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Cardiovascular regulation and autonomic function change across sleep stages and compared to wake. Little information is present in literature about cardiac control during sleep especially in relation to new information-theoretic quantities such as synergy and redundancy. In the present work we compute synergy and redundancy of baroreflex and non-baroreflex components of the cardiac control according to two information-theoretic approaches, namely predictive information decomposition (PID) and minimal mutual information (MMI) methods. We applied a bivariate approach to heart period (HP) and systolic arterial pressure (SAP) beat-to-beat variability series during sleep in a healthy subject. PID approach computes the net balance between synergy and redundancy, while MMI calculates the two quantities as separate entities. Results suggested that: i) redundancy was dominant over synergy during NREM phases; ii) redundancy increased during NREM phase; iii) synergy did not change across the sleep stages. We interpret this result as a consequence of the vagal enhancement, slowing and deepening of respiration during NREM phases. These preliminary findings support the potential of assessing redundancy/synergy of baroreflex-related and unrelated regulations during sleep to improve our knowledge about physiological mechanisms.

The study proposes an extension of cardiac baroreflex (cBR) sequence analysis, traditionally performed over spontaneous fluctuations of heart period and systolic arterial pressure, to typify peripheral resistance baroreflex (prBR) from spontaneous variations of peripheral resistances and diastolic arterial pressure. The prBR baroreflex sensitivity (BRS prBR ) and percentage of prBR sequences (SEQ% prBR ) were computed along with analogous quantities assessed over cBR (i.e. BRS cBR and SEQ% cBR ). The cBR and prBR were typified in healthy subjects at rest (REST) and during light bicycle ergometer exercise at 10 percent of the maximal effort (EXE). Both cBR and prBR were affected by EXE: indeed, BRS cBR and SEQ% prBR were significantly reduced. Moreover, while BRS cBR and BRS prBR were not significantly associated, SEQ% cBR and SEQ% prBR were, and the correlation coefficient was positive. This study suggests that prBR can be typified from spontaneous variabilities along with the more traditional cBR, thus enlarging the possibility of monitoring human cardiovascular control mechanisms.

