Impact of breath sample collection method and length of storage of breath samples in Tedlar bags on the level of selected volatiles assessed using gas chromatography-ion mobility spectrometry (GC-IMS).

The analysis of volatile organic compounds (VOCs) in exhaled air has attracted the interest of the scientific community because it provides the possibility of monitoring physiological and metabolic processes and non-invasive diagnostics of various diseases. However, this method remains underused in clinical practice as well as in research because of the lack of standardized procedures for the collection, storage and transport of breath samples, which would guarantee good reproducibility and comparability of results. The method of sampling, as well as the storage time of the breath samples in the polymer bags used for sample storage and transport, affect the composition and concentration of VOCs present in the breath samples. The aim of our study was to compare breath samples obtained using two methods with fully disposable equipment: a Haldane sampling tube intended for direct breath collection and breath samples exhaled into a transparent Tedlar bag. The second task was to monitor the stability of selected compounds of real breath samples stored in a Tedlar bag for 6 h. Gas chromatography coupled with ion mobility spectrometry (GC-IMS) implemented in the BreathSpec®device was used to analyse exhaled breath. Our results showed a significant difference in the signal intensity of some volatiles when taking a breath sample with a Haldane tube and a Tedlar bag. Due to its endogenous origin, acetone levels were significantly higher when the Haldane tube sampler was used while elevated levels of 2-propanol and unidentified VOC (designated as VOC 3) in the Tedlar bag samples likely originated from contamination of the Tedlar bags. The VOC stability study revealed compound-specific signal intensity changes of the selected VOCs with storage time in the Tedlar bags, with some volatiles showing increasing signal intensity during storage in Tedlar bags. This limits the use of Tedlar bags only for very limited time and carefully selected purpose. Our results highlight the importance of careful design and implementation of experiments and clinical protocols to obtain relevant and reliable results.

Respiratory Sinus Arrhythmia Mechanisms in Young Obese Subjects.

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.

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.

Arterial Stiffness and Endothelial Function in Young Obese Patients - Vascular Resistance Matters.

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 LFSAP (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 CAVI0 (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.

Comparison of short-term heart rate variability indexes evaluated through electrocardiographic and continuous blood pressure monitoring.

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.

A validity and reliability study of Conditional Entropy Measures of Pulse Rate Variability.

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.

Multiscale Information Decomposition Dissects Control Mechanisms of Heart Rate Variability at Rest and During Physiological Stress.

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.

Reliability of Short-Term Heart Rate Variability Indexes Assessed through Photoplethysmography.

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.

Towards understanding the complexity of cardiovascular oscillations: Insights from information theory.

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.

Role of respiration in the cardiovascular response to orthostatic and mental 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.

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

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.

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

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.

Basic cardiovascular variability signals: mutual directed interactions explored in the information domain.

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.

Causal analysis of short-term cardiovascular variability: state-dependent contribution of feedback and feedforward mechanisms.

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.

Heart rate and blood pressure control in obesity - how to detect early dysregulation?

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.

Causal coherence analysis of cardiovascular variables in obese preadolescents and adolescents.

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.

The effect of orthostatic stress on multiscale entropy of heart rate and blood pressure.

Cardiovascular control acts over multiple time scales, which introduces a significant amount of complexity to heart rate and blood pressure time series. Multiscale entropy (MSE) analysis has been developed to quantify the complexity of a time series over multiple time scales. In previous studies, MSE analyses identified impaired cardiovascular control and increased cardiovascular risk in various pathological conditions. Despite the increasing acceptance of the MSE technique in clinical research, information underpinning the involvement of the autonomic nervous system in the MSE of heart rate and blood pressure is lacking. The objective of this study is to investigate the effect of orthostatic challenge on the MSE of heart rate and blood pressure variability (HRV, BPV) and the correlation between MSE (complexity measures) and traditional linear (time and frequency domain) measures. MSE analysis of HRV and BPV was performed in 28 healthy young subjects on 1000 consecutive heart beats in the supine and standing positions. Sample entropy values were assessed on scales of 1-10. We found that MSE of heart rate and blood pressure signals is sensitive to changes in autonomic balance caused by postural change from the supine to the standing position. The effect of orthostatic challenge on heart rate and blood pressure complexity depended on the time scale under investigation. Entropy values did not correlate with the mean values of heart rate and blood pressure and showed only weak correlations with linear HRV and BPV measures. In conclusion, the MSE analysis of heart rate and blood pressure provides a sensitive tool to detect changes in autonomic balance as induced by postural change.

