Prevalence of antiplatelet therapy in patients with diabetes

The aim of the present study was to evaluate, by heart rate variability (HRV) with 24-hours ECG Holter (HRV), the circadian autonomic activity in offspring of type 2 diabetic subjects and the relation with insulin-resistance. METHODS: 50 Caucasian offsprings of type 2 diabetic subjects were divided in two groups: insulin-resistant offsprings (IR) and non insulin-resistant offsprings (NIR). Autonomic nervous activity was studied by HRV. Time domain and spectral analysis (low frequency, LF, and high frequency, HF, provide markers of sympathetic and parasympathetic modulation when assessed in normalized units) were evaluated. RESULTS. Time domain showed a reduction of total SDNN in IR (p < 0.001) and NIR (p 0.047) versus controls. Spectral analysis showed a total and night LF higher in IR and NIR than in control group (all p < 0.001). CONCLUSION. In frequency domain, the analysis of sympathetic (LF) and parasympathetic (HF) component evidenced an association between the offspring of type 2 diabetic subjects and a sympathetic overactivity. A global reduction and alteration of circadian rhythm of autonomic activity are present in offspring of type 2 diabetic patients with and without insulin resistance. The data of our study suggested that an autonomic impairment is associated with the familiarity for type 2 diabetes independently to insulin resistance and that an impairment of autonomic system activity could precede the insulin resistance.     

Cardiac Autonomic Activity During Human Sleep: Analysis of Sleep Stages and Sleep Cycles

In this study characteristics of cardiac functioning were investigated in nine subjects during their nocturnal sleep. The pre-ejection period and the high frequency component of heart rate variability were used as indices of cardiac sympathetic and parasympathetic activity of the autonomic nervous system respectively. Heart rate and the autonomic indices were assessed across physiological determined sleep stages and consecutive temporal sleep cycles. Repeated measures ANOVA analyses indicated a significant pattern of heart rate as a function of sleep stages, which was mirrored by parasympathetic activity. Further, a significant decrease of heart rate as a function of sleep cycles was mirrored by an increase of sympathetic activity. Moreover, non-REM/REM differences revealed a dominant role of parasympathetic activity during sleep stages as well as sleep cycles. These findings demonstrate that sympathetic activity is influenced by time asleep, whereas parasympathetic activity is influenced by the depth of sleep.     

Cardiac Autonomic Activity During Human Sleep: Analysis of Sleep Stages and Sleep Cycles

In this study characteristics of cardiac functioning were investigated in nine subjects during their nocturnal sleep. The pre-ejection period and the high frequency component of heart rate variability were used as indices of cardiac sympathetic and parasympathetic activity of the autonomic nervous system respectively. Heart rate and the autonomic indices were assessed across physiological determined sleep stages and consecutive temporal sleep cycles. Repeated measures ANOVA analyses indicated a significant pattern of heart rate as a function of sleep stages, which was mirrored by parasympathetic activity. Further, a significant decrease of heart rate as a function of sleep cycles was mirrored by an increase of sympathetic activity. Moreover, non-REM/REM differences revealed a dominant role of parasympathetic activity during sleep stages as well as sleep cycles. These findings demonstrate that sympathetic activity is influenced by time asleep, whereas parasympathetic activity is influenced by the depth of sleep.     

Heart Rate Variability and Skin Conductance During Repetitive TMS Course in Children with Autism

Autism spectrum disorder (ASD) is a developmental disorder marked by difficulty in social interactions and communication. ASD also often present symptoms of autonomic nervous system (ANS) functioning abnormalities. In individuals with autism the sympathetic branch of the ANS presents an over-activation on a background of the parasympathetic activity deficits, creating an autonomic imbalance, evidenced by a faster heart rate with little variation and increased tonic electrodermal activity. The objective of this study was to explore the effect of 12 sessions of 0.5 Hz repetitive transcranial magnetic stimulation (rTMS) over dorsolateral prefrontal cortex (DLPFC) on autonomic activity in children with ASD. Electrocardiogram and skin conductance level (SCL) were recorded and analyzed during each session of rTMS. The measures of interest were time domain (i.e., R–R intervals, standard deviation of cardiac intervals, NN50-cardio-intervals >50 ms different from preceding interval) and frequency domain heart rate variability (HRV) indices [i.e., power of high frequency (HF) and low frequency (LF) components of HRV spectrum, LF/HF ratio]. Based on our prior pilot studies it was proposed that the course of 12 weekly inhibitory low-frequency rTMS bilaterally applied to the DLPFC will improve autonomic balance probably through improved frontal inhibition of the ANS activity, and will be manifested in an increased length of cardiointervals and their variability, and in higher frequency-domain HRV in a form of increased HF power, decreased LF power, resulting in decreased LF/HF ratio, and in decreased SCL. Our post-12 TMS results showed significant increases in cardiac intervals variability measures and decrease of tonic SCL indicative of increased cardiac vagal control and reduced sympathetic arousal. Behavioral evaluations showed decreased irritability, hyperactivity, stereotype behavior and compulsive behavior ratings that correlated with several autonomic variables.     

