Influence of external periodic stimuli on heart rate variability in healthy subjects and in coronary heart disease patients

Frequency estimates of the heart rate variability (HRV) spectrum influenced by external periodic stimuli were studied in healthy subjects and patients with coronary heart disease (CHD). Sensory stimulation by periodic eye opening at a rate of 15, 10, 8, 6, or 5 times per minute, as well as spontaneous and controlled breathing at a rate of 15, 10, 8, 6, or 5 times per minute, was used. It was found that the spectral response to external periodic oscillations was determined by a frequency-dependent phenomenon, the maximal amplitude of heart rate variations being observed in the case of external stimuli at a frequency of 0.1 Hz. A resonance frequency in the 0.1-Hz range may be suggested to exist in the cardiovascular controls. Significant differences in the HRV frequency characteristics between CHD patients and healthy subjects were shown. CHD patients had a characteristic decline in HRV responses to external oscillations; the power of these responses did not depend on the frequency of external stimuli.     

Gender differences in autonomic cardiovascular regulation: spectral, hormonal, and hemodynamic indexes.

The autonomic nervous system drives variability in heart rate, vascular tone, cardiac ejection, and arterial pressure, but gender differences in autonomic regulation of the latter three parameters are not well documented. In addition to mean values, we used spectral analysis to calculate variability in arterial pressure, heart rate (R-R interval, RRI), stroke volume, and total peripheral resistance (TPR) and measured circulating levels of catecholamines and pancreatic polypeptide in two groups of 25 +/- 1.2-yr-old, healthy men and healthy follicular-phase women (40 total subjects, 10 men and 10 women per group). Group 1 subjects were studied supine, before and after beta- and muscarinic autonomic blockades, administered singly and together on separate days of study. Group 2 subjects were studied supine and drug free with the additional measurement of skin perfusion. In the unblocked state, we found that circulating levels of epinephrine and total spectral power of stroke volume, TPR, and skin perfusion ranged from two to six times greater in men than in women. The difference (men > women) in spectral power of TPR was maintained after beta- and muscarinic blockades, suggesting that the greater oscillations of vascular resistance in men may be alpha-adrenergically mediated. Men exhibited muscarinic buffering of mean TPR whereas women exhibited beta-adrenergic buffering of mean TPR as well as TPR and heart rate oscillations. Women had a greater distribution of RRI power in the breathing frequency range and a less negative slope of ln RRI power vs. ln frequency, both indicators that parasympathetic stimuli were the dominant influence on women's heart rate variability. The results of our study suggest a predominance of sympathetic vascular regulation in men compared with a dominant parasympathetic influence on heart rate regulation in women.     

迷走神经和交感神经系统不同活动状态对心率变异性的影响

实验在氯醛糖加氨基甲酸乙酯麻醉的新西兰兔上进行。记录血压、心率、心电图并对心电Ｒ－Ｒ间期（ＲＲＩ）作功率谱密度（ＰＳＤ）分析。以单调性电刺激和低频率的波动性电刺激分别刺激减压神经、疑核和右侧迷走神经外周端,观察到低频率的波动性刺激对增加ＰＳＤ中低频成分（ＬＦ）的作用比单调性电刺激更大（Ｐ〈０．０５）。注射新福林仅在头一个２５６个心动周期时间内引起总变异性（ＴＶ）、ＬＦ、ＰＳＤ中高频成分（ＨＦ）。Ｌ     

HRV spectral estimation based on constrained Gaussian modeling in the nonstationary case

The heart rate variability (HRV) spectral parameters are classically used for studying the autonomic nervous system, as they allow the evaluation of the balance between the sympathetic and parasympathetic influences on heart rhythm. However, this evaluation is usually based on fixed frequency regions, which does not allow possible variation, or is based on an adaptive individual time dependent spectral boundaries (ITSB) method sensitive to noisy environments. In order to overcome these difficulties, we propose the constrained Gaussian modeling (CGM) method that dynamically models the power spectrum as a two Gaussian shapes mixture. It appeared that this procedure was able to accurately follow the exact parameters in the case of simulated data, in comparison with a parameter estimation obtained with a rigid frequency cutting approach or with the ITSB algorithm. Real data results obtained on a classical stand-test and on the Fantasia database are also presented and discussed.     

