The utility of low frequency heart rate variability as an index of sympathetic cardiac tone: A review with emphasis on a reanalysis of previous studies

This article evaluates the suitability of low frequency (LF) heart rate variability (HRV) as an index of sympathetic cardiac control and the LF/high frequency (HF) ratio as an index of autonomic balance. It includes a comprehensive literature review and a reanalysis of some previous studies on autonomic cardiovascular regulation. The following sources of evidence are addressed: effects of manipulations affecting sympathetic and vagal activity on HRV, predictions of group differences in cardiac autonomic regulation from HRV, relationships between HRV and other cardiac parameters, and the theoretical and mathematical bases of the concept of autonomic balance. Available data challenge the interpretation of the LF and LF/HF ratio as indices of sympathetic cardiac control and autonomic balance, respectively, and suggest that the HRV power spectrum, including its LF component, is mainly determined by the parasympathetic system.     

Association of cardiac autonomic neuropathy with alteration of sympatho-vagal balance through heart rate variability analysis

Early sub-clinical assessment of severity of cardiac autonomic neuropathy (CAN) and intervention are of prime importance for risk stratification and early treatment in preventing sudden death due to silent myocardial infarction. The Ewing battery is currently the diagnostic tool of choice but is unable to detect sub-clinical disease and requires patient cooperation. Time and frequency domain analysis have several shortcomings including sensitivity to recording length, respiratory activity and non-stationarities in the ECG signal. An important step forward is to have a non-invasive method of detecting CAN that is robust against these shortcomings and has a higher sensitivity for the presence of both sub-clinical and overt clinical disease. This study presents a novel parameter, tone–entropy (T–E) that analyses heart rate variability (HRV) of 20 min lead II ECG recordings. Tone (T) represents sympatho-vagal balance and entropy (E) the autonomic regularity activity. Thirteen normal subjects without (CAN?) and 21 with CAN (CAN+) participated in this study. Among 21 CAN+ subjects, 13 are early CAN+ (eCAN+), eight are definite CAN+ (dCAN+) according to autonomic nervous system function tests as described by Ewing. The results showed that tone was higher and the entropy was lower in the dCAN+ group (T = ?0.033 to ?0.010 and E = 1.73–2.24) compared with the eCAN+ (T = ?0.0927 to ?0.0311 and E = 2.0–2.65) and normal (T = ?0.128 to ?0.0635 and E = 2.64–3.15) group. The research verified that T–E is a suitable method to determine the presence of CAN that correctly identifies experimentally induced changes in cardiac function akin to parasympathetic and sympathetic dysfunction and differentiates between stages in CAN disease progression identified using the Ewing battery.     

Mental stress inhibits pain perception and heart rate variability but not a nociceptive withdrawal reflex

AIM: Do distraction from- or attention to sural nerve stimulation affect pain, heart rate variability, and a spinal withdrawal reflex? MATERIAL AND METHODS: In 26 male volunteers, electrical stimulation at the distal cutaneous receptive field of the sural nerve elicited pain and a nociceptive withdrawal reflex. Intensity of pain was rated on a numeric rating scale. Electromyographic reflex responses were measured from biceps femoris muscle. Cardiac autonomic function was estimated by heart rate variability measures and was expressed in the time domain as mean of RR-intervals for normal heart beats (mean-RR) and standard deviation of all normal RR-intervals (SD-NN) and, in the frequency domain, where pure vagal activity was assessed by high frequency power (0.15-0.4 Hz). Low frequency power (0.04-0.15 Hz) reflects both parasympathetic and sympathetic control. Effect parameters were recorded before and during random distraction and attention. Distraction from sural nerve stimulation was induced by a mental arithmetic test, paced auditory serial addition task (PASAT), while attention was induced by concentrating on painful foot stimulation. RESULTS: Paced auditory serial addition task decreased mean-RR and SD-NN, frequency domain parameters, as well as pain (P<0.001). In contrast, PASAT did not change the spinal withdrawal reflex. Attention did not affect any effect parameter. CONCLUSION: Distraction by PASAT altered autonomic activity and inhibited pain but failed to affect withdrawal reflex responses, while attention had no effect on either parameter. Psychological distraction and attention may have different effects on noxious evoked pain perception and autonomic activity. Pain relief during PASAT probably involves supraspinal mechanisms.     

