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To characterize the differences in baroreflex sensitivity (BRS), blood pressure (BP), heart rate (HR) and respiration rate (RR) in preterm infants with a similar postconceptional age reached by various combinations of gestational and postnatal ages. To detect potential sex differences in assessed cardiovascular parameters. The study included 49 children (24 boys and 25 girls), postconceptional age 34.6+/-1.9 weeks. Two subgroups of infants were selected with the similar postconceptional age (PcA) and current weight, but differing in gestational (GA) and postnatal (PnA) ages, as well as two matched subgroups of boys and girls. Blood pressure (BP) was recorded continuously using Portapres device (FMS). A stationary segment of 250 beat-to-beat BP values was analyzed for each child. Baroreflex sensitivity (BRS) was calculated by cross-correlation sequence method. Despite the same PcA age and current weight, children with longer GA had higher BRS, diastolic and mean BP than children with shorter GA and longer PnA age. Postconceptional age in preterm infants is a parameter of maturation better predicting baroreflex sensitivity and blood pressure values compared to postnatal age. Sex related differences in BRS, BP, HR and RR were not found in our group of preterm infants.

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.

The dynamical interplay between brain and heart is mediated by several feedback mechanisms including the central autonomic network and baroreflex loop at a peripheral level, also for a short-term regulation. State of the art focused on the characterization of each regulatory pathway through a single stressor elicitation. However, no studies targeted the actual quantification of different mediating routes leading to the generation of heartbeat dynamics, particularly in case of combined exogenous stimuli. In this study, we propose a new approach based on computational modeling to quantify the contribution of multiple concurrent stimuli in modulating cardiovascular dynamics. In this preliminary attempt, the model estimates the high-frequency power of heartbeat dynamics, and derives disentangling coefficients quantifying the effect of multiple elicitations. Model evaluation is performed on healthy rate variability (HRV) series from fourteen healthy subjects undergoing physical (tilt-table) and mental stressors (aritmetics), as well as their combined administration. Results indicate that, at a group-wise level, in base of concurrent physical and mental elicitations, the physical stressor contributes for the 85% of the resulting heartbeat dynamics. These findings are in agreement with the current knowledge on heartbeat regulatory systems, providing valuable perspectives on the quantification of underlying generative mechanisms of HRV.

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.

We present a new method to quantify in the frequency domain the strength of directed interactions between linear stochastic processes. This issue is traditionally addressed by the directed coherence (DC), a popular causality measure derived from the spectral representation of vector autoregressive (AR) processes. Here, to overcome intrinsic limitations of the DC when it needs to be objectively quantified within specific frequency bands, we propose an approach based on spectral decomposition, which allows to isolate oscillatory components related to the pole representation of the vector AR process in the Z-domain. Relating the causal and non-causal power content of these components we obtain a new spectral causality measure, denoted as pole-specific spectral causality (PSSC). In this study, PSSC is compared with DC in the context of cardiovascular variability analysis, where evaluation of the spectral causality from arterial pressure to heart period variability is of interest to assess baroreflex modulation in the low frequency band (0.04-0-15 Hz). Using both a theoretical example in which baroreflex interactions are simulated, and real cardiovascular variability series measured from a group of healthy subjects during a postural challenge, we show that - compared with DC- PSSC leads to a frequency-specific evaluation of spectral causality which is more objective and more focused on the frequency band of interest.

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.

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.

Objective: Symbolic transformations of the cardiac interbeat interval series yield a coarse-grained description of the dynamical information of the underlying system and complement standard measures of heart rate variability. The most commonly utilized coarse graining procedures are strongly influenced by the presence of a few extreme values wasting precious symbols to code very unlikely values., Approach: Here, we used a transformation procedure that ensured the appearance of each symbol with equal probability using a short alphabet, A 4   =  {0, 1, 2, 3}, and a long alphabet, A 6   =  {0, 1, 2, 3, 4, 5}. The procedure was applied to the cardiac interbeat interval series of 17 healthy subjects, obtained during graded head-up tilt tests at tilt table inclinations of 0°, 15°, 30°, 45°, 60°, 75°, 90°. The dynamics of the symbolic series was assessed by the rate of symbolic pattern categories. Symbolic patterns of length three were grouped according to the variations of the symbols in each pattern: no variation (0V%), one variation (1V%), two like variations (2LV%) and two unlike variations (2UV%) of the symbols., Main Results: As for the alphabet A 4 , the linear regression analysis on tilt angle showed that 0V% increased with increasing tilt angle whereas 1V%, 2LV% and 2UV% decreased. As for the alphabet A 6 , the categories 0V%, and 1V% increased with increasing tilt angle whereas 2LV% and 2UV% decreased., Significance: The symbolic transformation ensuring a uniform distribution of the symbols is capable of reflecting changes in the cardiac autonomic nervous system during graded head-up tilt. This approach is more robust against outliers and data with skewed distributions compared to previously used symbolizations.

