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The analysis of volatile organic compounds (VOCs) present in various biological samples holds immense potential for non-invasive disease diagnostics and metabolic profiling. One of the biological fluids that are suitable for use in clinical practice is urine. Given the limited quantity of VOCs in the urine headspace, it's imperative to enhance their extraction into the gaseous phase and prevent any degradation of VOCs during the thawing process. The study aimed to test several key parameters (incubation time, temperature, and thawing) that can influence urine volatilome and monitor selected VOCs for their stability. The analysis in this study was performed using a BreathSpec® (G.A.S., Dortmund, Germany) device consisting of a gas chromatograph (GC) coupled with an ion mobility spectrometer (IMS). Testing three different temperatures and incubation times yielded a low number of VOCs (9 out of 34) that exhibited statistically significant differences. However, examining three thawing conditions revealed no VOCs with statistically significant changes. Thus, we conclude that urine composition remains relatively stable despite exposure to various thermal stresses. [ABSTRACT FROM AUTHOR]

Objective. Non-motor symptoms including those reflecting autonomic cardiovascular dysregulation are often present in Parkinson disease. It is unclear whether it is possible to detect cardiovascular autonomic dysregulation in the very early stage of Parkinson disease potentially supporting the concept of the upstream propagation of nervous system damage through autonomic nerves. We hypothesized that cardiovascular dysregulation should precede the motor symptoms and at the time of their occurrence autonomic dysregulation should be clearly demonstrable. Therefore, the aim of this study was to assess the various aspects of autonomic cardiovascular control in the very early stage of Parkinson disease. Approach. We performed prospective case-control study on 19 patients with Parkinson disease (<6 months after motor signs occurrence) and 19 healthy control subjects. For each phase of study protocol (supine, head-up tilt, supine recovery), we calculated a wide array of cardiovascular control related parameters reflecting cardiac chronotropic, cardiac inotropic and vasomotor control and baroreflex mediated cardiovascular response. Main results. We observed the well-preserved heart rate and blood pressure control in patients with early stage of Parkinson disease. However, causal analysis of interactions between heart rate and blood pressure oscillations revealed subtle differences in baroreflex function and baroreflex mediated vasoconstriction response to orthostasis. Furthermore, a tendency towards a decreased contraction strength in Parkinson disease was observed. Significance. Considering only subtle cardiovascular control impairment in our study employing a wide array of sensitive methods at the time when motor signs were clearly expressed, we suggest that motor signs dominated in this stage of Parkinson disease. [ABSTRACT FROM AUTHOR]

Arterial compliance (AC) decrease with aging is accelerated by factors associated with the progression of atherosclerotic process, including obesity. Prevalence of obesity increases not only in adult population but also in children and adolescents. The results of studies characterizing the effect of obesity on AC (often indirectly estimated by pulse wave velocity (PWV)) are contradictory. Considering the limitations of previously applied methods and the need to interpret AC values in the context of potential confounders or during various physiological states, the aim of this study was to compare AC of control and obese adolescents during four different physiological states: supine rest, head-up tilt (HUT), supine recovery and mental arithmetic (MA). AC was assessed by the method based on two-element Windkessel model as the ratio of a time constant t characterizing diastolic blood pressure decay and total peripheral resistance (TPR). In total, fifty healthy and normotensive subjects (40 females, 10 males, age 17.5 years (SD=1.1 years)) were examined - 25 obese and 25 age- and sex-matched control subjects. We observed significantly increased AC values during all phases in obese group. An increase in AC was also preserved after controlling for blood pressure influence. These results were confirmed using PWV based AC estimation. Interestingly, AC decreased similarly during stress phases (HUT, MA) in both groups. Lastly, TPR was decreased throughout the study protocol in obese subjects. In conclusion, AC is increased in young obese subjects consistently during various physiological states. Furthermore, changes of physiological states evoke similar response of AC in both groups indicating preserved autonomic control of elastic arteries. A decreased TPR in obese subjects points towards the influence of different maturation state of the arterial tree and/or changes in vasomotion possibly counterbalancing acceleration of atherosclerosis process. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cardiac stroke volume variation (SVV) measurement is one of the techniques to detect fluid-responsive hypovolemia in patients under mechanical ventilation. There is an ongoing effort to apply SVV for this purpose also in conscious patients. However, the effect of mental stress often occurring in conscious patients as a potential confounding factor on SVV is not known. The aim of our study was to compare effect of simulated hypovolemia and mental stress on SVV in healthy volunteers in the context of potential confounders - breathing pattern, respiratory sinus arrhythmia magnitude and sex. We examined 102 young healthy volunteers (58 females), mean age 18.6 years. Finger arterial blood pressure was recorded by volume-clamp photoplethysmographic method (Finometer Pro, FMS, Amsterdam, Netherland). From the blood pressure curve, a built in Model Flow algorithm calculated stroke volume values (SV) for each heartbeat. Respiratory volume was recorded using calibrated respiratory inductive plethysmography (RespiTrace, NIMS, Miami Beach, FL, USA). During four phases of examination protocol (supine rest, head-up tilt (HUT), supine recovery, mental arithmetic task (MA)) we analyzed SVV related to respiratory activity. While during HUT we found an expected increase in SVV together with mean SV decrease, SVV significantly decreased during MA. The observed changes during MA could be attributed to an increased respiratory rate and/or decreased respiratory sinus arrhythmia. Sex related differences in SVV responses to HUT and MA were observed. We conclude that mental stress together with respiratory sinus arrhythmia and respiratory pattern changes can significantly influence SVV as a potential index of fluid responsiveness in conscious patients. [ABSTRACT FROM AUTHOR]

