Changes In Heart Period Research Articles

Probing the arterial baroreflex: is there a ‘spontaneous’ baroreflex?

The arterial baroreflex is important for beat-to-beat arterial pressure control and its sensitivity has predictive value for clinical outcomes in a myriad of cardiovascular conditions. Given this, researchers have sought approaches for baroreflex assessment that are not invasive and easily obtained. These techniques have exploited the beat-by-beat parallel changes in arterial pressure and heart period to produce estimates that have been termed 'spontaneous' baroreflex indices. The two most commonly used analyses--frequency domain or spectral analyses and sequence analysis have been evaluated in both animals and humans. The animal data suggests an important baroreflex role in linking spontaneous heart period and pressure variabilities, but do not resolve the extent to which these fluctuations reflect baroreflex gain. The human data suggest a high correlation between spontaneous indices and pharmacologically derived baroreflex gain, but also indicate a poor correspondence between them. This may be due to the fact that short-term fluctuations in RR interval are not intimately and always linked to those in pressure via the baroreflex and thus simple observation of arterial pressure and heart period alone may not reveal the extent of arterial baroreflex involvement. If baroreflex function is to be assessed with the fewest and safest assumptions, the input to the system should be driven externally to create large and apparent responses. Nonetheless, spontaneous baroreflex indices may have predictive power; although it remains unknown whether spontaneous indices provide predictive power beyond that provided by heart rate variability indices alone.

Differential evaluation of the baroreceptor cardiac reflex effectiveness as a function of sequence length

Recently a new index of baroreceptor cardiac function has been proposed, the baroreflex effectiveness index (BEI). BEI was defined as the ratio between the number of systolic blood pressure (SBP) ramps (progressive beat-to-beat increases (“up”) or decreases (“down”)) followed by reflex changes in heart period and the total number of SBP ramps. In this study we tested BEI as a function of the length of cardiac sequences in which the reflex operates (3, 4, 5, and 6 beats) in human subjects in the laboratory. Results show an overall BEI of .65, with greater values for the “up” (.69) than for the “down” sequences (.62). These values are much higher than previously reported. When analyzed as a function of sequence length, BEI increases as sequence length decreases. This difference is more progressively observed in the “up” than in the “down” sequences. Both slope and overall blood pressure change of the SBP ramps increase as sequence length increases. Overall blood pressure change of the SBP ramps can predict BEI for the 4- ( r 2 ≈ .057) and 3-beat sequences ( r 2 ≈ .20). These results suggest the need to examine the effects of the setting/experimental manipulation on the average length of cardiac sequences, given that an observed change in BEI could be genuine or simply associated with a modification in the pattern of sequence length.

Paradoxical respiratory sinus arrhythmia in the anesthetized rat

This study examines respiratory sinus arrhythmia (RSA) in the isoflurane-anesthetized rat. In fifteen female Sprague–Dawley rats, we recorded continuous ECG and respiratory airflow before and after bilateral vagotomy. RSA was assessed using power spectral analysis and by plotting the normalised changes in heart period as a function of the time during the respiratory cycle. Contrary to descriptions of RSA in conscious rats, we observed in all rats in the current study a ‘reversed’ pattern of RSA in which heart rate decelerated during inspiration. Elimination of vagal efferent fibres to the heart by vagotomy did not abolish the presence of reversed RSA suggesting that the pattern of heart period variation is not neural, and may be largely mechanical. Vagotomy altered breathing by increasing respiratory period, tidal volume, and the time to peak inspiratory flow. These changes did not alter the magnitude of RSA but reduced the latency period between inspiratory onset and the onset of respiratory related prolongation of heart period. Periods of positive pressure ventilation were associated with reversal of the inspiratory cardiac-deceleration pattern of RSA to resemble the more widely described pattern of inspiratory cardiac-acceleration. We conclude that RSA is not a suitable measure of vagal tone during anesthesia in the rat and reiterate the caution that needs to be taken when working with anesthetized experimental models of cardiac control.