The hippocampus is not necessary for a place response but may be necessary for pliancy

Rats with kainate-colchicine hippocampal lesions (HL) and controls (C) were initially trained in the Morris water maze with procedures that deterred their prepotent thigmotaxic response. Training began with an escape platform that occupied nearly the entire pool. The area to which the rats could escape was made smaller by substituting smaller platforms as training progressed. In contrast to standard procedures, HL rats and C rats showed comparable performance during acquisition and preferentially searched the goal quadrant on probe trials during which the platform was removed. In a follow-up experiment, the platform was moved to a random position along the wall, which required a switch to a thigmotaxic response for most effective escape. HL rats that were thigmotaxic before place training did not switch to a thigmotaxic response as readily as did controls, behavior consistent with the view that hippocampal damage reduces pliancy.     

Alteration of cardiac autonomic functions in patients with major depression: a study using heart rate variability measures

BACKGROUND: Depression is associated with greater cardiac morbidity and mortality. One of the contributory factors for this may be altered cardiac autonomic activity in depression. However, cardiac autonomic involvement in depression remains controversial because of methodological issues. In this study, alteration of cardiac autonomic functions was studied in drug-naive patients with major depression without co-morbidity. Heart rate variability, a sensitive measure of neurocardiac autonomic regulation was used in addition to conventional methods of measuring cardiac autonomic functions. METHODS: We recruited 40 patients suffering from major depression, diagnosed based on DSM-IV-TR criteria. Their cardiac autonomic functions were measured using both conventional and heart rate variability measures. These were compared with those of age- and gender-matched healthy controls. RESULTS: Patients with major depression showed significantly lesser Valsalva ratio, maximum/minimum ratio and greater sympathovagal balance than healthy controls indicating decreased parasympathetic and increased sympathetic activity. CONCLUSIONS: Depression is associated with alteration of cardiac autonomic tone towards decreased parasympathetic activity and an increased sympathetic activity. It is possible that a common neurobiological dysfunction contributes to both depression and cardiac autonomic changes in the illness.     

Interaction between resting pulmonary ventilation function and cardiac autonomic function assessed by heart rate variability in young adults

An association between ambient air pollution and reduced cardiac autonomic function assessed by heart rate variability (HRV) mainly in elderly persons has been suggested by a number of epidemiological studies, but the link between the HRV and pulmonary function in humans remains unknown although such air pollution should primarily affect pulmonary function. To clarify this link, pulmonary ventilation parameters such as oxygen uptake (V(O(2))) and carbon dioxide output (V(CO(2))), as well as the HRV with spectral analysis (high- and low-frequency components of HRV, i.e., CCV(HF) and CCV(LF), reflecting cardiac parasympathetic and sympathetic activities, respectively), were measured in 66 healthy women aged 19-20 years after an overnight fast of 12 h. Significant correlations were found between the CCV(HF) of HRV and both the end-tidal carbon dioxide concentration (FET(CO(2))) and gas exchange ratio (V(CO(2))/V(O(2))) in the subjects (partial correlation coefficients r = 0.354 and 0.320, respectively), whereas there was no significant connection between the FET(CO(2)) and the V(CO(2))/V(O(2)). Similarly, the CCV(LF) correlated significantly with the resting tidal volume of lung (r = 0.364). These findings suggest that resting pulmonary ventilation function interacts with cardiac autonomic function assessed by the HRV, at least in healthy young adults, which may be useful for explaining the pathophysiology concerning the short-term effect of air pollution such as fine particulate matter on cardiovascular function.     

Heart rate variability as a measure of autonomic regulation of cardiac activity for assessing stress and welfare in farm animals -- a review

Measurement of heart rate variability (HRV) is a non-invasive technique that can be used to investigate the functioning of the autonomic nervous system, especially the balance between sympathetic and vagal activity. It has been proven to be very useful in humans for both research and clinical studies concerned with cardiovascular diseases, diabetic autonomic dysfunction, hypertension and psychiatric and psychological disorders. Over the past decade, HRV has been used increasingly in animal research to analyse changes in sympathovagal balance related to diseases, psychological and environmental stressors or individual characteristics such as temperament and coping strategies. This paper discusses current and past HRV research in farm animals. First, it describes how cardiac activity is regulated and the relationships between HRV, sympathovagal balance and stress and animal welfare. Then it proceeds to outline the types of equipment and methodological approaches that have been adapted and developed to measure inter-beats intervals (IBI) and estimate HRV in farm animals. Finally, it discusses experiments and conclusions derived from the measurement of HRV in pigs, cattle, horses, sheep, goats and poultry. Emphasis has been placed on deriving recommendations for future research investigating HRV, including approaches for measuring and analysing IBI data. Data from earlier research demonstrate that HRV is a promising approach for evaluating stress and emotional states in animals. It has the potential to contribute much to our understanding and assessment of the underlying neurophysiological processes of stress responses and different welfare states in farm animals.     

