Cardiovascular Variability Analysis and Baroreflex Estimation in Patients with Type 2 Diabetes in Absence of Any Manifest Neuropathy

Introduction

Indexes derived from spontaneous heart period (HP) and systolic arterial pressure (SAP) fluctuations can detect autonomic dysfunction in individuals with type 2 diabetes mellitus (DM) associated to cardiovascular autonomic neuropathy (CAN) or other neuropathies. It is unknown whether HP and SAP variability indexes are sensitive enough to detect the autonomic dysfunction in DM patients without CAN and other neuropathies.

Methods

We evaluated 68 males aged between 40 and 65 years. The group was composed by DM type 2 DM with no manifest neuropathy (n = 34) and healthy (H) subjects (n = 34). The protocol consisted of 15 minutes of recording of HP and SAP variabilities at rest in supine position (REST) and after active standing (STAND). The HP power in the high frequency band (HF, from 0.15 to 0.5 Hz), the SAP power in the low frequency band (LF, from 0.04 to 0.15 Hz) and BRS estimated via spectral approach and sequence method were computed.

Results

The HF power of HP was lower in DM patients than in H subjects, while the two groups exhibited comparable HF power of HP during STAND. The LF power of SAP was similar in DM and H groups at REST and increased during STAND in both groups. BRSs estimated in the HF band and via baroreflex sequence method were lower in DM than in H and they decreased further during STAND in both populations.

Conclusion

Results suggest that vagal control of heart rate and cardiac baroreflex control was impaired in type 2 DM, while sympathetic control directed to vessels, sympathetic and baroreflex response to STAND were preserved. Cardiovascular variability indexes are sensitive enough to typify the early, peculiar signs of autonomic dysfunction in type-2 DM patients well before CAN becomes manifest.     

Characteristics of autonomic nervous function in Zucker-fatty rats: investigation by power spectral analysis of heart rate variability.

We investigated the characteristics of autonomic nervous function in Zucker-fatty and Zucker-lean rats. For this purpose, a long-term electrocardiogram (ECG) was recorded from conscious and unrestrained rats using a telemetry system, and the autonomic nervous function was investigated by power spectral analysis of heart rate variability (HRV). Although heart rate (HR) in Zucker-fatty rats was lower than that in Zucker-lean rats throughout 24 h, apparent diurnal variation in HR was observed in both strains and HR during the dark period was significantly higher than that in light period. Diurnal variation in locomotor activity (LA) in Zucker-fatty rats was also observed, but LA was lower than that in Zucker lean rats, especially during the dark period. There were no significant differences, however, in high-frequency (HF) power, low-frequency (LF) power, and the LF/HF ratio between Zucker-fatty and Zucker-lean rats. The circadian rhythm of these parameters was mostly preserved in both strains of rats. Moreover, the effect of autonomic blockades on HRV was nearly the same in Zucker-fatty and Zucker-lean rats. These results suggest that the autonomic nervous function of insulin-resistant Zucker-fatty rats remain normal, from the aspect of power spectral analysis of HRV.     

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.     

Spectral analysis of heart rate variability in the beluga (<Emphasis Type="Italic">Delphinapterus leucas</Emphasis>) during exposure to acoustic noise

The spectral parameters of heart rate variability are a measure of activation of the sympathetic and parasympathetic branches of the mammalian autonomic nervous system. In this study, spectral analysis was used for the first time to evaluate the impact of acoustic noise (one of the major anthropogenic factors) on a cetacean. We analyzed cardiac intervals in a captive beluga (a member of the Odontoceti whales) in response to a 10-min band-pass acoustic noise at an intensity of 150–165 dB and frequency of 19–38 kHz. The beluga’s response to acoustic noise, when examined shortly after the animal’s capture, was characterized by a sharp tachycardia (the first phase) followed by a decrease in the heart rate (the second phase). Based on spectral analysis, the frequency range of heart rate oscillations in the beluga decreased during the period of tachycardia while shifting to a lower frequency range (below 0.01 Hz) as compared with the control conditions. Accordingly, the spectral power of low-frequency components was reduced. During the second phase, the range of heart rate variability oscillations expanded and fully recovered only after the noise had been turned off. After one year in captivity, no significant changes in the heart rate parameters (both in time and frequency domain) were recorded in response to a similar noise exposure. Therefore, the changes in the heart rate spectral components in the studied beluga exposed to acoustic noise were comparable to those recorded in terrestrial mammals and in humans in stressful and emotionally negative situations. The spectral characteristics of heart rate oscillations can be used as a quantitative measure of beluga whales’ response to acoustic noise as a stress factor.     