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.

Introduction: Cardiovascular system is the vitally important system in the dynamical adaptation process of the newborns to the extrauterine environment. To reliably detect immaturity in the given organ system, it is crucial to study the development of the organ functions in relation to maturation process. Objectives: The objective was to determine the changes in the spontaneous short-term blood pressure variability (BPV) and baroreflex sensitivity (BRS) reflecting various aspects of cardiovascular control during the process of maturation in preterm babies and to separate effects of gestational age and postnatal age. Methods: Thirty-three prematurely born infants without any signs of cardio-respiratory disorders (gestational age: 31.8, range: 27-36 weeks; birth weight: 1,704, range: 820-2,730 grams) were enrolled. Continuous peripheral blood pressure signal was obtained by non-invasive volume-clamp photoplethysmography method during supine rest. The recordings of 250 continuous beat-to-beat blood pressure values were processed by spectral analysis of BPV (assessed measures: total power, low frequency and high frequency powers of systolic BPV) and BRS calculation. For each infant we also assessed systolic, diastolic and mean blood pressures, heart rate and respiratory rate. Results: With the postconceptional age, BPV measures decreased (for total power: Spearman correlation coefficient r s = -0.345, P = 0.049; for low frequency power: r s = -0.365, P = 0.037; for high frequency power r s = -0.349; P = 0.046); and BRS increased significantly (r s = 0.448, P = 0.009). The further analysis demonstrated that these effects were more attributable to gestational age than to postnatal age. BRS correlated negatively with BPV magnitude (r s = -0.479 to -0.592, P = 0.001-0.005). Mean blood pressure and diastolic blood pressure increased during maturation (r s = 0.517 and 0.537, P = 0.002 and 0.001, respectively) while heart rate and respiratory rate decreased (r s = -0.366 and -0.516, P = 0.036 and 0.002, respectively). Conclusion: We conclude that maturation process is accompanied by an increased involvement of baroreflex buffering of spontaneous short-term blood pressure oscillations. Gestational age plays a dominant role not only in BPV changes but also in BRS, mean blood pressure, diastolic blood pressure and heart rate changes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Javorka, Haskova, Czippelova, Zibolen and Javorka.)