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.

At present, there are insufficient information about baroreflex sensitivity (BRS) and factors that determine BRS in premature newborns. The objective of this study was to determine the relationship between BRS and the characteristics that reflecting the intrauterine development (gestational age and birth weight), as well as postnatal development (postconception age and the actual weight of the child at the time of measurement). We examined 57 premature infants, who were divided into groups according to gestational age and postconception age as well as birth weight, and weight at the time of measurement. Continuous and noninvasive registration of peripheral blood pressure (BP) was performed in every child within 2-5 min under standard conditions using a Portapres (FMS) device. The results showed a close correlation of baroreflex sensitivity, heart rate and respiratory rate with gestational age, postconception age, birth weight and actual weight at the time of measurement premature newborns. An increase in the characteristics (ages and weights) resulted in increased BRS and diastolic arterial pressure (DAP), and in decreased heart and respiratory rates. Baroreflex sensitivity in the first week was in the group of very premature newborns the lowest (4.11 ms/mmHg) and in the light premature newborns was almost double (8.12 ms/mmHg). BRS increases gradually in relation to postnatal (chronological) and to postconception age as well as to birth and actual weight. The multifactor analysis of BRS identified birth weight and postconception age as the best BRS predictors. The two independent variables together explained 40 % of interindividual BRS variability.

Heart rate (HR) and heart rate variability (HRV) in newborns is influenced by genetic determinants, gestational and postnatal age, and other variables. Premature infants have a reduced HRV. In neonatal HRV evaluated by spectral analysis, a dominant activity can be found in low frequency (LF) band (combined parasympathetic and sympathetic component). During the first postnatal days the activity in the high frequency (HF) band (parasympathetic component) rises, together with an increase in LF band and total HRV. Hypotrophy in newborn can cause less mature autonomic cardiac control with a higher contribution of sympathetic activity to HRV as demonstrated by sequence plot analysis. During quiet sleep (QS) in newborns HF oscillations increase - a phenomenon less expressed or missing in premature infants. In active sleep (AS), HRV is enhanced in contrast to reduced activity in HF band due to the rise of spectral activity in LF band. Comparison of the HR and HRV in newborns born by physiological vaginal delivery, without (VD) and with epidural anesthesia (EDA) and via sectio cesarea (SC) showed no significant differences in HR and in HRV time domain parameters. Analysis in the frequency domain revealed, that the lowest sympathetic activity in chronotropic cardiac chronotropic regulation is in the VD group. Different neonatal pathological states can be associated with a reduction of HRV and an improvement in the health conditions is followed by changes in HRV what can be use as a possible prognostic marker. Examination of heart rate variability in neonatology can provide information on the maturity of the cardiac chronotropic regulation in early postnatal life, on postnatal adaptation and in pathological conditions about the potential dysregulation of cardiac function in newborns, especially in preterm infants.

In previous studies, one of the systolic time intervals - preejection period (PEP) - was used as an index of sympathetic activity reflecting the cardiac contractility. However, PEP could be also influenced by several other cardiovascular variables including preload, afterload and diastolic blood pressure (DBP). The aim of this study was to assess the behavior of the PEP together with other potentially confounding cardiovascular system characteristics in healthy humans during mental and orthostatic stress (head-up tilt test - HUT). Forty-nine healthy volunteers (28 females, 21 males, mean age 18.6 years (SD=1.8 years)) participated in the study. We recorded finger arterial blood pressure by volume-clamp method (Finometer Pro, FMS, Netherlands), PEP, thoracic fluid content (TFC) - a measure of preload, and cardiac output (CO) by impedance cardiography (CardioScreen® 2000, Medis, Germany). Systemic vascular resistance (SVR) - a measure of afterload - was calculated as a ratio of mean arterial pressure and CO. We observed that during HUT, an expected decrease in TFC was accompanied by an increase of PEP, an increase of SVR and no significant change in DBP. During mental stress, we observed a decrease of PEP and an increase of TFC, SVR and DBP. Correlating a change in assessed measures (delta values) between mental stress and previous supine rest, we found that deltaPEP correlated negatively with deltaCO and positively with deltaSVR. In orthostasis, no significant correlation between deltaPEP and deltaDBP, deltaTFC, deltaCO, deltaMBP or deltaSVR was found. We conclude that despite an expected increase of sympathetic activity during both challenges, PEP behaved differently indicating an effect of other confounding factors. To interpret PEP values properly, we recommend simultaneously to measure other variables influencing this cardiovascular measure.

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.

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.)