Effect of magnitopuncture on sympathetic and parasympathetic nerve activities in healthy drivers--assessment by power spectrum analysis of heart rate variability

The object of this study was to assess the effects of magnitopuncture applied to Dazhui (DU14) point and Neiguan (PC6) points on sympathetic and parasympathetic nerve activities by power spectrum analysis of heart rate variability in healthy drivers during simulated driving. Using power spectrum analysis, the low frequency (LF) and high frequency (HF) components of heart rate variability can be calculated reflecting the sympathetic and parasympathetic activity. The 40 healthy male subjects were randomly divided into two groups: A (study group) and B (control group). All subjects were required to be well rested before the experiment. The subjects of both groups were required to perform a simulated driving task for 3 h. During the driving, magnitopunctures were applied to the DU14 and PC6 points for A while the subject performed the task for 2.5 h, and for B magnitopunctures were applied to non-acupuncture points which were 1.5 cm away from the two acupuncture points respectively over the same time. Subjective response to a questionnaire was obtained after the simulated task in the two groups. At the end of the driving task the LF component in normalized units (NU) had decreased significantly (P<0.05) indicating a reduced sympathetic nerve activity and the HF component (NU) increased significantly (P<0.05) indicating a increased parasympathetic nerve activity for A compared with pre-stimulation while for B no significant differences were observed. There were significant group differences in LF (NU), HF (NU) and LF:HF at the end of the driving task (P<0.05). It was concluded that a modulating effect of magnitopuncture on sympathetic and parasympathetic nerve activities in healthy subjects was associated with the acupuncture points. The findings represent physiological evidence that magnitopuncture may reduce mental fatigue in healthy drivers. Electronic Publication     

The influence of mean heart rate on measures of heart rate variability as markers of autonomic function: a model study

Some studies have demonstrated that the assessments of autonomic activities from the alterations of heart rate variations (HRVs) after autonomic blockade and during exercise of high intensity by the spectral analysis of HRV seemed inconsistent with actual situation. The inconsistency is probably caused by the contributions of fluctuating magnitudes and mean levels of autonomic activities on HRV having not been clarified. The alterations of HRV after autonomic blockade and during exercise of high intensity using a mathematical model were simulated. The autonomic activity in normal condition was assumed first according to some experimental evidence. Then autonomic activities after sympathetic blockade, vagal blockade and during exercise of high intensity were appropriately adjusted accordingly. The HRVs in response to these given autonomic activities were simulated. We found that the effect on HRV influenced by the mean level of autonomic activity is helpful to explain alterations of HRV in these conditions. After vagal blockade, a largely reduced low frequency (LF) power could be caused by the reduced mean heartbeat interval induced by a decreased mean level of vagal activity. Increased low and high frequency powers after sympathetic blockade could be caused by the increased mean heartbeat interval induced by a decreased mean level of sympathetic activity. A decreased LF power during exercise of high intensity, in addition to the withdrawal of vagal activity, could also be caused by the decreased mean heartbeat interval induced by an increased mean level of sympathetic activity.     

Sympatho-inhibitory response of the heart as a result of short-term acupuncture-like stimulation of the rat hindlimb is not augmented when sympathetic tone is high as a result of hypercapnia

This study examined whether the sympatho-inhibitory response of the heart to acupuncture-like stimulation of a hindlimb in anesthetized rats depends on the sympathetic tone. Observed reductions in both cardiac sympathetic nerve activity and heart rate following short-term acupuncture-like stimulation of a hindlimb were not augmented when the sympathetic tone was high as a result of hypercapnia.     

