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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

Elevated psychosocial stress might favor the occurrence of cardiovascular disease; however, mechanisms are incompletely understood. We hypothesized that patients (n=126; 44±1 years of age) referred to an internal medicine clinic because of symptoms related to chronic psychosocial stress would demonstrate signs of autonomic dysregulation compared with controls (n=132; 42±1 years of age). We used autoregressive spectral analysis of RR interval variability to obtain indirect markers of sympathetic and of vagal (respectively, low-frequency and high-frequency components, both expressed in normalized units) oscillatory modulation of sinoatrial node, as well as of sympathetic vasomotor regulation (low-frequency component of systolic arterial pressure variability) and of cardiac baroreflex sensitivity (α-index). Higher values of systolic and diastolic arterial pressure (respectively, 124±1 versus 117±1 mm Hg and 80±1 versus 75±1 mm Hg; both P P P P

In the context of functional determinants of cardiovascular risk, a simple excess in body weight, as indexed by a rise in body mass index (BMI), plays a significant, well-recognized causal role. Conversely, BMI reductions toward normal result in an improvement of risk. Obesity is associated with impaired cardiac autonomic regulation (CAR), through either vagal or sympathetic mechanisms, which could favor the tendency to foster hypertension. Here we study the changing properties of the relationship between increasing grades of BMI and CAR in a population of 756 healthy subjects (age 35.9 ± 12.41 years, 37.4% males, 21.6% overweight, and 16% obese). Evaluation of CAR is based on autoregressive spectral analysis of short-term RR interval and systolic arterial pressure variability, from which a multitude of indices, treated overall as autonomic nervous system (ANS) proxies, is derived. Inspection of the study hypothesis that elevated BMI conditions associate significantly with alterations of CAR, independently of age and gender, is carried out using a mix of statistical transformations, exploratory factor analysis, non-parametric testing procedures, and graphical tools particularly well suited to address alterations of CAR as a disturbed process. In particular, to remove the effects of the inter-individual variability, deriving from components like age, gender or ethnicity, and to reduce the number of ANS proxies, we set up six age-and-gender-adjusted CAR indicators, corresponding to four ANS latent domains (oscillatory, amplitude, pressure, and pulse), cardiac baroreflex regulation, and autonomic nervous system index (ANSI). An impairment of the CAR indicators is overall evident in the overweight group and more marked in the obesity group. Empirical evidence is strong (9/9 concordant non-parametric test results) for pressure domain, almost strong (8/9) for ANSI, medium-strong for baroreflex (6/9) and pulse (7/9), weak for oscillatory (2/9) and amplitude (1/9) domains. In addition, the distribution of the CAR indicators corresponding to pressure, pulse, baroreflex, and ANSI is skewed toward the unfavorable abscissa extremity, particularly in the obese group. The significant association of increased BMI with progressive impairments of CAR regarding specifically the pressure domain and the overall ANS performance might underscore the strong hypertensive tendency observed in obesity.

Interests about the fine underpinnings of cardiovascular beat-by-beat variability have historical roots. Over the last decades, various aspects of the relationships between arterial pressure and heart period were taken as a proxy of the baroreflex in physiology and medicine, stimulating the interest of investigators in several interconnected scientific fields, in particular, bioengineering, neurophysiology, and clinical medicine. Studies of the overall system facilitated the emergence of a simplified negative (vagal) feedback model of the baroreflex and overshadowed the simultaneous interaction with excitatory, sympathetic positive-feedback mechanisms that would, however, better suit the model of a “paired antagonistic (parasympathetic/sympathetic) innervation of the internal organs.” From the bioengineering side, the simplicity of obtaining the series of subsequent RR intervals stimulated the analysis of beat-by-beat variations, providing a multitude of heart rate variability (HRV) indices considered as proxies of the underlying sympatho-vagal balance, and participating to the management of several important clinical conditions, such as hypertension. In this context, advanced statistical methods, used in an integrated manner and controlling for age and gender biases, might help shed new light on the relationship between cardiac baroreflex, assessed by the frequency domain index α, and the HRV indices with the varying of systolic arterial pressure (SAP) levels. The focus is also on a novel unitary Autonomic Nervous System Index (ANSI) built as a synthesis of HRV considering its three most informative proxies [RR, RR variance, and the rest-stand difference in the normalized power of low-frequency (LF) variability component]. Data from a relatively large set of healthy subjects (n = 1154) with a broad range of SAP [from normal (nNt = 778) to elevated (nHt = 232)] show that, e.g., α and ANSI significantly correlate overall (r = 0.523, p < 0.001), and that this correlation is lower in hypertensives (r = 0.444, p < 0.001) and higher in pre-hypertensives (r = 0.618, p < 0.001) than in normotensives (r = 0.5, p < 0.001). That suggests the existence of curvilinear “umbrella” patterns that might better describe the effects of the SAP states on the relationships between baroreflex and HRV. By a mix of robust, non-parametric and resampling statistical techniques, we give empirical support to this study hypothesis and show that the pre-hypertensive group results at the apex/bottom in most of the studied trends.