Background: Neonatal jaundice and its phototherapeutic treatment can lead to several side effects involving activation of autonomic control mechanisms., Aim: The aims of this study are to investigate the autonomic nervous system changes in icteric neonates using heart rate variability (HRV) and to assess the effect of phototherapy on short-term heart rate dynamics as an indicator of autonomic nervous control of cardiovascular system., Methods: HRV recordings from 20 icteric full-term neonates before, during and after phototherapy and from 20 healthy controls were analyzed. In addition to traditional time and frequency domain measures, heart rate complexity parameters including normalized complexity index (NCI), normalized unpredictability index (NUPI), pattern classification indices (0V%, 1V%, 2LV%, 2UV%) and irreversibility index (P%) on four time scales were evaluated. All measures were derived from data segments of 1000 RR intervals., Results: The analysis revealed higher values of 1V%, 2LV%, and lower P% in neonates with hyperbilirubinemia compared to controls. While HRV magnitude did not change, mean heart rate increased during and after the phototherapy. Nonlinear analysis showed a decrease of complexity, unpredictability and pattern classification measures 2LV% and 2UV%. In contrast, 0V% and irreversibility index P% were increased during and at least 30min after phototherapy., Conclusion: The results suggest a shifted autonomic balance in icteric neonates compared to the controls and its further alterations during phototherapy. As the nonlinear HRV parameters are independent of the linear methods, they can provide new information about the cardiac regulatory mechanisms and their changes in neonates., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Coarse graining of physiological time series such as the cardiac interbeat interval series by means of a symbolic transformation retains information about dynamical properties of the underlying system and complements standard measures of heart rate variability. The transformations of the original time series to the coarse grained symbolic series usually lead to a non-uniform occurrence of the different symbols, i.e. some symbols appear more often than others influencing the results of the subsequent symbolic series analysis. Here, we defined a transformation procedure to assure that each symbol appears with equal probability using a short alphabet {0,1,2,3} and a long alphabet {0,1,2,3,4,5}. The procedure was applied to the cardiac interbeat interval series RRi of 17 healthy subjects obtained during graded head-up tilt testing. The symbolic dynamics is analyzed by means of the occurrence of short sequences (`words') of length 3. The occurrence of words is grouped according to words without variations of the symbols (0V%), one variation (1V%), two like variations (2LV%) and two unlike variations (2UV%). Linear regression analysis with respect to tilt angle showed that for the short alphabet 0V% increased with increasing tilt angle whereas 1V%, 2LV% and 2UV% decreased. For the long alphabet 0V%, and 1V% increased with increasing tilt angle whereas 2LV% and 2UV% decreased. These results were slightly better compared to the results from non-uniform symbolic transformations reflecting the deviation from the mean. In conclusion, the symbolic transformation assuring the appearance of symbols with equal probability is capable of reflecting changes of the cardiac autonomic nervous system during graded head-up tilt. Furthermore, the transformation is independent of the time series' distribution.

The aim of the study was to evaluate short-term heart rate variability (HRV) as an index of cardiac autonomic control in rats with lipopolysaccharide (LPS)-induced endotoxemia. Animals were injected intraperitoneally with LPS (100 microg/kg b.w.) and control group with an equivalent volume of saline. ECG recordings were done before (base) and 60, 120, 180, 240 and 300 min after LPS or saline administration. 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. Heart tissue homogenates and plasma were analyzed to determine interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and oxidative stress level (TBARS). Administration of lipopolysaccharide was followed by continuous rise in colonic body temperature compared to saline-treated controls. Endotoxemia in rats was accompanied by significant decrease in HRV spectral activity in high-frequency range at maximal body temperature (logHFpower: 1.2+/-0.5 vs. 1.9+/-0.6 ms(2), P<0.01). Increased IL-6 was found in heart tissue homogenates of LPS rats (8.0+/-0.6 vs. 26.4+/-4.8 pg/ml, (P<0.05). In conclusions, reduced HRV in HF band may indicate a decreased parasympathetic activity in LPS-induced endotoxemia as basic characteristics of altered cardiac control during response to endotoxemia.