Involvement of the sympatho-vagal balance in the formation of respiration-dependent oscillations in the human cardiovascular system

The effect of deep breathing controlled in both rate and amplitude on the heart rate variability (HRV) and respiration-dependent blood flow oscillations was studied in the forearm and finger-pad skin of healthy 18- to 25-year-old volunteers. In order to reveal the effects of the divisions of the autonomic nervous system on the amplitudes of respiratory sinus arrhythmia (RSA) and skin blood flow oscillations, we studied the indices of the cardiovascular system in two groups of subjects with respectively lower and higher values of the sympatho-vagal balance. This index was calculated as a ratio of low frequency and high frequency HRV spectral power (LF/HF) under the conditions of spontaneous breathing. It was found that, in subjects with a predominant parasympathetic tone, the amplitudes of RSA and the rate of blood flow in the finger-pad skin were higher compared to subjects with a predominant sympathetic tone during respiration with the frequency lower than 4 cycle/min. In the forearm skin, where sympathetic innervation is weaker compared to the finger-pad skin, there were no significant differences in respiration-dependent oscillations of the rate of blood flow in two groups of subjects.     

Circadian and ultradian rhythms in heart rate variability.

AIM: Heart rate variability (HRV) patterns reflect the changing effect of sympathetic and parasympathetic modulation of the autonomic nervous system. While overall and circadian heart rate (HR) and HRV are well characterized by traditional measures, there is currently no method to measure ultradian cycles of HR and HRV. MATERIALS AND METHODS: HR/HRV for each 2-min interval was calculated using normal-to-normal interbeat intervals from overnight polysomnographic ECGs in 113 subjects, aged 58+/-10 years (65 male, 48 female). HR, SDNN2, high-frequency power (HF) and the LF (low-frequency power)/HF ratio were plotted. A curve-fitting algorithm, developed in MatLab, identified cyclic patterns of HR/HRV and extracted parameters to characterize them. Results were compared for older vs. younger patients, males vs. females, with vs. without severe sleep apnea, and for the upper and lower half of sleep efficiency. RESULTS: Ultradian patterns for different HR/HRV indices had variable correspondences with each other and none could be considered surrogates. Differences were seen for all comparison groups, but no one marker was consistently different across comparisons. CONCLUSION: Each HR/HRV parameter has its own rhythm, and the correspondence between these rhythms varies greatly across subjects. Quantification of ultradian patterns of HRV is feasible and could provide new insights into autonomic physiology.     

Cardiovascular reactivity to mental stress: relationship with menstrual cycle and gender

The purpose of the present study was to determine the fluctuation in cardiovascular reactivity to mental stress during the menstrual cycle by comparing heart rate variability (HRV), and other physiological and psychological data in females with those in males. Cardiovascular reactivity to two mental tasks was measured in 14 females during the follicular and luteal phase of menstruation over two menstrual cycles. The same tasks were subsequently given to a matched pair of males (N=14), at the same intervals as their corresponding females. Heart rate, blood pressure and HRV were used as indices of cardiovascular reactivity. Subjective mental workload was measured at the end of each task. Power spectral analysis of HRV showed that the high frequency (HF) component in HRV decreased more during the luteal phase than the follicular phase. The low frequency (LF) component in HRV and the LF/HF ratio in the luteal phase were significantly higher than that in the follicular phase. The LF component and the LF/HF ratio were significantly lower in females than in males; conversely, the HF component was significantly higher in females than in males. Neither significant effects of menstrual cycle, gender and mental stress nor any significant interactions were found for mental workload. These findings indicate that sympathetic nervous activity in the luteal phase is significantly greater than in the follicular phase whereas parasympathetic nervous activity is predominant in the follicular phase. The results also suggest that predominance of sympathetic nervous activity in males compared with a dominant parasympathetic nervous activity in females.     

