Heart rate variability in chronic heart failure

The analysis of heart rate variability (HRV) provides information about autonomic cardiovascular control in healthy subjects. In the past 15 years, several articles have been published regarding HRV and chronic heart failure (CHF). The results of these papers substantially demonstrated that HRV is significantly different in CHF patients compared to controls. Moreover, some variables derived from HRV analysis showed significant independent prognostic capacity. In particular, the reduction of variance (expressed as SDNN) and low-frequency spectral component of HRV (ranging from 0.03 to 0.15 Hz) seem related to an increased mortality in CHF. Nevertheless, these variables are not yet considered in clinical practice. A better understanding of the physiopathological basis of the reported alterations of HRV in CHF patients is required in order to permit its use as a clinical tool for prognosis and tailored therapy in individual CHF patients.     

Left vagus nerve stimulation with the neurocybernetic prosthesis has complex effects on heart rate and on its variability in humans

PURPOSE: The purpose of this study was to determine if stimulation of the left vagus nerve (LVNS) with the neurocybernetic prosthesis (NCP) in humans is, as claimed in the literature, without cardiac chronotropic actions. METHODS: We analyzed 228 h of ECG recorded from five subjects with intractable epilepsy who had not benefited from LVNS, for effects on instantaneous heart rate (IHR) and heart rate variability (HRV). RESULTS: There were two main cardiac responses: (a) bradycardia, and (b) tachycardia during the first half, followed by bradycardia during the second half of stimulation (biphasic response). Multiphasic responses characterized by alternating bradycardia and tachycardia were rarely observed. HRV was either increased or decreased depending on the subject and on the stimulation parameters. HRV as a function of HR also showed high interindividual variability, and interestingly, in one case behaved paradoxically, increasing at higher and decreasing at lower heart rates. CONCLUSIONS: LVNS at high intensities has complex effects on IHR and HRV, which show large interindividual variability. These spectra of cardiac responses reflect the interplay of autonomic, visceral, and somatic sensory afferences and the role of central structures in their integration. These findings also point to the need for more comprehensive studies of cardiac function in humans implanted with the NCP, using sensitive methods for data processing and analysis such as those developed for this study.     

Enhancement of heart rate variability by cholinergic stimulation with pyridostigmine in healthy subjects

The purpose of this study was to determine the effect of the oral administration of pyridostigmine bromide on indices of heart rate variability (HRV) in healthy young volunteers. Seventeen healthy participants (11 men, 6 women; aged 27 +/- 8 y) submitted to a randomized, crossover, double-blind protocol, in which they received 30 mg pyridostigmine bromide (PYR) or placebo orally at 8-hour intervals for 24 hours, on two separate days. Venous blood samples were collected 2 and 24 hours after the first dose for determination of serum cholinesterase activity. Holter tapes were recorded during the 24-hour period and analyzed using a semiautomatic technique to evaluate time- and frequency-domain indices of HRV and to build three-dimensional return maps for later quantification. Symptoms were mild and occurred similarly during administration of PYR and placebo (p = 0.140). Serum cholinesterase activity was reduced by 15% at 2 hours (p = 0.013) and by 14% at 24 hours (p = 0.010) after the first dose of PYR, but not after administration of placebo. Pyridostigmine administration caused a significant increase in the mean 24-hour R-R interval (placebo: 814 +/- 20 msec; PYR: 844 +/- 18 msec; p = 0.003) and in time-domain indices of HRV, such as the standard deviation of all R-R intervals (SDNN; placebo: 151 +/- 9 msec; PYR: 164 +/- 9 msec; p = 0.017), and the percentage of pairs of adjacent R-R intervals differing by more than 50 msec (pNN50; placebo: 12.8 +/- 1.8%; PYR: 13.9 +/- 1.5%; p = 0.029). Pyridostigmine had no significant effect on frequency-domain indices of HRV, but resulted in significant increase in P2, a parasympathetic index derived from the three-dimensional return map (placebo: 93 +/- 13 msec; PYR: 98 +/- 13 ms; p = 0.029). In conclusion, low-dose pyridostigmine reduced mean heart rate and increased HRV during a 24-hour period in healthy young subjects.     