We aimed to study the complexity and time asymmetry of short-term heart rate variability (HRV) as an index of complex neurocardiac control in response to stress using symbolic dynamics and time irreversibility methods. ECG was recorded at rest and during and after two stressors (Stroop, arithmetic test) in 70 healthy students. Symbolic dynamics parameters (NUPI, NCI, 0V%, 1V%, 2LV%, 2UV%), and time irreversibility indices (P%, G%, E) were evaluated. Additionally, HRV magnitude was quantified by linear parameters: spectral powers in low (LF) and high frequency (HF) bands. Our results showed a reduction of HRV complexity in stress (lower NUPI with both stressors, lower NCI with Stroop). Pattern classification analysis revealed significantly higher 0V% and lower 2LV% with both stressors, indicating a shift in sympathovagal balance, and significantly higher 1V% and lower 2UV% with Stroop. An unexpected result was found in time irreversibility: significantly lower G% and E with both stressors, P% index significantly declined only with arithmetic test. Linear HRV analysis confirmed vagal withdrawal (lower HF) with both stressors; LF significantly increased with Stroop and decreased with arithmetic test. Correlation analysis revealed no significant associations between symbolic dynamics and time irreversibility. Concluding, symbolic dynamics and time irreversibility could provide independent information related to alterations of neurocardiac control integrity in stress-related disease.

Attention deficit/hyperactivity disorder (ADHD) is associated with complex neurocardiac integrity. We aimed to study heart rate time asymmetry as a nonlinear qualitative feature of heart rate variability indicating complexity of cardiac autonomic control at rest and in response to physiological stress (orthostasis) in children suffering from ADHD. Twenty boys with ADHD and 20 healthy age-matched boys at the age of 8 to 12 years were examined. The continuous ECG was recorded in a supine position and during postural change from lying to standing (orthostasis). Time irreversibility indices - Porta's (P%), Guzik's (G%) and Ehlers' (E) - were evaluated. Our analysis showed significantly reduced heart rate asymmetry indices at rest (P%: 49.8 % vs. 52.2 %; G%: 50.2 % vs. 53.2 %; p<0.02), and in response to orthostatic load (P%: 52.4 % vs. 54.5 %, G%: 52.3 % vs. 54.5 %; p<0.05) associated with tachycardia in ADHD children compared to controls. Concluding, our study firstly revealed the altered heart rate asymmetry pattern in children suffering from ADHD at rest as well as in response to posture change from lying to standing (orthostasis). These findings might reflect an abnormal complex cardiac regulatory system as a potential mechanism leading to later cardiac adverse outcomes in ADHD.

Introduction: The dynamics of cardiovascular variables are modulated by respiration. The aim of this study was to assess baroreflex function in normal subjects based on the joint symbolic dynamics of heart rate, blood pressure and respiration., Methods: ECG, continuous blood pressure and respiration were recorded in ten healthy subjects during rest in the supine position and upon standing. Beat-to-beat time series of heart rate, systolic blood pressure and respiratory phase were extracted and transformed into binary symbol sequences. Words of length two that were reflective of baroreflex activity were statistically analysed with respect to the respiratory phase., Results: Symbolic analysis showed a significant influence of the respiratory phase on the occurrence of baroreflex patterns. Upon standing, the frequency of baroreflex words increased and the effect of respiration appeared to be reduced., Conclusions: Symbolic dynamics provide a simple representation of cardiovascular dynamics and may be useful for assessing baroreflex function., (© 2013.)

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.

Heart rate fluctuates beat by beat in a complex manner. The aim of this study was to develop a framework for entropy assessment of heart rate fluctuations on multiple time scales. We employed the Lempel-Ziv algorithm for lossless data compression to investigate the compressibility of RR interval time series on different time scales, using a coarse-graining procedure. We estimated the entropy of RR interval time series of 20 young and 20 old subjects and also investigated the compressibility of randomly shuffled surrogate RR time series. The original RR time series displayed significantly smaller compression entropy values than randomized RR interval data. The RR interval time series of older subjects showed significantly different entropy characteristics over multiple time scales than those of younger subjects. In conclusion, data compression may be useful approach for multiscale entropy assessment of heart rate variability.

Decreased baroreflex sensitivity is an early sign of autonomic dysfunction in patients with type-1 diabetes mellitus. We evaluated the repeatability of a mild baroreflex sensitivity decrease in diabetics with respect to their heart rate. Finger blood pressure was continuously recorded in 14 young diabetics without clinical signs of autonomic dysfunction and in 14 age-matched controls for 42 min. The recordings were divided into 3-min segments, and the mean inter-beat interval (IBI), baroreflex sensitivity in ms/mm Hg (BRS) and mHz/mm Hg (BRSf) were determined in each segment. These values fluctuated in each subject within 42 min and therefore coefficients of repeatability were calculated for all subjects. Diabetics compared with controls had a decreased mean BRS (p=0.05), a tendency to a shortened IBI (p=0.08), and a decreased BRSf (p=0.17). IBI correlated with BRS in diabetics (p=0.03); this correlation was at p=0.12 in the controls. BRSf was IBI independent (controls: p=0.81, diabetics: p=0.29). We conclude that BRS is partially dependent on mean IBI. Thus, BRS reflects not only an impairment of the quick baroreflex responses of IBI to blood pressure changes, but also a change of the tonic sympathetic and parasympathetic heart rate control. This is of significance during mild changes of BRS. Therefore, an examination of the BRSf index is highly recommended, because this examination improves the diagnostic value of the measurement, particularly in cases of early signs of autonomic dysfunction.

