Investigation of biophysical features of interaction between 0.1 Hz oscillations in heart rate variability and distal blood flow variability

We studied biophysical features of interaction between 0.1 Hz oscillations in heart rate variability (HRV) and distal blood flow (DBF) variability in healthy subjects and patients after acute myocardial infarction (MI). 125 patients after acute MI (72 male and 53 female) aged between 30 and 83 years and 33 healthy subjects (23 male and 10 female) aged between 20 and 46 years were included in the study. The duration of prospective study of MI patients was one year. We estimated the delay in coupling between 0.1 Hz oscillations in H RV and DBF variability. It is found out that in healthy subjects the delay in coupling from heart rate to DBF is less than delay in coupling from DBF to heart rate. Acute MI results mainly in disruption of coupling from heart rate to DBF. This coupling is partially restored in one year after acute MI, but the delay in coupling remains significantly smaller than in healthy subjects. The features of coupling from DBF to heart rate are restored in MI patients within three weeks after infarction. After this period the delay in this coupling in MI patients is approximately the same as it is in healthy subjects.     

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.     

Mechanisms of Periodic Heart Rate Oscillations: A Study Using Controlled Breathing Tests

An orthostatic test with frequency-controlled breathing (with periods of 4, 6, 8, 10, and 12 s) was used to analyze frequency estimates of the heart rate variability (HRV) spectrum in the low frequency (LF) and high frequency (HF) ranges in 36 volunteers (26 men and 10 women) aged 19–21 years without signs of heart or respiratory pathology. The subjects took a breath at the moment of an auditory signal. There were no other requirements for the respiration rhythm. Variables were compared using Wilcoxon’s test for pairwise comparisons; correlations were estimated by Spearman’s rank correlation R test. The sensitivities of the LF and HF ranges of the HRV spectrum to periodic respiratory perturbations at different frequencies were demonstrated to differ from each other. Autonomous 0.10- and 0.25-Hz circuits of oscillatory processes were found in HRV. The transition zone of influence of these circuits was located in the region around 0.125 Hz. The characteristics of the 0.10- and 0.25-Hz oscillations in HRV were studied. It was demonstrated that the 0.10-Hz oscillatory process is a potent mechanism of heart rate control, is affected by external factors, and determines the dynamics of the autonomic nervous state of the body, while the 0.25-Hz process is a regulatory mechanism of medium strength, is resistant to external factors, and characterizes the adaptation reserve of the autonomic nervous control of the heart rate, as well as the autonomic nervous state of the body. Resonance responses in the HRV spec-trum can be used for studying the characteristics of the 0.10- and 0.25-Hz oscillations.__________Translated from Fiziologiya Cheloveka, Vol. 31, No. 3, 2005, pp. 76–83.Original Russian Text Copyright © 2005 by Kiselev, Kirichuk, Posnenkova, Gridnev.     

Internal synchronization of the main 0.1-Hz rhythms in the autonomic control of the cardiovascular system

Synchronization parameters of 0.1-Hz rhythms isolated from the heart rate and the oscillations of the blood volume in microcirculatory vessels were studied in 12 healthy subjects and 32 patients with acute myocardial infarction. Recordings of the electrocardiogram and the pulsogram from the distal phalanx of the index finger, as well as mechanical recording of respiration with the body in a horizontal position, were performed. In patients with myocardial infarction, the recordings were performed during the first three to five days and the third week after the infarction. Synchronization was tested by plotting phase differences and calculating the total percentage of phase synchronization. Synchronization parameters of 0.1-Hz rhythms were high in healthy subjects. In patients with acute myocardial infarction, synchronization of 0.1-Hz rhythms was considerably poorer. The data obtained suggest that the studied 0.1-Hz rhythms are two independent oscillatory processes that are synchronized in healthy subjects. However, this interaction may be disturbed in cardiovascular pathologies, e.g., myocardial infarction.     