Autonomic nervous system (ANS) activity and imbalance between its sympathetic and parasympathetic components are important factors contributing to the initiation and progression of many cardiovascular disorders related to obesity. The results on respiratory sinus arrhythmia (RSA) magnitude changes as a parasympathetic index were not straightforward in previous studies on young obese subjects. Considering the potentially unbalanced ANS regulation with impaired parasympathetic control in obese patients, the aim of this study was to compare the relative contribution of baroreflex and non-baroreflex (central) mechanisms to the origin of RSA in obese vs. control subjects. To this end, we applied a recently proposed information-theoretic methodology - partial information decomposition (PID) - to the time series of heart rate variability (HRV, computed from RR intervals in the ECG), systolic blood pressure (SBP) variability, and respiration (RESP) pattern measured in 29 obese and 29 age- and gender-matched non-obese adolescents and young adults monitored in the resting supine position and during postural and cognitive stress evoked by head-up tilt and mental arithmetic. PID was used to quantify the so-called unique information transferred from RESP to HRV and from SBP to HRV, reflecting, respectively, non-baroreflex and RESP-unrelated baroreflex HRV mechanisms, and the redundant information transferred from (RESP, SBP) to HRV, reflecting RESP-related baroreflex RSA mechanisms. Our results suggest that obesity is associated: (i) with blunted involvement of non-baroreflex RSA mechanisms, documented by the lower unique information transferred from RESP to HRV at rest; and (ii) with a reduced response to postural stress (but not to mental stress), documented by the lack of changes in the unique information transferred from RESP and SBP to HRV in obese subjects moving from supine to upright, and by a decreased redundant information transfer in obese compared to controls in the upright position. These findings were observed in the presence of an unchanged RSA magnitude measured as the high frequency (HF) power of HRV, thus suggesting that the changes in ANS imbalance related to obesity in adolescents and young adults are subtle and can be revealed by dissecting RSA mechanisms into its components during various challenges., (Copyright © 2020 Javorka, Krohova, Czippelova, Turianikova, Mazgutova, Wiszt, Ciljakova, Cernochova, Pernice, Busacca and Faes.)

Aim: Motivated by the paradoxical and differing results of the early atherosclerosis related indices - Cardio-Ankle Vascular Index (CAVI) reflecting arterial stiffness and Reactive Hyperemia Index (RHI) evaluating endothelium dependent flow-induced vasodilation - in obesity, we aimed to assess CAVI and RHI in obese adolescents and young adults in the context of differences in systemic vascular resistance (SVR)., Methods: We examined 29 obese (14f, 15.4 [12.3-18.5] y; BMI: 33.2±4.4 kg.m -2 ) and 29 non-obese gender and age matched adolescents and young adults (BMI: 21.02±2.3 kg.m -2 ). CAVI and RHI were measured using VaSera VS-1500 (Fukuda Denshi, Japan) and Endo-PAT 2000 (Itamar Medical, Israel), respectively. Hemodynamic measures were recorded using volume-clamp plethysmography (Finometer Pro, FMS, Netherlands) and impedance cardiography (CardioScreen 2000, Medis GmbH, Germany). SVR and sympathetic activity related indices - Velocity Index (VI) and Heather Index (HI), and LF SAP (spectral power in low frequency band of systolic blood pressure oscillations) were determined., Results: In obese group, CAVI (4.59±0.88 vs. 5.18±0.63, p=0.002) and its refined version CAVI 0 (6.46±1.39 vs.7.33±0.99, p=0.002) were significantly lower. No significant difference in RHI was found. SVR and sympathetic activity indices were all significantly lower in the obese group than in the non-obese group. RHI correlated positively with SVR (r=0.390, p=0.044) in obese subjects., Conclusion: Our results indicate that both indices used for the detection of early atherosclerotic changes are influenced by vascular tone. Vascular resistance could influence CAVI and RHI results impairing their interpretation.

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.

In this work, we present the feasibility to use a simpler methodological approach for the assessment of the short-term complexity of Heart Rate Variability (HRV). Specifically, we propose to exploit Pulse Rate Variability (PRV) recorded through photoplethysmography in place of HRV measured from the ECG, and to compute complexity via a linear Gaussian approximation in place of the standard model-free methods (e.g., nearest neighbor entropy estimates) usually applied to HRV. Linear PRV-based and model-free HRV-based complexity measures were compared via statistical tests, correlation analysis and Bland-Altman plots, demonstrating an overall good agreement. These results support the applicability of the simpler proposed approach, which is faster and easier-to-implement, making our approach eligible for portable/wearable devices and thus broadening the out-of-lab accessibility of autonomic indexes.