Unlabelled: We aimed to study heart rate time irreversibility--a nonlinear qualitative characteristics of heart rate variability indicating complexity of cardiac autonomic control at rest and in response to physiological stress (orthostasis) in never-treated major depressive disorder (MDD) adolescent female patients., Methods: We studied 20 MDD girls and 20 healthy age-matched girls at the age of 15 to 18 years. The ECG was recorded in supine position and in response to position change from lying to standing (orthostasis). Time irreversibility analysis was performed using Porta's (P%), Guzik's (G%) and Ehlers' (E) index. The depressive disorder severity was evaluated using Montgomery-Asberg Depression Rating Scale (MADRS) and Children's Depression Inventory (CDI)., Results: Resting heart rate time irreversibility indices (logG%, logP%, Ehlers' index) were significantly reduced in MDD female patients without significant differences in response to orthostasis in MDD girls compared to controls. No significant correlations between time irreversibility and MDD severity were observed., Conclusion: This study revealed the impaired heart rate asymmetry pattern indicating an altered complexity of cardiac autonomic regulation in adolescent female patients suffering from MDD., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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.

Pregnancy leads to physiological changes in various parameters of the cardiovascular system. The aim of this study was to investigate longitudinal changes in the structure and complexity of heart rate variability (HRV) and QT interval variability during the second half of normal gestation. We analysed 30-min high-resolution ECGs recorded monthly in 32 pregnant women, starting from the 20th week of gestation. Heart rate and QT variability were quantified using multiscale entropy (MSE) and detrended fluctuation analyses (DFA). DFA of HRV showed significantly higher scaling exponents towards the end of gestation (p<0.0001). MSE analysis showed a significant decrease in sample entropy of HRV with progressing gestation on scales 1-4 (p<0.05). MSE analysis and DFA of QT interval time series revealed structures significantly different from those of HRV with no significant alteration during the second half of gestation. In conclusion, pregnancy is associated with increases in long-term correlations and regularity of HRV, but it does not affect QT variability. The structure of QT time series is significantly different from that of RR time series, despite its close physiological dependence., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

In this study we tested whether joint evaluation of the frequency (f(cs)) at which maxima of power in the cross-spectra between the variability in systolic blood pressure and inter-beat intervals in the range of 0.06-0.12 Hz occur together with the quantification of baroreflex sensitivity (BRS) may improve early detection of autonomic dysfunction in type 1 diabetes mellitus (T1DM). We measured 14 T1DM patients (age 20.3-24.2 years, DM duration 10.4-14.2 years, without any signs of autonomic neuropathy) and 14 age-matched controls (Co). Finger arterial blood pressure was continuously recorded by Finapres for one hour. BRS and f(cs) were determined by the spectral method. Receiver-operating curves (ROC) were calculated for f(cs), BRS, and a combination of both factors determined as F(z)=1/(1+exp(-z)), z=3.09-0.013*BRS-0.027*f(cs). T1DM had significantly lower f(cs) than Co (T1DM: 88.8+/-6.7 vs. Co: 93.7+/-3.8 mHz; p<0.05), and a tendency towards lower BRS compared to Co (T1DM: 10.3+/-4.4 vs. Co: 14.6+/-7.1 ms/mm Hg; p=0.06). The ROC for Fz showed the highest sensitivity and specificity (71.4 % and 71.4 %) in comparison with BRS (64.3 % and 71.4 %) or f(cs) (64.3 % and 64.3 %). The presented method of evaluation of BRS and f(cs) forming an integrated factor Fz could provide further improvement in the risk stratification of diabetic patients.

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.

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., (Copyright © 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background & Objective: ADHD is one of the most common mental disorders among children. We hypothesized that ADHD is associated with the impairment of the cardiac autonomic regulation. The aim of this study was to evaluate the cardiac autonomic regulation in children with ADHD at the rest and during orthostasis using short-term heart rate variability (HRV) analysis., Methods: Eighteen children with ADHD admitted to the Department of Children and Adolescent Psychiatry, Clinic of Psychiatry, University Hospital in Martin, Slovak Republic between January and September 2006 and 18 matched healthy subjects were recruited. HRV analysis was carried out in three positions: supine (S1)-orthostasis (O)-supine (S2). Evaluated parameters were: the mean R-R interval, mean squared successive difference (MSSD), spectral powers in low (LF) and high frequency (HF) bands, total power (TP), coefficients of component variance (CCV LF, CCV HF), LF/HF ratio., Results: The mean R-R interval was significantly shorter in ADHD group compared to controls in all positions (P<0.05, P<0.001). S1: The parameters MSSD, CCV HF, logHFpower were significantly lower (P<0.05, P<0.05, P<0.01) and ratio LF/HF was significantly higher (P<0.05) in ADHD group compared to controls. O: The parameters MSSD, CCVHF, logHFpower, logTP were significantly lower in ADHD group compared to controls (P<0.01, P<0.05, P<0.01, P<0.01). S2: The parameters MSSD and logHFpower were significantly lower in children with ADHD compared to controls (P<0.05)., Interpretation & Conclusion: The children with ADHD had decreased cardiac vagal modulation and tachycardia in supine positions with altered ability of dynamic activation of the autonomic nervous system in response to orthostasis indicating changes in the cardiac autonomic regulation. Further studies need to be done on a larger sample to confirm these findings and to understand the underlying mechanisms.

