Cardiac Parasympathetic Regulation Research Articles

Heart Rate and Heart Rate Variability in Healthy Preterm-Born Young Adults and Association with Vitamin D: A Wearable Device Assessment.

Prematurity has been associated with impaired parasympathetic cardiac regulation later in life. Changes in heart rate (HR) and heart rate variability (HRV) may indicate a risk for future cardiac dysfunction. The putative role of Vitamin D on cardiac autonomic function in individuals born preterm (PT) remains unknown. This study involves monitoring autonomic cardiac regulation and Vitamin D concentrations in 30 PT and 16 full-term (FT) young adults in a free-living context. The PT subjects were born between 1994 and 1997 at Oulu University Hospital. The inclusion criteria were (1) being born ≤ 32 gestation weeks or (2) being born < 34 gestation weeks with a birth weight under 1500 g. Participants wore an Oura ring sleep tracer, a smart ring device, for 2 weeks to monitor cardiac autonomic function. Parameters related to autonomic cardiac regulation, lowest nighttime resting HR, and the root mean square of successive differences (RMSSD) to describe HRV were collected. PT males exhibited a tendency toward lower RMSSD (71.8 ± 22.6) compared to FT males (95.63 ± 29.0; p = 0.10). Female participants had a similar mean RMSSD in the FT and PT groups at 72.04 ± 33.2 and 74.0 ± 35.0, respectively. Serum 25-hydroxyvitamin D concentration did not correlate with cardiac autonomic function parameters. When assessing the lowest resting nighttime HRs and HRVs in a long-term, real-world context, healthy female PT young adults performed similarly to their FT peers. In contrast, the present study's results suggest that male PT young adults exhibit impaired autonomic cardiac function, potentially putting them at risk for cardiovascular disease later in adulthood.

Cardiac Rhythms and Variation in Hibernating Arctic Ground Squirrels.

AbstractThe dramatic decrease in heart rate (HR) during entrance into hibernation is not a mere response to the lowering of core body temperature (Tb) but a highly regulated fall, as the decrease in HR precedes the drop in Tb. This regulated fall in HR is thought to be mediated by increased cardiac parasympathetic activity. Conversely, the sympathetic nervous system is thought to drive the increase of HR during arousal. Despite this general understanding, we lack temporal information on cardiac parasympathetic regulation throughout a complete hibernation bout. The goal of this study was to fill this gap in knowledge by using Arctic ground squirrels implanted with electrocardiogram/temperature telemetry transmitters. Short-term HR variability (root mean square of successive differences [RMSSD]), an indirect measure of cardiac parasympathetic regulation, was calculated in 11 Arctic ground squirrels. RMSSD, normalized as RMSSD/RR interval (RRI), increased fourfold during early entrance (from to , ). RMSSD/RRI peaked after HR dropped by over 90% and Tb fell by 70%. Late entrance was delineated by a decline in RMSSD/RRI while Tb continued to decrease. During arousal, HR started to increase 2 h before Tb, with a concurrent decrease in RMSSD/RRI to a new minimum. As Tb increased to a maximum during interbout arousal, HR declined, and RMSSD/RRI increased. These data suggest that activation of the parasympathetic nervous system initiates and regulates the HR decrease during entrance into hibernation and that withdrawal of parasympathetic activation initiates arousal. We conclude that cardiac parasympathetic regulation persists throughout all phases of a hibernation bout-a feature of the autonomic nervous system's regulation of hibernation that was not appreciated previously.

Features of autonomic cardiovascular control during cognition in major depressive disorder.