Objective: This study assessed the long-term effect of the eversion technique for carotid endarterectomy (e-CEA) on arterial baroreflex and peripheral chemoreflex function., Methods: The study included 13 patients who underwent, between 2001 and 2006, bilateral e-CEA and 16 who underwent bilateral standard CEA (s-CEA) to eliminate the complicating effects of intact contralateral carotid sinus function. Exclusion criteria were age >70 years, diabetes mellitus, chronic pulmonary disease, ischemic cardiac disease or medical therapy with β-blockers, cardiac arrhythmia, neurologic deficits, carotid restenosis, and previous neck or chest surgery or irradiation. Young and aged-matched healthy individuals were recruited as controls. All patients underwent standard cardiovascular reflex tests, including lying-to-standing, orthostatic hypotension, deep breathing, and Valsalva maneuver. Autonomic cardiovascular modulation was indirectly evaluated by spectral analysis of heart rate variability and systolic arterial pressure variability. The chemoreflex sensitivity to hypoxia was obtained during classic rebreathing tests from the slopes of the linear regression of minute ventilation (VE) vs arterial oxygen saturation measured by pulse oximetry (SpO2%) and partial pressure of end-tidal oxygen (PetO2)., Results: Patients (16 men; age, 62.4 ± 8.0 years) were enrolled after a mean interval of 24 ± 17 months from the last CEA. All were asymptomatic, and results of standard tests were negative. Residual baroreflex performance was documented in both patient groups, although reduced, compared with young controls. Notably, baroreflex sensitivity (msec/mm Hg) was better maintained after e-CEA than after s-CEA at rest (young controls, 19.93 ± 9.50; age-matched controls, 7.75 ± 5.68; e-CEA, 13.85 ± 14.54; and s-CEA, 3.83 ± 1.15; analysis of variance [ANOVA], P = .001); and at standing (young controls, 7.83 ± 2.55; age-matched controls, 3.71 ± 1.59; e-CEA, 7.04 ± 5.62; and s-CEA 3.57 ± 3.80; ANOVA, P = .001). Similarly, chemoreflex sensitivity to hypoxia was maintained in both patient groups, which did not differ from each other, and was reduced compared with controls (controls vs patient groups ΔVE/ΔSpO2: -1.37 ± 0.33 vs -0.33 ± 0.08 and SpO2% -0.29 ± 0.13 L/min; P = .002; ΔVE/ΔPetO2: -0.20 ± 0.1 vs -0.01 ± 0.0 and -0.07 ± 0.02 L/min/mm Hg; P = .04, ANOVA with least significant difference correction for multiple comparisons)., Conclusions: Our data show that e-CEA, even when performed on both sides, preserves baroreflexes and chemoreflexes and, therefore, does not confer permanent carotid sinus denervation. Also, e-CEA does not increase long-term arterial pressure variability, and this suggests that perioperative hemodynamic derangements can be attributed to the temporary effects of surgical trauma., (Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Objectives: This study addressed the relationship between spontaneous baroreflex sensitivity and carotid mechanical properties in a clinical setting., Methods: In 191 normal volunteers (age range 20-60 years, mean 44 ± 13), spontaneous indices of baroreflex regulation were obtained noninvasively in the time (baroreflex slope, BRS) and frequency domains (α index and systolic arterial pressure-RR interval transfer gain) as well as using an exogenous autoregressive causal model (A.XAR); carotid mechanical properties were estimated by ultrasound. The link between mechanical measures and spontaneous baroreflex indices was explored by multivariate analysis and linear modeling., Results: Participants were divided into five groups according to age decades. With advancing age we observed a decrease in spontaneous baroreflex indices (BRS from 31.2 to 16.3; α index from 27.4 to 13.6; RR-SAP gain at high frequency from 31 ± 3.0 to 14 ± 3.0 ms/mmHg all P < 0.001) and increase in carotid intima-media thickness (IMT: from 0.53 to 0.69 mm; P < 0.001) and stiffness (local wave speed: from 4.0 to 6.9 m/s; both P < 0.001). A significant correlation was found between spontaneous indices of baroreflex sensitivity and carotid mechanical properties, particularly wave speed (r = -0.328, P < 0.001). After adjusting for age and sex, a significant correlation remained between RR-SAP gain and wave speed and between A.XAR and IMT. Factor analysis and automatic linear modeling confirmed the observation that mechanical carotid properties are strong predictors of the age-related reduction of spontaneous baroreflex., Conclusion: A significant correlation between spontaneous baroreflex indices and local carotid mechanical properties supports the idea that they should be considered in the physiology of baroreflex regulation.

Background: The baroreflex is one of the most important short-term cardiovascular autonomic control mechanisms. Its interactions with other reflexes, mainly cardiopulmonary reflexes, are of paramount importance in controlling heart rate., Objectives: This study assesses the coupling between baroreflex and respiration during a progressive bicycle mild dynamical exercise., Methods: The coupling was assessed by symbolic analysis and conditional entropy., Results: Findings suggested the close relationship between the baroreflex sequences and the phase of respiratory signal and, thus, the interference between baroreflex and cardiopulmonary reflexes., Conclusions: Indexes describing baroreflex based on spontaneous variability are strongly affected by cardiopulmonary influences.

This brief review summarizes current knowledge on the neural mechanisms of cardiovascular regulation during exercise in space, with specific emphasis on the role of the arterial baroreflex and the muscle metaboreflex, with the attendant modifications in autonomic nervous system activity, in determining the cardiovascular responses to exercise in microgravity conditions. Available data suggest that the muscle metaboreflex is enhanced during dynamic exercise in space and that the potentiation of the muscle metaboreflex affects the vagally mediated arterial baroreflex contribution to HR control.