The purpose of this paper is to investigate the effect of orthostatic challenge on recurrence plot based complexity measures of heart rate and blood pressure variability (HRV and BPV). HRV and BPV complexities were assessed in 28 healthy subjects over 15 min in the supine and standing positions. The complexity of HRV and BPV was assessed based on recurrence quantification analysis. HRV complexity was reduced along with the HRV magnitude after changing from the supine to the standing position. In contrast, the BPV magnitude increased and BPV complexity decreased upon standing. Recurrence quantification analysis (RQA) of HRV and BPV is sensitive to orthostatic challenge and might therefore be suited to assess changes in autonomic neural outflow to the cardiovascular system.

Detection of subclinical autonomic dysfunction in patients with diabetes mellitus (DM) is of vital importance for risk stratification and subsequent management. Heart rate variability (HRV) analysis is a sensitive tool for assessment of cardiovascular autonomic dysfunction. As the heart is controlled by non-linear deterministic system, the non-linear dynamics measures should be preferred. Recurrence plot (RP) is able to analyse recurrences within system dynamics. The aim of the study was to detect heart rate dysregulation in DM by RP and to ascertain which of the recurrence quantification analysis (RQA) measures are changed in patients with DM compared to control group. We analysed HRV recordings from 17 young patients with type 1 DM and 17 healthy matched control subjects. RQA was performed on RPs with a fixed value of recurrence points percentage. From RQA measures based on diagonal lines, we have found higher percentage of determinism in DM group (P=0.038). Trapping time measure was also higher in DM (P=0.022). RQA revealed changes in dynamics recurrences with reduced complexity of heart rate control in young diabetic patients. As RQA parameters are independent of overall HRV, parameters of RP should be used together with linear HRV parameters for better description of heart rate dysregulation in patients with diabetics.

Multiscale entropy (MSE) analysis provides information about complexity on various time scales. The aim of this study was to test whether MSE is able to detect autonomic dysregulation in young patients with diabetes mellitus (DM). We analyzed heart rate (HR) oscillations, systolic (SBP) and diastolic blood pressure (DBP) signals in 14 patients with DM type 1 and 14 age- and sex-matched healthy controls. SampEn values (scales 1-10) and linear measures were computed. HR: among the linear measures of heart rate variability significant differences between groups were only found for RMSSD (p = 0.043). MSE was significantly reduced on scales 2 and 3 in DM (p = 0.023 and 0.010, respectively). SBP and DBP: no significant differences were detected with linear measures. In contrast, MSE analysis revealed significantly lower SampEn values in DM on scale 3 (p = 0.039 for SBP; p = 0.015 for DBP). No significant correlations were found between MSE and linear measures. In conclusion, MSE analysis of HR, SBP and DBP oscillations is able to detect subtle abnormalities in cardiovascular control in young patients with DM and is independent of standard linear measures.

Objective: The aim of this study was to test whether new heart rate variability (HRV) complexity measures provide diagnostic information regarding early subclinical autonomic dysfunction in diabetes mellitus (DM)., Methods: HRV in DM type 1 patients (n=17, 10f, 7m) aged 12.9-31.5 years (duration of DM 12.4+/-1.2 years) was compared to a control group of 17 healthy matched probands. The length of R-R intervals was measured over 1h using a telemetric ECG system. In addition to linear measures, we assessed HRV complexity measures, including multiscale entropy (MSE), compression entropy and various symbolic dynamic measures (Shannon and Renyi entropies, normalized complexity index (NCI), and pattern classification)., Results: HRV magnitude was significantly reduced in patients with DM. Several HRV complexity parameters (MSE at scales 2-4, Renyi entropy, NCI) were also significantly reduced in diabetics. MSE indices and compression entropy did not correlate with linear measures., Conclusions: The magnitude and complexity of HRV are reduced in young patients with DM, indicating vagal dysfunction., Significance: The quantification of HRV complexity in combination with its magnitude may provide an improved diagnostic tool for cardiovascular autonomic neuropathy in DM.