Previous research has suggested reduced parasympathetic cardiac regulation during cognitive activity in major depressive disorder (MDD). However, little is known about possible abnormalities in sympathetic control and cardiovascular reactivity. This study aimed to provide a comprehensive analysis of autonomic cardiovascular control in the context of executive functions in MDD. Thirty six MDD patients and 39 healthy controls participated. Parameters of sympathetic (pre-ejection period, PEP) and parasympathetic control (high and low frequency heart rate variability, HF HRV, LF HRV; and baroreflex sensitivity, BRS) as well as RR interval were obtained at rest and during performance of executive function tasks (number-letter task, n-back task, continuous performance test, and Stroop task). Patients, as compared to controls, exhibited lower HF HRV and LF HRV during task execution and smaller shortenings in PEP and RR interval between baseline and tasks. They displayed longer reaction times during all conditions of the tasks and more omission errors and false alarms on the continuous performance test. In the total sample, on-task HF HRV, LF HRV and BRS, and reactivity in HF HRV, LF HRV, and PEP, were positively associated with task performance. As performance reduction arose independent of executive function load of the tasks, the behavioral results reflect impairments in attention and processing speed rather than executive dysfunctions in MDD. Abnormalities in cardiovascular control during cognition in MDD appear to involve both divisions of the autonomic nervous system. Low tonic parasympathetic control and blunted sympathetic reactivity imply reduced physiological adjustment resources and, by extension, provide suboptimal conditions for cognitive performance.

Increased epoch-to-epoch parasympathetic cardiac regulation in participants with posttraumatic stress disorder compared to those with panic disorder and control participants

BackgroundResearch on the link between respiratory sinus arrhythmia (RSA) and posttraumatic stress disorder (PTSD) has largely focused on average levels of RSA. However, given that rapid shifts in parasympathetic tone are necessary to maintain adaptive cardiac variability, the exclusive focus on these tonic estimates provides an incomplete quantification of parasympathetic cardiac regulation. MethodThe present study is a secondary analysis of previously published data. This analysis aimed to address this limitation by examining the dynamic regulatory effect of the parasympathetic nervous system on heart rate. As such, we examined epoch-to-epoch parasympathetic cardiac regulation – operationalized as the lagged relationship between RSA and heart rate (HR) across consecutive 30-s epochs – across a single night in participants with PTSD, panic disorder (PD), comorbid PTSD and PD (PTSD + PD), and healthy controls. Electrocardiogram and respiratory signals were continuously recorded from 23 participants with PTSD, 14 with PD, 16 with PTSD + PD, and 16 control participants over a single night of sleep in a laboratory setting. ResultsNo group differences in tonic RSA were observed; however, participants with PTSD only and PTSD + PD exhibited significantly greater epoch-to-epoch parasympathetic cardiac regulation over the night than those with PD only and control participants. Moreover, greater severity of hyperarousal symptoms was significantly associated with increased epoch-to-epoch parasympathetic cardiac regulation among participants with PTSD only and PTSD + PD. DiscussionThese data provide preliminary evidence for an upregulatory parasympathetic response to self-reported hyperarousal in participants with PTSD only and PTSD + PD reflected by increased epoch-to-epoch parasympathetic cardiac regulation.

Interaction Between Cortical Auditory Processing and Vagal Regulation of Heart Rate in Language Tasks: A Randomized, Prospective, Observational, Analytical and Cross-Sectional Study

Cortical auditory evoked potentials (CAEP) throughout a language task is beneficial during psychophysiological evaluation to advance identification of language disorders. So as to better comprehend human communication and to provide additional elements for neuropsychological examinations we aimed to (1) examine the influence of language tasks on cortical auditory processing and vagal control of heart rate and (2) to verify a possible association between the parasympathetic cardiac regulation and cortical auditory processing in language tasks. This study was completed with 49 women. The subjects were separated into two groups: (1) phonological language tasks (N = 21) and (2) semantic (N = 21) language tasks. Heart rate variability (HRV) and CAEP were evaluated before and after the tests. HRV reduced (small effect size) and P3 wave latency increased after the phonological task. Identical variables were significantly correlated after the phonological task and linear regression indicated significant interaction between pNN50 (percentage of adjacent RR intervals with a difference of duration greater than 50 milliseconds) and P3 latency (16.9%). In conclusion, phonological language tasks slightly reduced parasympathetic control of HR and increased cognitive effort. The association between HRV and CAEP are anticipated to be involved in this mechanism.

