Mirjana M. Platiša

Reflection of heart rate regulation on linear and nonlinear heart rate variability measures

The aim of this study was to examine the dependence of heart rate variability (HRV) measures on RR interval length and to find out relationships between linear and nonlinear measures. The spectral powers in very low (VLF), low (LF) and high (HF) frequency regions, short-term scaling exponent alpha(1) and sample entropy (SampEn) were determined. All spectral powers increased with increasing RR interval length until they reached a plateau. Neighbouring spectral powers were strongly correlated. The largest fraction of the spectrum consisted of VLF (from about 40 to 95%) and the smallest of HF, although HF was most sensitive to changes in RR interval length. SampEn is also increased with increasing RR interval, reaching a plateau. The dependence of alpha(1) on RR showed a deflection point at 0.5 s. Nonlinear measures can be expressed by spectral powers: alpha(1) by a linear function of ln(LF/HF) and SampEn by a quadratic function of ln HF. We concluded that during the day an increase of HR up to 120 beats min(-1) was reflected in a reduction in HF and LF and to a smaller extent in VLF and by decreased complexity and increased correlation in RR interval series. In sleep, HRV measures are at a plateau. We suggest that below intrinsic value, HR is regulated mainly by changes of parasympathetic activity, reflected in linear and nonlinear HRV measures.

Dependence of heart rate variability on heart period in disease and aging

The aim of this study was to compare the dependence of heart rate variability (HRV) on heart period (RR interval length) under different physiological and pathological states in order to detect changes in HR modulation. The dependence of HRV on the RR interval length in healthy elderly subjects, congestive heart failure (CHF) patients and one patient with a transplanted heart (T) was compared with healthy young subjects. Spectral powers, sample entropy (SampEn) and short-term fractal scaling exponent (alpha1) were determined from 24 h free-running recordings. For the same HR, HRV measures were different in different groups. In healthy subjects HRV measures depended on RR interval length and all spectral powers were highly correlated, although reduced in elderly subjects. SampEn at high HR was the most sensitive quantity to changes induced by aging. In disease, CHF and T, an achievable HR range was decreased, all spectral powers were reduced, but correlated, and the dependence of HRV measures on RR was lost. There was an evident difference in the dependence of nonlinear on linear measures between young subjects and all the other studied groups. In disease the reduction in autonomic control was associated with the decrease in short-range correlation and regularity in RR series. We have concluded that the analysis of HRV measures as functions of RR interval length can reveal important aspects of HR control that might be lost in averaging.

Linear and non‐linear heart rate variability measures in chronic and acute phase of anorexia nervosa

Previous results on heart rate variability (HRV) analysis in anorexia nervosa (AN) include some apparently conflicting data. In order to find out the reason for different results and to improve understanding of autonomic control in AN we compare HRV in acute and chronic AN. Spectral powers, fractal scaling exponent and sample entropy were computed from 24 h RR series derived from Holter ECG recordings in 17 anorexic patients, nine chronic and eight healthy women. We found that all linear and non‐linear HRV measures change in different direction in acute and chronic AN. Acute AN is characterized by decreased HR and increased HRV. In chronic AN, HR is increased, HRV reduced and the difference between awake and sleeping values is high. HRV measures are associated with body mass index only in chronic AN. As HRV measures are significantly different between acute and chronic AN, we propose that HRV analysis might provide additional data in clinical practice.

Complexity of heartbeat interval series in young healthy trained and untrained men

The origin of heart rate variability (HRV) is largely in parasympathetic activity. The direct influence of sympathetic activity and other control mechanisms, especially at an increased HR, is not well understood. The objectives of the study were to investigate the influence of increasing HR on the properties of heartbeat interval (RR) series in young healthy subjects. ECG was recorded in 9 trained and 11 untrained young men during supine rest, standing, incremental running exercise and relaxation. During exercise, a breath-to-breath gas exchange was monitored. The RR time series analysis included the spectral analysis, detrended fluctuations analysis method and sample entropy (SampEn) calculation. During exercise, spectral powers were reduced dramatically in both groups. The dependence of short-term scaling exponent (alpha(1)) on the RR included a characteristic maximum, while SampEn for the same value of the RR had a minimum. The value of HR corresponding to the maximum of alpha(1) and minimum of SampEn (IHR) corresponded to the intrinsic HR obtained by an autonomic blockade. In trained subjects, the curves alpha(1) versus RR and SampEn versus RR were moved toward larger RR, compared with control. For HR values higher than IHR, alpha(1) decreased and SampEn increased. These results reveal that the complexity of the heart rhythm above intrinsic HR decreases with an increase in HR. We suggest that at the highest HR intrinsic heart control is reflected in the heart rhythm. We point out the possibility of developing a new non-invasive method for the determination of intrinsic HR from the curve alpha(1) versus RR.

Nonlinear properties of cardiac rhythm and respiratory signal under paced breathing in young and middle-aged healthy subjects

We examined the effects of gender and age in young and middle-aged subjects on the level of cardio-respiratory interaction by analyzing properties of cardiac, respiratory and cardiac-respiratory regulatory mechanisms under paced breathing. In 56 healthy subjects, ECG (RR interval) and respiratory signal were simultaneously acquired in supine position at paced (0.1-0.45 Hz, steps of 0.05 Hz) and spontaneous breathing. The participants were divided into gender matched group of young adults (19-25 years old) and middle-aged adults (35-44 years old). Power spectral analysis was applied on RR interval time series and spectral components in very low frequency (VLF), low frequency (LF) and high frequency (HF) ranges were computed. We also calculated sample entropy of RR interval series (SampEnRR), respiratory series (SampEnResp), and their cross-sample entropy (cross-SampEn). Under paced breathing, reduction of all spectral powers with age (p<0.05) is not gender dependent but reduction of some entropy measures is; SampEnRR and SampEnResp were lower only in men (p<0.05). In the middle-aged subjects, effect of gender on spectral measures is significant; males had lower HF (p < 0.05). Pattern of dependencies of SampEn and cross-SampEn on paced breathing frequency were significantly different in men (young vs. middle-aged, p = 0.001 and p = 0.037) and in middle-aged subjects (females vs. males, p = 0.011 and p = 0.008). In middle-aged males, lower entropy measures indicated reduced and less complex partial cardiac and respiratory control, and central cardio-respiratory control. In conclusion, in healthy middle-aged subjects changes in cardio-respiratory coupling are detectable only in males.