Autonomic neuropathy is a common complication of the diabetes mellitus (DM). The significance of its early diagnosis is very high because the mortality of the patients with this complication is elevated. Considering the effort to apply new mathematical methods to cardiac dysregulation diagnosis, the major aim of the study was to ascertain which of the new heart rate variability (HRV) parameters are different in young patients with DM type 1 compared with control group. The next aim was to assess the HRV changes during prolonged (40 min) supine rest. The heart rate was continuously recorded during supine rest in 17 young patients with DM type 1 (10 women, 7 men) aged 22.4 +/- 1.0 years (mean +/- SEM). The control group consisted of 17 healthy matched probands. The HRV (time/frequency domains, Poincare and sequence plots, sample entropy) was analysed in two intervals - T1 starting at fifth minute and T2 starting at 30th minute of supine rest. The major results of our study are: the reduced Poincare plot pattern measures in the young DM group; the lower percentage of points in the third quadrant of sequence plot (this parameter was not correlated with the mean heart rate) and significant changes in HRV during supine rest in DM group (in contrast to control subjects). In conclusion, HRV parameters based on nonlinear dynamics were able to distinguish cardiac dysregulation in young patients with DM from the control group. The percentage of points in the third quadrant of sequence plot provides information that is not dependent on mean heart rate. Poincare and sequence plots, together with the rate of HRV changes during supine rest, can provide clinically relevant information usable in diagnosis of the cardiac dysregulation.

The assessment of cardiovascular (and respiratory) parameters changes provides an information about the control systems involved and about their complex regulation. Methods based on nonlinear dynamics are able to quantify characteristics of the biosignal, that cannot be detected by conventional analysis methods. The sequence plot analysis is one of them. The aim of this paper is to provide basic information about this simple method and its application in the physiological research and in the clinical practice.

During physical exercise, heart rate (HR) increases by parasympathetic withdrawal and increase of sympathetic activity to the heart. HR variability (HRV) in time and frequency domains provides information about autonomic control of the cardiovascular system. Non-linear analysis using the Poincaré plot method is able to reveal supplementary information about cardiac autonomic control. The aim of this study was to determine the association between HRV parameters, the initial increase of HR at the onset of exercise (on-response) and HR decrease in the recovery phase after acute exercise (off-response). HR was continuously monitored in 17 healthy male subjects (mean age: 20.3 +/- 0.2 (SEM) years) at rest (25 min supine; 5 min standing), during exercise (8 min of step test at 70% of maximal power output) and in the recovery phase (30 min supine). HRV analysis in time and frequency domains and evaluation of the Poincaré plot measures (length, widths) were performed on selected segments of HR time series. HR on- and off-responses were quantified using an exponential curve fitting technique. The time constants T(on) and T(off), representing the rate of on- and off-responses to exercise, were computed. Postexercise HRV indices and time constant of on-response - T(on) - to exercise were negatively correlated. From preexercise HRV indices, only Poincaré plot parameters were correlated with T(on). No correlation between HRV indices and parameters of off-response was found. In conclusion, preexercise HRV parameters are not closely correlated with the rate of cardioacceleration at the onset of exercise and cannot predict the rate of HR recovery. On the other hand, postexercise HRV parameters are related to the rate of initial adjustment of HR to exercise referring to the importance of rapid HR on-response for a faster recovery after exercise.

Physical exercise is associated with parasympathetic withdrawal and increased sympathetic activity resulting in heart rate increase. The rate of post-exercise cardiodeceleration is used as an index of cardiac vagal reactivation. Analysis of heart rate variability (HRV) and complexity can provide useful information about autonomic control of the cardiovascular system. The aim of the present study was to ascertain the association between heart rate decrease after exercise and HRV parameters. Heart rate was monitored in 17 healthy male subjects (mean age: 20 years) during the pre-exercise phase (25 min supine, 5 min standing), during exercise (8 min of the step test with an ascending frequency corresponding to 70% of individual maximal power output) and during the recovery phase (30 min supine). HRV analysis in the time and frequency domains and evaluation of a newly developed complexity measure - sample entropy - were performed on selected segments of heart rate time series. During recovery, heart rate decreased gradually but did not attain pre-exercise values within 30 min after exercise. On the other hand, HRV gradually increased, but did not regain rest values during the study period. Heart rate complexity was slightly reduced after exercise and attained rest values after 30-min recovery. The rate of cardiodeceleration did not correlate with pre-exercise HRV parameters, but positively correlated with HRV measures and sample entropy obtained from the early phases of recovery. In conclusion, the cardiodeceleration rate is independent of HRV measures during the rest period but it is related to early post-exercise recovery HRV measures, confirming a parasympathetic contribution to this phase.

