Cardiac Vagal Control Research Articles

Central activation of cardiac vagal nerve by α2-adrenergic stimulation is impaired in streptozotocin-induced type 1 diabetic rats

To elucidate the abnormality of cardiac vagal control in streptozotocin-induced type 1 diabetic rats, we measured left ventricular myocardial interstitial acetylcholine (ACh) release in response to α2-adrenergic stimulation as an index of in vivo cardiac vagal nerve activity. A cardiac microdialysis technique was applied to the rat left ventricle, and the effect of α2-adrenergic stimulation by intravenous medetomidine (100 μg/kg) on myocardial interstitial ACh levels was examined in anesthetized diabetic rats (4-6 weeks after intraperitoneal streptozotocin) and age-matched control rats (protocol 1). The effect of electrical vagal nerve stimulation on ACh levels was also examined in separate rats (protocol 2). In protocol 1, medetomidine increased the ACh levels in control (from 1.76 ± 0.65 to 3.13 ± 1.41 nM, P < 0.05, n = 7) but not in diabetic rats (from 2.01 ± 0.47 to 1.62 ± 0.34 nM, not significant, n = 7). In protocol 2, electrical vagal nerve stimulation at 20 Hz significantly increased the ACh levels in both control (from 1.49 ± 0.26 to 6.39 ± 1.81 nM, P < 0.001, n = 6) and diabetic rats (from 1.77 ± 0.54 to 6.98 ± 1.38 nM, P < 0.001, n = 6). In conclusion, medetomidine-induced central vagal activation was impaired in diabetic rats, whereas peripheral cardiac vagal control of ACh release was preserved. The impairment of central vagal activation may lead to relative sympathetic predominance and promote cardiovascular complications in diabetes.

Vagal Tank Theory: The Three Rs of Cardiac Vagal Control Functioning - Resting, Reactivity, and Recovery.

The aim of this paper is to set the stage for the vagal tank theory, showcasing a functional resource account for self-regulation. The vagal tank theory, building on neurophysiological, cognitive and social psychology approaches, will introduce a physiological indicator for self-regulation that has mainly been ignored from cognitive and social psychology, cardiac vagal control (also referred to as cardiac vagal activity). Cardiac vagal control reflects the contribution of the vagus nerve, the main nerve of the parasympathetic nervous system, to cardiac regulation. We propose cardiac vagal control to be an indicator of how efficiently self-regulatory resources are mobilized and used. Three systematic levels of cardiac vagal control analysis are suggested: resting, reactivity, and recovery. Based on this physiological indicator we derive the metaphor of the vagal tank, which can get depleted and replenished. Overall, the vagal tank theory will enable to integrate previous findings from different disciplines and to stimulate new research questions, predictions, and designs regarding self-regulation.

Vagal Mediation of Low-Frequency Heart Rate Variability During Slow Yogic Breathing.

Changes in heart rate variability (HRV) associated with breathing (respiratory sinus arrhythmia) are known to be parasympathetically (vagally) mediated when the breathing rate is within the typical frequency range (9-24 breaths per minute [bpm]; high-frequency HRV). Slow yogic breathing occurs at rates below this range and increases low-frequency HRV power, which may additionally reflect a significant sympathetic component. Yogic breathing techniques are hypothesized to confer health benefits by increasing cardiac vagal control, but increases in low-frequency HRV power cannot unambiguously distinguish sympathetic from parasympathetic contributions. The aim of this study was to investigate the autonomic origins of changes in low-frequency HRV power due to slow-paced breathing. Six healthy young adults completed slow-paced breathing with a cadence derived from yogic breathing patterns. The paced breathing took place under conditions of sympathetic blockade, parasympathetic (vagal) blockade, and placebo. HRV spectral power was compared under 11 breathing rates during each session, in counterbalanced order with frequencies spanning the low-frequency range (4-9 bpm). HRV power across the low-frequency range (4-9 bpm) was nearly eliminated (p = .016) by parasympathetic blockade (mean (SD) spectral power at breathing frequency = 4.1 (2.1)) compared with placebo (69.5 (8.1)). In contrast, spectral power during sympathetic blockade 70.2 (9.1) and placebo (69.5 (8.1)) was statistically indistinguishable (p = .671). These findings clarify the interpretation of changes in HRV that occur during slow-paced breathing by showing that changes in low-frequency power under these conditions are almost entirely vagally mediated. Slow-paced breathing is an effective tool for cardiac vagal activation.

Inconsistent relation of nonlinear heart rate variability indices to increasing vagal tone in healthy humans.

