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It has been proposed that sympathoexcitation is responsible for vascular desensitization to α 1 -adrenoceptor stimulation during lipopolysaccharide (LPS)-induced systemic inflammation. The present study tested this hypothesis by examining the effects of sympatho-deactivation with the α 2 -adrenoceptor agonist, dexmedetomidine, on mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and vascular reactivity to phenylephrine in conscious rats with cardiac autonomic blockade (methylatropine and atenolol) following LPS administration. In male, adult Sprague-Dawley rats ( n  =   5 per group), RSNA and MAP were continuously recorded over 1-h periods, before and after LPS administration (20 mg/kg iv), and finally after infusion of either saline or dexmedetomidine (5  μ g/kg, then 5  μ g/kg/h iv). A full dose - response curve to phenylephrine was constructed under each condition. After pooling data from both groups of rats ( n  =   10), LPS significantly ( P  =   0.005) decreased MAP (from 115 ± 1 to 107 ± 2 mmHg), increased RSNA (to 403 ± 46% of baseline values) and induced 4 to 5-fold increases in the half-maximal effective dose (ED 50 ) of phenylephrine (from 1.02 ± 0.09 to 4.76 ± 0.51  μ g/kg). During saline infusion, RSNA progressively decreased while vascular reactivity did not improve. Treatment with dexmedetomidine decreased MAP, returned RSNA to near pre-endotoxemic levels, but only partially restored vascular reactivity to phenylephrine (ED 50 was still threefold increased as compared with baseline values). These findings indicate that only part of the decrease in vascular reactivity to α 1 -adrenoceptor stimulation during endotoxemia can be accounted for by sympathetic activation, at least on a short-term basis., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

The study compares permutation-based and coarse-grained entropy approaches for the assessment of complexity of short heart period (HP) variability recordings. Shannon permutation entropy (SPE) and conditional permutation entropy (CPE) are computed as examples of permutation-based entropies, while the k-nearest neighbor conditional entropy (KNNCE) is calculated as an example of coarse-grained conditional entropy. SPE, CPE and KNNCE were applied to ad-hoc simulated autoregressive processes corrupted by increasing amounts of broad band noise and to real HP variability series recorded after complete vagal blockade obtained via administration of a high dose of atropine (AT) in nine healthy volunteers and during orthostatic challenge induced by 90° head-up tilt (T90) in 15 healthy individuals. Over the simulated series the performances of SPE and CPE degraded more rapidly with the amplitude of the superimposed broad band noise than those of KNNCE. Over real data KNNCE identified the expected decrease of the HP variability complexity both after AT and during T90. Conversely SPE and CPE detected the decrease of HP variability complexity solely during T90 as a likely result of the more favorable signal-to-noise ratio during T90 than after AT. Results derived from both simulations and real data indicated that permutation-based entropies had a larger susceptibility to broad band noise than KNNCE. We recommend caution in applying permutation-based entropies in presence of short HP variability series characterized by a low signal-to-noise ratio.

We studied causal relations among heart period (HP), systolic arterial pressure (SAP) and respiration (R) according to the definition of Granger causality in the time domain. Autonomic pharmacological challenges were used to alter the complexity of cardiovascular control. Atropine (AT), propranolol and clonidine (CL) were administered to block muscarinic receptors, β-adrenergic receptors and centrally sympathetic outflow, respectively. We found that: (i) at baseline, HP and SAP interacted in a closed loop with a dominant causal direction from HP to SAP; (ii) pharmacological blockades did not alter the bidirectional closed-loop interactions between HP and SAP, but AT reduced the dominance of the causal direction from HP to SAP; (iii) at baseline, bidirectional interactions between HP and R were frequently found; (iv) the closed-loop relation between HP and R was unmodified by the administration of drugs; (v) at baseline, unidirectional interactions from R to SAP were often found; and (vi) while AT induced frequently an uncoupling between R and SAP, CL favoured bidirectional interactions. These results prove that time domain measures of Granger causality can contribute to the description of cardiovascular control by suggesting the temporal direction of the interactions and by separating different causality schemes (e.g. closed loop versus unidirectional relations).