Health and distress predictors of heart rate variability in fibromyalgia and other forms of chronic pain

ObjectiveTo examine health, psychological, and autonomic impairment differences between individuals with fibromyalgia and those with other chronic benign pain in these conditions. The possible role of the autonomic nervous system in the maintenance of chronic benign pain can be examined using heart rate variability (HRV), which measures the interplay between the excitatory sympathetic and the inhibitory parasympathetic nervous system. Predictors of HRV will also be examined.MethodsThis study examined resting HRV in a sample of 84 patients with chronic benign pain, a subgroup of whom had fibromyalgia. Participants completed a battery of self-report measures and underwent measurements of resting HRV.ResultsIndividuals with fibromyalgia experienced higher levels of depression (t (82) = ? 2.27, p < .05) and significantly greater difficulty with physical functioning (t (75.8) = 2.65, p < .01) than did those with other chronic benign pain, there were no significant differences in any of the HRV indices. Across all pain conditions, we found that age, gender, physical health functioning, pain anxiety, and pain sensations were all significant predictors of HRV, suggesting that each are involved in the relationship between chronic benign pain and autonomic function.ConclusionsThese findings emphasize the importance of addressing psychological distress and physical functioning in chronic pain populations and specifically fibromyalgia. Future research can further examine the role of physical health functioning, psychological distress, and pain severity in the relationship between chronic pain and autonomic abnormalities.     

Cholinergic stimulation with pyridostigmine increases heart rate variability and baroreflex sensitivity in rats

OBJECTIVE: Impaired parasympathetic modulation increases the risk for sudden death in patients with heart diseases. Therefore, cholinergic stimulation may have a potential protective role. The aim of this study was to verify the effects of pyridostigmine bromide, a reversible cholinesterase inhibitor, on heart rate (HR), blood pressure (BP), HR and BP variability, and baroreflex sensitivity (BS). METHODS: Male Wistar rats were divided in two groups: (1) treated with pyridostigmine in drinking water (7 days, n=10; PYR) and (2) a control group (n=12; CTR). BP was recorded in freely moving rats, and HR and BP variability were quantified by the standard deviation (S.D.) of the mean values during a 30-min period and by spectral analysis. BS was assessed by the ratio between pulse interval and BP power spectra (spontaneous BS) and also by the changes on HR produced by phenylephrine and sodium nitroprusside-induced BP changes. RESULTS: Treated rats had a PYR intake of 7.91+/-1.90 mg/day (approximately 31 mg/kg/day). There were no differences between groups concerning resting HR (P=0.158), systolic BP (P=0.481), and BP variability (P=0.201). On the other hand, treatment with PYR increased HR variability on the time domain (S.D.-PYR: 13.5+/-5.3 ms vs. CTR: 9.9+/-3.6 ms; P=0.034) and frequency domain (Total power--PYR: 208.3+/-157.7 ms(2) vs. CTR: 109.2+/-65.6 ms(2); P=0.030). BS was also augmented with PYR for both the spontaneous method (High frequency band--PYR: 2.55+/-1.06 ms/mm Hg vs. CTR: 1.85+/-0.60 ms/mm Hg; P=0.033) and the drug-induced reflex bradycardia (PYR: 2.48+/-1.02 bpm/mm Hg vs. CTR: 1.54+/-0.58 bpm/mm Hg; P=0.024) and reflex tachycardia (PYR: 4.08+/-1.04 bpm/mm Hg vs. CTR: 2.95+/-1.30 bpm/mm Hg; P=0.037). CONCLUSIONS: In conclusion, treatment with pyridostigmine increased HR variability and BS in normal rats with no modifications on basal hemodynamic parameters. Considering that reduced HR variability and baroreflex sensitivity are independent risk factors in heart disease, the present results support the concept that cholinergic stimulation with pyridostigmine may become a therapeutic option for vagal dysfunction.     

Linear and non-linear 24 h heart rate variability in chronic heart failure

It has recently been demonstrated that SDNN of heart rate variability (HRV) is a useful independent prognostic tool in chronic heart failure (CHF). The purpose of the present study was to evaluate if spectral and non-linear analysis of 24-h HRV, considered markers of autonomic cardiac modulation, contain independent prognostic information in CHF patients. Twenty normal subjects and thirty consecutive outpatients with clinically stable CHF were studied for 2 years. Periods of 300 R-R intervals were analyzed from Holter recordings. The power spectral analysis, the slope of the linear relationship between log-power versus log-frequency (1/f), and the complexity content (using corrected conditional entropy; CCE) of the R-R series were calculated. The normalized power of the low frequency spectral component (LF) and the 1/f slope were significantly lower in patients compared to controls (respectively 30.1 +/- 3.0 vs. 48.6 +/- 3.4 and -1.27 +/- 0.04 vs. -1.08 +/- 0.05; P < 0.05). Moreover, the patients who died during the study presented a reduced LF (20.9 +/- 4.1 vs. 35.5 +/- 3.5 nu; P < 0.05) and a steeper 1/f slope (-1.40 +/- 0.09 vs. -1.21 +/- 0.04 nuts, P < 0.05) compared to survivors. These results remained significant in a logistic model including heart rate and SDNN. The information content present in spectral and non-linear analysis of HRV in CHF patients has prognostic relevance independently from the time domain measures of HRV. In particular, the reduction of LF power seems the best indicator among those considered.     