Dissection of long-range heart rate variability: Controlled induction of prognostic measures by activity in the laboratory

ObjectivesWe sought to determine whether the long-range measures of heart rate variability (HRV)—the standard deviation of sequential 5-min heart period mean values (SDANN) and the heart period spectral amplitude in the ultra-low frequency band <0.0033 Hz (ULF)—had their origins partly in physical activity. BackgroundThe SDANN and ULF are prognostic HRV factors whose physiologic origins are obscure. Their discontinuous presence throughout the day suggested that they arise from changes in heart period due to activity. MethodsHeart period sequences were recorded from 14 patients with left ventricular dysfunction and 14 control subjects during an unrestricted 24-h day, 4-h supine rest, and 4-h epoch with scripted activities. ResultsThe SDANN was higher during activity than during rest (74 ± 23 ms vs. 43 ± 17 ms, p < 0.0001), as were ULF magnitudes (p < 0.0001). The increase in SDANN was due to specific activities that contributed heavily (p < 0.0001 by analysis of variance); for example, a 10-min walk and 90-min rest each contributed 22% of total SDANN. Patients with heart disease had a lower SDANN and ULF and a higher mean heart rate than control subjects during all recordings. The proportional ranges in heart period were the same in the two groups during controlled, scripted activities but were wider in control subjects than in patients during ambulatory recordings, suggesting decreased activity by patients. ConclusionsActivity increases SDANN by increasing the range of heart periods. Patients with diminished ventricular function have a reduced SDANN on ambulatory electrocardiograms, possibly and partly because of a higher mean heart rate and reduced variations in physical activity.

Logit50: A nonlinear transformation of pNN50 with improved statistical properties

The traditional time domain heart rate variability index pNN50 is a percentage scale-based measure of large beat-to-beat changes in heart period that may reflect parasympathetic neural activity impinging on the sino-atrial node. However, pNN50 exhibits nonlinear saturation effects near 0% and 100% that may adversely affect its statistical properties. The purpose of this paper is to propose a revision of pNN50, Logit50, that is the natural logarithm of the odds of the occurrence of large beat-to-beat differences in R-R interval. Using five clinical and normal sample data sets, the revised Logit50 index is shown to retain the computational simplicity and interpretability of the pNN50, but to have better metric properties in statistical and clinical applications. In particular, the Logit50 is demonstrated to be relatively unaffected by the positive distributional skew that is common in most statistical applications of pNN50.

Entropy, entropy rate, and pattern classification as tools to typify complexity in short heart period variability series.

An integrated approach to the complexity analysis of short heart period variability series (approximately 300 cardiac beats) is proposed and applied to healthy subjects during the sympathetic activation induced by head-up tilt and during the driving action produced by controlled respiration (10, 15, and 20 breaths/min, CR10, CR15, and CR20 respectively). The approach relies on: 1) the calculation of Shannon entropy (SE) of the distribution of patterns lasting three beats; 2) the calculation of a regularity index based on an entropy rate (i.e., the conditional entropy); 3) the classification of frequent deterministic patterns (FDPs) lasting three beats. A redundancy reduction criterion is proposed to group FDPs in four categories according to the number and type or of heart period changes: a) no variation (0V); b) one variation (1V); and c) two like variations (2LV); 4) two unlike variations (2UV). We found that: 1) the SE decreased during tilt due to the increased percentage of missing patterns; 2) the regularity index increased during tilt and CR10 as patterns followed each other according to a more repetitive scheme; and 3) during CR10, SE and regularity index were not redundant as the regularity index significantly decreased while SE remained unchanged. Concerning pattern analysis we found that: a) at rest mainly three classes (0V, 1V, and 2LV) were detected; b) 0V patterns were more likely during tilt; c) 1V and 2LV patterns were more frequent during CR10; and d) 2UV patterns were more likely during CR20. The proposed approach based on quantification of complexity allows a full characterization of heart period dynamics and the identification of experimental conditions known to differently perturb cardiovascular regulation.