It is unclear whether the complexity of the variability of the systolic arterial pressure (SAP) provides complementary information to that of the heart period (HP). The complexity of HP and SAP variabilities was assessed from short beat-to-beat recordings (i.e., 256 cardiac beats). The evaluation was made during a pharmacological protocol that induced vagal blockade with atropine or a sympathetic blockade (beta-adrenergic blockade with propranolol or central sympathetic blockade with clonidine) alone or in combination, during a graded head-up tilt, and in patients with Parkinson's disease (PD) without orthostatic hypotension undergoing orthostatic challenge. Complexity was quantified according to the mean square prediction error (MSPE) derived from univariate autoregressive (AR) and multivariate AR (MAR) models. We found that: 1) MSPE(MAR) did not provide additional information to that of MSPE(AR); 2) SAP variability was less complex than that of HP; 3) because HP complexity was reduced by either vagal blockade or vagal withdrawal induced by head-up tilt and was unaffected by beta-adrenergic blockade, HP was under vagal control; 4) because SAP complexity was increased by central sympathetic blockade and was unmodified by either vagal blockade or vagal withdrawal induced by head-up tilt, SAP was under sympathetic control; 5) SAP complexity was increased in patients with PD; and 6) during orthostatic challenge, the complexity of both HP and SAP variabilities in patients with PD remained high, thus indicating both vagal and sympathetic impairments. Complexity indexes derived from short HP and SAP beat-to-beat series provide complementary information and are helpful in detecting early autonomic dysfunction in patients with PD well before circulatory symptoms become noticeable.

Detrended fluctuation analysis (DFA) is the most popular method for assessing the fractal characteristics of heart rate (HR). Traditionally, short-term and long-term scale coefficients, α(1) and α(2), are calculated from DFA. We recently showed that the traditional approach oversimplifies a more complex phenomenon better represented by a continuous spectrum of scale coefficients. In this paper we present a DFA based method for describing the HR fractal dynamics with a temporal spectrum of scale exponents, α(t), rather than by a model of lumped parameters, α(1) and α(2). Since α(t) is a function of the temporal scale, its interpretation is facilitated when conditions with different mean HR are compared. In this work, we reanalyze HR data, collected by our group in previous studies, by applying the proposed α(t) spectrum. We quantify the effects of gender, ageing, posture and activity level, and the alterations induced by exposure to high and very-high altitude hypoxia, on α(t). Most of the results may be interpreted in terms of changes of cardiac autonomic regulation, and indicate clearly that the new proposed DFA spectrum provides a more faithful and interpretable description of the HR fractal dynamics than traditional α(1) and α(2) scale coefficients.

How the autonomic nervous system influences the fractal dynamics of heart rate (HR) and blood pressure (BP) remains unclear. The purpose of our study was to separately assess cardiac vagal and sympathetic (cardiac vs. vascular) influences on fractal properties of HR and BP as described by scale exponents of detrended fluctuation analysis (DFA). R-R intervals, systolic and diastolic BP were measured in nine supine volunteers before and after administration of autonomic blocking agents (atropine, propranolol, atropine+propranolol, clonidine). Spectra of DFA scale exponents, α(t), were calculated for scales between 5 and 100 s. HR and BP scale structures differed at baseline, being α(t) of HR <1, with a minimum between 10 and 20 s followed by a higher plateau between 40 to 80 s, while α(t) of BP decreased with t from values >1. Comparison of atropine and propranolol with baseline and combined cardiac parasympathetic and sympathetic blockade (atropine+propranolol) indicated opposite influences of vagal and cardiac sympathetic outflows on HR exponents. The vagal outflow adds white-noise components, amplifying differences with BP exponents; the cardiac sympathetic outflow adds Brownian motion components at short scales and contributes to the plateau between 40 and 80 s. Overall sympathetic inhibition by clonidine decreased short- and long-term exponents of HR, and short-term exponents of BP, so that their α(t) spectra had different means but similar profiles. Therefore, cardiac vagal, cardiac sympathetic and vascular sympathetic outflows contribute differently to HR and BP fractal structures. Results are explained by different distribution and dynamics of acetylcholine receptors and of α- and β-adrenergic receptors between heart and vasculature.

Background: We sought to determine whether online use of a beat-by-beat cardiovascular index, CARDEAN (Alpha-2, Lyon, France), modifies the incidence of patient movement during colonoscopy under anesthesia., Methods: Monitoring included an electrocardiogram, oscillometric and noninvasive beat-by-beat arterial blood pressure, O2 saturation, bispectral index (BIS), and CARDEAN. CARDEAN consists of beat-by-beat Finapres (Ohmeda, Madison, WI) combined with an algorithm that detects hypertension followed by tachycardia and produces an index scaled 0 to 100. The anesthesiologist was denied access to Finapres and CARDEAN. Propofol was adjusted to keep 4060. The primary outcome was the number of observed movements., Results: Data were analyzed in 146 patients (control: 75; CARDEAN: 71). The doses of propofol and alfentanil were similar in both groups. When BIS was <60, movements were less frequent in the CARDEAN group (3.3 movements/100 min [2.3-4.8]) than in the control group (6.7 [5.3-8.5]) (odds ratio: 0.5 [0.32; 0.76], P = 0.001). During the first 10 minutes of the procedure, the incidence of movements was 38% and 59% in the CARDEAN and control groups, respectively (P = 0.04)., Conclusion: With BIS <60, CARDEAN-guided opioid administration is associated with a reduction of 51% of clinically unpredictable movements in unparalyzed patients undergoing colonoscopy. More studies are required to refine the role of CARDEAN in surgical settings.