In the literature, several methods have been proposed for the assessment of the baroreflex sensitivity from spontaneous variability of heart period and systolic arterial pressure. The present study compares the most utilized approaches for the evaluation of the spontaneous baroreflex sensitivity (i.e. sequence-based, spectral, cross-spectral and model-based techniques) over a protocol capable of inducing a progressive decrease of the baroreflex sensitivity in the presence of a relevant respiratory drive (i.e. a stepwise dynamic bicycle exercise at 10%, 20% and 30% of the maximum nominal individual effort) in 16 healthy humans. Results demonstrated that the degree of correlation among the estimates is related to the structure of the model explicitly or implicitly assumed by the method and depends on the experimental condition (i.e. on the physiological mechanisms contemporaneously active with baroreflex, e.g. cardiopulmonary reflexes). However, even in the presence of a significant correlation, proportional and/or constant biases can be present, thus rendering spontaneous baroreflex estimates not interchangeable. We suggest that the comparison among different baroreflex sensitivity estimates might elucidate physiological mechanisms responsible for the relationship between heart period and systolic arterial pressure.

Background: Sleep disorders are associated to a number of cardiovascular disturbances that might increase cardiovascular risk. Sleep deprivation, in particular, might, by inducing autonomic dysregulation, raise arterial pressure and hypertensive risk. Available evidence however is contradictory., Methods: We tested the main hypothesis that one night sleep deprivation in 24 volunteers might alter hemodynamics (heart rate and Arterial Pressure - AP), autonomic regulation (mono and bivariate spectral analysis of RR and non invasive AP variability) and baroreflex control (spectral index alpha and spontaneous baroreflex slope), performance indices (reaction time) and subjective stress (questionnaires and salivary cortisol). Volunteers were studied in normal living conditions and while kept in isolation and confinement, to test the presence of possible bias related to environmental stress., Results: Results indicate that there were no differences between normal living conditions and isolation and confinement (Intraclass Correlation Coefficient >0.75 for most variables). Conversely, after one night sleep deprivation subjects felt tired (p<0.05), and performance deteriorated (p<0.05), while cortisol profile was substantially maintained, hemodynamic parameters did not change and HRV and index alpha increased slightly., Conclusions: Findings support the contention that one night sleep deprivation, in absence of significant additional stress or disturbances, does not lead to increased arterial pressure values or to changes in autonomic or baroreflex profiles that could conceivably favor hypertension development, but induces the expected increase in tiredness and reduction in performance.

Estimation of the baroreflex gain has become an important tool in clinical practice in order to assess cardiac autonomic system control. Spectral analysis and sequence analysis techniques based on the spontaneous variability of systolic arterial pressure and heart period have been proposed to evaluate the baroreflex gain. These analyses can be significantly altered by the presence of nonstationarities. Recently, the empirical mode decomposition (EMD), a signal processing technique particularly suitable for nonstationary series, has been proposed as a new tool for data analysis. The aim of this study is to propose EMD-based approaches to the evaluation of the baroreflex gain to account for the possible presence of nonstationarities of systolic arterial pressure and heart period series.

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.

In adults, initial stages of hypertension are associated with elevated sympathetic drive and significant alterations in indirect autonomic markers. There is growing evidence that children in the highest-pressure percentiles will be more likely to develop hypertension in adulthood, although mechanisms are not understood. We assessed whether computer analysis of RR interval and arterial blood pressure variability could detect early autonomic alterations in childhood hypertension, as assessed by noninvasive time and frequency domain measures of baroreflex regulation. We studied 75 children, subdivided in 3 subgroups of similar age (9.7+/-0.2 years): control subjects, prehypertensive children (ie, children with arterial pressure values >90th and <95th percentile for age, gender, and height), and children in the hypertensive range (ie, >95th percentile; systolic arterial pressure: 97+/-3/57+/-2, 121+/-5/70+/-1, and 128+/-2/80+/-2 mm Hg, respectively). We observed that hypertensive children demonstrate a significant impairment of the baroreflex as compared with control subjects (index alpha: 20+/-2 and 40+/-4 ms/mm Hg; spontaneous baroreflex slope: 20+/-2 and 37+/-5; ms/mm Hg; P<0.05 in both cases) and reduced RR variance. A similar baroreflex impairment is also observed in children whose arterial pressure falls short of this limit, ie, in the prehypertensive range. In conclusion, hypertensive children display a marked baroreflex impairment. A similar baroreflex impairment is also observed in the prehypertensive state. Baroreflex assessment could furnish additional information in the clinical assessment of pediatric hypertension.