Effects of psychological stress on autonomic control of heart in rats.

The aim of this study was to examine the effects of psychological stress on autonomic control of the heart in rats. For this purpose, we evoked anxiety-like or fear-like states in rats by means of classical conditioning and examined changes in autonomic nervous activity using an implanted telemetry system and power spectral analysis of heart rate variability. Anxiety-like states resulted in a significant increase in heart rate (HR), low frequency (LF) power, and LF/HF ratio, with no change in high frequency (HF) power. Fear-like states resulted in a significant increase in HR and a significant decrease in HF power with no significant change in both LF power and LF/HF ratio, although LF/HF ratio increased slightly. These results suggest that autonomic balance becomes predominant in sympathetic nervous activity in both anxiety-like and fear-like states. These changes in rats correspond to changes which are relevant to cardiovascular diseases in humans under many kinds of psychological stress. Therefore, the experimental design of this study is a useful experimental model for investigating the effects of psychological stress on autonomic control of the heart in humans.     

Optimal frequency ranges for extracting information on cardiovascular autonomic control from the blood pressure and pulse interval spectrograms in mice

The analysis of blood pressure (BP) and heart rate (HR) variability by spectral methods has proven a useful tool in many animal species for the assessment of the vagal and sympathetic contributions to oscillations of BP and HR. Continuous BP measurements obtained in mice by telemetry were used to characterize the spectral bandwidths of autonomic relevance by using an approach with no a priori. The paradigm was based on the autonomic blockades obtained with conventional drugs (atropine, prazosin, atenolol). The spectral changes were estimated in all of the combinations of spectral bandwidths. The effect of hydralazine was also tested using the same systematic analysis, to detect the zones of sympathetic activation resulting reflexly from the vasodilatory action of the drug. Two zones of interest in the study of the autonomic control of BP and HR were observed. The first zone covered the 0.15-0.60 Hz range of the systolic BP spectrum and corresponds to the low-frequency zone (or Mayer waves). This zone reflects sympathetic control since the power spectral density of this zone was significantly reduced with alpha1-adrenoceptor blockade (prazosin), while it was significantly amplified as a result of a reflex sympathetic activation (hydralazine). The second zone covered the 2.5-5.0 Hz range of the pulse interval spectrum and corresponded to the high-frequency zone (respiratory sinus arrhythmia) under vagal control (blocked by atropine). These zones are recommended for testing the autonomic control of circulation in mice.     

A new algorithm for wavelet-based heart rate variability analysis

One of the most promising non-invasive markers of the activity of the autonomic nervous system is heart rate variability (HRV). HRV analysis toolkits often provide spectral analysis techniques using the Fourier transform, which assumes that the heart rate series is stationary. To overcome this issue, the Short Time Fourier Transform (STFT) is often used. However, the wavelet transform is thought to be a more suitable tool for analyzing non-stationary signals than the STFT. Given the lack of support for wavelet-based analysis in HRV toolkits, such analysis must be implemented by the researcher. This has made this technique underutilized.This paper presents a new algorithm to perform HRV power spectrum analysis based on the Maximal Overlap Discrete Wavelet Packet Transform (MODWPT). The algorithm calculates the power in any spectral band with a given tolerance for the band's boundaries. The MODWPT decomposition tree is pruned to avoid calculating unnecessary wavelet coefficients, thereby optimizing execution time. The center of energy shift correction is applied to achieve optimum alignment of the wavelet coefficients. This algorithm has been implemented in RHRV, an open-source package for HRV analysis. To the best of our knowledge, RHRV is the first HRV toolkit with support for wavelet-based spectral analysis.     

