Input for baroreflex analysis: which blood pressure signal should be used?

The baroreflex (BR) is an important physiological regulatory mechanism which reacts to blood pressure perturbations with reflex changes of target variables such as the heart period (electrocardiogram derived RR interval) or the peripheral vascular resistance (PVR). Evaluation of cardiac chronotropic (RR as a target variable) and vascular resistance (target PVR) BR arms was in previous studies mainly based on the use of the spontaneous variability of the systolic or diastolic blood pressure (SBP, DBP), respectively, as the input signals. The use of other blood pressure measures such as the mean blood pressure (MBP) as an input signal for BR analysis is still under investigation. Making the assumption that the strength of coupling along the BR indicates the more appropriate input signal for baroreflex analysis, we employ partial spectral decomposition to assess in the frequency domain the causal coupling from SBP, MBP or DBP to RR or PVR. Noninvasive beat-to-beat recording of RR, SBP, MBP and DBP and PVR was performed in 39 and 36 volunteers in whom orthostatic and cognitive loads were evoked respectively through head-up tilt and mental arithmetic task. At rest, the MBP was most tightly coupled with RR, in contrast to the analysis of the vascular resistance BR arm where the results showed similar importance of all blood pressure input signals. During orthostasis, the increased importance of SBP as the input signal for BR analysis along the cardiac chronotropic arm was demonstrated. In addition, the gain from MBP to RR was more sensitive to physiological state changes compared to gains with SBP or DBP signal as inputs. We conclude that the coupling strength depends not only on the analysed baroreflex arm but also on the selection of the input blood pressure signal and the physiological state. The MBP signal should be more frequently used for the cardiac baroreflex analysis

Ondansetron prevents changes in respiratory pattern provoked by LiCl: A new approach for studying pro-emetic states in rodents?

There are a limited number of biological indices for assessing pro-emetic states in laboratory rodents as they do not possess the vomiting response. In the present study we tested the hypothesis that in rats, pro-emetic intervention would affect the respiratory pattern. To this end, using whole-body plethysmography, in adult male Wistar rats we recorded respiration after i.p. administration of either the emetic agent LiCl or Ringer. Quantification of respiratory signals (from 5 to 35 min post-injection) revealed that post-LiCl, mean respiratory rate was significantly lower (126 ± 9 vs. 178 ± 10 cpm, p 200 cpm) from 25 ± 3% to 9 ± 2% (p = 0.004). Thus, reduction of the mean respiratory rate by LiCl was predominantly due to reduced contribution of high-frequency breathing that is normally associated with motor activity and/or arousal. Non-linear multifractal analysis of respiratory signals revealed that post-LiCl, respiration becomes less random and more orderly. 5-HT3 antagonist ondansetron prevented respiratory changes elicited by LiCl. We conclude that the observed changes likely reflect effects of LiCl on animals' motion, and that this effect is mediated via 5-HT3 receptors. Providing that the effects observed in our study were quite robust, we suggest that simple and non-invasive respiratory monitoring may be a promising approach for studying emesis in rodents.S. Ngampramuan, M. Baumert, B. Czippelova and E. Nalivaik

Information Domain Analysis of Respiratory Sinus Arrhythmia Mechanisms

Ventilation related heart rate oscillations - respiratory sinus arrhythmia (RSA) - originate in human from several mechanisms. Two most important of them - the central mechanism (direct communication between respiratory and cardiomotor centers), and the peripheral mechanism (ventilation-associated blood pressure changes transferred to heart rate via baroreflex) have been described in previous studies. The major aim of this study was to compare the importance of these mechanisms in the generation of RSA non-invasively during various states by quantifying the strength of the directed interactions between heart rate, systolic blood pressure and respiratory volume signals. Seventy-eight healthy volunteers (32 male, age range: 16.02-25.77 years, median age: 18.57 years) participated in this study. The strength of mutual interconnections among the spontaneous beat-to-beat oscillations of systolic blood pressure (SBP), R-R interval (RR signal) and respiration (volume changes - RESP signal) was quantified during supine rest, orthostatic challenge (head-up tilt, HUT) and cognitive load (mental arithmetics, MA) using bivariate and trivariate measures of cardio-respiratory information transfer to separate baroreflex and nonbaroreflex (central) mechanisms. Our results indicate that both basic mechanisms take part in RSA generation in the intact cardiorespiratory control of human subjects. During orthostatic and mental challenges baroreflex based peripheral mechanism becomes more important