Hilbert-Huang transform for analysis of heart rate variability in cardiac health

This paper introduces a modified technique based on Hilbert-Huang transform (HHT) to improve the spectrum estimates of heart rate variability (HRV). In order to make the beat-to-beat (RR) interval be a function of time and produce an evenly sampled time series, we first adopt a preprocessing method to interpolate and resample the original RR interval. Then, the HHT, which is based on the empirical mode decomposition (EMD) approach to decompose the HRV signal into several monocomponent signals that become analytic signals by means of Hilbert transform, is proposed to extract the features of preprocessed time series and to characterize the dynamic behaviors of parasympathetic and sympathetic nervous system of heart. At last, the frequency behaviors of the Hilbert spectrum and Hilbert marginal spectrum (HMS) are studied to estimate the spectral traits of HRV signals. In this paper, two kinds of experiment data are used to compare our method with the conventional power spectral density (PSD) estimation. The analysis results of the simulated HRV series show that interpolation and resampling are basic requirements for HRV data processing, and HMS is superior to PSD estimation. On the other hand, in order to further prove the superiority of our approach, real HRV signals are collected from seven young health subjects under the condition that autonomic nervous system (ANS) is blocked by certain acute selective blocking drugs: atropine and metoprolol. The high-frequency power/total power ratio and low-frequency power/high-frequency power ratio indicate that compared with the Fourier spectrum based on principal dynamic mode, our method is more sensitive and effective to identify the low-frequency and high-frequency bands of HRV.     

A measure of heart rate variability is sensitive to orthostatic challenge in women with chronic fatigue syndrome

The use of symptoms generated by head up tilt (HUT) is not a useful tool in identifying chronic fatigue syndrome (CFS). We investigated whether heart rate variability (HRV) assessed early during HUT might be useful. A sample of 46 female subjects (24 with CFS and 22 sedentary, age-matched healthy controls; CON) who had exhibited no difference in time to syncope during tilt was examined for HRV responses to 10 min of 70 degrees HUT after 5 min of baseline in the supine position. HRV data were analyzed by the method of coarse graining spectral analysis. Variables compared between groups included mean and standard deviation (SD(RRI)) of RR intervals (RRI), amplitudes of low- (A(LF); 0.04-0.15 Hz) and high-frequency (A(HF); >0.15 Hz) harmonic as well as aperiodic, fractal (A(FR); 1/f(beta)) spectral components, the spectral exponent beta, and the difference in these values between baseline and HUT for each subject. In the supine baseline, only mean RRI was significantly (P < 0.01) lower in CFS than in CON. During HUT, however, mean RRI (P < 0.01), SD(RRI) (P < 0.01), A(HF) (P < 0.05), and A(FR) (P < 0.01) were significantly lower in CFS than in CON. When the difference in values between baseline and HUT for each subject was examined, only the difference for A(FR) (deltaA(FR)) was significantly (P < 0.01) lower in CFS than in CON, suggesting that A(FR)is a disease-specific response of HRV to HUT. When a cut-off level was set to deltaA(FR) = -2.7 msec, the sensitivity and the specificity in differentiating CFS from controls were 90% and 72%, respectively. The data suggest that a decrease in aperiodic fractal component of HRV in response to HUT can be used to differentiate patients with CFS from CON.     

Involvement of the sympatho-vagal balance in the formation of respiration-dependent oscillations in the human cardiovascular system

The effect of deep breathing controlled in both rate and amplitude on the heart rate variability (HRV) and respiration-dependent blood flow oscillations was studied in the forearm and finger-pad skin of healthy 18- to 25-year-old volunteers. In order to reveal the effects of the divisions of the autonomic nervous system on the amplitudes of respiratory sinus arrhythmia (RSA) and skin blood flow oscillations, we studied the indices of the cardiovascular system in two groups of subjects with respectively lower and higher values of the sympatho-vagal balance. This index was calculated as a ratio of low frequency and high frequency HRV spectral power (LF/HF) under the conditions of spontaneous breathing. It was found that, in subjects with a predominant parasympathetic tone, the amplitudes of RSA and the rate of blood flow in the finger-pad skin were higher compared to subjects with a predominant sympathetic tone during respiration with the frequency lower than 4 cycle/min. In the forearm skin, where sympathetic innervation is weaker compared to the finger-pad skin, there were no significant differences in respiration-dependent oscillations of the rate of blood flow in two groups of subjects.     