Using acoustic features of mothers’ infant-directed speech to predict changes in infant biobehavioral state

Infant directed speech is marked by exaggerated frequency modulation and strong high frequency power, features that may provide physiological cues for mobilization or calming (Porges and Lewis, 2010; Kolacz et al., 2018). We examined whether these features predicted changes in infant biobehavioral state during the Still Face Paradigm, a stressor in which the mother withdraws and reinstates social cues. 98 mother-infant dyads participated when infants were 4-8 months old. Infant heart rate and respiratory sinus arrhythmia (a measure of cardiac parasympathetic control) were derived from an electrocardiogram (ECG). Infant behavioral distress was measured by vocal, facial, and body movement distress. Mothers’ vocalizations were measured using spectral analysis within designated frequency bands and modulation using a 2-dimensional fast Fourier transform of the audio spectrogram. Maternal frequency modulation predicted decreases in infant heart rate (p = .030), mid-frequency acoustic power (500–5000 Hz) predicted increases in cardiac parasympathetic regulation in infants with low parasympathetic tone (p = .024), and high frequency power predicted increases in infant behavioral distress in infants who were not initially distressed (p = .011). These results suggest that mothers’ vocal frequency band power and modulation may be aspects of infant-directed speech that are relevant for regulating infant biobehavioral state.

Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus

Bradykinin (BK), a component of the kallikrein-kininogen-kinin system exerts multiple effects via B1 and B2 receptor activation. In the cardiovascular system, bradykinin has cardioprotective and vasodilator properties. We investigated the effect of BK on cardiac-projecting neurons of nucleus ambiguus, a key site for the parasympathetic cardiac regulation. BK produced a dose-dependent increase in cytosolic Ca2+ concentration. Pretreatment with HOE140, a B2 receptor antagonist, but not with R715, a B1 receptor antagonist, abolished the response to BK. A selective B2 receptor agonist, but not a B1 receptor agonist, elicited an increase in cytosolic Ca2+ similarly to BK. Inhibition of N-type voltage-gated Ca2+ channels with ω-conotoxin GVIA had no effect on the Ca2+ signal produced by BK, while pretreatment with ω-conotoxin MVIIC, a blocker of P/Q-type of Ca2+ channels, significantly diminished the effect of BK. Pretreatment with xestospongin C and 2-aminoethoxydiphenyl borate, antagonists of inositol 1,4,5-trisphosphate receptors, abolished the response to BK. Inhibition of ryanodine receptors reduced the BK-induced Ca2+ increase, while disruption of lysosomal Ca2+ stores with bafilomycin A1 did not affect the response. BK produced a dose-dependent depolarization of nucleus ambiguus neurons, which was prevented by the B2 receptor antagonist. In vivo studies indicate that microinjection of BK into nucleus ambiguus elicited bradycardia in conscious rats via B2 receptors. In summary, in cardiac vagal neurons of nucleus ambiguus, BK activates B2 receptors promoting Ca2+ influx and Ca2+ release from endoplasmic reticulum, and membrane depolarization; these effects are translated in vivo by bradycardia.

Sequence of cardiovascular autonomic alterations after fingolimod initiation.

Homeostasis between heart rate and blood pressure is based on several interacting regulatory reflexes, which become influenced by fingolimod initiation. The aim of this study was to determine the sequence of changes in cardiovascular autonomic regulation after fingolimod initiation. Twenty-seven patients with relapsing-remitting multiple sclerosis underwent continuous electrocardiogram recording during the first 6hr after the first dose of fingolimod. In addition to the time interval between two consecutive R-peaks (RRinterval), blood pressure and heart rate variability (HRV) were measured on hourly basis. Cardiac parasympathetic and sympathetic regulation were assessed by the different components of HRV. HRV demonstrated an enhancement in cardiac parasympathetic regulation starting 1hr after the first dose of fingolimod. Blood pressure started to decrease 2hrand sympathetic cardiac regulation 3hr after fingolimod initiation. Recovery in RR interval, systolic and diastolic blood pressure, as well as in cardiac autonomic regulation started after 5hr postdose, whereas pulse pressure (difference between systolic and diastolic blood pressure) continued to increase at the time of hospital discharge. RR interval, blood pressure, as well as the parasympathetic and sympathetic components of cardiac autonomic regulation alter sequentially in different temporal pattern after fingolimod initiation. These findings enhance the understanding of the effects of fingolimod initiation on cardiovascular autonomic regulation in real life.