Ten estimates of baroreflex sensitivity (BRS) were compared during progressive graded exercise: they were computed from sequence method, spectral and cross-spectral analysis methods, and parametric model-based methods. Results showed baroreflex control of heart rate (HR) changes as a function of the intensity of exercise, as well as the resetting phenomenon. Sequence, spectral and cross-spectral methods generally provided higher estimates than parametric model-based ones. This bias was particularly evident during exercise, and in the high frequency (HF) respiratory band. Results may suggest that the interaction of respiration and baroreflex function play an important in the cardiovascular adaptation from rest to exercise and from exercise to the recovery period.

Spontaneous baroreflex function and vascular changes were assessed in young adults during dynamical mild exercise. Windkessel time constant was assessed by two different methods: two-element windkessel model, and by an autoregressive (AR) model, while the baroreflex sensitivity (BRS, ms/mmHg) was assessed by the sequence method. Results showed a change in the baroreflex control of heart rate (HR) with the severity of exercise, as well as the resetting phenomenon. Methods used to estimate the windkessel time constant were poorly correlated. Subject by subject correlation was found between the BRS and the time constant derived from the AR model within exercise and recovery period. These results may suggest that reflex mechanisms controlling HR may also participate in controlling peripheral circulation or, viceversa, BRS is influenced by vascular tone.

One of the most important features of prolonged weightlessness is a progressive impairment of muscular function with a consequent decrease in exercise capacity. We tested the hypothesis that the impairment in musculo-skeletal function that occurs in microgravity results in a potentiation of the muscle metaboreflex mechanism and also affects baroreflex modulation of heart rate (HR) during exercise. Four astronauts participating in the 16 day Columbia shuttle mission (STS-107) were studied 72-71 days before launch and on days 12-13 in-flight. The protocol consisted of 6 min bicycle exercise at 50% of individual V(o2,max) followed by 4 min of postexercise leg circulatory occlusion (PECO). At rest, systolic (S) and diastolic (D) blood pressure (BP), R-R interval and baroreflex sensitivity (BRS) did not differ significantly between pre- and in-flight measurements. Both pre- and in-flight, SBP increased and R-R interval and BRS decreased during exercise, whereas DBP did not change. During PECO preflight, SBP and DBP were higher than at rest, whereas R-R interval and BRS recovered to resting levels. During PECO in-flight, SBP and DBP were significantly higher whereas R-R interval and BRS remained significantly lower than at rest. The part of the SBP response (delta) that was maintained by PECO was significantly greater during spaceflight than before (34.5 +/- 8.8 versus 13.8 +/- 11.9 mmHg, P = 0.03). The tachycardic response to PECO was also significantly greater during spaceflight than preflight (-141.5 +/- 25.2 versus - 90.5 +/- 33.3 ms, P = 0.02). This study suggests that the muscle metaboreflex is enhanced during dynamic exercise in space and that the potentiation of the muscle metaboreflex affects the vagally mediated arterial baroreflex contribution to HR control.