Nonlinear PD2i heart rate complexity algorithm detects autonomic neuropathy in patients with type 1 diabetes mellitus.

OBJECTIVE: The aim of this study was to test whether a new heart rate variability (HRV) complexity measure, the Point Correlation Dimension (PD2i), provides diagnostic information regarding early subclinical autonomic dysfunction in diabetes mellitus (DM). We tested the ability of PD2i to detect diabetic autonomic neuropathy (DAN) in asymptomatic young DM patients without overt neuropathy and compared them to age- and gender-matched controls. METHODS: HRV in DM type 1 patients (n=17, 10 female, 7 male) aged 12.9-31.5 years (duration of DM 12.4±1.2 years) was compared to that in a control group of 17 healthy matched probands. The R-R intervals were measured over 1h using a telemetric ECG system. RESULTS: PD2i was able to detect ANS dysfunction with p=0.0006, similar to the best discriminating MSE scale, with p=0.0002. CONCLUSIONS: The performance of PD2i to detect DAN in asymptomatic DM patients is similar to the best discriminative power of previously published complexity measures. SIGNIFICANCE: The PD2i algorithm may prove to be an easy to perform and clinically useful tool for the early detection of autonomic neuropathy in DM type 1 patients, especially given its minimal data requirements.

Baroreflex analysis in diabetes mellitus: linear and nonlinear approaches.

The aim of our study was to employ novel nonlinear synchronization approaches as a tool to detect baroreflex impairment in young patients with subclinical autonomic dysfunction in Type 1 diabetes mellitus (DM) and compare them to standard linear baroreflex sensitivity (BRS) methods. We recorded beat-to-beat pulse interval (PI) and systolic blood pressure (SBP) in 14 DM patients and 14 matched healthy controls. We computed the information domain synchronization index (IDSI), cross-multiscale entropy, joint symbolic dynamics, information-based similarity index (IBSI) in addition to time domain and spectral measures of BRS. This multi parametric analysis showed that baroreflex gain is well-preserved, but the time delay within the baroreflex loop is significantly increased in patients with DM. Further, the level of similarity between blood pressure and heart rate fluctuations was significantly reduced in DM. In conclusion, baroreflex function in young DM patients is changed. The quantification of nonlinear similarity and baroreflex delay in addition to baroreflex gain may provide an improved diagnostic tool for detection of subclinical autonomic dysfunction in DM.

Cardiac autonomic regulation is impaired in girls with major depression.

UNLABELLED: We aimed to study short-term heart rate variability (HRV) as an index of cardiac autonomic control in never-treated major depressive disorder (MDD) adolescent patients using linear and nonlinear analysis. METHODS: We have examined 20 MDD girls and 20 healthy age-matched girls at the age of 15 to 18yr. The ECG was recorded in three positions: the 1st supine rest, orthostasis, the 2nd supine position. HRV magnitude was quantified by time and frequency-domain analysis (mean RR interval, SDRR, RMSSD, spectral powers in low [LF] and high frequency [HF] bands). In addition to linear measures, HRV complexity was assessed by nonlinear (symbolic dynamics) indices: normalized complexity index (NCI), normalized unpredictability index (NUPI), and pattern classification measures (0V%, 1V%, 2LV%, 2UV%). RESULTS: HRV magnitude (RMSSD, SDRR, LF and HF powers) was significantly decreased in MDD group in a supine rest and after posture change. HRV complexity was significantly reduced (lower NCI) in the standing position. Pattern classification analysis revealed significantly higher 0V% and lower 2LV% in MDD group in supine position and orthostasis. CONCLUSION: The HRV linear and nonlinear analysis revealed decreased magnitude and complexity of heart rate time series indicating altered neurocardiac regulation in girls with major depression without pharmacotherapy.