Direct projections from hypothalamic orexin neurons to brainstem cardiac vagal neurons

Orexin neurons are known to augment the sympathetic control of cardiovascular function, however the role of orexin neurons in parasympathetic cardiac regulation remains unclear. To test the hypothesis that orexin neurons contribute to parasympathetic control we selectively expressed channelrhodopsin-2 (ChR2) in orexin neurons in orexin-Cre transgenic rats and examined postsynaptic currents in cardiac vagal neurons (CVNs) in the dorsal motor nucleus of the vagus (DMV). Simultaneous photostimulation and recording in ChR2-expressing orexin neurons in the lateral hypothalamus resulted in reliable action potential firing as well as large whole-cell currents suggesting a strong expression of ChR2 and reliable optogenetic excitation. Photostimulation of ChR2-expressing fibers in the DMV elicited short-latency (ranging from 3.2ms to 8.5ms) postsynaptic currents in 16 out of 44 CVNs tested. These responses were heterogeneous and included excitatory glutamatergic (63%) and inhibitory GABAergic (37%) postsynaptic currents. The results from this study suggest different sub-population of orexin neurons may exert diverse influences on brainstem CVNs and therefore may play distinct functional roles in parasympathetic control of the heart.

Modulation of sphingosine receptors influences circadian pattern of cardiac autonomic regulation.

Fingolimod is an oral sphingosine‐1‐phospate (S1P) receptor modulator for the treatment of relapsing‐remitting multiple sclerosis (RRMS). In addition to therapeutic effects on lymphoid and neural tissue, fingolimod influences cardiovascular system by specific S1P‐receptor modulation. The effects of S1P‐receptor modulation on the endogenous circadian pattern of cardiac autonomic regulation (CAR), however, are not known. We examined the effects of fingolimod on the circadian pattern of CAR. Ambulatory 24‐h ECG recordings were undertaken in 27 RRMS patients before fingolimod (baseline), at the day of fingolimod initiation (1D) and after 3 months of fingolimod treatment (3M). The mean time between two consecutive R‐peaks (RR‐interval) and mean values for measures of heart rate variability (HRV) in time‐ and frequency domain were calculated from ECG recording at daytime and nighttime. The mean night:day‐ratio of RR‐interval was 1.23 ± 0.12 at baseline, decreased temporarily at 1D (1.16 ± 0.12; P < 0.01) and was higher at 3M (1.32 ± 0.11; P < 0.001) than at baseline. The night:day‐ratio of HRV parameters reflecting parasympathetic cardiac regulation (pNN50, rMSSD, HFnu) decreased at 1D but recovered back to baseline at 3M (P < 0.05 for all). On the other hand, the night:day‐ratio of TP, a parameter reflecting overall HRV gradually decreased and was lower at 3M than at baseline (P < 0.05). Our findings suggest that physiological relation between the circadian pattern of RR‐interval and overall HRV as well as parasympathetic cardiac regulation becomes uncoupled during fingolimod treatment. In addition, fingolimod shifts the circadian equilibrium of CAR toward greater daytime dominance of overall HRV. Accordingly, S1P‐receptor modulation influences circadian pattern of CAR.

Common molecular mechanism of the hepatic lesion and the cardiac parasympathetic regulation in chronic hepatitis C infection: a critical role for the muscarinic receptor type 3.