Information transfer and information modification to identify the structure of cardiovascular and cardiorespiratory networks

none6siTo fully elucidate the complex physiological mechanisms underlying the short-term autonomic regulation of heart period (H), systolic and diastolic arterial pressure (S, D) and respiratory (R) variability, the joint dynamics of these variables need to be explored using multivariate time series analysis. This study proposes the utilization of information-theoretic measures to measure causal interactions between nodes of the cardiovascular/cardiorespiratory network and to assess the nature (synergistic or redundant) of these directed interactions. Indexes of information transfer and information modification are extracted from the H, S, D and R series measured from healthy subjects in a resting state and during postural stress. Computations are performed in the framework of multivariate linear regression, using bootstrap techniques to assess on a single-subject basis the statistical significance of each measure and of its transitions across conditions. We find patterns of information transfer and modification which are related to specific cardiovascular and cardiorespiratory mechanisms in resting conditions and to their modification induced by the orthostatic stress.Faes, L; Nollo, G; Krohova, J; Czippelova, B; Turianikova, Z; Javorka, MFaes, Luca; Nollo, Giandomenico; Krohova, J; Czippelova, B; Turianikova, Z; Javorka, M

Cardiovascular and respiratory variability during orthostatic and mental stress: a comparison of entropy estimators

none8siThe aim of this study is to characterize cardiovascular and respiratory signals during orthostatic and mental stress as reflected in indices of entropy and complexity, providing a comparison between the performance of different estimators. To this end, the heart rate variability, systolic blood pressure, diastolic blood pressure and respiration time series were extracted from the recordings of 61 healthy volunteers undergoing a protocol consisting of supine rest, head-up tilt test and mental arithmetic task. The analysis was performed in the information domain using measures of entropy and conditional entropy, estimated through model-based (linear) and model-free (binning, nearest neighbor) approaches. Our results show that different types of stress elicited different responses in the employed indices. On one hand, entropy mainly reflected known changes in the variance of physiological time series. On the other hand, the information conveyed by conditional entropy allowed to characterize the complexity of the four time series during the two stress tasks: we found that cardiac and vascular dynamics underwent a reduction in complexity as a consequence of postural stress, while vascular and respiratory complexity increased as a result of mental stress. As for the performance of different estimators, we did not find substantial differences between model-based and model-free approaches, possibly indicating that significant non-linear dynamics did not appear in the studied conditions.Valente, M; Javorka, M; Turianikova, Z; Czippelova, B; Krohova, J; Nollo, G Faes, LValente, M; Javorka, M; Turianikova, Z; Czippelova, B; Krohova, J; Nollo, Giandomenico; Faes, Luc

Redundancy and synergy in interactions among basic cardiovascular oscillations

The cardiovascular control system comprises a complex network of various control mechanisms operating on many time scales resulting in complex and mutually interconnected output signals (e.g. heart rate, systolic and diastolic blood pressures). The analysis of these interconnections could noninvasively provide an information on the regulatory mechanisms involved in cardiovascular control and thus could be potentially applied to better characterize cardiovascular dysregulation in pathological conditions. Our study demonstrates that the strength of interactions among signals changes with the time scale and as a response to changed autonomic state (orthostasis compared to supine rest). Novel insight regarding the interaction between two signals (sources) when influencing a target (third) signal could be obtained by the information-theoretic analysis of sources' redundancy and synergy

Selection of blood pressure signal for baroreflex analysis

This study aims to evaluate the strength of the causal coupling among systolic, mean and diastolic blood pressure (SBP, MBP and DBP) with heart period (RR interval) (evaluating cardiac chronotropic baroreflex arm) and peripheral vascular resistance (PVR) (evaluating vascular resistance baroreflex arm) in frequency domain using partial spectral decomposition method. We recorded beat-to-beat RR, SBP, MBP and DBP and PVR values in 39 volunteers during supine rest and head-up tilt. Our results showed that during supine rest the most dominant causal coupling was from DBP to RR in both low and high frequency bands and significantly decreased during orthostasis. The strength of spectral couplings characterized the vascular resistance baroreflex arm did not differ during supine rest in low frequency band and SBP {PVR} direction dominated during HUT in both frequency bands