Prior work has found that linear heart rate variability (HRV) indices do not accurately reflect cardiac vagal control, and nonlinear indices of HRV have been proposed as alternative tools that may better capture cardiac vagal effects. We used progressive low dose atropine to induce changes in cardiac vagal tone to test the hypotheses that nonlinear HRV indices accurately reflect cardiac vagal control, and that their changes in response to low dose atropine correlate with those in RR interval. Changes in RR interval and HRV indices during intravenous injections of saline (control) and 6 cumulative doses of atropine (from 1.4 to 7.2 μg/kg) during controlled breathing at 15 breaths per minute were assessed in 14 young healthy individuals. As expected, low dose atropine increased average RR interval (vagotonic effect). There was no strong association between vagotonic changes in RR interval and the majority of nonlinear HRV indices, either within or among subjects. These data suggest an inconsistent relationship between responses of nonlinear HRV indices and RR interval to changes in cardiac vagal tone. Therefore, nonlinear HRV indices may not be reliable indices of cardiac vagal control in healthy humans.

Nocturnal Heart Rate Variability Spectrum Characterization in Preschool Children With Asthmatic Symptoms.

Asthma is a chronic lung disease that usually develops during childhood. Despite that symptoms can almost be controlled with medication, early diagnosis is desirable in order to reduce permanent airway obstruction risk. It has been suggested that abnormal parasympathetic nervous system (PSNS) activity might be closely related with the pathogenesis of asthma, and that this PSNS activity could be reflected in cardiac vagal control. In this work, an index to characterize the spectral distribution of the high frequency (HF) component of heart rate variability (HRV), named peakness ($\wp$), is proposed. Three different implementations of $\wp$, based on electrocardiogram (ECG) recordings, impedance pneumography (IP) recordings and a combination of both, were employed in the characterization of a group of preschool children classified attending to their risk of developing asthma. Peakier components were observed in the HF band of those children classified as high-risk ( $p < 0.005$), who also presented reduced sympathvoagal balance. Results suggest that high-risk of developing asthma might be related with a lack of adaptability of PSNS.

Kava for Generalized Anxiety Disorder: A Review of Current Evidence

Generalized anxiety disorder (GAD) is a chronic and debilitating condition characterized by persistent and overpowering anxiety. Treatment of GAD with antidepressants and benzodiazepines is only moderately effective and not free from side effects. Kava (Piper methysticum) has been explored as a potential phytotherapeutic option for GAD. To perform a systematic review and meta-analysis of the available evidence on Kava as a treatment for GAD. Systematic search of English-language publications from major databases for clinical trials reporting the effects of Kava for the treatment of GAD. Twelve articles were included in this review. Evidence supporting Kava as an effective treatment for GAD was found in two placebo-controlled trials and a reference-controlled trial. One negative trial demonstrated that Kava was not more effective than placebo. Meta-analyses of the results of three placebo-controlled trials (n = 130) favored Kava for GAD treatment with effect sizes between 0.59 and 0.99 (standard mean difference) without reaching statistical significance. Kava is an appealing treatment option to GAD patients who are more attune to natural remedies or lifestyle approaches to reduce stress. Positive patient experiences and improvement of vagal cardiac control due to Kava treatment were also reported in the literature. Kava is safe and well tolerated for short-term (4-8 weeks) therapeutic use at a dosage of 120-280 mg per day of Kavalactones, regardless of dosage schedule. Current evidence, although promising, is insufficient to confirm the effect of Kava for GAD treatment beyond placebo. New evidence is expected from a large, multisite ongoing trial.

Differences in Autonomic Recovery Following Maximal Resistance Exercise in Young and Older Adults