Baroreflex sensitivity in the elderly: influence of age, breathing and spectral methods

Baroreflex sensitivity (BRS) has been proposed as a diagnostic parameter for neurological disorders and as a survival-prognosis parameter in diabetic and cardiac patients. Therefore reference values and the reproducibility of BRS were assessed, taking into account the possible influence of age, gender, test conditions and some analysis variants. Healthy subjects (n=191) were randomly selected from the 50-75-year-old general population (the Hoorn Study). Variations in blood pressure and heart rate were recorded non-invasively during three breathing modes: spontaneous (3 min), slow metronome (1 min; 6 breaths/min=0.1 Hz) and fast metronome (1 min; 15 breaths/min=0.25 Hz), all in a supine position. From these recordings, BRS was assessed as the transfer gain between changes in blood pressure and heart period, and as the alpha coefficient. BRS values ranged from 5.0 to 8.9 ms.mmHg(-1). Slow metronome breathing resulted in higher BRS values than fast breathing, while during spontaneous breathing BRS in the low-frequency band was lower than that in the high-frequency band (respiratory origin). BRS values decreased with lower coherence criteria. BRS-alpha was significantly higher than BRS-gain. While regression analysis showed no gender differences, BRS decreased with age. Therefore age-specific reference values were calculated. The reproducibility of BRS values was in general moderate, with reliability coefficients ranging from 43 to 81% and coefficients of variation ranging from 34 to 59%. In conclusion, this study shows age, breathing mode, frequency and coherence threshold to affect measures of BRS. Therefore these factors should be considered in clinical studies; appropriate reference values are given.

Modes of baroreceptor-sympathetic coordination.

We tested the hypothesis that the cardiac-related rhythm in sympathetic nerve discharge (SND) results from the forcing of a central oscillator to the frequency of the heart beat by pulse-synchronous baroreceptor afferent nerve activity. For this purpose, time series analysis was used to examine the phase relations between the brachial arterial pulse (AP) and cardiac-related activity recorded from the postganglionic inferior cardiac sympathetic nerve (CN) in urethan-anesthetized cats. Specifically, we made cycle-by-cycle measurements of peak systolic blood pressure, heart period, CN burst amplitude, and the phase angle (and corresponding interval) between peak systole and the next peak of CN activity. As the steady-state level of systolic blood pressure was raised by increasing the rate of a constant intravenous infusion of phenylephrine, we observed transitions from no phase-locking of CN activity to the AP to either phase-locking of variable strength or phase walk through part of the cardiac-cycle on the time scale of respiration. Phase walk is defined as a progressive and systematic change in the phase lag of cardiac-related CN activity relative to peak systole. Raising blood pressure strengthened phase-locking and either increased or decreased the mean interval between peak systole and the next peak of CN activity even when the change in heart period was small. CN burst amplitude and the interval between peak systole and the next peak of CN activity were inversely related, but the strength of the relationship varied considerably with experimental conditions. The relationship was strongest during phase walk. Step-wise increases in blood pressure induced by abdominal aortic obstruction led to an abrupt increase in the phase lag of CN activity relative to peak systole even when heart rate was not changed. We refer to such changes as sharp phase transitions that are a general property of dynamical nonlinear systems. The results support the view that the cardiac-related rhythm in SND is a forced nonlinear oscillation rather than the consequence of periodic inhibition of randomly generated activity.

Child and mother cardiac vagal tone: Continuity, stability, and concordance across the first 5 years.

In this prospective longitudinal study, vagal tone and heart period were measured at 2 months and at 5 years in children and their mothers to evaluate the development of vagal regulation at rest and during an environmental task. Child baseline vagal tone and heart period were discontinuous; mother baseline vagal tone was discontinuous, but heart period was continuous. Group mean baseline-to-task change in vagal tone and heart period were continuous in both children and mothers. Children reached adult levels of baseline vagal tone by 5 years and did not differ from their mothers in baseline-to-task change in vagal tone or heart period. Baseline vagal tone tended to be stable, but baseline heart period and baseline-to-task change in vagal tone and heart period were unstable in children; both were stable in mothers. Baseline-to-task change in vagal tone showed consistent child-mother concordance. These findings contribute to understanding psychophysiological development, especially the ontogenesis of the vagal system and its regulatory capacity.