BackgroundThe pathophysiological overlapping between Sjorgen’s Syndrome (SS) and HCV, presence of anti- muscarinic receptor type 3 (M3R) antibodies in SS, the role that M3R plays in the regulation of the heart rate, has led to the assumption that cardiovagal dysfunction in HCV patients is caused by anti-M3R antibodies elicited by HCV proteins or by their direct interaction with M3R.ResultsTo identify HCV protein which possibly is crossreactive with M3R or which binds to this receptor, we performed the Informational Spectrum Method (ISM) analysis of the HCV proteome. This analysis revealed that NS5A protein represents the most probable interactor of M3R or that this viral protein could elicit antibodies which modulate function of this receptor. Further detailed structure/function analysis of NS5A and M3R performed by the ISM method extended with other Digital Signal processing (DSP) approaches revealed domains of these proteins which participate in their crossreactivity or in their direct interaction, representing promising diagnostic and therapeutic targets.ConclusionsApplication of the ISM with other compatible bioinformatics methods offers new perspectives for identifying diagnostic and therapeutic targets for complicated forms of HCV and other viral infections. We show how the electron-ion interaction potential (EIIP) amino-acid scale used in the ISM combined with a robust, high performance hydrophobicity scale can provide new insights for understanding protein structure/function and protein-protein interactions.

Integrating affective and cognitive correlates of heart rate variability: A structural equation modeling approach

High frequency heart rate variability (HRV) is a measure of neurocardiac communication thought to reflect predominantly parasympathetic cardiac regulation. Low HRV has been associated empirically with clinical and subclinical levels of anxiety and depression and, more recently, high levels of HRV have been associated with better performance on some measures of executive functioning (EF). These findings have offered support for theories proposing HRV as an index measure of a broad, self-regulatory capacity underlying aspects of emotion regulation and executive control. This study sought to test that proposition by using a structural equation modeling approach to examine the relationships of HRV to negative affect (NA) and EF in a large sample of U.S. adults ages 30s–80s. HRV was modeled as a predictor of an NA factor (self-reported trait anxiety and depression symptoms) and an EF factor (performance on three neuropsychological tests tapping facets of executive abilities). Alternative models also were tested to determine the utility of HRV for predicting NA and EF, with and without statistical control of demographic and health-related covariates. In the initial structural model, HRV showed a significant positive relationship to EF and a nonsignificant relationship to NA. In a covariate-adjusted model, HRV's associations with both constructs were nonsignificant. Age emerged as the only significant predictor of NA and EF in the final model, showing inverse relationships to both. Findings may reflect population and methodological differences from prior research; they also suggest refinements to the interpretations of earlier findings and theoretical claims regarding HRV.

Exercise training-induced bradycardia: evidence for enhanced parasympathetic regulation without changes in intrinsic sinoatrial node function.

The mechanisms responsible for exercise-induced reductions in baseline heart rate (HR), known as training bradycardia, remain controversial. Therefore, changes in cardiac autonomic regulation and intrinsic sinoatrial nodal (SAN) rate were evaluated using dogs randomly assigned to either a 10- to 12-wk exercise training (Ex, n = 15) or an equivalent sedentary period (Sed, n = 10). Intrinsic HR was revealed by combined autonomic nervous system (ANS) blockade (propranolol + atropine, iv) before and after completion of the study. At the end of the study, SAN function was further evaluated by examining the SAN recovery time (SNRT) following rapid atrial pacing and the response to adenosine in anesthetized animals. As expected, both the response to submaximal exercise and baseline HR significantly (P < 0.01) decreased, and heart rate variability (HRV; e.g., high-frequency R-R interval variability) significantly (P < 0.01) increased in the Ex group but did not change in the Sed group. Atropine also induced significantly (P < 0.01) greater reductions in HRV in the Ex group compared with the Sed group; propranolol elicited similar HR and HRV changes in both groups. In contrast, neither intrinsic HR (Ex before, 141.2 ± 6.7; Ex after, 146.0 ± 8.0 vs. Sed before, 143.3 ± 11.1; Sed after, 141.0 ± 11.3 beats per minute), the response to adenosine, corrected SNRT, nor atrial fibrosis and atrial fibrillation inducibility differed in the Ex group vs. the Sed group. These data suggest that in a large-animal model, training bradycardia results from an enhanced cardiac parasympathetic regulation and not from changes in intrinsic properties of the SAN.