Heart rate self-affinity is often assessed by detrended fluctuations analysis, obtaining two coefficients only: a short-term (alpha(1)) exponent and a long-term (alpha(2)) exponent. Our aim is to show the limits of this approach and alternatively propose the estimation of the whole spectrum of local exponents alpha(n) for heart rate and blood pressure. To illustrate the advantages of this approach, we assess the effects of autonomic activations and age on alpha(n). We measured ECG and arterial pressure in 60 volunteers for 10 min, considering three conditions at increasing sympathetic activation: supine rest, sitting, and sitting during exercise. We computed alpha(n) of R-R intervals and systolic, mean, and diastolic blood pressures, as the slope of the detrended fluctuations function in a log-log plot. Volunteers were divided into age groups and compared. Results indicate that: 1) alpha(1) cannot be defined because short-term coefficients decrease with n, while alpha(2) cannot be defined only for blood pressure during supine rest; 2) heart rate and blood pressure scaling structures differ during supine rest but not during exercise; and 3) age effects appear mainly in supine rest, explaining discrepant results in literature. In conclusion, we recommend estimating the whole alpha(n) spectrum before possibly providing the "two-exponent" description only.

Intravenous B-type natriuretic peptide (BNP) enhances the bradycardia of reflexes from the heart, including the von Bezold-Jarisch reflex, but its site of action is unknown. The peptide is unlikely to penetrate the blood-brain barrier but could act on afferent or efferent reflex pathways. To investigate the latter, two types of experiment were performed on urethane-anesthetized (1.4 g/kg iv) rats. First, the activity was recorded extracellularly from single cardiac vagal motoneurons (CVMs) in the nucleus ambiguus. CVMs were identified by antidromic activation from the cardiac vagal branch and by their barosensitivity. Phenyl biguanide (PBG), injected via the right atrium in bolus doses of 1-5 mug to evoke the von Bezold-Jarisch reflex, caused a dose-related increase in CVM activity and bradycardia. BNP infusion (25 pmol.kg(-1).min(-1) iv) significantly enhanced both the CVM response to PBG (n = 5 rats) and the reflex bradycardia, but the log-linear relation between those two responses over a range of PBG doses was unchanged by BNP. The reflex bradycardia was not enhanced in five matched time-control rats receiving only vehicle infusions. In five other rats the cervical vagi were cut and the peripheral right vagus was stimulated supramaximally at frequencies of 1-20 Hz. The bradycardic responses to these stimuli were unchanged before, during, and after BNP infusion. We conclude that systemic BNP in a moderate dose enhances the von Bezold-Jarisch reflex activation of CVM, in parallel with the enhanced reflex bradycardia. That enhancement is due entirely to an action before the vagal efferent arm of the reflex pathway.

Objective: Unexpected intraoperative movement may be detrimental during delicate surgery. This study tested retrospectively an algorithm based on beat-by-beat circulatory variables (incorporated into a Cardiovascular depth of anesthesia index: CARDEAN in relationship to unexpected movement, and compared its performance to that of the electroencephalogram (EEG)-derived index: BIS-XP 4.0., Methods: 40 ASA I or II patients presenting for knee surgery had EEG (BIS XP 4.0), beat-by-beat (Finapres) finger non-invasive blood pressure (BP), conventional brachial BP and electrocardiogram (EKG) monitors attached. Anesthesia was induced and maintained with propofol and remifentanil. Before incision, the propofol concentration was set to maintain BIS < 60. From incision to emergence, the anesthesiologist was denied access to BIS or Finapres. Anesthesia adjustment was titrated at the discretion of the anesthesiologist according to conventional signs only: brachial BP, EKG, eyelash reflex, movement. Occurrences of movement and eye signs (divergence of eyeballs, tears, corneal reflex, eyelash reflex) were observed. The CARDEAN algorithm was written retrospectively and tested vs. BIS., Results: 11 movements occurred in 8 patients. CARDEAN > 60 predicted movement in 30% of the cases, 15 to 274 s before movement (sensitivity: 100%, specificity: 95%; relative operating curve ROC = 0.98; prediction probability pk = 0.98). BIS > 60 predicted movement in 19% of cases (sensitivity: 64%; specificity: 94%, ROC: 0.85, pk: 0.85)., Conclusion: Retrospectively, a cardiovascular index predicted unexpected intraoperative movements. Prospective validation is needed.