Physiological and behavioral regulation in two-year-old children with aggressive/destructive behavior problems.

A sample of 99 two-year-old children was selected on the basis of parents' responses to two administrations of the Child Behavior Checklist for two- to three-year-olds. Forty-nine of these children displayed symptoms of aggressive/destructive (externalizing) problems that were in the borderline clinical range (labelled "high risk") and 50 children displayed few such symptoms ("low risk"). The children were assessed in a series of laboratory procedures that were intended to be emotionally and behaviorally challenging, during which time heart rate was recorded and behavior was observed. To assess physiological regulation, resting measures of heart period and respiratory sinus arrhythmia (RSA), and heart period change and RSA suppression were derived from these procedures. To assess emotional and behavioral regulation, children's affect and on-task versus types of off-task behaviors were measured. Results indicated that children in the high-risk group did not differ from children in the low-risk group on the resting measure of heart period. Boys displayed lower heart rate than did girls, regardless of risk group. However, boys in the low-risk group differed from boys in the high-risk group in terms of resting measures of RSA. Children in the high-risk group did display significantly and consistently lower RSA suppression (physiological regulation) during the challenging situations than did the children in the low-risk group. High-risk children displayed more negative affect and dysregulated emotion regulation behaviors than did the low risk children. These findings are discussed in terms of the development of behavioral and emotional regulation that underlie adaptive versus maladaptive behavior.

Dynamic counterbalance between direct and indirect vagal controls of atrioventricular conduction in cats.

The vagal system regulates the atrioventricular conduction time (TAV) via two opposing mechanisms: a direct effect on the atrioventricular node and an indirect effect through changes in heart period (TAA). To evaluate how dynamic vagal activation affects TAV, we stimulated the vagal nerve with frequency-modulated Gaussian white noise and estimated the transfer function from vagal stimulation to the TAV response under conditions of no pacing and constant pacing in anesthetized cats. The effect of changes in TAA on TAV was estimated by a random-pacing protocol. The transfer function from vagal stimulation to TAV has low-pass filter characteristics. Constant pacing increased the maximum step response in TAV (2.4 +/- 1.2 vs. 6.3 +/- 2.2 ms/Hz, P < 0.01). The time constant did not differ between the vagal effect on TAV and that on TAA (2.9 +/- 1.2 vs. 2.3 +/- 0.5 s). Because changes in TAA reciprocally affected TAV without significant delay, the direct and indirect effects were dynamically counterbalanced and exerted stable TAV transient response during vagal stimulation under normal sinus rhythm.

Reproducibility of baroreflex sensitivity measured by a neck suction method

Lord et al. [1] report wide intra-subject variability of different non-invasive measures of baroreflex sensitivity (BRS) and caution against over-interpretation of minor differences. The authors do not discuss an alternative non-invasive measure of BRS, i.e. the neck suction technique [2–4]. As a preliminary investigation prior to a study of the recovery of cardiovascular reflexes following injury, we have assessed the within-day and between-day variability of the baroreflex measured using the neck suction technique. Healthy male subjects (n 12, mean age 31.6 years ; range 21–41 years) were studied in the fasting state after micturition. Subjects underwent testing twice, 20 min apart at the same times, on each of 2 days, 7 days apart. Brief applications of negative pressure were applied during held expiration using an R wave-triggered solenoid device. Multiple pressures were applied, each for five consecutive R–R intervals, in random order. The relationship between change in heart period before and after neck suction was determined and plotted against negative pressure. The slope of this relationship, determined by least-squares linear regression, is a measure of baroreflex sensitivity [4]. The median and range of BRS plus the median within-day and between-day variability of the slopes (all four slopes), measured as coefficient of variation, are shown in Table 1. Variability is of a similar magnitude to those of the other techniques reported by Lord et al. [1]. The application of positive as well as negative pressure offers the possibility of examining the full range of response of

Heart period and heart period variability during sleep on the MIR space station.