Time–frequency analysis of variabilities of heart rate, systolic blood pressure and pulse transit time before and after exercise using the recursive autoregressive model

Time–frequency (T–F) analysis is often used to study the non-stationary cardiovascular oscillations such as heart rate and blood pressure variabilities in dynamic situations. This study intends to use the T–F recursive autoregressive technique to investigate variability in pulse transit time (PTT), which is a cardiovascular parameter of emerging interest due to its potential to estimate blood pressure non-invasively, continuously and without a cuff. Recent studies suggest that PTT is not only related to systolic blood pressure (SBP) but also to heart rate. Therefore, in this study, variability of PTT is analyzed together with the variabilities of R–R interval (RRI) from electrocardiogram and beat-to-beat SBP on 9 normotensive subjects before and shortly after three successive bouts of treadmill exercise. The results showed that both low frequency (LF) and high frequency (HF) components were found in the spectra of RRI, SBP and PTT in the 5-min recordings collected before and after exercise. Compared to the baseline, a decrease in the power of the HF component of RRI followed by an increase in its LF component indicated firstly a vagal withdrawal and then sympathetic activity enhancement after successive bouts of exercise. On the other hand, although changes in the LF and HF components of PTT were more similar to those of SBP than of RRI, the LF/HF ratio of SBP was almost 4 times higher than that of PTT. Based on the results, it is therefore suggested that the relationship between SBP and PTT is frequency-dependent.     

Assessment of Heart Autonomic Control on the Basis of Spectral Analysis of Heart Rate Variability

An orthostatic test with frequency-controlled breathing (with a respiration period of 10 s) or spontaneous breathing was used to analyze frequency estimates of the heart rate variability (HRV) in the low-frequency (LF) and high-frequency (HF) ranges in young men and women. It was demonstrated that the spectral components of HRV bear no signs of sex differentiation, suggesting a uniform structural organization of the system of autonomic nervous control of the heart (SANCH) in humans. The LF component of the HRV spectrum is a marker of the functional state of the SANCH; it should be studied under conditions of controlled breathing at a frequency of 0.1 Hz. The HF and LF components of the HRV characterize the state of the SANCH at a given moment and do not reflect directly its adaptation reserve. The HF component of the HRV is interesting as a parameter that may be used for estimating the changes in the adaptation reserve of heart autonomic control. It is preferable to analyze this component in the absence of external disturbances in the LF range of the spectrum.     

Relationship between cortical electrical and cardiac autonomic activities in the awake lizard, Gallotia galloti

ECG and EEG signals were simultaneously recorded in lizards, Gallotia galloti, both in control conditions and under autonomic nervous system (ANS) blockade, in order to evaluate possible relationships between the ANS control of heart rate and the integrated central nervous system activity in reptiles. The ANS blockers used were prazosin, propranolol, and atropine. Time-domain summary statistics were derived from the series of consecutive R-R intervals (RRI) of the ECG to measure beat-to-beat heart rate variability (HRV), and spectral analysis techniques were applied to the EEG activity to assess its frequency content. Both prazosin and atropine did not alter the power spectral density (PSD) of the EEG low frequency (LF: 0.5-7.5 Hz) and high frequency (HF: 7.6-30 Hz) bands, whereas propranolol decreased the PSD in these bands. These findings suggest that central beta-adrenergic receptor mechanisms could mediate the reptilian waking EEG activity without taking part any alpha(1)-adrenergic and/or cholinergic receptor systems. In 55% of the lizards in control conditions, and in approximately 43% of the lizards under prazosin and atropine, a negative correlation between the coefficient of variation of the series of RRI value (CV(RRI)) and the mean power frequency (MPF) of the EEG spectra was found, but not under propranolol. Consequently, the lizards' HRV-EEG-activity relationship appears to be independent of alpha(1)-adrenergic and cholinergic receptor systems and mediated by beta-adrenergic receptor mechanisms.     