Assessment of autonomic function by the spectral analysis of heart rate variability: an examination in a mirror drawing task]

The effect of an experimental task on autonomic function was investigated by spectral analysis of heart rate variability in 13 male college students. Power spectral density of heart rate variability has been said to contain two significant components: respiratory sinus arrhythmia (RSA) as an index of cardiac vagal activity, and Mayer wave related sinus arrhythmia (MWSA) as an index of sympathetic activity with vagal modulation. Those two components were examined during a task of mirror drawing on the CRT. In order to eliminate the effect of respiratory rate on RSA, the respiratory rate was controlled at 15 breaths/min. Furthermore, the coefficient of variance of R-R interval (CV-RR) and the fluctuation of plethysmograph (PTG) were calculated simultaneously. Results indicated that, while RSA decreased significantly, MWSA did not change during the task. On the other hand, neither CV-RR nor PTG showed any significant differences during the task. These findings indicated that cardiac parasympathetic activity was diminished in the mirror drawing task. The significance of spectral analysis of heart rate variability were discussed.     

Underestimation of cardiac vagal control in regular exercisers by 24-hour heart rate variability recordings

Objective

To examine whether ceiling effects at long inter beat intervals (IBIs)cause an underestimation of cardiac vagal control in regular exercisers by time and frequency-domain measures of respiratory sinus arrhythmia (RSA).

Methods

24-hour ECG and respiration recordings were performed in 26 regularly exercising subjects, actively engaged in aerobic training for the past year, and enrolled in supervised training in the six weeks pre-study, and in 26 age- and sex-matched non-exercisers. Sleep and waking levels of cardiac vagal control were estimated by RSA obtained through the peak-valley method, by the standard deviation of the IBIs, the root mean square of successive IBIs, and the high frequency IBI spectral power.

Results

In 11 of the exercisers the IBI-RSA relationship was characterized by a quadratic relationship. This reflected a ceiling effect at very long IBI values attained by regular exercisers, particularly during the nighttime recording. Irrespective of this ceiling effect, RSA as well as other heart rate variability (HRV) measures was still significantly larger in the exercisers with a quadratic IBI-RSA relationship than in non-exercisers or exercisers with a linear IBI-RSA relationship.

Conclusions

We conclude that a subgroup of regular exercisers is characterized by a low heart rate paired to high levels of cardiac vagal control. In these exercisers, vagal control is underestimated from HRV measures in ambulatory recordings. Inspection of the IBI-RSA relationship should be routinely added when HRV measures are used to index cardiac vagal control.     

Estimation of the following cardiac output using sympathetic tone and hemodynamics for the control of a total artificial heart.

A sympathetic neurogram is potentially useful for the development of a real time total artificial heart (TAH) control system. We used sympathetic tone and hemodynamic derivatives to estimate the following cardiac output in acute animal experiments using adult mongrel dogs. Moving averages of the mean left atrial pressure and mean aortic pressure were used as parameters of the preload and afterload, respectively. Renal sympathetic nerve activity (RSNA) was employed as a parameter of sympathetic tone. Equations for the following cardiac output were calculated using multiple linear regression analysis of the time series data. A significant correlation was observed between the estimated and following measured cardiac output. These results suggest the potential usefulness of the sympathetic neurogram for the real time TAH automatic control system.     

The high frequency component of heart rate variability reflects cardiac parasympathetic modulation rather than parasympathetic ‘tone’

This study was designed to evaluate the effect of modulating cardiac parasympathetic input on the high frequency component of heart rate variability. We stimulated the right vagus nerve with three different stimulation patterns in anaesthetized, vagotomized and spinal anaesthetized dogs. We kept the mean stimulation frequency constant; controlled the amplitude of modulation with programmed stimulation patterns, and analysed the resulting heart rate variability by power spectral analysis. Constant frequency vagal stimulation increased the cardiac interval, but did not change heart rate variability markedly. There was a slight increase, from 11 pL 2 to 27 pL 11 ms², in the high frequency component. However, when the instantaneous stimulation frequency oscillated between 4 and 17 Hz during 5 s period, we could produce a marked heart rate variation, with 91 pL 9% of the variation corresponding to the frequency of the modulation (0.20 Hz). The high frequency component was 12932 pL 7701 ms². With an increased magnitude of modulation, i.e. the difference between minimum and maximum instantaneous frequency, the high frequency component increased to 32711 pL 17943 ms². Thus, the high frequency component of heart rate variability reflects the magnitude of fluctuation in the cardiac parasympathetic input rather than parasympathetic ‘tone’.     