The long-term acclimation of cardiac rhythms to microgravity was studied in four astronauts aboard the Russian space station MIR during wakefulness and sleep. Sleep polygraphies were obtained between the third and the 30th day in space and, in addition, prior to mission on the ground. From each of the sleep polygraphies, beat-to-beat intervals of cardiac rhythms were determined. The response of heart period and heart period variability to the stimulus microgravity was tested during sleep across sleep stages and during waking. A lengthening of heart period by about 100 ms was found in space compared to measurements on the ground. The slowing of heart rate was more pronounced for non-REM sleep than for REM sleep. A systematic change in heart period in relation to the duration of the stay in space could not be detected. An analysis of heart period variability in the high frequency (respiratory sinus arrhythmia) band supports the hypothesis that the decrease of heart rate under microgravity is produced by an increase in parasympathetic activity. Testing the response of cardiac rhythms to microgravity across distinct behavioural states seems to be a powerful tool to investigate the cardiovascular system.

The Use of Autonomic Components to Improve Cardiovascular Assessment of Mental Workload in Flight..

Principal components analysis of multiple psychophysiological measures of cardiovascular activity was used to derive the underlying sympathetic and parasympathetic information needed to represent the autonomic space for heart period. This method was applied to cardiac data that were previously collected during a full-mission flight simulation from volunteer commercial pilots (Corwin et al., 1989). Pilots flew both low- and high-workload mission scenarios in 2 separate test sessions. The autonomic components provided increased diagnosticity regarding the autonomic mode of control for heart period change between scenarios and across flight phases. Heart period was shorter (faster heart rate) during the high- than low-workload scenario because of uncoupled sympathetic activation. Heart period change across flight phases was due primarily to coupled reciprocal modes of autonomic control during the low-workload scenario. However, heart period change across phases was due to multiple modes of control, including coactivation, during the high-workload scenario. Further, heart period and the Sympathetic component score were significantly reliable across test sessions.

A biofeedback system of baroreceptor cardiac reflex sensitivity.

The evidence presently available suggests that the parasympathetic nervous system and sympathetic-parasympathetic interactions could play a role in the pathophysiology of cardiovascular disorders and, specifically, in hypertension. A loss of sensitivity of the baroreceptor reflex is one of the fundamental mechanisms underlying the deficits found in parasympathetic cardiac control. The baroreceptor reflex is a basic mechanism for the regulation of blood pressure, a powerful source of vagal afferent input to the central nervous system, and one of the most important physiological mechanisms affecting efferent cardiac vagal activity. This paper describes a computerized system for the on-line analysis of the baroreceptor cardiac reflex function using the noninvasive spontaneous sequence method in the time domain. The system provides feedback of the baroreceptor reflex sensitivity (the change in heart period per unit change in systolic blood pressure) differentially both when the systolic blood pressure is increasing and when it is decreasing. The accuracy of the described system has been tested against the conventional off-line procedure. None of the parameters supplied by the analysis show a significant difference between the on-line and off-line methods. These results confirm the accuracy of the on-line system to analyze baroreceptor cardiac reflex function.

T-wave amplitude: relationships to phasic RSA and heart period changes

T-Wave Amplitude (TWA) has been suggested as an indicator of sympathetic influence on myocardial performance, but critics have argued that TWA is confounded by parasympathetic influence or that it is a non-specific feature of tachycardia. To help clarify the issue, we examined TWA as a function of parasympathetic activity, using cardiac vagal control as measured by high frequency components of heart period variability (respiratory sinus arrhythmia) and of interbeat intervals (IBI), across several stressful tasks. Sixteen male subjects were exposed to Valsalva, Serial Subtraction and Cold-Pressor tasks. After controlling for between-person variance, it was found that RSA did not contribute to TWA and that IBI contributed dependably to TWA only during the Valsalva maneuver, when heart rate was driven very high. In light of these results, we recommend that TWA continue to be considered a candidate indicator of sympathetic influence on myocardial performance, although caution should be used if heart rate is dramatically elevated.