Multiscale time irreversibility of heart rate and blood pressure variability during orthostasis

Time irreversibility is a characteristic feature of non-equilibrium, complex systems such as the cardiovascular control mediated by the autonomic nervous system (ANS). Time irreversibility analysis of heart rate variability (HRV) and blood pressure variability (BPV) represents a new approach to assess cardiovascular regulatory mechanisms. The aim of this paper was to assess the changes in HRV and BPV irreversibility during the active orthostatic test (a balance of ANS shifted towards sympathetic predominance) in 28 healthy young subjects.We used three different time irreversibility indices— Porta’s, Guzik’s and Ehler’s indices (P%, G%and E, respectively) derived from data segments containing 1000 beat-to-beat intervals on four timescales. We observed an increase in the HRV and a decrease in the BPV irreversibility during standing compared to the supine position. The postural change in irreversibility was confirmed by surrogate data analysis. The differences were more evident in G% and E than P% and for higher scale factors. Statistical analysis showed a close relationship between G% and E. Contrary to this, the association between P% and G% and P% and E was not proven. We conclude that time irreversibility of beat-to-beat HRV and BPV is significantly altered during orthostasis, implicating involvement of the autonomous nervous system in its generation.L. Chladekova, B. Czippelova, Z. Turianikova, I. Tonhajzerova, A. Calkovska, M. Baumert and M. Javork

Repolarization variability independent of heart rate during sympathetic activation elicited by head-up tilt

The fraction of repolarization variability independent of RR interval variability is of clinical interest. It has been linked to direct autonomic nervous system (ANS) regulation of the ventricles in healthy subjects and seems to reflect the instability of the ventricular repolarization process in heart disease. In this study, we sought to identify repolarization measures that best reflect the sympathetic influences on the ventricles independent of the RR interval. ECG was recorded in 46 young subjects during supine and then following 45 degrees head-up tilt. RR intervals and five repolarization features (QTend, QTpeak, RTend, RTpeak, and TpTe) were extracted from the ECG recordings. Repolarization variability was separated into RR-dependent and RR-independent variability using parametric spectral analysis. Results show that LF power of TpTe is independent of RR in both supine and tilt, while the LF power of QTend and RTend independent of RR and respiration increases following tilt. We conclude that TpTe is independent of RR and is highly affected by respiration. QTend and RTend LF power might reflect the sympathetic influences on the ventricles elicited by tilt. Graphical abstract.Fatima El-Hamad, Michal Javorka, Barbora Czippelova, Jana Krohova, Zuzana Turianikova, Alberto Porta, Mathias Baumer

Univariate and multivariate conditional entropy measures for the characterization of short-term cardiovascular complexity under physiological stress

Objective: A defining feature of physiological systems under the neuroautonomic regulation is their dynamical complexity. The most common approach to assess physiological complexity from short-term recordings, i.e. to compute the rate of entropy generation of an individual system by means of measures of conditional entropy (CE), does not consider that complexity may change when the investigated system is part of a network of physiological interactions. This study aims at extending the concept of short-term complexity towards the perspective of network physiology, defining multivariate CE measures whereby multiple physiological processes are accounted for in the computation of entropy rates. Approach: Univariate and multivariate CE measures are computed using state-of-the-art methods for entropy estimation and applied to time series of heart period (H), systolic (S) and diastolic (D) arterial pressure, and respiration (R) variability measured in healthy subjects monitored in a resting state and during conditions of postural and mental stress. Main results: Compared with the traditional univariate metric of short-term complexity, multivariate measures provide additional information with plausible physiological interpretation, such as (i) the dampening of respiratory sinus arrhythmia and activation of the baroreflex control during postural stress; (ii) the increased complexity of heart period and blood pressure variability during mental stress, reflecting the effect of respiratory influences and upper cortical centers; (iii) the strong influence of D on S, mediated by left ventricular ejection fraction and vascular properties; (iv) the role of H in reducing the complexity of D, related to cardiac run-off effects; and (v) the unidirectional role of R in influencing cardiovascular variability. Significance: Our results document the importance of employing a network perspective in the evaluation of the short-term complexity of cardiovascular and respiratory dynamics across different physiological states