Cardiovascular autonomic function correlates with the response to aerobic training in healthy sedentary subjects

Individual responses to aerobic training vary from almost none to a 40% increase in aerobic fitness in sedentary subjects. The reasons for these differences in the training response are not well known. We hypothesized that baseline cardiovascular autonomic function may influence the training response. The study population included sedentary male subjects (n = 39, 35 +/- 9 yr). The training period was 8 wk, including 6 sessions/wk at an intensity of 70-80% of the maximum heart rate for 30-60 min/session. Cardiovascular autonomic function was assessed by measuring the power spectral indexes of heart rate variability from 24-h R-R interval recordings before the training period. Mean peak O2 uptake increased by 11 +/- 5% during the training period (range 2-19%). The training response correlated with age (r = -0.39, P = 0.007) and with the values of the high-frequency (HF) spectral component of R-R intervals (HF power) analyzed over the 24-h recording (r = 0.46, P = 0.002) or separately during the daytime hours (r = 0.35, P = 0.028) and most strongly during the nighttime hours (r = 0.52, P = 0.001). After adjustment for age, HF power was still associated with the training response (e.g., P = 0.001 analyzed during nighttime hours). These data show that cardiovascular autonomic function is an important determinant of the response to aerobic training among sedentary men. High vagal activity at baseline is associated with the improvement in aerobic power caused by aerobic exercise training in healthy sedentary subjects.     

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.     

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.     

Coarse-graining spectral analysis: new method for studying heart rate variability.

Heart rate variability (HRV) spectra are typically analyzed for the components related to low- (less than 0.15 Hz) and high- (greater than 0.15 Hz) frequency variations. However, there are very-low-frequency components with periods up to hours in HRV signals, which might smear short-term spectra. We developed a method of spectral analysis suitable for selectively extracting very-low-frequency components, leaving intact the low- and high-frequency components of interest in HRV spectral analysis. Computer simulations showed that those low-frequency components were well characterized by fractional Brownian motions (FBMs). If the scale invariant, or self-similar, property of FBMs is considered a new time series (x') was constructed by sampling only every other point (course graining) of the original time series (x). Evaluation of the cross-power spectra between these two (Sxx') showed that the power of the FBM components was preserved, whereas that of the harmonic components vanished. Subtraction of magnitude of Sxx from the autopower spectra of the original sequence emphasized only the harmonic components. Application of this method to HRV spectral analyses indicated that it might enable one to observe more clearly the low- and high-frequency components characteristic of autonomic control of heart rate.     

Assessment of spectral analysis of heart rate variability in patients with history of atrial fibrillation by means of age-dependent parameters

Heart rate variability evaluation is a useful diagnostic tool for autonomic nervous balance assessment. The role of the autonomic nervous system in aetiology of atrial fibrillation is sometimes clear as a trigger from a patient's history, but mostly it acts as a modulating factor which is not easy to detect. The present study demonstrates results of spectral analysis of short-term heart rate variability during ortho-clinostatic tests processed by means of age-dependent parameters. An original telemetric system and a unique method for heart rate variability assessment, developed by the Faculty of Physical Culture, were applied for the first time to examine patients with the history of atrial fibrillation.     

Autonomic Activity Assessed by Heart Rate Spectral Analysis Varies with Fat Distribution in Obese Women