Objective: To assess the relationship between insulin resistance and baroreflex gain (BRS) in the context of the metabolic syndrome., Design: Observational population study., Patients: We studied the healthy population of a small Mediterranean island (Linosa, about 0.5 square miles, 450 inhabitants) where genetic, psychosocial and behavioral bias is likely to be minimal for historical and social reasons., Measures: Baroreflex gain (BRS, by the frequency domain alpha index) and indices of autonomic regulation of the sino-atrial (SA) node derived from spectral analysis of RR interval variability were obtained, together with metabolic and behavioral indicators in the 144 participating subjects (age range 20-82 years). Carotid artery thickness (CCA) was also obtained with computer-aided ultrasound techniques. Insulin resistance was estimated by the homeostasis model assessment (HOMA), and subjects divided in tertiles accordingly., Results: BRS appeared to be reduced progressively with increasing levels of HOMA (respectively, 21.0 +/- 2.6, 17.7 +/- 1.7, 15.7 +/- 1.9 ms/mmHg, P < 0.03), while spectral indices of autonomic SA regulation appeared to be only insignificantly affected. Conversely, CCA was significantly increased with increasing HOMA (P < 0.024). Furthermore, BRS appeared to be significantly correlated with various elements of the metabolic syndrome, with CCA and abdominal obesity showing the strongest link., Conclusions: In an otherwise healthy population, BRS, but not spectrally derived indices of SA node autonomic regulation, are progressively reduced with increasing severity of insulin resistance, possibly as a consequence of attendant carotid artery thickening.

Background: Chronic orthostatic intolerance (COI) is a common and disabling autonomic syndrome of unclear pathophysiology. We tested the hypothesis that baroreflex and autonomic responses to graded lower body suction (LBNP, up to -40 mmHg) could be altered in COI patients., Methods: Electrocardiogram (ECG), non-invasive arterial blood pressure and respiratory activity were measured during progressive LBNP (seven patients and seven volunteers). Lumped arterial baroreflex sensitivity (alpha index), and its arterial and cardiopulmonary components, were assessed by multivariate closed-loop analysis of RR interval and systolic arterial pressure (SAP) spontaneous variabilities and respiration. Monovariate spectral analysis of RR interval and SAP variability provided markers of autonomic regulation of the sinoatrial (SA) node and of vascular sympathetic modulation., Results: Similar reductions in overall and cardiopulmonary baroreflex gain were observed in both groups in response to graded LBNP. In contrast, only controls demonstrated a selective increase in arterial baroreflex sensitivity, at low-grade LBNP. Clear increases in the low-frequency component of RR interval variability (LFRR) [and decreases in the high-frequency component of RR interval variability (HFRR), both in normalized units] were observed in controls with graded LBNP, while insignificant changes occurred in COI patients, who showed, conversely, exaggerated sympathetic vasomotor responses [as assessed by the low frequency component of SAP variability (LFSAP)]., Conclusions: Patients with chronic orthostatic intolerance show distinct signs of altered baroreflex and autonomic regulation of the SA node and of the vasculature in response to graded LBNP.

Objective: To examine the relationship between heart rate variability (HRV) and baroreflex sensitivity (BRS)., Design: An observational study, with no intervention, in 55 volunteers with a wide range of arterial pressure (60-90/115-185 mmHg)., Methods: Volunteers were studied first in the laboratory, with continuous measurement of systolic arterial pressure and electrocardiogram to obtain a frequency domain measure of baroreflex sensitivity (index alpha). Immediately afterwards, while the individual was ambulant, a Holter recording was obtained in order to compute time domain [standard deviation of consecutive normal R-R intervals (SDNN) and the percentage of successive R-R differences > 50 ms (PNN50)], and frequency domain measures of HRV. Linear correlation was used to test the statistical link between index alpha and HRV indices., Results: Significant correlations were observed between index alpha and SDNN (r = 0.30; P < 0.02) and PNN50 (r = 0.48; P < 0.001), and between index alpha and total power (r = 0.53; P < 0.001), and absolute powers of the 0.0001-0.04 Hz components of R-R interval variability in 24 h (r = 0.47; P < 0.001)., Conclusion: The major findings of this study are the clear demonstration of a significant correlation between a laboratory measure of baroreflex sensitivity and 24 h measures of HRV, obtained immediately afterwards. Notably, this correlation was found with both time domain and absolute, but not normalized, spectral measures of R-R interval variability. In addition, different levels of individual activity, as assessed by separate examination of daytime and night-time periods, did not seem to influence this relationship.