Correlation properties of heartbeat dynamics

In this study, we investigate correlation properties of fluctuations in heart interbeat (RR) time series in a broad range of physiological and pathological conditions. Using detrended fluctuation analysis (DFA) method we determined short-term (α1) and long-term (α2) scaling exponent. In addition, we calculated standard deviation of RR intervals (SDRR) as the simplest variability measure. We found that the difference between α1 and α2 is related to RR interval length. At the shortest RR intervals, which correspond to extreme physiological and pathological conditions, we found the highest reduction of variability and the biggest difference between scaling exponents. In this case, DFA reveals a white noise over short scales (α1 about 0.5) and strongly correlated noise over large scales (α2 about 1.5). With an increase in RR interval, accompanied by increased variability (increase in parasympathetic control), the difference between α1 and α2 decreases. The difference between scaling exponents disappeared in a state of efficient autonomic control. We suggest that the complexity in heart rhythm is achieved through coupling between intrinsically controlled heart rhythm and autonomic control, and that the model of stochastic resonance mechanism could be applied to this system.

Uncoupling of cardiac and respiratory rhythm in atrial fibrillation

Abstract Rearranged origin of heart rhythm in patients with atrial fibrillation (AF) influences the regulation of the heart and consequently the respiratory rhythm, and the bidirectional interaction of these rhythms not documented. Hence, we examined coupling of the RR interval and the respiration (Resp) signal by coherence, Granger causality and the cross-sample entropy method of time series analysis in patients with AF and a healthy control group. In healthy subjects, the influence of respiration on cardiac rhythm was found as increased coherence at the breathing frequency (BF) range, significantly stronger interaction and synchrony from Resp to RR than from RR to Resp. On the contrary, in patients with AF, coherence at BF diminished, there were no causal interactions between signals in both directions, which resulted in equally great asynchrony between them. In AF, the absence of full functionality of the sinoatrial node, as an integrator of neural cardiac control, resulted in diminished vagal modulation of heart periods and consequently impaired bidirectional cardio-respiratory interaction.

RR interval–respiratory signal waveform modeling in human slow paced and spontaneous breathing

Our aim was to model the dependence of respiratory sinus arrhythmia (RSA) on the respiratory waveform and to elucidate underlying mechanisms of cardiorespiratory coupling. In 30 subjects, RR interval and respiratory signal were recorded during spontaneous and paced (0.1Hz/0.15Hz) breathing and their relationship was modeled by a first order linear differential equation. This model has two parameters: a0 (related to the instantaneous degree of abdominal expansion) and a1 (referring to the speed of abdominal expansion). Assuming that a0 represents slowly adapting pulmonary stretch receptors (SARs) and a1 SARs in coordination with other stretch receptors and central integrative coupling; then pulmonary stretch receptors relaying the instantaneous lung volume are the major factor determining cardiovagal output during inspiration. The models results depended on breathing frequency with the least error occurring during slow paced breathing. The role of vagal afferent neurons in cardiorespiratory coupling may relate to neurocardiovascular diseases in which weakened coupling among venous return, arterial pressure, heart rate and respiration produces cardiovagal instability.

Quantification of the acute effect of a low dose of red wine by nonlinear measures of RR and QT interval series in healthy subjects

The measures of nonlinear properties of RR interval and QT interval time series are sensitive to physiologically- or pathologically-induced complexity/regularity changes, but were not used to estimate the effect of alcohol intake. We wanted to examine the potential of these measures to quantify the acute effect of a low dose of red wine in healthy subjects. In separate experiments, fourteen young volunteers drank 200ml of red wine and a control drink with equal concentration of ethanol. ECG in supine position was recorded 20min before and 60min after drink intake. RR interval and QT interval series were extracted from ECG and we calculated variability, scaling exponents (α1 and α2) and sample entropy (SampEn) for both series. Systolic and diastolic blood pressures (BP) were measured every 10min. The immediate effect of both the drinks was equal: HR, BP and QT variability exhibited a sudden increase and then a decrease. However, the prolonged effect of wine and the control drink was different. Wine decreased both BP (p<0.05) and reduced complexity of RR and QT series (increased scaling exponents and decreased SampEn). The control drink prolonged QT and RR intervals (p<0.05). These results point out that the nonlinear properties of RR and QT interval series could be used to differentiate the effect of wine and ethanol. Changes in RR and QT interval series induced by a low dose of red wine are more detectable by methods that quantify the structure of the series than by methods that quantify their variability.

Contractions of the whole and longitudinally cut rat's portal vein

To investigate the role of lateral interactions, we quantified spontaneous contractions of whole and longitudinally cut rat´s portal vein in vitro. The disruption of the wall had no effect on basic frequency determined from spectra and complexity index (CI) calculated by multiscale entropy analysis. Endothelium was disrupted and nonfunctional in all samples. Considering amplitude, frequency and CI we identified two modes of contractions. Neither mode of contractions nor the effect of aminopyridine (4-AP) depended on the integrity of the wall. We concluded that contractions in vitro originate in smooth muscle cells without involvement of the endothelium and lateral interactions.