Obesity in humans has been associated with altered autonomic nervous system activity. The objective of this study was to examine the relationship between autonomic function and body fat distribution in 16 obese, postmenopausal women using power spectrum analysis of heart rate variability. Using this technique, a low frequency peak (0.04-0.12 Hz) reflecting mixed sympathetic and parasympathetic activity, and a high frequency peak (0.22-0.28 Hz) reflecting parasympathetic activity, were identified from 5-minute consecutive heart rate data (both supine and standing). Autonomic activity in upper body (UBO) vs. lower body obesity (LBO)(by waist-to-hip ratio) and subcutaneous vs. visceral obesity (by CT scan) was evaluated. Power spectrum data were log transformed to normalize the data. The results showed that standing, low-frequency power (reflecting sympathetic activity) and supine, high-frequency power (reflecting parasympathetic activity) were significantly greater in UBO than in LBO, and in visceral compared to subcutaneous obesity. Women with combined UBO and visceral obesity had significantly higher cardiac sympathetic and parasympathetic activity than any other subgroup. We conclude that cardiac autonomic function as assessed by heart rate spectral analysis varies in women depending on their regional body fat distribution.     

Causal relationships between heart period and systolic arterial pressure during graded head-up tilt

In physiological conditions, heart period (HP) affects systolic arterial pressure (SAP) through diastolic runoff and Starling's law, but, the reverse relation also holds as a result of the continuous action of baroreflex control. The prevailing mechanism sets the dominant temporal direction in the HP-SAP interactions (i.e., causality). We exploited cross-conditional entropy to assess HP-SAP causality. A traditional approach based on phases was applied for comparison. The ability of the approach to detect the lack of causal link from SAP to HP was assessed on 8 short-term (STHT) and 11 long-term heart transplant (LTHT) recipients (i.e., less than and more than 2 yr after transplantation, respectively). In addition, spontaneous HP and SAP variabilities were extracted from 17 healthy humans (ages 21-36 yr, median age 29 yr; 9 females) at rest and during graded head-up tilt. The tilt table inclinations ranged from 15 to 75° and were changed in steps of 15°. All subjects underwent recordings at every step in random order. The approach detected the lack of causal relation from SAP to HP in STHT recipients and the gradual restoration of the causal link from SAP to HP with time after transplantation in the LTHT recipients. The head-up tilt protocol induced the progressive shift from the prevalent causal direction from HP to SAP to the reverse causality (i.e., from SAP to HP) with tilt table inclination in healthy subjects. Transformation of phases into time shifts and comparison with baroreflex latency supported this conclusion. The proposed approach is highly efficient because it does not require the knowledge of baroreflex latency. The dependence of causality on tilt table inclination suggests that "spontaneous" baroreflex sensitivity estimated using noncausal methods (e.g., spectral and cross-spectral approaches) is more reliable at the highest tilt table inclinations.     

Relationship Between Respiratory Sinus Arrhythmia, Heart Period, and Caregiver-Reported Language and Cognitive Delays in Children with Autism Spectrum Disorders

The present study examines the relationship between autonomic activity and cognitive/language delays in children with autism spectrum disorder (ASD). Baseline levels of respiratory sinus arrhythmia (RSA) and heart period (HP) were assessed in 23 4–7-year old children diagnosed with ASD. The relationship between RSA, HP, and ASD behavioral symptoms was examined. Similar to prior studies on typically developing children, lower basal RSA was related to more caregiver-reported language and cognitive delays, and to the lack of language.     

有氧锻炼对心脏自主神经调节的影响：心率变异性分析结果

为阐明有氧锻炼对心脏自主神经调节功能的影响,以及这种变化与卧位／坐位下体负压（ＬＢＮＰ）作用下的心率调节及立位耐力之间是否有一定联系,用频域、动态谱及非线性指标较全面分析了大学生有氧锻炼６个月前、后心率变异性（ＨＲＶ）的变化。结果表明：常规ＡＲ谱分析的批处理结果只能代表一段时间内ＨＲＶ信号的平均统计特性,方差大,得不出有显著意义的结果。而时变ＡＲ谱则可反映ＬＢＮＰ作用下心迷走撤除及交感激活的动态过程。非线性的β估计得不出有显著意义的结果;但ＡｐＥｎ分析则可敏感地检测出有氧锻炼关联的心率动力学细微变化,且初步揭示ΔＡｐＥｎ与立位耐力变化（ΔＤＮＰ）间显著相关。以上对阐明有氧锻炼对心率动力学调节的影响以及改进ＨＲＶ信号分析工作均有一定意义。     