Phase and frequency locking of 0.1-Hz oscillations in heart rate and baroreflex control of blood pressure by breathing of linearly varying frequency as determined in healthy subjects

Functional interaction was studied between the subsystems that ensure autonomic control of the heart rate (HR) and blood pressure (BP) and give rise to 0.1-Hz oscillations in R-R intervals (RRI) and photoplethysmogram (PPG). Twenty-five recordings were obtained from 18- to 32-year-old healthy persons (six women and nineteen men). The RRI and PPG were recorded simultaneously while the respiration rate of a subject in the sitting position increased linearly from 0.05 Hz to 0.25 Hz within 25 min. Phase and frequency locking of 0.1-Hz oscillations by breathing proved to be possible in both RRI and PPG. The intervals of phase and frequency locking of oscillations by respiration differed in duration and relative position. These distinctions suggest that the mechanisms of autonomic 0.1-Hz control of HR and BP are functionally independent.     

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.     

Age dependency and correlation of heart rate variability,blood pressure variability and baroreflex sensitivity

Simultaneous analysis of heart rate variability (HRV), blood pressure variability (BPV) and baroreflex sensitivity (BRS) with different types of measures may provide non-duplicative information about autonomic cardiovascular regulation. Therefore, a multiple signal analysis of cardiovascular time series will enhance the physiological understanding of neuro cardiovascular regulation with deconditioning in bedrest or related gravitational physiological studies. It has been shown that age is an important determinant of HRV and BRS in healthy subjects. Whereas in the case of BPV, the effect of aging seems to depend upon the activity status of the subjects. In view of the facts that most of the previous works were dealing with only the variability of one kind of cardiovascular parameters in one study with conventional time-domain and/or frequency-domain analysis, we therefore designed the present work to compare the HRV, BPV and BRS between young and middle-aged male healthy subjects in one study with the same subjects using various techniques, including the approximate entropy (ApEn) measurement, a statistic quantifying HRV "complexity" derived from non-linear dynamics.     

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.     

Mechanisms of blood pressure and heart rate variability: an insight from low-level paraplegia

It is still unclear whether the low-frequency oscillation in heart rate is generated by an endogenous neural oscillator or by a baroreflex resonance. Our aim was to investigate this issue by analyzing blood pressure and heart rate variability and the baroreflex function in paraplegic subjects with spinal cord injury below the fourth thoracic vertebra. These subjects were selected because they represent a model of intact central neural drive to the heart, with a partially impaired autonomic control of the vessels. In our study, arterial blood pressure and ECG were recorded in 33 able-bodied controls and in 33 subjects with spinal cord lesions between the fifth thoracic and the fourth lumbar vertebra 1) during supine rest (lowest sympathetic activation), 2) sitting on a wheelchair (light sympathetic activation), and 3) during exercise (moderate sympathetic activation). Blood pressure and heart rate spectra, coherence, and baroreflex function (sequence technique) were estimated in each condition. Compared with controls, paraplegic subjects showed a reduction of the low-frequency power of blood pressure and heart rate, and, unlike controls, a 0.1-Hz peak did not appear in their spectra. Sympathetic activation increased the 0.1-Hz peak of blood pressure and heart rate and the coherence at 0.1 Hz in controls only. Paraplegic subjects also had significantly lower baroreflex effectiveness and greater blood pressure variability. In conclusion, the disappearance of the 10-s oscillation of heart rate and blood pressure in subjects with spinal cord lesion supports the hypothesis of the baroreflex nature of this phenomenon.     

Effect of dietary omega-3 fatty acids on the heart rate and the heart rate variability responses to myocardial ischemia or submaximal exercise