迷走神经在心率变异性中的作用

采用功率谱和近似熵 (approximateentropy ,ApEn)的方法 ,分析清醒家兔在双侧迷走神经保留 ,右、左侧迷走神经切断以及双侧迷走神经同时切断时心搏间期 (RRI)的变化。结果显示 :双侧迷走神经保留时功率谱中高频功率 (HF)、低频功率 (LF)及ApEn值均高于双侧及单侧迷走神经切断时 (P <0 0 5 ) ,LF/HF比值最小 ;切断单侧迷走神经 ,ApEn变小 ,LF/HF比值在右侧迷走神经切断时增大 ,而切断左侧迷走时LF/HF比值无明显变化 ;双侧迷走神经切断后LF/HF比值最大 ,ApEn最低。结果表明 :心率变异主要由迷走神经调节 ,右侧迷走神经起主要作用 ;传统心率变异性测量方法与非线性方法所得结果一致     

Clinical correlates of frequency analyses of cardiovascular control after spinal cord injury

Spinal cord injury (SCI) has profound effects on cardiovascular autonomic function due to injury to descending autonomic pathways, and cardiovascular diseases are the leading causes of morbidity and mortality after SCI. Evaluation of cardiovascular autonomic dysfunction after SCI and appraisal of simple noninvasive autonomic assessments that are clinically meaningful would be useful to SCI clinicians and researchers. We aimed to assess supine and upright cardiovascular autonomic function from frequency analyses of heart rate and blood pressure variability (HRV and BPV) after SCI. We studied 26 subjects with chronic cervical or thoracic SCI and 17 able-bodied controls. We continuously recorded R-R interval (RRI, by ECG) and beat-to-beat blood pressure (by Finometer) in supine and seated positions. Cardiovascular control was assessed from spectral analysis of RRI and blood pressure time series. Cardiac baroreflex control was assessed from cross-spectral analyses of low-frequency spectra. Supine and upright low-frequency HRV and BPV were reduced in cervical SCI subjects, as were total BPV and HRV. Supine high-frequency HRV was reduced in thoracic SCI subjects. Cardiac baroreflex delay was increased in cervical SCI subjects. Supine frequency domain indexes were correlated with sympathetic skin responses, orthostatic cardiovascular responses, and plasma catecholamine levels. SCI results in reduced sympathetic drive to the heart and vasculature and increased baroreflex delay in cervical SCI subjects and reduced cardiac vagal tone in thoracic SCI subjects. Frequency analyses of autonomic function are related to clinical measures of autonomic control after SCI and provide useful noninvasive clinical tools with which to assess autonomic completeness of injury following SCI.     

Nonlinear dynamics of heart rate variability in cocaine-exposed neonates during sleep

The aim of this study was to determine the effects of prenatal cocaine exposure (PCE) on the dynamics of heart rate variability in full-term neonates during sleep. R-R interval (RRI) time series from 9 infants with PCE and 12 controls during periods of stable quiet sleep and active sleep were analyzed using autoregressive modeling and nonlinear dynamics. There were no differences between the two groups in spectral power distribution, approximate entropy, correlation dimension, and nonlinear predictability. However, application of surrogate data analysis to these measures revealed a significant degree of nonlinear RRI dynamics in all subjects. A parametric model, consisting of a nonlinear delayed-feedback system with stochastic noise as the perturbing input, was employed to estimate the relative contributions of linear and nonlinear deterministic dynamics in the data. Both infant groups showed similar proportional contributions in linear, nonlinear, and stochastic dynamics. However, approximate entropy, correlation dimension, and nonlinear prediction error were all decreased in active versus quiet sleep; in addition, the parametric model revealed a doubling of the linear component and a halving of the nonlinear contribution to overall heart rate variability. Spectral analysis indicated a shift in relative power toward lower frequencies. We conclude that 1) RRI dynamics in infants with PCE and normal controls are similar; and 2) in both groups, sympathetic dominance during active sleep produces primarily periodic low-frequency oscillations in RRI, whereas in quiet sleep vagal modulation leads to RRI fluctuations that are broadband and dynamically more complex.     