PER3 polymorphism and cardiac autonomic control: effects of sleep debt and circadian phase

A variable number tandem repeat polymorphism in the coding region of the circadian clock PERIOD3 (PER3) gene has been shown to affect sleep. Because circadian rhythms and sleep are known to modulate sympathovagal balance, we investigated whether homozygosity for this PER3 polymorphism is associated with changes in autonomic nervous system (ANS) activity during sleep and wakefulness at baseline and after sleep deprivation. Twenty-two healthy participants were selected according to their PER3 genotype. ANS activity, evaluated by heart rate (HR) and HR variability (HRV) indexes, was quantified during baseline sleep, a 40-h period of wakefulness, and recovery sleep. Sleep deprivation induced an increase in slow-wave sleep (SWS), a decrease in the global variability, and an unbalance of the ANS with a loss of parasympathetic predominance and an increase in sympathetic activity. Individuals homozygous for the longer allele (PER3(5/5)) had more SWS, an elevated sympathetic predominance, and a reduction of parasympathetic activity compared with PER3(4/4), in particular during baseline sleep. The effects of genotype were strongest during non-rapid eye movement (NREM) sleep and absent or much smaller during REM sleep. The NREM-REM cycle-dependent modulation of the low frequency-to-(low frequency + high frequency) ratio was diminished in PER3(5/5) individuals. Circadian phase modulated HR and HRV, but no interaction with genotype was observed. In conclusion, the PER3 polymorphism affects the sympathovagal balance in cardiac control in NREM sleep similar to the effect of sleep deprivation.     

Assessment of Cardiac Autonomic Modulation during Adolescent Obesity

Objective: To investigate the cardiovascular autonomic function in pediatric obesity of different duration by using standard time domain, spectral heart rate variability (HRV), and nonlinear methods. Research Methods and Procedures: Fifty obese children (13.9 ± 1.7 years) were compared with 12 lean subjects (12.9 ± 1.6 years). Obese children were classified as recent obese (ROB) (<4 years), intermediate obese (IOB) (4 to 7 years), and long‐term obese (OB) (>7 years). In all participants, we performed blood pressure (BP) measurements, laboratory tests, and 24‐hour electrocardiogram/ambulatory BP monitoring. The spectral power was quantified in total power, very low‐frequency (LF) power, high‐frequency (HF) power, and LF to HF ratio. Total, long‐term, and short‐term time domain HRV were calculated. Poincaré plot and quadrant methods were used as nonlinear techniques. Results: All obese groups had higher casual and ambulatory BP and higher glucose, homeostasis model assessment, and triglyceride levels. All parameters reflecting parasympathetic tone (HF band, root mean square successive difference, proportion of successive normal‐to‐normal intervals, and scatterplot width) were significantly and persistently reduced in all obese groups in comparison with lean controls. LF normalized units, LF/HF, and cardiac acceleration (reflecting sympathetic activation) were significantly increased in the ROB group. In IOB and OB groups, LF, but not nonlinear, measures were similar to lean controls, suggesting biphasic behavior of sympathetic tone, whereas nonlinear analysis showed a decreasing trend with the duration of obesity. Long‐term HRV measures were significantly reduced in ROB and IOB. Discussion: Autonomic nervous system changes in adolescent obesity seem to be related to its duration. Nonlinear methods of scatterplot and quadrant analysis permit assessment of autonomic balance, despite measuring different aspects of HRV.     

How is autonomic nervous system activity in subjects who are sleepy but are unable to sleep in the daytime?

We investigated changes in the activity of the autonomic nervous system (ANS) in the relaxed condition in subjects who felt sleepy, but were unable to sleep. A total of 1021 subjects underwent daytime polysomnography. The sleep latency (SL) and the visual analog scale (VAS) were used to assess “immediate” objective and subjective sleepiness, respectively. The subjects were assigned to an “Alert-Alert” group (VAS ≤ 25 mm, SL ≥ 8 min), a “Sleepy-Alert” group (VAS ≥ 75 mm, SL ≥ 8 min), or a “Sleepy-Sleepy” group (VAS ≥ 75 mm, SL ≤ 4 min). In order to assess the ANS, the spectral analysis and the geometric method were used. The ANS data collected during the relaxed condition (after lights off, post-LO) was compared to that obtained during the control condition (before lights off, pre-LO). From the spectral analysis, a significant decrease of sympathetic function and an increase of parasympathetic function at post-LO in the Sleepy-Sleepy group, a tendency for sympathetic function decrease at post-LO in the Alert-Alert group, and no significant changes to sympathetic and parasympathetic function in the Sleepy-Alert group were observed. The results from the geometric method supported the results of the spectral analysis in the Alert-Alert group and the Sleepy-Sleepy group. The results of this study suggest that the ANS plays a role in individuals who are unable to sleep even though they feel sleepy and are given the opportunity to sleep.