The consumption of omega-3 polyunsaturated fatty acids (n-3 PUFAs) has been reported to decrease resting heart rate (HR) and increase heart rate variability (HRV). However, the effects of n-3 PUFAs on these variables in response to a physiological stress (e.g., exercise or acute myocardial ischemia), particularly in postmyocardial infarction (MI) patients, are unknown. Therefore, HR and HRV (high frequency and total R-R interval variability) were evaluated at rest, during submaximal exercise, and during a 2-min coronary artery occlusion at rest and before and 3 mo after n-3 PUFA treatment in dogs with healed MI (n = 59). The dogs were randomly assigned to either placebo (1 g/day corn oil, n = 19) or n-3 PUFA supplement (docosahexaenoic acid + eicosapentaenoic acid ethyl esters; 1 g/day, n = 6; 2 g/day, n = 12; or 4 g/day, n = 22) groups. The treatment elicited significant (P < 0.01) dose-dependent increases in right atrial n-3 PUFA levels but dose-independent reductions in resting HR and increases in resting HRV. In contrast, n-3 PUFAs did not attenuate the large changes in HR or HRV induced by either the coronary occlusion or submaximal exercise. These data demonstrate that dietary n-3 PUFA decreased resting (i.e., preexercise or preocclusion) HR and increased resting HRV but did not alter the cardiac response to physiologic challenges.     

The application of surface plethysmography for heart rate variability analysis after GSM radiofrequency exposure

The aim of the present study was to test whether the electromagnetic field emitted by standard GSM mobile phones results in changes in heart rate (HR) and heart rate variability (HRV) of 35 healthy young male and female subjects. Two parallel signals, electrocardiogram and infrared surface plethysmogram were recorded and compared to test their validity for the analysis. Plethysmographic recording is proved to be a fast and reliable method for HRV measurements. In the radiofrequency (RF) exposure study, there was no significant difference in the values of HR and HRV between the RF and the sham groups. Our preliminary study demonstrates that, in our experimental conditions, RF fields emitted by cellular phones do not cause observable effects on the regulation of heart rate of healthy, young adults.     

Role of genetic and environmental influences on heart rate variability in middle-aged men

Our aim was to estimate causal relationships of genetic factors and different specific environmental factors in determination of the level of cardiac autonomic modulation, i.e., heart rate variability (HRV), in healthy male twins and male twins with chronic diseases. The subjects were 208 monozygotic (MZ, 104 healthy) and 296 dizygotic (DZ, 173 healthy) male twins. A structured interview was used to obtain data on lifetime exposures of occupational loading, regularly performed leisure-time sport activities, coffee consumption, smoking history, and chronic diseases from 12 yr of age through the present. A 5-min ECG at supine rest was recorded for the HRV analyses. In univariate statistical analyses based on genetic models with additive genetic, dominance genetic, and unique environmental effects, genetic effects accounted for 31-57% of HRV variance. In multivariate statistical analysis, body mass index, percent body fat, coffee consumption, smoking, medication, and chronic diseases were associated with different HRV variables, accounting for 1-11% of their variance. Occupational physical loading and leisure-time sport activities did not account for variation in any HRV variable. However, in the subgroup analysis of healthy and diseased twins, occupational loading explained 4% of the variability in heart periods. Otherwise, the interaction between health status and genetic effects was significant for only two HRV variables. In conclusion, genetic factors accounted for a major portion of the interindividual differences in HRV, with no remarkable effect of health status. No single behavioral determinant appeared to have a major influence on HRV. The effects of medication and diseases may mask the minimal effect of occupational loading on HRV.     

Mathematical model of heart rate variability

The study presents a mathematical model of non-linear dynamics of the heart rate variability (HRV). The model is based on quantitative characteristics of pulse conduction in the heart conducting system: the delays of sinoatrial (SA) and atrioventricular (AV) pulse conduction and refractors periods of the SA and AV nodes. The model predicts heart rate disturbances in fast electric activity of the atria, increase in the delay of the AV conduction, the critical value of atrial period where transition to non-linear dynamics of the heart rate variability starts. The correlation between indexes of HRV and period of stimulation of atria for 1-contour cardiac control model has been demonstrated.     

Multivariate and multiorgan analysis of cardiorespiratory variability signals: the CAP sleep case.