Heart rate variability (HRV) analysis represents an important tool for the characterization of complex cardiovascular control. HRV indexes are usually calculated from electrocardiographic (ECG) recordings after measuring the time duration between consecutive R peaks, and this is considered the gold standard. An alternative method consists of assessing the pulse rate variability (PRV) from signals acquired through photoplethysmography, a technique also employed for the continuous noninvasive monitoring of blood pressure. In this work, we carry out a thorough analysis and comparison of short-term variability indexes computed from HRV time series obtained from the ECG and from PRV time series obtained from continuous blood pressure (CBP) signals, in order to evaluate the reliability of using CBP-based recordings in place of standard ECG tracks. The analysis has been carried out on short time series (300 beats) of HRV and PRV in 76 subjects studied in different conditions: resting in the supine position, postural stress during 45° head-up tilt, and mental stress during computation of arithmetic test. Nine different indexes have been taken into account, computed in the time domain (mean, variance, root mean square of the successive differences), frequency domain (low-to-high frequency power ratio LF/HF, HF spectral power, and central frequency), and information domain (entropy, conditional entropy, self entropy). Thorough validation has been performed using comparison of the HRV and PRV distributions, robust linear regression, and Bland-Altman plots. Results demonstrate the feasibility of extracting HRV indexes from CBP-based data, showing an overall relatively good agreement of time-, frequency-, and information-domain measures. The agreement decreased during postural and mental arithmetic stress, especially with regard to band-power ratio, conditional, and self-entropy. This finding suggests to use caution in adopting PRV as a surrogate of HRV during stress conditions.

Heart rate variability (HRV; variability of the RR interval of the electrocardiogram) results from the activity of several coexisting control mechanisms, which involve the influence of respiration (RESP) and systolic blood pressure (SBP) oscillations operating across multiple temporal scales and changing in different physiological states. In this study, multiscale information decomposition is used to dissect the physiological mechanisms related to the genesis of HRV in 78 young volunteers monitored at rest and during postural and mental stress evoked by head-up tilt (HUT) and mental arithmetics (MA). After representing RR, RESP and SBP at different time scales through a recently proposed method based on multivariate state space models, the joint information transfer T RESP , SBP → RR is decomposed into unique, redundant and synergistic components, describing the strength of baroreflex modulation independent of respiration ( U SBP → RR ), nonbaroreflex ( U RESP → RR ) and baroreflex-mediated ( R RESP , SBP → RR ) respiratory influences, and simultaneous presence of baroreflex and nonbaroreflex respiratory influences ( S RESP , SBP → RR ), respectively. We find that fast (short time scale) HRV oscillations-respiratory sinus arrhythmia-originate from the coexistence of baroreflex and nonbaroreflex (central) mechanisms at rest, with a stronger baroreflex involvement during HUT. Focusing on slower HRV oscillations, the baroreflex origin is dominant and MA leads to its higher involvement. Respiration influences independent on baroreflex are present at long time scales, and are enhanced during HUT.

Cardiovascular complexity is a feature of healthy physiological regulation, which stems from the simultaneous activity of several cardiovascular reflexes and other non-reflex physiological mechanisms. It is manifested in the rich dynamics characterizing the spontaneous heart rate and blood pressure variability (HRV and BPV). The present study faces the challenge of disclosing the origin of short-term HRV and BPV from the statistical perspective offered by information theory. To dissect the physiological mechanisms giving rise to cardiovascular complexity in different conditions, measures of predictive information, information storage, information transfer and information modification were applied to the beat-to-beat variability of heart period (HP), systolic arterial pressure (SAP) and respiratory volume signal recorded non-invasively in 61 healthy young subjects at supine rest and during head-up tilt (HUT) and mental arithmetics (MA). Information decomposition enabled to assess simultaneously several expected and newly inferred physiological phenomena, including: (i) the decreased complexity of HP during HUT and the increased complexity of SAP during MA; (ii) the suppressed cardiorespiratory information transfer, related to weakened respiratory sinus arrhythmia, under both challenges; (iii) the altered balance of the information transferred along the two arms of the cardiovascular loop during HUT, with larger baroreflex involvement and smaller feedforward mechanical effects; and (iv) an increased importance of direct respiratory effects on SAP during HUT, and on both HP and SAP during MA. We demonstrate that a decomposition of the information contained in cardiovascular oscillations can reveal subtle changes in system dynamics and improve our understanding of the complexity changes during physiological challenges., (Copyright © 2018. Published by Elsevier Ltd.)