The fractal structure of heart rate is usually quantified by estimating a short-term (alpha(1)) and a long-term (alpha(2)) scaling exponent by Detrended Fluctuations Analysis (DFA). Evidence, however, has been provided that heart rate is a multifractal signal, better characterized by a large number of scaling exponents. Aim of this study is to verify whether two scaling exponents only from DFA provide a sufficiently accurate description of the possibly multifractal nature of cardiovascular signals. We measured ECG and finger arterial pressure in 33 volunteers for 10 minutes during each of 3 conditions: supine rest (SUP); sitting at rest (SIT); light physical exercise (EXE). DFA was applied on the beat-by-beat series of R-R interval (RRI) and mean arterial pressure (MAP). We then computed the local scaling exponent alpha(n), defined as the slope of the detrended fluctuation function F(n) around the beat scale n, in a log-log plot. If alpha(1) and alpha(2) correctly model the multiscale structure of blood pressure and heart rate, we should find that alpha(n) is constant over a short-term and a longterm range of beat scales. Results show that only the long-term alpha2 exponent provides a relatively good approximation of the multiscale structure of RRI and MAP. Moreover, posture and physical activity have important effects on local scaling exponents, and on the range of beat scales n where alpha(n) can be approximated by a constant alpha2 coefficient.

This study compared spontaneous baroreflex sensitivity (BRS) estimates obtained from an identical set of data by 11 European centers using different methods and procedures. Noninvasive blood pressure (BP) and ECG recordings were obtained in 21 subjects, including 2 subjects with established baroreflex failure. Twenty-one estimates of BRS were obtained by methods including the two main techniques of BRS estimates, i.e., the spectral analysis (11 procedures) and the sequence method (7 procedures) but also one trigonometric regressive spectral analysis method (TRS), one exogenous model with autoregressive input method (X-AR), and one Z method. With subjects in a supine position, BRS estimates obtained with calculations of alpha-coefficient or gain of the transfer function in both the low-frequency band or high-frequency band, TRS, and sequence methods gave strongly related results. Conversely, weighted gain, X-AR, and Z exhibited lower agreement with all the other techniques. In addition, the use of mean BP instead of systolic BP in the sequence method decreased the relationships with the other estimates. Some procedures were unable to provide results when BRS estimates were expected to be very low in data sets (in patients with established baroreflex failure). The failure to provide BRS values was due to setting of algorithmic parameters too strictly. The discrepancies between procedures show that the choice of parameters and data handling should be considered before BRS estimation. These data are available on the web site (http://www.cbi.polimi.it/glossary/eurobavar.html) to allow the comparison of new techniques with this set of results.

Heart rate variability is a recognized parameter for assessing autonomous nervous system activity. Fourier transform, the most commonly used method to analyze variability, does not offer an easy assessment of its dynamics because of limitations inherent in its stationary hypothesis. Conversely, wavelet transform allows analysis of nonstationary signals. We compared the respective yields of Fourier and wavelet transforms in analyzing heart rate variability during dynamic changes in autonomous nervous system balance induced by atropine and propranolol. Fourier and wavelet transforms were applied to sequences of heart rate intervals in six subjects receiving increasing doses of atropine and propranolol. At the lowest doses of atropine administered, heart rate variability increased, followed by a progressive decrease with higher doses. With the first dose of propranolol, there was a significant increase in heart rate variability, which progressively disappeared after the last dose. Wavelet transform gave significantly better quantitative analysis of heart rate variability than did Fourier transform during autonomous nervous system adaptations induced by both agents and provided novel temporally localized information.

Ten patients presenting for aorto-coronary bypass surgery were premedicated with their regular dose of propranolol and nitrates and diazepam 0.15 mg x kg-1 by mouth, morphine 0.15 mg x kg-1 and scopolamine 0.4 mg intramuscularly, 60 to 90 minutes before arrival in the operating room. Venous, arterial and pulmonary artery catheterizations were done under local anaesthesia. No significant changes were noted in systolic blood pressure and rate pressure product. Heart rate was decreased after internal jugular puncture and for the remainder of the study. PaCO2 increased and PaO2 decreased from values obtained the day before operation. Cardiovascular stability during vascular catheterization was achieved by emphasizing a detailed preoperative explanation, maintenance of beta-blockade up to the time of operation, substantial sedative premedication, and the liberal use of local anaesthesia.