Signals from different systems are analyzed during sleep on a beat-to-beat basis to provide a quantitative measure of synchronization with the heart rate variability (HRV) signal, oscillations of which reflect the action of the autonomic nervous system. Beat-to-beat variability signals synchronized to QRS occurrence on ECG signals were extracted from respiration, electroencephalogram (EEG) and electromyogram (EMG) traces. The analysis was restricted to sleep stage 2. Cyclic alternating pattern (CAP) periods were detected from EEG signals and the following conditions were identified: stage 2 non-CAP (2 NCAP), stage 2 CAP (2 CAP) and stage 2 CAP with myoclonus (2 CAP MC). The coupling relationships between pairs of variability signals were studied in both the time and frequency domains. Passing from 2 NCAP to 2 CAP, sympathetic activation is indicated by tachycardia and reduced respiratory arrhythmia in the heart rate signal. At the same time, we observed a marked link between EEG and HRV at the CAP frequency. During 2 CAP MC, the increased synchronization involved myoclonus and respiration. The underlying mechanism seems to be related to a global control system at the central level that involves the different systems.     

Heart rate variability in women exposed to very cold air (−110 °C) during whole-body cryotherapy

Heart rate monitoring was used to measure heart rate variability (HRV) at thermoneutral conditions (Ta 24 °C) in healthy women resting in supine position before and after acute and after repeated (3 times a week during a 3-month period) whole-body cryotherapies (WBC), at −110 °C. The observed acute cooling-related increase in high frequency power (HFP) of RR-intervals indicates an increase in cardiac parasympathetic modulation. After 3 months of repeated WBC the increase in parasympathetic tone was attenuated, which may be interpreted as an adaptation of autonomic function. The repeated WBC exposures-related increase in resting low frequency power (LFP) of RR-intervals during the 3 months resembles the response observed related to exercise training.     

Low to high frequency ratio of heart rate variability spectra fails to describe sympatho-vagal balance in cardiac patients

Heart rate variability (HRV) reflects an influence of autonomic nervous system on heart work. In healthy subjects, ratio between low and high frequency components (LF/HF ratio) of HRV spectra represents a measure of sympatho-vagal balance. The ratio was defined by the authorities as an useful clinical tool, but it seems that it fails to summarise sympatho-vagal balance in a clinical setting. Value of the method was re-evaluated in several categories of cardiac patients. HRV was analysed from 24-hour Holter ECGs in 132 healthy subjects, and 2159 cardiac patients dichotomised by gender, median of age, diagnosis of myocardial infarction or coronary artery surgery, left ventricular systolic function and divided by overall HRV into several categories. In healthy subjects, LF/HF ratio correlated with overall HRV negatively, as expected. The paradoxical finding was obtained in cardiac patients; the lower the overall HRV and the time-domain indices of vagal modulation activity were the lower the LF/HF ratio was. If used as a measure of sympatho-vagal balance, long-term recordings of LF/HF ratio contradict to clinical finding and time-domain HRV indices in cardiac patients. The ratio cannot therefore be used as a reliable marker of autonomic activity in a clinical setting.     

Transfer function analysis of heart rate variability in response to water intake: correlation with gastric myoelectrical activity.

We utilized transfer function analysis of heart rate variability (HRV) and respiration to investigate the effect of water intake on gastric myoelectrical activity and its relationship to vagal activity. The electrogastrography (EGG) and HRV were recorded simultaneously before and after drinking 500 ml of water in 10 healthy subjects. We observed good linearity between lung volumes and HRV signals at a ventilatory rate between 0.2 and 0.4 Hz before and after water intake. The EGG power of 3 cycles/min increased remarkably after the water intake. We found that there was a significant increase in the magnitude of the respiration-HRV transfer function after water intake (P < 0.05). The EGG 3 cycles/min power was positively correlated with the transfer magnitude throughout the study (r = 0.54, P = 0.01). These results confirm that transfer function analysis of HRV sensitively identifies subtle changes in the respiratory sinus arrhythmia that occurs with water intake. The present findings suggest that transfer function analysis of HRV and respiration after water intake can be used to evaluate vagal nervous activity in the human gut.     