Holter ECG monitoring of sympathovagal fluctuation during bronchoscopy.

The changes of autonomic nervous activity during bronchoscopic procedures are closely related to the development of cardiovascular complications. We aimed to evaluate the changes of autonomic nervous activity during bronchoscopic procedures using R-R interval variability from electrocardiograms (ECGs) obtained during diagnostic bronchoscopy. Twenty-four patients who underwent bronchoscopy were included. Continuous ECG was recorded prior to, during and after the bronchoscopic procedure. Time and frequency domain analyses of heart rate variability were performed. Heart rate increased significantly after pre-medication compared with that before pre-medication and increased further during bronchoscopy. The coefficient of variation (CVRR ) values after pre-medication and during bronchoscopy were significantly higher than those before pre-medication (P = 0.031 and P = 0.041, respectively). The low frequency (LF) power decreased during bronchoscopy. LF powers obtained after bronchoscopy were significantly lower than those obtained before bronchoscopy (P < 0.041). The high-frequency (HF) power was found to be decreased during bronchoscopy. In particular, HF powers obtained after bronchoscopy were significantly lower than those obtained before bronchoscopy (P < 0.019). Although the LF/HF ratios increased after pre-medication, they decreased temporarily during the bronchoscope insertion. This study shows for the first time that Holter ECG monitoring during diagnostic bronchoscopy was associated with activation of cardiac sympathetic and withdrawal of cardiac parasympathetic regulation, which may contribute to the occurrence of cardiac events during bronchoscopic procedures. So, Holter ECG monitoring during bronchoscopic procedures may confer reduction in cardiovascular events.

Exercise training induced bradycardia: evidence for enhanced parasympathetic regulation without changes in “intrinsic” sino‐atrial node function (881.5)

Although bradycardia is a well‐established consequence of endurance exercise training, the mechanisms responsible for this reduction in baseline heart rate (HR) remain controversial. Therefore, changes in cardiac autonomic regulation and intrinsic sino‐atrial nodal (SAN) rate were evaluated using mixed‐breed dogs randomly assigned to either a 10‐wk exercise training (ET, n = 15) or an equivalent sedentary period (SP, n = 10). Intrinsic HR was revealed by combined autonomic neural blockade (propranolol HCl, 1.0 mg/kg + atropine sulfate, 50 ug/kg, i.v.) before and after completion of the 10‐wk study. At the end of the study, SAN function was further evaluated by examining the SAN recovery time (SNRT) following rapid atrial pacing (1 min at 3.3 ‐ 10Hz). As expected, baseline HR decreased and heart rate variability [HRV, indices of cardiac vagal tone ‐ as measured by the high frequency component of R‐R variability (HF) and R‐R interval standard deviation (SD)] increased in the ET (HR pre 113.4 ± 3.9, post 105.2 ± 3.9 beats/min; HF pre 7.0 ± 0.2, post 8.2 ± 0.2 ln ms2; SD pre 57.8 ± 100.5 ± 9.2 ms) but not in the SP group (HR pre 113.0 ± 10.3, post 122.4 ± 5.4 beats/min; HF pre 7.4 ± 0.5, post 7.0 ± 0.6 ln ms2; SD pre 62.2 ± 9.9, post 63.6 ± 7.3 ms). Atropine induced significantly (ANOVA, P &lt;0.01) greater reductions in HRV in the ET (HF pre ‐6.9 ± 0.3. post ‐7.6 ln ms2; SD, pre ‐50.0 ± 3.7, post ‐90.6 ± 9.7 ms) as compared to the SP (HF ‐7.1 ± 0.5, post ‐6.6 ± 0.5 ln ms2; SD pre ‐66.0 ± 11.3, post ‐59.2 ± 6.8 ms) group. In contrast, neither intrinsic HR (e.g., ET pre 141.2 ± 6.7, post 146.0 ± 8.0; SP pre 149.8 ± 8.9, Post 150.0 ± 12.6 beats/min) nor SNRT (HR corrected) differed in the ET and SP groups. These data suggest that endurance exercise training induced changes in baseline HR result from an enhanced cardiac parasympathetic regulation and not from changes in the intrinsic function of the sino‐atrial node.