Background: Although cardiovascular rehabilitation and exercise training have substantial benefits in various ischemic heart disease (IHD) risk factors and subsequent prognosis after major IHD events, there is a paucity of information about its effects on autonomic regulation (such as heart rate variability [HRV] and baroreflex gain), particularly considering its arterial and cardiopulmonary components., Methods: We studied 40 patients (aged 60 +/- 6 y) after major IHD events, including 29 who underwent a comprehensive phase II cardiac rehabilitation and exercise training program and 11 controls who did not attend cardiac rehabilitation. Specifically, we determined whether active training improves prognostic indices of autonomic regulation of the SA node and whether changes in baroreflex gain could be ascribed to the arterial or to the cardiopulmonary component of the overall arterial pressure/heart period baroreflex., Results: Only patients with IHD undergoing active rehabilitation demonstrated a significant increase in R-R interval, in its variance, in overall gain of arterial pressure/heart period baroreflex (7.44 +/- 1.20 ms/mm Hg to 12.12 +/- 1.48 ms/mm Hg, P <.001) and in peak oxygen consumption (Delta = 2.45 mL/kg/min, P <.001). Separate examination of the selective arterial and cardiopulmonary components showed that only the latter increased significantly (6.17 +/- 1.09 ms/mm Hg to 10.62 +/- 1.56 ms/mm Hg; P <.01)., Conclusions: Cardiac rehabilitation is associated with significant improvements in autonomic markers of neural regulation of the SA node, such as increases in R-R variance and the gain of the overall spontaneous baroreflex, with specific improvements in the cardiopulmonary component as opposed to the arterial baroreflex component of this system. These improvements may further explain the reduction in morbidity and mortality noted after formal cardiac rehabilitation and exercise training programs.

The coherence function measures the amount of correlation between two signals x and y as a function of the frequency, independently of their causal relationships. Therefore, the coherence function is not useful in deciding whether an open-loop relationship between x and y is set (x acts on y, but the reverse relationship is prevented) or x and y interact in a closed loop (x affects y, and vice versa). This study proposes a method based on a bivariate autoregressive model to derive the strength of the causal coupling on both arms of a closed loop. The method exploits the definition of causal coherence. After the closed-loop identification of the model coefficients, the causal coherence is calculated by switching off separately the feedback or the feedforward path, thus opening the closed loop and fixing causality. The method was tested in simulations and applied to evaluate the degree of the causal coupling between two variables known to interact in a closed loop mainly at a low frequency (LF, around 0.1 Hz) and at a high frequency (HF, at the respiratory rate): the heart period (RR interval) and systolic arterial pressure (SAP). In dogs at control, the RR interval and the SAP are highly correlated at HF. This coupling occurs in the causal direction from the RR interval to the SAP (the mechanical path), while the coupling on the reverse causal direction (the baroreflex path) is not significant, thus pointing out the importance of the direct effects of respiration on the RR interval. Total baroreceptive denervation, by opening the closed loop at the level of the influences of SAP on RR interval, does not change these results. In elderly healthy men at rest, the RR interval and SAP are highly correlated at the LF and the HF. At the HF, a significant coupling in both causal directions is found, even though closed-loop interactions are detected in few cases. At the LF, the link on the baroreflex pathway is negligible with respect to that on the reverse mechanical one. In heart transplant recipients, in which SAP variations do not cause RR interval changes as a result of the cardiac denervation, the method correctly detects a significant coupling only on the pathway from the RR interval to the SAP.

Background: Newer techniques to evaluate baroreflex sensitivity (BRS) are based on the analysis of blood pressure (BP) and heart rate (HR) time series in the time or frequency domain. These novel approaches are steadily gaining popularity, since they do not require injection of vasoactive substances, nor do they rely on a complex experimental set-up., Aim: This review outlines and compares some basic features of the latest methods to assess spontaneous baroreflex function., Results: Modern techniques for the estimation of spontaneous BRS are based on a variety of signal processing schemes and derive information on the baroreflex function from different perspectives. Thus factors such as respiration and other non-stationary agents may have different influences on the estimates provided by each of these approaches. Notwithstanding such individual specificity, however, it has been observed that in several physiological and pathophysiological conditions these techniques often provide comparable information on BRS changes over time, particularly when the estimates are averaged over time windows of a few minutes., Conclusions: Due to the general agreement in the pattern of BRS among most modern methods, it seems reasonable to employ the most validated of these techniques, for which data obtained in several studies are already available.