Vagus nerve stimulation improves severely impaired heart rate variability in a patient with Lennox-Gastaut-Syndrome

Vagus nerve stimulation (VNS) is a new therapeutic option for refractory epilepsy. We report a patient with Lennox-Gastaut-Syndrome (LGS) and a severe impairment of heart rate variability (HRV), we could demonstrate in our patient that HRV was improved by VNS.     

Closed-loop intracranial stimulation alters movement timing in humans

Background

A prime objective driving the recent development of human neural prosthetics is to stimulate neural circuits in a manner time-locked to ongoing brain activity. The human supplementary motor area (SMA) is a particularly useful target for this objective because it displays characteristic neural activity just prior to voluntary movement.

Comparison of heart rate variability in patients with chronic fatigue syndrome and controls

Recent studies have reported a close association between chronic fatigue syndrome and neurally mediated hypotension. We hypothesized that this association may result from an abnormality in autonomic function among patients with chronic fatigue syndrome, which may be detectable using an analysis of heart rate variability. We prospectively studied 19 patients who fulfilled the Centers for Disease Control criteria for chronic fatigue syndrome and 11 controls. Each subject underwent a two-stage tilt-table test while wearing a Holter monitor. Heart rate variability was assessed in the supine baseline position and during upright tilt using frequency domain parameters. In the baseline supine position, high frequency (HF) power, low frequency (LF) power, and the ratio of low frequency power to high frequency power (LF/HF ratio) were similar. In both patient groups, upright tilt resulted in a similar decrease in HF power, increase in LF power, and increase in the LF/HF ratio. In conclusion, autonomic function, as assessed using an analysis of heart rate variability, does not differ in the baseline supine state, nor in response to upright tilt among patients with chronic fatigue syndrome and healthy controls.     

Effects of light and sleep stages on heart rate variability in humans.

Effects of light intensity and sleep stages on heart rate variability (HRV) were investigated in young healthy subjects. The low-frequency (LF)/high-frequency (HF) ratio was significantly increased by exposing either to bright lights of 10 000 lx or to extreme darkness (< 0.01 lx), while HF and LF components of HRV were not changed, when compared with those under dim light (100 lx). However, LF was significantly increased at REM sleep, when compared with that at the pre-sleep wake. In contrast, HF was increased at all stages of sleep, and the LF/HF ratio was decreased at slow wave sleep during the baseline night.     

Assessment of the primary effect of aging on heart rate variability in humans

Beat-to-beat heart rate variability (HRV), reflecting cardiac autonomic control mechanisms, is known to change with age. However, the degree to which this change is mediated by aging per se or by physiologic changes characteristic of normative aging is still unclear. This study was designed to examine the association of aerobic fitness, body habitus or obesity, and blood pressure with age-related changes in HRV. Resting HRV data was recorded from 373 healthy subjects (124 men, 249 women; are range, 16–69 y) and analyzed by coarse-graining spectral analysis to decompose the total spectral power into its harmonic and fractal components. The low- and high-frequency (LF, 0.0–0.15 Hz; HF, >0.15 Hz) harmonic components were calculated from the former, whereas the latter was used to calculate the integrated power (FR) and the spectral exponent , which were, in turn, used to evaluate the overall complexity of HRV. Factor analysis was performed to test whether potentially age-related changes in the components of HRV might be observed secondarily through other variables affecting HRV. Significant (p<0.05) age-related changes in the harmonic (HF and LF) and fractal (FR and ) components of HRV were generally consistent with those described in the literature. In addition, factor analysis showed that there was a unique common factor that primarily explained correlations among age, HF, and (p<0.05) without the contributions from LF, FR, aerobic fitness, body habitus or obesity, and blood pressure. It was concluded that, in this population-based sample, age-related changes in HF and , both of which reflect vagal modulation of heart rate, were primarily mediated by aging per se and not by physiologic changes characteristic of normative aging.     