Background Autonomic nervous system (ANS) regulation may be altered in functional diseases, including irritable bowel syndrome (IBS), but published data are not clear to date. The aim of the study was to analyze ANS function in IBS subjects classified by Rome III criteria and healthy controls using standardized technique. Methods ANS activity was evaluated by autoregressive spectral analysis of RR interval and systolic arterial pressure variabilities, to obtain indices of sympatho-vagal modulation of the heart and of spontaneous cardiac baroreflex (α index). A symptom list was used to score 18 somatic complaints (score 0–180) (4SQ). Fatigue and stress were assessed through the use of a global scoring index (0–10). Key Results We enrolled 41 IBS subjects (29 F, age 40 ± 2 years) and 42 healthy matched controls. Heart rate was higher in IBS than control subjects (69 ± 2 vs 61 ± 1; p

Introduction: Altered profile of RR variability and reduced baroreflex gain, as autonomic proxies, are observed in hypertensive individuals. Aim: To assess whether using logistic models and cross-validation techniques autonomic proxies can be used to identify clinical hypertensive and normotensive groups. Methods: An observational study on 405 individuals (155 mild hypertensive and 250 controls). We used four steps for statistical analysis: preliminary descriptive statistics; logistic regression modelling; detection of best parsimonious set of variables; and concordance analysis between clinical and autonomic hypertension profile. Results: Accuracy index (rate of correct identifications of normotensive and hypertensive states), computed on each of the four gradually more complex logistic models (from A to D), reached its highest value (82.7%), in the most complete model D, including autonomic nervous system indices (RR variability and baroreflex gain), age and sex. Measures of predictive performance increased from the simplest model to the most complex one [model D, positive predictive value (PPV) = 0.767, negative predictive value (NPV) = 0.866], with higher specificity than sensitivity. A parsimonious set of autonomic proxies (Mean RR, Delta_RRLFnu – i.e. change from rest to standing up – baroreflex gain combined with age and sex) led to an accuracy index of 80.5%, thus proving to have discriminant and predictive powers in detecting hypertension very similar to the whole set of the explicative variables comprised in the complete model D. Conclusion: The clinical value of the observation that the information collectively carried by a small subset of indirect autonomic proxies may identify either hypertensive or normotensive groups needs to be further investigated.

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 (V E ) vs arterial oxygen saturation measured by pulse oximetry (SpO 2 %) and partial pressure of end-tidal oxygen (PetO 2 ). 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 ΔV E /ΔSpO 2 : –1.37 ± 0.33 vs –0.33 ± 0.08 and SpO 2 % –0.29 ± 0.13 L/min; P = .002; ΔV E /ΔPetO 2 : –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.

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; 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 α: 20±2 and 40±4 ms/mm Hg; spontaneous baroreflex slope: 20±2 and 37±5; ms/mm Hg; P

Caregiving, an important component of cancer patient treatment, may set forth a cascade of stress responses such as sympatho-adrenal activation, immuno-humoral changes and an unhealthy lifestyle, which could be hazardous to caregivers' health. In this observational study, we addressed whether autonomic nervous system (ANS) regulation and perception of stress would be altered in a group of 58 health cancer caregivers as compared to 60 controls. We employed non invasive autoregressive spectral analysis of cardiovascular variabilities and ad hoc questionnaires. Caregivers show, in addition to signs of psychological involvement, a clear autonomic imbalance, suggestive of sympathetic predominance at rest and of a reduction of vagal cardiac regulation (overall gain of baroreflex -index alpha- was respectively of 17.5+/-1.5 versus 25.1+/-1.8 msec/mmHg, p<

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. (C) 2001 Lippincott Williams & Wilkins

To the Editor: While several papers support the physiological and clinical relevance of indices quantifying the sensitivity of spontaneous baroreflex control of heart rate (BRS),1 Lipman et al2 claim that they are unable to properly explore baroreflex function because spontaneous BRS was found to be quantitatively different from BRS values provided by the vasoactive drug injection technique and is unrelated to common carotid artery distensibility. We believe that this conclusion is not supported by Lipman’s data, for the following reasons. 1. The time honored (and still valuable) method for assessing BRS through vasoactive drugs injection3,4 cannot be a “gold standard”5 due to pharmacological alteration of baroreceptor activity through both changes in blood pressure (BP) and unquantifiable mechanical distortion of the vessel;6 direct drug effect on the sinus node;7 simultaneous stimulation of cardiopulmonary stretch receptors; and limited reproducibility of the few spot BRS estimates obtainable.1,8 2. Pharmacological and spontaneous BRS values are significantly correlated in most instances,9 as demonstrated by Parlow et al in a study10 not cited by Lipman et al. Moreover, spontaneous and drug-related BRS values display directionally similar changes under different conditions, thus reflecting virtually superimposable baroreflex physiology. …