A double exogenous autoregressive (XXAR) causal parametric model was used to estimate the baroreflex gain (alpha(XXAR)) from spontaneous R-R interval and systolic arterial pressure (SAP) variabilities in conscious dogs. This model takes into account 1) effects of current and past SAP variations on the R-R interval (i.e., baroreflex-mediated influences), 2) specific perturbations affecting R-R interval independently of baroreflex circuit (e.g., rhythmic neural inputs modulating R-R interval independently of SAP at frequencies slower than respiration), and 3) influences of respiration-related sources acting independently of baroreflex pathway (e.g., rhythmic neural inputs modulating R-R interval independently of SAP at respiratory rate, including the effect of stimulation of low-pressure receptors). Under control conditions, alpha(XXAR) = 14.7 +/- 7.2 ms/mmHg. It decreases after nitroglycerine infusion and coronary artery occlusion, even though the decrease is significant only after nitroglycerine, and it is completely abolished by total arterial baroreceptor denervation. Moreover, alpha(XXAR) is comparable to or significantly smaller than (depending on the experimental condition) the baroreflex gains derived from sequence, power spectrum [at low frequency (LF) and high frequency (HF)], and cross-spectrum (at LF and HF) analyses and from less complex causal parametric models, thus demonstrating that simpler estimates may be biased by the contemporaneous presence of regulatory mechanisms other than baroreflex mechanisms.

Objectives: In usual models of cardiovascular regulation, arterial pressure drives RR interval through a simple baroreflex, and the influence of respiration is dismissed. We examined the applicability of a trivariate autoregressive model to obtain separate values of the gain of the arterial and non-arterial, i.e. cardiopulmonary, components of the lumped baroreflex, employing spontaneous RR interval, systolic arterial pressure and respiration variability., Design: We studied 30 normal subjects (age 37 +/- 1 years), both at rest and during standing, a condition known to enhance sympathetic activity while reducing venous return. Electrocardiogram was obtained by telemetry, arterial pressure by Finapres and respiration with a piezoelectric respiratory belt Data were acquired with a PC and processed with an ad hoc Windows program., Methods: We employed an additive and a linear multivariate approach to approximate overall gain of the arterial pressure-heart beat period baroreflex (alphalumped) and of its arterial (alphaart) and non-arterial, i.e. cardiopulmonary (alphacp), components, from continuous beat-by-beat series of RR interval, systolic arterial pressure variability and respiration, without using any non-physiological intervention., Results: The overall baroreflex gain at rest (alphalumped = 23.7 +/- 3.4 ms/mmHg) was subdivided into arterial (alphaart = 5.2 +/- 1.0 ms/mmHg) and cardiopulmonary (alphacp = 18.5 +/- 3.2ms/mmHg) components. During active orthostatism, alphaluumped was diminished to 10.0 +/- 2.2 ms/ mmHg. In addition, standing selectively reduced alphacp to 4.8 +/- 1.3 ms/mmHg, while alphaart was not significantly changed., Conclusions: A trivariate autoregressive model, that considers explicitly the influence of respiration, can subdivide overall, lumped, arterial pressure-heart period baroreflex gain, into two separate components, alphaart and alphacp. Only the latter is reduced by active orthostatism.