The association of heart rate variability with parkinsonian motor symptom duration.

PurposeImpaired cardiovascular autonomic regulation is a non-motor symptom of Parkinson's disease (PD) and may increase long-term morbidity. This study applied frequency-domain analysis of heart rate variability (HRV) to understand the progression of sympathetic and parasympathetic cardiac regulation in patients with PD.Materials and MethodsIn this cross-sectional study, 21 male and 11 female Taiwanese patients with advanced PD and 32 healthy gender- and age-matched subjects were enrolled. To minimize artifacts due to subject motion, daytime electrocardiograms for 5 minutes were recorded in awake patients during levodopa-on periods and controls. Using fast Fourier transformation, heart rate variables were quantified into a high-frequency power component [0.15-0.45 Hz, considered to reflect vagal (parasympathetic) regulation], low-frequency power component (0.04-0.15 Hz, reflecting mixed sympathetic and parasympathetic regulation), and low-frequency power in normalized units (reflecting sympathetic regulation). The significance of between-group differences was analyzed using the paired t-test. Pearson correlation analysis and stepwise regression analysis were applied to assess the correlation of patient age, PD duration, and disease severity (represented by the Unified Parkinson's Disease Rating Scale) with each heart rate variables.ResultsImpaired HRV is significantly correlated with the duration of PD, but not with disease severity and patient age. Meanwhile, parasympathetic heart rate variable is more likely than sympathetic heart rate variable to be affected by PD.ConclusionPD is more likely to affect cardiac parasympathetic regulation than sympathetic regulation by time and the heart rate variables have the association with Parkinsonian motor symptom duration.

Normal values for heart rate variability parameters in children 6–8 years of age: the PANIC Study

Measurement of heart rate variability (HRV) is a useful method for examining cardiac autonomic control. HRV has been measured in many studies among adults, but research on this topic among children is limited. We therefore defined reference values for a large number of HRV parameters among children. The subjects were a population sample of 465 mainly prepubertal children 6-8years of age. Electrocardiogram (ECG) was recorded at rest, and 1- and 5-min ECG samples were selected for HRV analyses. HRV data were analysed in boys and girls separately to study possible gender differences in HRV parameters. Pearson's coefficients for correlation of age, maturity stage, height, weight and body mass index - standard deviation score (BMI-SDS) with HRV parameters were computed to study whether these factors confounded the definition of the reference values for HRV parameters. We found no statistically significant differences in HRV parameters between genders. Therefore, we defined the reference values for all HRV parameters as 5th, 25th, 50th, 75th and 95th percentiles from the ECG samples in all children, but not in boys and girls separately. Age, maturity stage, height, weight and BMI-SDS had weak, if any, associations with HRV parameters, suggesting that they did not confound the definition of the reference values. Same reference values for HRV parameters can be used in boys and girls. Although 5-min ECG recordings are preferable for measuring HRV, also 1-min recordings provide reliable data on most HRV parameters, especially those that mainly describe cardiac parasympathetic regulation.

The effect of pentobarbital anesthesia on “intrinsic” heart rate.