The gold standard method to monitor heart rate variability (HRV) comprises measuring the time series of interbeat interval durations from electrocardiographic (ECG) recordings. However, due to the widespread use, simplicity and usability of photoplethysmographic (PPG) techniques, monitoring pulse rate variability (PRV) from pulse wave recordings has become a viable alternative to standard HRV analysis. The present study investigates the accuracy of PRV, measured as a surrogate of HRV, for the quantification of descriptive indexes computed in the time domain (mean, variance), frequency domain (low-to-high frequency power ratio LF/HF, HF band central frequency) and information domain (entropy, conditional entropy). We analyze short time series (300 intervals) of HRV measured from the ECG and of PRV acquired from Finometer device in 76 subjects monitored in the resting supine position (SU) and in the upright position during head-up tilt (HUT). Time, frequency and information domain indexes are computed for each HRV and PRV series and, for each index, the comparison between the two approaches is performed through statistical comparison of the distributions across subjects, robust linear regression, and Bland-Altman plots. Results of the comparison indicate an overall good agreement between PRV-based and HRV-based indexes, with an accuracy that is slightly lower during HUT than during SU, and for the band-power ratio and conditional entropy. These results suggest the feasibility of PRV-based assessment of HRV descriptive indexes, and suggest to further investigate the agreement in conditions of physiological stress.

The objective of this study was to determine the response of heart rate and blood pressure variability (respiratory sinus arrhythmia, baroreflex sensitivity) to orthostatic and mental stress, focusing on causality and the mediating effect of respiration. Seventy-seven healthy young volunteers (46 women, 31 men) aged 18.4 ± 2.7 yr underwent an experimental protocol comprising supine rest, 45° head-up tilt, recovery, and a mental arithmetic task. Heart rate variability and blood pressure variability were analyzed in the time and frequency domain and modeled as a multivariate autoregressive process where the respiratory volume signal acted as an external driver. During head-up tilt, tidal volume increased while respiratory rate decreased. During mental stress, breathing rate increased and tidal volume was elevated slightly. Respiratory sinus arrhythmia decreased during both interventions. Baroreflex function was preserved during orthostasis but was decreased during mental stress. While sex differences were not observed during baseline conditions, cardiovascular response to orthostatic stress and respiratory response to mental stress was more prominent in men compared with women. The respiratory response to the mental arithmetic tasks was more prominent in men despite a significantly higher subjectively perceived stress level in women. In conclusion, respiration shows a distinct response to orthostatic versus mental stress, mediating cardiovascular variability; it needs to be considered for correct interpretation of heart rate and blood pressure phenomena.

To 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.

The 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.

The study of short-term cardiovascular interactions is classically performed through the bivariate analysis of the interactions between the beat-to-beat variability of heart period (RR interval from the ECG) and systolic blood pressure (SBP). Recent progress in the development of multivariate time series analysis methods is making it possible to explore how directed interactions between two signals change in the context of networks including other coupled signals. Exploiting these advances, the present study aims at assessing directional cardiovascular interactions among the basic variability signals of RR, SBP and diastolic blood pressure (DBP), using an approach which allows direct comparison between bivariate and multivariate coupling measures. To this end, we compute information-theoretic measures of the strength and delay of causal interactions between RR, SBP and DBP using both bivariate and trivariate (conditioned) formulations in a group of healthy subjects in a resting state and during stress conditions induced by head-up tilt (HUT) and mental arithmetics (MA). We find that bivariate measures better quantify the overall (direct  +  indirect) information transferred between variables, while trivariate measures better reflect the existence and delay of directed interactions. The main physiological results are: (i) the detection during supine rest of strong interactions along the pathway RR  →  DBP  →  SBP, reflecting marked Windkessel and/or Frank-Starling effects; (ii) the finding of relatively weak baroreflex effects SBP  →  RR at rest; (iii) the invariance of cardiovascular interactions during MA, and the emergence of stronger and faster SBP  →  RR interactions, as well as of weaker RR  →  DBP interactions, during HUT. These findings support the importance of investigating cardiovascular interactions from a network perspective, and suggest the usefulness of directed information measures to assess physiological mechanisms and track their changes across different physiological states.