Relation of heart rate recovery to heart rate variability in persons with paraplegia

Purpose  

Heart rate recovery (HRR) after treadmill exercise testing is an index of cardiac autonomic activity in non-disabled persons, but it is unknown if this is also the case in individuals with spinal cord injury (SCI). We investigated the relationship between HRR after maximal arm exercise testing and resting autonomic activity in persons with paraplegia.     

Reproducibility of heart rate and blood pressure variability in patients with chronic obstructive pulmonary disease

Abstract. Wide variations in respiratory rate and hypoxic stimulation of chemoreceptors may produce unreliable autonomic results in patients with COPD. We studied the reproducibility of two consecutive measurements of heart rate variability (HRV) and blood pressure variability (BPV) by time frequency analysis in patients with COPD while controlling respiratory rate and oxygen hemoglobin saturation (SaO₂). Reproducibility was assessed by paired t-tests and correlation analyses between repeated measures. Correlation analyses of the log transformed low (LF) and high frequency (HF) HRV were 11.5 ± 1.1 in measurement A and 11.5 ± 1.0 in measurement B (r = 0.89, p < 0.0001), and 10.5 ± 1.1 in measurement A and 10.6 ± 1.1 in measurement B (r = 0.89, p < 0.0001) respectively. The log transformed LF and HF BPV were 4.9 ± 1.3 in measurement A and 5.3 ± 0.9 in measurement B (r = 0.70, p < 0.0002), and 6.4 ± 1.3 in measurement A and 6.6 ± 1.2 in measurement B (R = 0.71 p < 0.0001) respectively. In conclusion, time frequency analysis of HRV and BPV is reproducible and reliable in patients with COPD while controlling their respiratory rate and oxygen hemoglobin saturation. Reproducibility of these measurements may allow for a non-invasive evaluation of autonomic tone in response to treatments in COPD patients.     

Transcutaneous electrical nerve stimulation at different frequencies on heart rate variability in healthy subjects

Sympathetic and parasympathetic nervous system imbalance has been strongly associated to sudden cardiac death. Among the non-pharmacological treatment, transcutaneous electrical nerve stimulation (TENS) represents a possible therapeutic intervention to reduce sympathetic excitation and improve the sympatho-vagal balance in different clinical conditions. We aimed to verify acute effects of high and low transcutaneous electrical nerve stimulation (TENS) frequencies by the evaluation of heart rate variability. Seven healthy volunteers received an application of low frequency (10-Hz) and high frequency (100-Hz) TENS. After 10-Hz, there was decrease of LF normalized units (n.u.) component (32.7±5.9 vs 18.3±3.4, p<0.002) and increase of HF n.u. (60.9±4.3 vs 72.6±8.9, p<0.016). In contrast, after 100-Hz there was increase of LF n.u. (31.5±16.1 vs 41.6±12.2, p<0.019) and reduction of HF n.u. (63.9±15.3 vs 53.7±12.3, p<0.031). In conclusion, TENS modulates sympathetic and parasympathetic activity in a frequency dependent manner.     

A model of chronic pain in the rat: high-resolution neuroanatomical approach identifies alterations in multiple opioid systems in the periaqueductal grey

Inoculation of the tail base of rats with Mycobacterium butyricum led to an arthritic swelling and inflammation of the limbs which displayed a hyperalgesia to noxious pressure: these effects peaked at 3 weeks postinoculation. In vitro autoradiography of coronal sections of rat brain was used for a parallel determination of binding to mu-, delta- and kappa-opioid binding sites. In only two regions, the dorsomedial and dorsolateral parts of the periaqueductal grey (PAG), was a significant change seen: this comprised an increase in binding to kappa-sites, whereas mu- and delta-sites therein were unaffected. This region was analysed for opioid peptides derived from each of the three opioid peptide families known. While no change was seen in levels of immunoreactive (ir)-dynorphin1-17 A (DYN) and ir-Met-enkephalin, a decrease was detected in those of ir-beta-endorphin (beta-EP): this change was restricted to the PAG. These data demonstrate a highly localized and selective influence of chronic arthritic pain upon multiple opioid systems in the PAG of the rat, a structure playing a key role in the control of pain and in the expression of the antinociceptive actions of opioids. The data suggest a possible significance of PAG pools of beta-EP and kappa-receptors in the response to and modulation of chronic pain.     

