not change in a statistically significant manner. Conclusion: Besides altering steady-state hemodynamics, a thoracic sympathectomy causes relatively small, though measurable changes in cardiovascular control, in particular of peripheral vasomotion

The vagus nerves of rabbits under anesthesia were stimulated to test the effects on heart rate. Repeated stimuli were delivered either at a constant frequency (`tetanic') or in short bursts, one burst per heartbeat (`pulsatile stimulation') at variable moments in the cardiac cycle. The heart rate dynamics in response to short-lasting increases or decreases of ongoing stimulation were studied. Strong stimuli had a short-delay effect on heart rate: 100-120 ms; if stimulation was pulsatile the effects of decreased vagal stimulation could influence the ongoing cycle. However, in the case of tetanic stimulation the delay was much longer, up to 300 ms. It is concluded that observed changes in heart rate from one beat to the next are not always due to the same changes in underlying vagal activity. When using heart rate variability to probe the autonomic nervous system one should realize that the probe itself is highly non-linear.

We tested the reliability of noninvasive cardiac output (CO) measurement in different body positions by pulse contour analysis (COpc) 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 (COrebr) was used as a reference method. Twelve subjects (age 21–34 yr) were studied: 1) six in whom COrebr and COpc were measured in the standing and 6° head-down tilt (HDT) postures and 2) six in whom CO was measured in the 30° HDT, supine, 30° head up-tilt (HUT), and 70° HUT postures on a tilt table. The COrebr-to-COpcratio in (near) the supine position during rebreathing was used as the calibration factor for COpcmeasurements. Calibrated COpc(COcal sup) consistently overestimated CO in the upright posture. The drop in CO with upright posture was underestimated by ∼50%. COcal sup and COrebr values did not differ in the 30° HDT position. Changes in the COrebr-to-COpcratio are highly variable among subjects in response to a change in posture. Therefore, COpc must be recalibrated for each subject in each posture.

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.

Aims Since many type 2 diabetes patients experience postprandial hypotension, the aim of this study was to unravel meal-related changes in systemic hemodynamics and autonomic nervous system (ANS)-balance. Methods Forty-two age-matched males (15 type 2 diabetes; 12 metabolic syndrome; 15 controls) without overt autonomic neuropathy received a standardized high-fat mixed meal after an overnight fast. Hemodynamic variables were measured by finger plethysmography. Fourier analysis was used to calculate the low-/high-frequency (LF/HF)-ratio, a marker of autonomic nervous system-balance, and baroreceptor reflex sensitivity (BRS). Results Following the meal, diastolic blood pressure (DBP) decreased in type 2 diabetes patients only, paralleled by a significant decrement in systemic vascular resistance (SVR) and an increase in cardiac index. All groups showed an increase in postprandial heart rate. Controls, but not metabolic syndrome or type 2 diabetes patients, showed a meal-related increase in LF/HF-ratio. When combining all study subjects, homeostatic model assessment-insulin resistance (HOMA-IR) was inversely correlated with changes in DBP, SVR, LF/HF-ratio and BRS. Conclusions Based on these data, we hypothesize that in patients with uncomplicated type 2 diabetes, insulin resistance hampers adequate meal-induced sympathetic activation, leading to a decrease in SVR and resulting in a postprandial drop in DBP.