While it is well established that pentobarbital alters cardiac autonomic regulation, the effects of this anesthetic agent on intrinsic heart rate (HRi) remain to be determined. Therefore, HRi, was measured in purpose‐bred mixed breed dogs (n = 11, 22.2 ± 0.9 kg, age 1–3 y) by means of combined adrenergic (propranolol HCl 1.0 mg/kg, i.v.) and muscarinic (atropine sulfate 50 ug/kg iv.) receptor inhibition before (Control, Con) and, at least one week later, during pentobarbital anesthesia (Pen, 30–40 mg/kg, i.v). Pentobarbital significantly (ANOVA, P&lt;0.01) depressed the high frequency component (0.24 – 1.04 Hz, an index of cardiac parasympathetic regulation) of heart rate variability (Con, 7.2 ± 0.4 vs. Pen, 1.0 ± 0.4 ln ms2) and increased baseline heart rate (Con, 105.9 ± 8.7 vs. Pen, 139.1 ± 6.8 beats/min) but decreased HRi (Con, 148.7 ± 6.7 vs. Pen, 128.9 ± 5.3 beats/min). The nonselective adenosine antagonist aminophylline (10 mg/kg, i.v.) did not alter heart rate variability (0.4 ± 0.3 ln ms2) but restored HRi to control (i.e., without pentobarbital) values (141.5 ± 6.7 beats/min). These data suggest that pentobarbital both alters cardiac autonomic regulation and depresses intrinsic heart rate. These data further indicate that the activation of adenosine receptors may play an important role in this apparent depression of cardiac pacemaker rate.

Sex differences in cardiac autonomic regulation and in repolarisation electrocardiography

The review summarises the present knowledge on the sex differences in cardiac autonomic regulations and in related aspects of electrocardiography with particular attention to myocardial repolarisation. Although some of the sex differences are far from fully established, multitude of observations show consistent differences between women and men. Despite more pronounced parasympathetic cardiac regulation, women have higher resting heart rate and lower baroreflex sensitivity. Of the electrocardiographic phenomena, women have longer QT interval duration, repolarisation sequence more synchronised with the inverse of the depolarisation sequence, and likely increased regional heterogeneity of myocardial repolarisation. Studies investigating the relationship of these sex disparities to hormonal differences led frequently to conflicting results. Although sex hormones seem to play a key role by influencing both autonomic tone and electrophysiological properties at the cellular level, neither the truly relevant hormones nor their detailed actions are known. Physiologic usefulness of the described sex differences is also unknown. The review suggests that new studies are needed to advance the understanding of the physiologic mechanisms responsible for these inequalities between women and men and provides key methodological suggestions that need to be followed in future research.

The effect of heart rate on the heart rate variability response to autonomic interventions

Heart rate variability (HRV), the beat-to-beat variation in either heart rate (HR) or heart period (R-R interval), has become a popular clinical and investigational tool to quantify cardiac autonomic regulation. However, it is not widely appreciated that, due to the inverse curvilinear relationship between HR and R-R interval, HR per se can profoundly influence HRV. It is, therefore, critical to correct HRV for the prevailing HR particularly, as HR changes in response to autonomic neural activation or inhibition. The present study evaluated the effects of HR on the HRV response to autonomic interventions that either increased (submaximal exercise, n = 25 or baroreceptor reflex activation, n = 20) or reduced (pharmacological blockade: β-adrenergic receptor, muscarinic receptor antagonists alone and in combination, n = 25, or bilateral cervical vagotomy, n = 9) autonomic neural activity in a canine model. Both total (RR interval standard deviation, RRSD) and the high frequency (HF) variability (HF, 0.24–1.04 Hz) were determined before and in response to an autonomic intervention. All interventions that reduced or abolished cardiac parasympathetic regulation provoked large reductions in HRV even after HR correction [division by mean RRsec or (mean RRsec)2 for RRSD and HF, respectively] while interventions that reduced HR yielded mixed results. β-adrenergic receptor blockade reduced HRV (RRSD but not HF) while both RRSD and HF increased in response to increases in arterial blood (baroreceptor reflex activation) even after HR correction. These data suggest that the physiological basis for HRV is revealed after correction for prevailing HR and, further, that cardiac parasympathetic activity is responsible for a major portion of the HRV in the dog.