Temporal contribution of body movement to very long-term heart rate variability in humans

A newly developed, very long-term ( approximately 7 days) ambulatory monitoring system for assessing beat-to-beat heart rate variability (HRV) and body movements (BM) was used to study the mechanism(s) responsible for the long-period oscillation in human HRV. Data continuously collected from five healthy subjects were analyzed by 1) standard auto- and cross-spectral techniques, 2) a cross-Wigner distribution (WD; a time-frequency analysis) between BM and HRV for 10-s averaged data, and 3) coarse-graining spectral analysis for 600 successive cardiac cycles. The results showed 1) a clear circadian rhythm in HRV and BM, 2) a 1/f (beta)-type spectrum in HRV and BM at ultradian frequencies, and 3) coherent relationships between BM and HRV only at specific ultradian as well as circadian frequencies, indicated by significant (P < 0.05) levels of the squared coherence and temporal localizations of the covariance between BM and HRV in the cross-WD. In a single subject, an instance in which the behavioral (mean BM) and autonomic [HRV power >0.15 Hz and mean heart rate (HR)] rhythmicities were dissociated occurred when the individual had an irregular daily life. It was concluded that the long-term HRV in normal humans contained persistent oscillations synchronized with those of BM at ultradian frequencies but could not be explained exclusively by activity levels of the subjects.     

Heart rate variability in weightlifters

On the basis of the literature and original data, heart rate variability (HRV) in weightlifters has been studied. The results showed that the distribution mode (a parameter of mathematical analysis that is equal to the most frequent length of RR intervals) indicates the intensity of physical exercise. Specific changes in the autonomic balance in athletes as dependent on their degree of training and sports qualification are important characteristics of adaptations to physical loads. For example, the degree of training of weightlifters is reflected by the level of the respiratory component as an index of the activity of the parasympathetic nervous system. Adaptation to physical exercise leads to an increase in the power of the spectrum of neurohumoral modulation and to changes in the ratio between the levels of the total spectral power of HRV.     

Heart rate variability and spontaneous baroreflex sequences in supine healthy volunteers subjected to nasal positive airway pressure.

To determine the dynamic effects of short-term nasal positive airway pressure (nPAP) on cardiovascular autonomic control, continuous recordings of noninvasively obtained hemodynamic measurements and heart rate variability (HRV) were obtained in 10 healthy subjects during frequency-controlled breathing (between 0.20 and 0.24 Hz) in supine posture under different pressures of nPAP ranging from 3 to 20 cmH(2)O. HRV was assessed using spectral analysis of the R-R interval. The slope of the regression line between spontaneous systolic blood pressure and pulse interval changes was taken as an index of the sensitivity of arterial baroreflex modulation of heart rate (sequence method). Application of nPAP resulted in a pressure-dependent decrease of cardiac output and stroke volume (P < 0.05, ANOVA) and in an increase in total peripheral resistance (P < 0.03, ANOVA). Hemodynamic changes under increasing nPAP were accompanied by a decrease in total power of HRV despite mean R-R interval remaining unchanged. The overall decrease in HRV was accompanied by a reduction across all frequency bands when absolute units were used (P < 0.01). When the power of low frequency and high frequency was calculated in normalized units, a diminished high frequency and an increased low-to-high frequency ratio were observed (P < 0.05). Compared with low levels of nPAP, pressure levels of >10 cmH(2)O were associated with a significant decline in the mean slope of spontaneous baroreceptor sequences (P < 0.04). These findings indicate that short-term administration of nPAP in normal subjects exerts significant alterations in R-R interval variability and spontaneous baroreflex modulation of heart rate.     

A new method in applying power spectral statistics to examine cardio-respiratory interactions in fish

Power spectral analysis (PSA) provides a powerful tool for determining frequency oscillations in time signals, and it is accepted that mammals can show distinct components in the heart rate (fH) spectrum that are synchronous with ventilatory frequency (fV). Using similar signal processing techniques, these fundamental components at fV are not apparent in the spectrum calculated from fish fH. Here we compare conventional PSA on the R-R interval tachogram generated from ECG traces recorded in rats and fish, with PSA on the raw ECG waveform. The rat R-R tachogram showed a defined sigmoidal component, whereas the fish R-R tachogram was a more chaotic waveform. In agreement with the literature, PSA of these respective waveforms produced a component at the same frequency as ventilation in the rat, but of lower frequency than ventilation for the fish. Applying PSA to the rat ECG produced a spectrum with a fundamental component of similar frequency to that observed in the R-R tachogram spectrum, indicating that the latter adequately contained heart rate variability (HRV) oscillations. However, PSA of the ECG in fish contrasted with that from the R-R tachogram, with components observed in the latter spectrum being absent from the former. This suggests that the frequency components determined by PSA on the fish R-R tachogram were not true components, but were aliased (or folded-back) from higher up in the spectrum. Using established aliasing equations, recalculation of these peaks showed that their true frequency was similar to that of the ventilatory frequency for individual fish. The extent of cardio-respiratory interaction, resulting in fV < f(H/2) in rats but fV > f(H/2) in fish, is suggested to be the origin of the differences observed.     