脑中风患者心率变异的初步分析

目的：探讨中风后植物神经的变化规律及其变化机制。方法：采用反映植物神经功能折心率变异指标，对其时域指标进行分析、应用方差分析及ｔ检验，比较了健康对照组与中风组的心率变异情况。结果：（１）中风组ＳＤＮＮ及ＨＲＶＩ均明显低于健康对照组。（２）中风组随病程的处长，其心率变异逐渐增高，到半年后基本恢复到对照组的水平。     

Effect of chronic epilepsy on heart rate variability: a case-control study

BACKGROUND; Dysfunction of the autonomic cardiac regulation is thought to be related to higher mortality in epileptic patients. OBJECTIVE: We tried to study changes in sympathetic and parasympathetic activities in patients with chronic epilepsy and repetitive generalized tonic-clonic (GTC) seizures. DESIGN, TIME AND SETTING: A case-control study was conducted at the Buddhist Tzu Chi General Hospital between July 2006 and May 2009.MATERIALS: The study included 15 male and 15 female patients (mean age ± S.D.: 33.40 ± 12.64 years) who had chronic epilepsy and repetitive GTC seizures and 15 male and 15 female healthy control subjects (age: 32.20 ± 9.53 years). METHODS: Lead I electrocardiograms were taken in 5 minutes during an interictal period in the daytime among the epilepsy and control gourps. Frequency-domain analysis of heart rate variability was performed with fast Fourier Transformation and the data were subsequently converted to heart rate interval, high frequency (HF; 0.15-0.45 Hz) power, low frequency (LF; 0.04-0.15 Hz) power, and LF/(HF+LF) expressed in normalized units (LF%). Differences in the data between the groups were compared using Student’s t-test.MAIN OUTCOME MEASURES: The LF component contributed from both sympathetic and parasympathetic divisions. The HF component represented vagal (parasympathetic) regulation and the LF% was considered to mirror sympathetic regulation. RESULTS: All 30 patients have idiopathic or cryptogenic epilepsy lasting 19.01  10.22 years. All patients had GTC seizures with or without other types of seizures, but 16 of them had GTC seizures only. There was no significant between-group difference in age, height, weight and body mass index. The epilepsy group had a significantly lower mean heart rate interval, a significantly higher LF%, and a significantly lower high frequency power. CONCLUSION: Patients with chronic epilepsy have faster heart rates during interictal periods and it may be attributed to higher sympathetic and lower parasympathetic activity.     

Heart rate variability in ischemic heart disease

Major untoward events, such as life-threatening arrhythmias and acute coronary events, have been suggested to be triggered by the activation of the autonomic nervous system in patients with coronary artery disease. Analysis of heart rate variability by conventional time and frequency domain methods, as well as by newer methods derived from nonlinear system theory, has offered a novel approach for studying the abnormalities in cardiovascular neural regulation in ischemic heart disease. Heart rate variability has been shown to be altered among patients with ischemic heart disease as compared to their age-matched controls without the evidence of ischemic heart disease. There are also obvious differences in various measures of heart rate variability between patients with uncomplicated coronary artery disease and those with coronary artery disease with complicated myocardial infarction. Impaired high-frequency oscillations of heart rate is the most prominent feature in patients with uncomplicated coronary artery disease, suggesting mainly an impairment in vagal autonomic regulation. Patients with prior myocardial infarction have a reduced overall heart rate variability, and a specific spectral pattern with a reduced low-frequency spectral component has been observed in patients with prior myocardial infarction and impaired left ventricular function. Recent studies have shown that the new nonlinear measures, particularly fractal analysis methods of heart rate dynamics, can detect subtle changes in heart rate behavior that are not easily detected by traditional analysis methods from ambulatory recordings. Patients with prior myocardial infarction have steeper power-law slope analyzed from the ultra and very low-frequency spectral bands, and they also have more random short-term heart rate dynamics analyzed by the detrended fluctuation method. A large body of data indicate that reduced overall heart rate variability is associated with an increased risk of mortality and nonfatal cardiac events in patient with ischemic heart disease. Of particular note, recent studies indicate that fractal analysis methods perform even better than the traditional analysis methods of heart rate variability as predictors of death and the onset of life-threatening arrhythmic events in post-infarction populations. These findings support the notion that heart rate variability analysis methods, such as fractal and complexity measures as well as conventional techniques, give valuable clinical information among patients with ischemic heart disease.