     

Quantifying cardiac sympathetic and parasympathetic nervous activities using principal dynamic modes analysis of heart rate variability

The ratio between low-frequency (LF) and high-frequency (HF) spectral power of heart rate has been used as an approximate index for determining the autonomic nervous system (ANS) balance. An accurate assessment of the ANS balance can only be achieved if clear separation of the dynamics of the sympathetic and parasympathetic nervous activities can be obtained, which is a daunting task because they are nonlinear and have overlapping dynamics. In this study, a promising nonlinear method, termed the principal dynamic mode (PDM) method, is used to separate dynamic components of the sympathetic and parasympathetic nervous activities on the basis of ECG signal, and the results are compared with the power spectral approach to assessing the ANS balance. The PDM analysis based on the 28 subjects consistently resulted in a clear separation of the two nervous systems, which have similar frequency characteristics for parasympathetic and sympathetic activities as those reported in the literature. With the application of atropine, in 13 of 15 supine subjects there was an increase in the sympathetic-to-parasympathetic ratio (SPR) due to a greater decrease of parasympathetic than sympathetic activity (P=0.003), and all 13 subjects in the upright position had a decrease in SPR due to a greater decrease of sympathetic than parasympathetic activity (P<0.001) with the application of propranolol. The LF-to-HF ratio calculated by the power spectral density is less accurate than the PDM because it is not able to separate the dynamics of the parasympathetic and sympathetic nervous systems. The culprit is equivalent decreases in both the sympathetic and parasympathetic activities irrespective of the pharmacological blockades. These findings suggest that the PDM shows promise as a noninvasive and quantitative marker of ANS imbalance, which has been shown to be a factor in many cardiac and stress-related diseases.     

Heart Rate Variability as an Indicator of Chronic Stress Caused by Lameness in Dairy Cows

Most experimental studies on animal stress physiology have focused on acute stress, while chronic stress, which is also encountered in intensive dairy cattle farming–e.g. in case of lameness–, has received little attention. We investigated heart rate (HR) and heart rate variability (HRV) as indicators of the autonomic nervous system activity and fecal glucocorticoid concentrations as the indicator of the hypothalamic–pituitary–adrenal axis activity in lame (with locomotion scores 4 and 5; n = 51) and non-lame (with locomotion scores 1 and 2; n = 52) Holstein-Friesian cows. Data recorded during the periods of undisturbed lying–representing baseline cardiac activity–were involved in the analysis. Besides linear analysis methods of the cardiac inter-beat interval (time-domain geometric, frequency domain and Poincaré analyses) non-linear HRV parameters were also evaluated. With the exception of standard deviation 1 (SD1), all HRV indices were affected by lameness. Heart rate was lower in lame cows than in non-lame ones. Vagal tone parameters were higher in lame cows than in non-lame animals, while indices of the sympathovagal balance reflected on a decreased sympathetic activity in lame cows. All geometric and non-linear HRV measures were lower in lame cows compared to non-lame ones suggesting that chronic stress influenced linear and non-linear characteristics of cardiac function. Lameness had no effect on fecal glucocorticoid concentrations. Our results demonstrate that HRV analysis is a reliable method in the assessment of chronic stress, however, it requires further studies to fully understand the elevated parasympathetic and decreased sympathetic tone in lame animals.     

Clinical correlates of frequency analyses of cardiovascular control after spinal cord injury

Spinal cord injury (SCI) has profound effects on cardiovascular autonomic function due to injury to descending autonomic pathways, and cardiovascular diseases are the leading causes of morbidity and mortality after SCI. Evaluation of cardiovascular autonomic dysfunction after SCI and appraisal of simple noninvasive autonomic assessments that are clinically meaningful would be useful to SCI clinicians and researchers. We aimed to assess supine and upright cardiovascular autonomic function from frequency analyses of heart rate and blood pressure variability (HRV and BPV) after SCI. We studied 26 subjects with chronic cervical or thoracic SCI and 17 able-bodied controls. We continuously recorded R-R interval (RRI, by ECG) and beat-to-beat blood pressure (by Finometer) in supine and seated positions. Cardiovascular control was assessed from spectral analysis of RRI and blood pressure time series. Cardiac baroreflex control was assessed from cross-spectral analyses of low-frequency spectra. Supine and upright low-frequency HRV and BPV were reduced in cervical SCI subjects, as were total BPV and HRV. Supine high-frequency HRV was reduced in thoracic SCI subjects. Cardiac baroreflex delay was increased in cervical SCI subjects. Supine frequency domain indexes were correlated with sympathetic skin responses, orthostatic cardiovascular responses, and plasma catecholamine levels. SCI results in reduced sympathetic drive to the heart and vasculature and increased baroreflex delay in cervical SCI subjects and reduced cardiac vagal tone in thoracic SCI subjects. Frequency analyses of autonomic function are related to clinical measures of autonomic control after SCI and provide useful noninvasive clinical tools with which to assess autonomic completeness of injury following SCI.     