Heart rate variability signal processing: A quantitative approach as an aid to diagnosis in cardiovascular pathologies

The heart rate variability (HRV) signal carries important information about the systems controlling heat rate and blood pressure, mainly elicited by autonomic nervous system (sympathetic and parasympathetic) controls. The present paper illustrates methods of HRV signal processing by using autoregressive (AR) modeling and power spectral density estimate. The information enhanced in this way seems to be particularly sensitive in discriminating various cardiovascular pathologies (hypertension, myocardial infarction, diabetic neuropathy, etc.). This method provides a simple non-invasive analysis, based on the processing of spontaneous oscillations in heart rate. Particular emphasis is directed to the algorithms used and to their direct application by using proper computerized techniques: only a few paradigmatical examples will be illustrated as preliminary results.     

Capsaicin increases modulation of sympathetic nerve activity in rats: measurement using power spectral analysis of heart rate fluctuations

We assessed the sympatho-vagal activities of the heart after administration of capsaicin by measuring the power spectral analysis in rats. There were major two frequency components of heart rate variability, which we defined as high (1.0 Hz <, HF) and low (LF, < 1.0 Hz) frequency components. Vagal blockade by atropine abolished the high frequency component, and lowered the amplitude of the low frequency component. On the other hand, under conditions of sympathetic blockade by propranolol, the low frequency component was reduced. Combined vagal and sympathetic blockade abolished all heart rate fluctuations. We analyzed the low and high frequency components by integrating the spectrum for the respective band width. The rats administered capsaicin had a higher heart rate and sympathetic nervous system index (LF/HF) than the control group of rats. These results suggest that power spectral analysis is an effective and noninvasive method for detecting subtle changes in autonomic activity in response to the intake of foods or drugs.     

Statin therapy restores sympathovagal balance in experimental heart failure.

Inhibitors of hydroxymethylglutaryl-CoA reductase or statins have been shown to alleviate endothelial dysfunction. Their effects on constitutive nitric oxide synthase in the central nervous system may hypothetically affect the autonomic balance in sympathoexcitatory states, such as chronic heart failure (CHF). To address this issue, simvastatin (SIM) (0.3, 1.5, or 3 mg. kg-1. day-1 po) was given to rabbits with pacing-induced CHF over a 3-wk period. Normal and CHF vehicle-treated rabbits served as controls. Autonomic balance was assessed by measuring heart rate variability, including power spectral analysis (PSA). In addition, changes in resting heart rate were assessed before and after vagal and sympathetic autonomic blockade by atropine and metoprolol, respectively. The SD for all intervals was 8.9 +/- 0.7 ms in normal, 4.9 +/- 0.6 ms in CHF (P < 0.01), 3.8 +/- 0.6 ms in CHF with 0.3 mg. kg-1. day-1 SIM (P < 0.001), 5.7 +/- 0.9 in CHF with 1.5 mg. kg-1. day-1 SIM (P < 0.05), and 7.2 +/- 0.5 in CHF with 3.0 mg. kg-1. day-1 SIM. Similarly, total power was 40.5 +/- 6.3 ms2 in normal, 10.1 +/- 3.0 ms2 in CHF (P < 0.01), 6.0 +/- 1.6 ms2 in CHF with 0.3 mg. kg-1. day-1 SIM (P < 0.01), 13.2 +/- 3.9 ms2 in CHF with 1.5 mg. kg-1. day-1 SIM (P < 0.05), and 22.0 +/- 3.0 ms2 in CHF with 3.0 mg. kg-1. day-1 SIM. Both PSA data for low (0.625-0.1875 Hz) and high frequencies (0.1875-0.5625 Hz) showed recovery in CHF animals on medium and high SIM doses without changes in the low-to-high-frequency ratio. SIM beneficially affects autonomic tone in CHF as seen by the reversal of depressed HRV and total power of PSA. These data have important implications for the treatment of patients with autonomic imbalance.