The noninvasive assessment of spontaneous temporal physiological parameters variations can provide valuable information about control systems involved in their complex regulations. Recently, in addition to conventional measures describing variability in time and frequency domains, methods based on nonlinear dynamics are increasingly used in physiology. The graphical analysis using Poincaré plot analysis with subsequent qualitative and quantitative analysis is one of them. The aim of this paper is to provide basic information about this method and its application in physiological research and clinical praxis.

The aim of this study was to ascertain the persistence of heart rate and blood pressure oscillations at the onset of voluntary apnea in humans and to assess the dependence of the fluctuations parameters on the chemoreceptor activity. In 24 young subjects (10 males, 14 females, mean age 20.4 years) heart rate (represented by its reciprocal value--RR-intervals), systolic blood pressure (SBP) and diastolic blood pressure (DBP) during controlled breathing (CB) of atmospheric air and oxygen followed by apnea were recorded continuously. The cosine functions were then fitted by nonlinear regression analysis to the heart rate, SBP and DBP oscillations during CB and at the onset of apnea. The parameters of oscillations were different during atmospheric air breathing compared to oxygen breathing. During oxygen breathing there was an increase of the RR-interval oscillations--relative bradycardia and enhanced magnitude of respiratory sinus arythmia. During apnea, the base level of the blood pressure oscillations was higher after breathing of atmospheric air compared to oxygen breathing. At least one cosine-like wave oscillation was present at the onset of apnea in the heart rate, SBP and DBP and the second wave was present in all assessed parameters in at least 70% of recordings. The oscillations in RR-intervals are, to some extent, independent of blood pressure oscillations. No significant gender differences were found either in the duration of breath holding or in the RR and SBP oscillations parameters.

Apnea, especially in preterm newborns (AoP) is one of the common problems encountered at neonatal units. Numerous factors are likely to play a role in the etiology of apnea. Recent data sugest a role for genetic predisposition of AoP. It seems, that physiological rather than pathological immaturity of the respiratory, or cardiorespiratory control, play a major part in the pathophysiology of AoP. Immaturity of the brainstem, cerebral cortex, receptors of the lungs and the airways as well as of the chemoreceptors contribute to the development of apnea in preterm newborns. Several neurotransmitters (GABA, adenosin, endorphins) and their maturational changes are including in pathogenesis of apnea, too. The instability of the upper airway in preterm infants, asynchrony of musculature of the upper airway and diaphragm, pathological changes in the upper airway and malformations of the central nervous system might also contribute to the occurrence and severity of AoP. In newborns, apnea occurs more frequently in active sleep than in quiet sleep and the frequency of apnea in active sleep is higher in the warm conditions. Durations of apnea correlate with the body heat loss. Cardiovascular changes during apnea - bradycardia, peripheral vasoconstriction and various changes in peripheral blood flow and pressure occur together with changes in ECG. The standard clinical management of apnea includes non-pharmacological treatment (eliciting arousal reactions and reflex breathing by mechanical skin, or mucosa stimulations), pharmacological treatment (methylxanthines are preferred) and application of continuous positive airway pressure (CPAP) or in severe apnea - mechanical ventilation.

Apnea, especially in preterm newborns (AoP) is one of the common problems encountered at neonatal units. Numerous factors are likely to play a role in the etiology of apnea. Recent data sugest a role for genetic predisposition of AoP. It seems, that physiological rather than pathological immaturity of the respiratory, or cardiorespiratory control, play a major part in the pathophysiology of AoP. Immaturity of the brainstem, cerebral cortex, receptors of the lungs and the airways as well as of the chemoreceptors contribute to the development of apnea in preterm newborns. Several neurotransmitters (GABA, adenosin, endorphins) and their maturational changes are including in pathogenesis of apnea, too. The instability of the upper airway in preterm infants, asynchrony of musculature of the upper airway and diaphragm, pathological changes in the upper airway and malformations of the central nervous system might also contribute to the occurrence and severity of AoP. In newborns, apnea occurs more frequently in active sleep than in quiet sleep and the frequency of apnea in active sleep is higher in the warm conditions. Durations of apnea correlate with the body heat loss. Cardiovascular changes during apnea - bradycardia, peripheral vasoconstriction and various changes in peripheral blood flow and pressure occur together with changes in ECG. The standard clinical management of apnea includes non-pharmacological treatment (eliciting arousal reactions and reflex breathing by mechanical skin, or mucosa stimulations), pharmacological treatment (methylxanthines are preferred) and application of continuous positive airway pressure (CPAP) or in severe apnea - mechanical ventilation. [ABSTRACT FROM AUTHOR]