1. We assessed the effects of changing levels of sympathetic drive on the gain of baroreflex control of the sino-atrial node, in normotensive and hypertensive subjects. 2. Autoregressive spectral and cross-spectral analysis of R-R interval and systolic arterial pressure (non-invasive Finapres method) variabilities providing an estimate of baroreflex gain through the frequency domain index alpha were performed on data from 63 normotensive and 78 mild hypertensive subjects. Subjects were studied at rest and during active orthostatism, which induces sympathetic predominance. Seven control subjects and 14 hypertensive subjects were also studied after chronic atenolol treatment, to attenuate beta-adrenoceptor-mediated responses. 3. In both normotensive and hypertensive subjects, the index alpha was reduced by active standing and increased by chronic beta-adrenoceptor blockade. Furthermore, at rest, the index alpha was correlated with R-R variance and appeared significantly reduced with age. The age-related negative correlation of the index alpha was no longer evident during the standing-induced increase in sympathetic drive, in both normotensive and hypertensive subjects. 4. The index alpha, a non-invasive frequency domain estimate of the overall gain of baroreflex control of the sino-atrial node, which appears to be reduced in essential hypertension, is negatively modulated by physiological increases in sympathetic drive, and augmented by pharmacological blockade of beta-adrenoceptors. 5. In essential hypertension the enhanced sympathetic drive present already at rest, and the simultaneous reduction of the gain of baroreflex mechanisms, are the expression of a complex alteration in neural cardiovascular control.

Alessia Riglietti,1,&ast; Francesco Fanfulla,2,&ast; Massimo Pagani,3 Daniela Lucini,3,4 Mara Malacarne,3,4 Mauro Manconi,5– 7 Guido Ferretti,8,9 Fabio Esposito,10,11 Carlo W Cereda,12 Marco Pons1 1Department of Pulmonology, Regional Hospital of Lugano (EOC), Lugano, 6900, Switzerland; 2Respiratory Function and Sleep Unit – Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy; 3Exercise Medicine Unit, Istituto Auxologico Italiano, MIlan, 20133, Italy; 4University of Milan, BIOMETRA Department, Milan, Italy; 5Sleep and Epilepsy Center, Neurocenter of the Southern Switzerland, Regional Hospital (EOC) of Lugano, Lugano, Switzerland; 6Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland; 7Department of Neurology, University Hospital, Inselspital, Bern, Switzerland; 8Department APSI, University of Geneva, Geneva, Switzerland; 9Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy; 10Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy; 11IRCCS Istituto Ortopedico Galeazzi, Milan, Italy; 12Stroke Center EOC, Department of Neurology, Neurocenter of Southern Switzerland Regional Hospital (EOC) of Lugano, Lugano, Switzerland&ast;These authors contributed equally to this workCorrespondence: Mauro ManconiRegional Hospital of Lugano, Via Tesserete, 46, Lugano, 6903, SwitzerlandTel +41-91-8116825Email mauro.manconi@eoc.chIntroduction: Sleep-related breathing disorders are highly prevalent in patients with ischemic stroke. Among sleep-disordered breathing disorders, obstructive sleep apnea is the most represented one, but central sleep apnea, isolated or in the context of a periodic breathing/Cheyne–Stokes respiration, is frequently reported in these patients. Altered baroreflex responses have been reported in the acute phases of a cerebral event.Methods: We conducted, in a group of patients with ischemic stroke (n=60), a prospective 3-month follow-up physiological study to describe the breathing pattern during sleep and baroreflex sensitivity in the acute phase and in the recovery phase.Results: In the acute phase, within 10 days from the onset of symptoms, 22.4% of patients had a normal breathing pattern, 40.3% had an obstructive pattern, 16.4% had a central pattern, and 29.9% showed a mixed pattern. Smaller variations in the Apnea–Hypopnea Index were found in normal breathing and obstructive groups (ΔAHI 2.1± 4.1 and − 2.8± 11.6, respectively) in comparison with central and mixed patterns (ΔAHI − 6.9± 15.1 and − 12.5± 13.1, respectively; ANOVA p=0.01). The obstructive pattern became the most frequent pattern, in 38.3% of patients at baseline and 61.7% of patients at follow-up. Modification of baroreflex sensitivity over time was influenced by the site of the lesion and by the sleep disorder pattern in the acute phase (MANOVA p=0.005).Conclusion: We suggest that a down-regulation of autonomic activity, possibly related to reduced vagal modulation, may help the recovery after stroke, or a transitory disconnection from the cortical node that participates in the regulation of sympathetic outflow.Keywords: sleep-disordered breathing, baroreflex, chemoreflex, brain lesion