Reflex inhibition of heart rate and efferent cardiac sympathetic outflow induced by colorectal distension in anesthetized rats

Colorectal distensions of 60 and 80 mmHg significantly reduced heart rate (HR) and cardiac sympathetic nerve activity in anesthetized rats. This bradycardiac response was not influenced by the intravenous administration of atropine, but was abolished by propranolol, suggesting that it was elicited by sympathetic but not vagal efferent nerves.     

The reproducibility of power spectrum analysis of heart rate variability before and after a standardized meal

We tested the reproducibility of the heart rate variability (HRV) measurements before and after a standardized meal. Heart rate recordings were obtained in 14 healthy subjects tested in a reclining position before and after a standardized meal on two separated occasions, apart by a 1-2-week interval. We measured three components of HRV: sympathetic activity (SYMP), parasympathetic activity (PSYMP) and the ratio of SYMP/PSYMP under controlled breathing and noncontrolled breathing conditions. We observed that all components were reproducible during noncontrolled breathing condition, whereas only PSYMP was reproducible during controlled breathing condition. Our results thus indicate that HRV measurements could be a useful, noninvasive and nonexpensive method to provide SYMP and SYMP/PSYMP in feeding behavior studies when measured under noncontrolled breathing conditions. Nonetheless, using a controlled breathing condition may be relevant when assessing the effect of various interventions or drugs on parasympathetic activity.     

A novel autonomic activation measurement method for stress monitoring: non-contact measurement of heart rate variability using a compact microwave radar

We developed a novel method for non-contact monitoring of stress-induced autonomic activation through the back of a chair, using a compact 24 GHz microwave radar (8 x 5 x 3 cm), without large-scale equipment and placing a heavy burden on the monitored individual. Following a silent period of 120 s, audio stimuli using a composite tone of 2,120 and 2,130 Hz sine-waves at 95 dB were conducted for 120 s. From dorsal, LF/HF of HRV reflecting sympatho-vagal balance was determined by microwave radar with the maximum entropy method using eight volunteers (mean age 23 +/- 1 years). Mean LF/HF measured by non-contact and contact (using electrocardiography for reference) methods during audio stimuli increased 34 and 37%, respectively, as compared with those of the silent period. Maximum cross-correlations between contact and non-contact measurements averaged 0.73 +/- 0.10. Our method appears to be promising for future monitoring of stress-induced autonomic activation of operators and may reduce stress-induced accidents.     

Effects of vital exhaustion on cardiac autononomic nervous functions assessed by heart rate variability at rest in middle-aged male workers

We investigated the effects of vital exhaustion (VE) on cardiac autonomic functions in relation to working conditions such as overtime and frequent business trips, and to lifestyles such as smoking on 52 healthy middle-aged male workers. VE was evaluated by an abbreviated Maastricht Vital Exhaustion Questionnaire. Cardiac autonomic function atsupine rest was assessed by spectral analysis of heart rate variability inanannual healthcheckup.Themeanamplitudeofthehigh frequency(HF: 0.15-0.4 Hz) component was lowerinthe high-VE group, whereas no significant difference in the ratio ofthe low frequency (LF: 0.04-0.15 Hz) component powerto HF power (the LF/HF ratio) was observed among VE groups. There were significant interactive effects of VE and smoking on HF amplitude, and of VE and frequent business trips on the LF/HF ratio. VE symptoms were related to the suppression of the cardiac parasympathetic nervous functionat rest in middle-aged male workers, but not to the alteration in sympathovagal balance. Smoking and overwork such as frequent business trips may amplify the autonomic dysfunction in relation to VE among workers with a pronounced feeling of VE.     

Dissociation of temporal dynamics of heart rate and blood pressure responses elicited by conditioned fear but not acoustic startle

Fear-inducing stimuli were hypothesized to elicit fast heart rate (HR) responses but slow mean arterial blood pressure (MAP) responses and thus were studied in auditory fear conditioning and acoustic startle at high temporal resolution in freely moving mice and rats. Fear-induced instantaneous acceleration of HR reaching maximum physiological values and subsequent recovery to baseline were observed. The MAP response consisted of an immediate, mild, and transient increase followed by a sluggish, profound elevation and slow recovery. HR and MAP responses served as reliable indicators of conditioned fear in mice with dissociated temporal dynamics. Unconditioned auditory stimuli, including acoustic startle stimuli, elicited only fast, mild, and transient MAP and HR elevations in mice and rats, reflecting arousal and attention under these experimental conditions.