Heart period variability during vagal nerve stimulation

Vagal nerve stimulation is an emerging therapy for epilepsy, yet little is known regarding the effects of this stimulation on heart period variability. We selected 10 patients (two female, eight male) who were receiving high-frequency, high-intensity left vagal nerve stimulation for intractable epilepsy. Electrocardiogram data were recorded for a 7 min baseline, 2.5 min of stimulation and a 7 min post-stimulation period. We found no significant changes in average heart period, instantaneous changes of successive R-to-R intervals greater than 50 ms or fractal dimension. We also found no significant changes in the total power in the 0.0-0.04 Hz, 0.04-0.12 Hz and 0.2-0.4 Hz bands with stimulation of the left vagus nerve. This study suggests that left vagal nerve stimulation has little acute effect on the cardiac rhythm or heart period variability.

Temporally localized contributions to measures of large-scale heart rate variability.

The purpose of this work was to determine the temporal origins of the standard deviation of successive 5-min mean heart period sequences (SDANN) and the power of the ultralow-frequency (ULF) spectral band (< 0.0033 Hz). We hypothesized that SDANN and ULF might have their origins in changes in human activity rather than slow oscillatory rhythms. Heart period sequences were obtained from 24-h Holter electrocardiograms of 10 healthy ambulatory subjects. There was no evidence of any persistent oscillation within the ULF band. Using moving 4-h windows in short-time Fourier transforms, we showed that the amplitude of ULF fluctuated markedly, particularly during times bordering sleep. The local ULF amplitude correlated (r = 0.59 +/- 0.09) with large-scale changes in heart period quantified with 2- and 4-h wavelet transforms. Local SDANN also fluctuated, mainly around times of sleep. Although the 24-h SDANN and ULF values correlated highly, there was little correlation between their temporal distributions (r = 0.10 +/- 0.25). The temporal distributions of measures of long-range heart period variability suggest that they reflect changes in human activity levels.

Quantifying electrocardiogram RT-RR variability interactions.

A dynamic linear parametric model is designed to quantify the dependence of ventricular repolarisation duration variability on heart period changes and other immeasurable factors. The model analyses the beat-to-beat series of the RR duration and of the interval between R- and T-wave apexes (RT period). Directly from these two signals, a parametric identification procedure and spectral decomposition techniques allow RT variability to be divided into RR-related and RR-unrelated parts and allow the RT-RR transfer function to be calculated. RT variability is driven by RR changes at low frequency (LF, around 0.1 Hz) and high frequency (HF, at the respiratory rate), whereas, at very low frequencies, the RR-unrelated contribution to the total RT variability is remarkable. During tilt at LF the RR-related RT percentage power increases (p < 0.02), the RR-unrelated RT percentage power remains unchanged, the gain of the RT-RR relationship largely increases (p < 0.001), and the phase is not significantly modified. Both the RR-related and the RR-unrelated RT percentage powers at LF are not affected by controlled respiration, and an increase in the RT-RR gain at HF is observed (p < 0.02). The proposed analysis may help to describe the regulation of the ventricular repolarisation process and to extract indexes quantifying the coupling between heart period and ventricular repolarisation interval changes.

Cardiac autonomic nervous system activity in obese and never-obese young men.

Autonomic nervous system (ANS) activity in age-matched, weight-stable, free-living, ad libitum-fed, obese (OB) and never-obese (NO) young men (body mass index means [SD], 38.5 [3.9] and 22.0 [1.7], respectively) was evaluated by sequential blockade of cardiac autonomic innervation with weight-adjusted doses of parasympathetic (atropine) and sympathetic (esmolol) blockers so as to produce maximal effects on heart rate. Change in heart period (interbeat interval) from baseline, induced by atropine, defined parasympathetic control (PC), and the subsequent change, after esmolol administration, defined sympathetic control (SC). The heart period, after PC and SC blockade, defined intrinsic heart period (I). In the OB group, baseline heart period and PC were lower, and SC and I were higher, than in the NO group. The results in the OB, relative to the NO subjects, are similar to those reported in a previous study of NO subjects who had undergone a 10% weight gain by overfeeding. These findings suggest that the ANS of individuals with obesity is chronically altered in a way that would tend to oppose their excessive adiposity, and that these autonomic changes are more likely to be responses to other forces that induce obesity, rather than being primary agents in the production of the disease.