Baroreflex function is usually assessed from spontaneous oscillations of blood pressure (BP) and cardiac RR interval assuming a unidirectional influence from BP to RR. However, the interaction of BP and RR is bidirectional-RR also influences BP. Novel methods based on the concept of Granger causality were recently developed for separate analysis of feedback (baroreflex) and feedforward (mechanical) interactions between RR and BP. We aimed at assessing the proportion of the two causal directions of the interactions between RR and systolic BP (SBP) oscillations during various conditions, and at comparing causality measures from SBP to RR with baroreflex gain indexes. Arterial BP and ECG signals were noninvasively recorded in 16 young healthy volunteers during supine rest, mental arithmetics, and head-up tilt test, as well as during the combined administration of these stressors. The causal interactions between beat-to-beat RR and SBP signals were analyzed in time, frequency, and information domains. The baroreflex gain was assessed in the frequency domain using non-causal and causal measures of the transfer function from SBP to RR. We found a consistent increase in the baroreflex coupling strength from SBP to RR during head-up tilt, an insensitivity of the coupling strength along the non-baroreflex direction to both stressors, and no significant effect of mental arithmetics on the feedback coupling strength. It indicates that the proportion of causal interactions between SBP and RR significantly varies during different conditions. The increase in the coupling from SBP to RR with tilt was not accompanied by concomitant variations of the transfer function gain, suggesting that causality and gain analyses are complementary and assess different aspects of the baroreflex regulation of heart rate.

Obesity is accompanied by many severe complications including various cardiovascular disorders. An impairment of cardiovascular control by autonomic nervous system could be one of the possible links between obesity and cardiovascular complications development. The aim of this study was to compare spontaneous heart rate and systolic blood pressure oscillations reflecting cardiovascular autonomic control of young obese subjects with normal control subjects by linear and nonlinear methods and to find sensitive markers of early autonomic dysregulation. Continuous recordings of beat-to-beat systolic blood pressure and RR intervals from ECG were obtained from 40 obese subjects (25 female, age 14·2 [13·1-16·1] (median [interquartile range]) years) and gender and age matched non-obese control subjects. In addition to linear measures (time and frequency domain), we performed recurrence quantification analysis (RQA) and multiscale entropy analysis for both signals. While no significant differences in heart rate and systolic blood pressure dynamics were detected by linear measures and MSE, analysis of recurrence plots from RR intervals time series showed significant differences - indices trapping time and maximal length of vertical from RQA were significantly higher in obese compared to control group. We conclude that heart rate and blood pressure control by autonomic nervous system in young obese subjects is relatively well preserved. However, novel RQA-related measures are able to detect early subtle abnormalities in cardiac autonomic control in obese subjects indicating decreased signal complexity., (© 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Obesity during adulthood has been associated with cardiovascular disease, but its adverse effects during adolescence are less well established. The aim of this study was to probe cardiovascular control in obese adolescence by studying causal coherence between cardiovascular variables. Sixty minutes of resting ECG and finger blood pressure were recorded in 19 obese and 19 non-obese subjects in the supine position to measure pair-wise spectral coherence in the low frequency band between heart rate, systolic and diastolic blood pressure, pulse pressure, total peripheral resistance and left ventricular ejection time. We observed that causal coherences in {systolic blood pressure → total peripheral resistance} and {left ventricular ejection time → systolic blood pressure} directions were significantly decreased in obese preadolescents and adolescents when compared to the healthy control group, despite the lack of difference in the magnitude of oscillations of cardiovascular variables. In conclusion, causal coherence analysis of cardiovascular variables may give new insight into cardiovascular dysregulation in young obese subjects.

Ageing has been associated with changes in cardiac electrophysiology that result in QT interval prolongation. The effect of age on rate-adaptation dynamics of the QT interval is less well understood. The aim of this study was to assess age-related changes in the temporal relationship between QT and RR interval variability. Resting ECG of 20 young and 20 elderly healthy subjects were analyzed. Beat-to-beat RR and QT interval time series were automatically extracted. Coupling between QT and RR was assessed by means of the QT variability index, coherence in the frequency domain, rate-corrected QT interval, cross-multiscale entropy, information based similarity index and joint symbolic dynamics. In addition to QT interval prolongation (433 ± 31 versus 405 ± 33 ms, p = 0.008), elderly subjects were characterized by a significantly increased QT variability index (-1.26 ± 0.28 versus -1.52 ± 0.22 ms, p < 0.0001), reduced coherence in high (0.11 ± 0.09 versus 0.29 ± 0.14 ms, p = 0.003), and low frequency bands (0.20 ± 0.16 versus 0.49 ± 0.15 ms, p < 0.0001), reduced information domain synchronization index (0.13 ± 0.07 versus 0.19 ± 0.05 ms, p = 0.001) as well as increased entropy and disparity in joint symbolic dynamics of QT and RR interval time series. In conclusion, ageing is associated with decoupling of QT variability from heart rate variability. Complexity analysis in addition to standard metrics may provide additional insight.