Phenotypic screening for heart rate variability in the mouse

We developed a technology for heart rate (HR) variability (HRV) analysis in the mouse for characterization of HR dynamics, modulated by vagal and sympathetic activity. The mouse is the principal animal model for studying biological processes. Mouse strains are now available harboring gene mutations providing fundamental insights into molecular mechanisms underlying cardiac electrical diseases. Future progress depends on enhanced understanding of these fundamental mechanisms and the implementation of methods for the functional analysis of mouse cardiovascular physiology. By telemetric techniques, standard time and frequency-domain measures of HRV were computed with and without autonomic blockade, and baroreflex sensitivity testing was performed. HR modulation in the high-frequency component is predominantly mediated by the parasympathetic nervous system, whereas the low-frequency component is under the influence of both the parasympathetic and sympathetic systems. The presented technology and protocol allow for assessment of autonomic regulation of the murine HR. Phenotypic screening for HR regulation in mice will further enhance the value of the mouse as a model of heritable electrophysiological human disease.     

Noninvasive cardiac psychophysiology as a tool for translational science with marmosets

The importance of marmosets for comparative and translational science has grown in recent years because of their relatively rapid development, birth cohorts of twins, family social structure, and genetic tractability. Despite this, they remain understudied in investigations of affective processes. In this methodological note, we establish the validity of using noninvasive commercially available equipment to record cardiac physiology and compute indices of autonomic nervous system activity—a major component of affective processes. Specifically, we recorded electrocardiogram and impedance cardiogram, from which we derived heart rate, respiration rate, measures of high‐frequency heart rate variability (indices of parasympathetic autonomic nervous system activity), and ventricular contractility (an index of sympathetic autonomic nervous system activity). Our methods produced physiologically plausible data, and further, animals with increased heart rates during testing were also more reactive to isolation from their social partner and presentation of novel objects, though no relationship was observed between reactivity and specific indices of parasympathetic or sympathetic nervous system activity.     

Ingestion of coffee polyphenols suppresses deterioration of skin barrier function after barrier disruption,concomitant with the modulation of autonomic nervous system activity in healthy subjects

The aim of this study was to evaluate the effect of consumption of coffee polyphenols (CPPs) on the autonomic nervous system activity and decreased skin barrier function caused by sodium dodecyl sulfate (SDS) treatment. In this single-blind, placebo-controlled study, ten healthy male subjects consumed either a beverage containing CPPs or a placebo beverage for four weeks. CPPs significantly suppressed the deterioration in skin barrier function and skin moisture content induced by SDS treatment after the third week. Furthermore, in the heart rate variability analysis, CPPs significantly produced an increase in parasympathetic nervous activity, and a decrease in sympathetic nervous activity after the four weeks of beverage consumption. These results suggest that CPPs might influence the regulation of the autonomic nervous system and contribute to the suppressive effect on deterioration of skin barrier function.     

体位改变对Beagle犬心脏自主神经控制的影响

目的观察体位改变对Beagle犬心脏自主神经控制的影响。方法利用大动物无创生理遥测技术,监测清醒活动状态下雌性Beagle犬在静态姿势（lying、standing、sitting、hanging）和运动（walking）姿势下的心电图（ECG）,并用HRV功率谱分析其自主神经功能。结果在静态姿势下,Beagle犬RR间期（RRI）、RR间期的标准差SDNN（SDNN）、相邻RR间期差值平方和的均方根RMSSD（RMSSD）、相邻R-R间期差值〉50 ms的窦性个数占心搏总数的百分比pNNabs（50）（pNNabs（50））、TP总功率（TP）、VLF极低频功率（VLF）、标准化高频功率（HFnorm）均明显高于运动状态（P〈0.05,P〈0.01）,而心率（HR）、标准化低频功率（LFnorm）和低频功率/高频功率（LF/HF）平衡指数则明显低于运动状态（P〈0.05,P〈0.01）。结论不同体位姿势在静息状态下以迷走神经活动兴奋为主,相反,在运动状态下以交感神经活动兴奋为主;体位姿势改变能引起心率的变化,必然影响心脏自主神经控制能力,其主要取决于迷走神经活动强弱有关,且导致LF/HF均衡性的破坏。     

Autonomic control of heart rate during exercise studied by heart rate variability spectral analysis.