Decreased fractal component of human heart rate variability during non-REM sleep

The physiological significance of the fractal component of short-term, spontaneous heart rate variability (HRV) in humans remains unclear. The aim of the present study was to gain further information about the respective fractal components by extracting them from HRV, blood pressure variability (BPV), and instantaneous lung volume (ILV) time series via coarse graining spectral analysis in nine healthy subjects during waking and sleep states. The results show that the contribution made by the fractal component to the total variance in the beat-to-beat R-R interval declined significantly as the depth of non-rapid eye movement (non-REM) sleep increased, that the ILV time series was largely periodic (i.e., nonfractal), and that BPV was unaffected by sleep stage. Finally, the fractal component of HRV during REM sleep was found to be quite similar to that seen during waking. These results suggest that mechanisms involving electroencephalographic desynchronization and/or conscious states of the brain are reflected in the fractal component of HRV.     

Heart rate variability biofeedback as a method for assessing baroreflex function: a preliminary study of resonance in the cardiovascular system

This study describes the use of a biofeedback method for the noninvasive study of baroreflex mechanisms. Five previously untrained healthy male participants learned to control oscillations in heart rate using biofeedback training to modify their heart rate variability at specific frequencies. They were instructed to match computer-generated sinusoidal oscillations with oscillations in heart rate at seven frequencies within the range of 0.01–0.14 Hz. All participants successfully produced high-amplitude target-frequency oscillations in both heart rate and blood pressure. Stable and predictable transfer functions between heart rate and blood pressure were obtained in all participants. The highest oscillation amplitudes were produced in the range of 0.055–0.11 Hz for heart rate and 0.02–0.055 Hz for blood pressure. Transfer functions were calculated among sinusoidal oscillations in the target stimuli, heart rate, blood pressure, and respiration for frequencies at which subjects received training. High and low target-frequency oscillation amplitudes at specific frequencies could be explained by resonance among various oscillatory processes in the cardiovascular system. The exact resonant frequencies differed among individuals. Changes in heart rate oscillations could not be completely explained by changes in breathing. The biofeedback method also allowed us to quantity characteristics of inertia, delay, and speed sensitivity in baroreflex system. We discuss the implications of these findings for using heart rate variability biofeedback as an aid in diagnosing various autonomic and cardiovascular system disorders and as a method for treating these disorders.     

Heart rate variability as a marker of cardiovascular dysautonomia in post-COVID-19 syndrome using artificial intelligence

IntroductionCardiovascular dysautonomia comprising postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH) is one of the presentations in COVID-19 recovered subjects. We aim to determine the prevalence of cardiovascular dysautonomia in post COVID-19 patients and to evaluate an Artificial Intelligence (AI) model to identify time domain heart rate variability (HRV) measures most suitable for short term ECG in these subjects.MethodsThis observational study enrolled 92 recently COVID-19 recovered subjects who underwent measurement of heart rate and blood pressure response to standing up from supine position and a 12-lead ECG recording for 60 s period during supine paced breathing. Using feature extraction, ECG features including those of HRV (RMSSD and SDNN) were obtained. An AI model was constructed with ShAP AI interpretability to determine time domain HRV features representing post COVID-19 recovered state. In addition, 120 healthy volunteers were enrolled as controls.ResultsCardiovascular dysautonomia was present in 15.21% (OH:13.04%; POTS:2.17%). Patients with OH had significantly lower HRV and higher inflammatory markers. HRV (RMSSD) was significantly lower in post COVID-19 patients compared to healthy controls (13.9 ± 11.8 ms vs 19.9 ± 19.5 ms; P = 0.01) with inverse correlation between HRV and inflammatory markers. Multiple perceptron was best performing AI model with HRV(RMSSD) being the top time domain HRV feature distinguishing between COVID-19 recovered patients and healthy controls.ConclusionPresent study showed that cardiovascular dysautonomia is common in COVID-19 recovered subjects with a significantly lower HRV compared to healthy controls. The AI model was able to distinguish between COVID-19 recovered patients and healthy controls.