Heart rate dynamics in iNOS knockout mice

Nitric oxide has both an inhibitory and excitatory role in the regulation of pre-ganglionic sympathetic neurons, involving the iNOS and nNOS systems respectively. The aim of the present study was to examine cardiovascular autonomic activity in iNOS knockout mice using spectral analysis of heart rate variability (HRV), and to determine the role of iNOS in altered HRV in endotoxaemia. Electrocardiograms were recorded in anaesthetised mice, and the R-R intervals digitized for spectral analysis of HRV and cardiac rhythm regularity using sample entropy analysis. The basal heart rate was higher in iNOS knockout mice compared with controls (465+/-8 vs 415+/-13 beat/min P<0.05), with a significant increase in the low frequency power of HRV spectra in iNOS knockout mice compared with controls (49.4+/-4.3 vs 33.8+/-5.6 normalized units, P<0.05), consistent with increased cardiac sympathetic activity. Endotoxaemia is known to decrease HRV, but the role of iNOS is unknown. LPS (20 mg/kg i.p) increased basal heart rate in both wild type and iNOS knockout mice, but caused a depression of HRV and sample entropy in both groups. Studies in isolated beating atria showed that the changes of HRV under basal or post-LPS conditions disappeared in vitro, suggesting that the autonomic system is responsible for altered HRV. We conclude that disruption of iNOS gene leads to an increase in the low frequency power of HRV consistent with increased cardiac sympathetic activity. These data also demonstrate that LPS-induced decrease of HRV is independent of iNOS.     

The Forgotten Role of Central Volume in Low Frequency Oscillations of Heart Rate Variability

The hypothesis that central volume plays a key role in the source of low frequency (LF) oscillations of heart rate variability (HRV) was tested in a population of end stage renal disease patients undergoing conventional hemodialysis (HD) treatment, and thus subject to large fluid shifts and sympathetic activation. Fluid overload (FO) in 58 chronic HD patients was assessed by whole body bioimpedance measurements before the midweek HD session. Heart Rate Variability (HRV) was measured using 24-hour Holter electrocardiogram recordings starting before the same HD treatment. Time domain and frequency domain analyses were performed on HRV signals. Patients were retrospectively classified in three groups according to tertiles of FO normalized to the extracellular water (FO/ECW%). These groups were also compared after stratification by diabetes mellitus. Patients with the low to medium hydration status before the treatment (i.e. 1st and 2nd FO/ECW% tertiles) showed a significant increase in LF power during last 30 min of HD compared to dialysis begin, while no significant change in LF power was seen in the third group (i.e. those with high pre-treatment hydration values). In conclusion, several mechanisms can generate LF oscillations in the cardiovascular system, including baroreflex feedback loops and central oscillators. However, the current results emphasize the role played by the central volume in determining the power of LF oscillations.     

The nature of very low frequency component of the heart rate variability and the role of sympathetic-parasympathetic interactions

A method of separate monitoring "instant" changes of the VLF, LF and HF power spectral components of heart rate variability, has been developed. The power of the LF and HF spectral components were proved to be continuously changing. The period of these power fluctuations could stay within 15 to 150 sec. Comparison of the heart rate variability spectrum with LF and HF spectral components power fluctuations' spectrums has shown that the frequencies of the LF and HF spectral components power fluctuations stay within the VLF range. The co-operative spectrum form of these fluctuations repeats the form of the VLF peak. In cases when the LF and HF spectral components power fluctuations' periods do not coincide, VLF has two peaks. The frequency of one VLF peak coincides with frequency of the HF power fluctuations, and the frequency of another--with the frequency of LF power fluctuations.