Spectral analysis of heart rate variability (HRV) might provide an index of relative sympathetic (SNS) and parasympathetic nervous system (PNS) activity during exercise. Eight subjects completed six 17-min submaximal exercise tests and one resting measurement in the upright sitting position. During submaximal tests, work rate (WR) was increased for the initial 3 min in a ramp fashion until it reached constant WRs of 20 W, or 30, 60, 90, 100, and 110% of the predetermined ventilatory threshold (Tvent). Ventilatory profile and alveolar gas exchange were monitored breath by breath, and beat-to-beat HRV was measured as R-R intervals of an electrocardiogram. Spectral analysis was applied to the HRV from 7 to 17 min. Low-frequency (0-0.15 Hz) and high-frequency (0.15-1.0 Hz) areas under power spectra (LO and HI, respectively) were calculated. The indicator of PNS activity (HI) decreased dramatically (P less than 0.05) when the subjects exercised compared with rest and continued to decrease until the intensity reached 60% Tvent. The indicator of SNS activity (LO/HI) remained unchanged up to 100% Tvent, whereas it increased abruptly (P less than 0.05) at 110% Tvent. The results suggested that (cardiac) PNS activity decreased progressively from rest to a WR equivalent to 60% Tvent, and SNS activity increased only when exercise intensity exceeded Tvent.     

Are Complexity Metrics Reliable in Assessing HRV Control in Obese Patients During Sleep?

Obesity is associated with cardiovascular mortality. Linear methods, including time domain and frequency domain analysis, are normally applied on the heart rate variability (HRV) signal to investigate autonomic cardiovascular control, whose imbalance might promote cardiovascular disease in these patients. However, given the cardiac activity non-linearities, non-linear methods might provide better insight. HRV complexity was hereby analyzed during wakefulness and different sleep stages in healthy and obese subjects. Given the short duration of each sleep stage, complexity measures, normally extracted from long-period signals, needed be calculated on short-term signals. Sample entropy, Lempel-Ziv complexity and detrended fluctuation analysis were evaluated and results showed no significant differences among the values calculated over ten-minute signals and longer durations, confirming the reliability of such analysis when performed on short-term signals. Complexity parameters were extracted from ten-minute signal portions selected during wakefulness and different sleep stages on HRV signals obtained from eighteen obese patients and twenty controls. The obese group presented significantly reduced complexity during light and deep sleep, suggesting a deficiency in the control mechanisms integration during these sleep stages. To our knowledge, this study reports for the first time on how the HRV complexity changes in obesity during wakefulness and sleep. Further investigation is needed to quantify altered HRV impact on cardiovascular mortality in obesity.     

Increased heart rate variability in mice overexpressing the Cu/Zn superoxide dismutase

Cu/Zn superoxide dismutase (SOD1) is implicated in various pathological conditions including Down's syndrome, neurodegenerative diseases, and afflictions of the autonomic nervous system (ANS). To assess the SOD1 contribution to ANS dysfunction, especially its influence on cardiac regulation, we studied the heart rate variability (HRV) and cardiac arrhythmias in conscious 12-month-old male and female transgenic mice for the human SOD1 gene (TghSOD1). TghSOD1 mice presented heart rate reduction as compared with control FVB/N individuals. All HRV parameters reflecting parasympathetic activity were increased in TghSOD1. Pharmacological studies confirmed that the parasympathetic tone was exacerbated and the sympathetic pathway was functional in TghSOD1 mice. A high frequency of atrioventricular block and premature ventricular contractions was observed in TghSOD1. By biochemical assays we found that SOD1 activities were multiplied by 9 and 4 respectively in the heart and brainstem of transgenic mice. A twofold decrease in cholinesterase activity was observed in the heart but not in the brainstem. We demonstrate that SOD1 overexpression induces an ANS dysfunction by an exacerbated vagal tone that may be related to impaired cardiac activity of the cholinesterases and may explain the high occurrence of arrhythmias.