Aging is associated with negative changes in autonomic function and an increased risk of cardiovascular disease. The risk of a sudden cardiovascular event is elevated during and immediately following vigorous exercise, potentially due to increased sympathetic dominance. Because resistance exercise provides a large hypertensive stimulus and young adults show reduced cardiac vagal control during recovery, further exploration of the effects of an acute bout of resistance exercise on autonomic function and recovery in older adults is required.PurposeTo evaluate the effects of high‐intensity lower body resistance exercise on autonomic modulation in young (YA) and older adults (OA).MethodsThirty‐five YA (17 female, 26±5 years, BMI: 23.8±3.2 kg/m2) and 25 OA (14 female, 60±6 years, BMI: 29.9±5.4 kg/m2) completed 3 sets of 10 repetitions of maximal isokinetic knee flexion/extension on a force dynamometer in a semi‐recumbent position. Throughout the protocol, participants were instrumented with a 3‐lead ECG and finger‐photoplethysmography for continuous heart rate and blood pressure recordings. Time and spectral components of heart rate (HRV) and blood pressure variability (BPV), non‐invasive indices of autonomic function, were analyzed using five‐minute segments at baseline and 5‐minutes post‐resistance exercise.ResultsAt baseline, OA had higher systolic and mean blood pressure, as well as lower root mean square of successive differences (RMSSD), low‐frequency (LF) RRI, high‐frequency (HF) RRI, and baroreceptor sensitivity (BRS) (p&lt;0.05). At 5‐minutes post‐exercise, LF/HF ratio and LF systolic blood pressure increased (p&lt;0.05). RMSSD, HF RRI, and BRS, were greater at baseline for YA and all variables decreased at 5‐min, while older adults did not change over time (interactions, p&lt;0.05).ConclusionsThese results suggest YA exhibited parasympathetic withdrawal 5‐minutes post‐exercise, whereas OA either did not exhibit parasympathetic withdrawal or had already recovered at 5 min post exercise, but this cannot be distinguished from our data. Both groups appear to have elevated sympathetic modulation at 5‐min, as indicated by RRI, LF/HF and LF BPV. Further investigation of the response during exercise is required. However, there are clear differences in autonomic recovery following maximal resistance exercise in OA.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Cardiac vagal flexibility and accurate personality impressions: Examining a physiological correlate of the good judge.

Research has long sought to identify which individuals are best at accurately perceiving others' personalities or are good judges, yet consistent predictors of this ability have been difficult to find. In the current studies, we revisit this question by examining a novel physiological correlate of social sensitivity, cardiac vagal flexibility, which reflects dynamic modulation of cardiac vagal control. We examined whether greater cardiac vagal flexibility was associated with forming more accurate personality impressions, defined as viewing targets more in line with their distinctive self-reported profile of traits, in two studies, including a thin-slice video perceptions study (N = 109) and a dyadic interaction study (N = 175). Across studies, we found that individuals higher in vagal flexibility formed significantly more accurate first impressions of others' more observable personality traits (e.g., extraversion, creativity, warmth). These associations held while including a range of relevant covariates, including cardiac vagal tone, sympathetic activation, and gender. In sum, social sensitivity as indexed by cardiac vagal flexibility is linked to forming more accurate impressions of others' observable traits, shedding light on a characteristic that may help to identify the elusive good judge and providing insight into its neurobiological underpinnings.

Resting heart rate variability is associated with ex-Gaussian metrics of intra-individual reaction time variability

The relationships between vagally mediated heart rate variability (vmHRV) and the cognitive mechanisms underlying performance can be elucidated with ex-Gaussian modeling—an approach that quantifies two different forms of intra-individual variability (IIV) in reaction time (RT). To this end, the current study examined relations of resting vmHRV to whole-distribution and ex-Gaussian IIV. Subjects (N = 83) completed a 5-minute baseline while vmHRV (root mean square of successive differences; RMSSD) was measured. Ex-Gaussian (sigma, tau) and whole-distribution (standard deviation) estimates of IIV were derived from reaction times on a Stroop task. Resting vmHRV was found to be inversely related to tau (exponential IIV) but not to sigma (Gaussian IIV) or the whole-distribution standard deviation of RTs. Findings suggest that individuals with high vmHRV can better prevent attentional lapses but not difficulties with motor control. These findings inform the differential relationships of cardiac vagal control to the cognitive processes underlying human performance.

Heart rate variability associated with grey matter volumes in striatal and limbic structures of the central autonomic network

Previous neuroimaging studies have highlighted the functional neural correlates of cardiac vagal activity, providing convergent evidence that the cardiac vagal function is controlled by a number of brain regions in the central autonomic network (CAN). However, it remains largely unknown whether the underlying anatomical basis of those identified regions are associated with individual difference in vagal function. To address the above issue, this study used a large sample of healthy subjects (n = 185) and voxel-based morphometry (VBM) analysis to verify brain morphometry associated with vagal control and the associations varied as a function of gender and age. Our results showed that high frequency component of heart rate variability (HF-HRV) was negatively correlated with grey matter volumes in the right putamen, caudate, amygdala, insula, superior temporal gyrus, temporal pole, and parahippocampal gyrus, demonstrating brain morphological variation in the right-sided striatal and limbic structures of the CAN associated with individual difference in cardiac vagal function. Additionally, gender and age effects on the relationship between cardiac vagal control and brain morphometry were not significant in the current dataset. These findings underscore the importance of striatal and limbic structures in parasympathetic control, and shed light on the underlying anatomical substrates of cardiac vagal activity.

Behavioral depression is associated with increased vagally mediated heart rate variability in adult female cynomolgus monkeys (Macaca fascicularis)

IntroductionDepressive symptoms (DS) in humans are associated with decreased resting state vagal activity, but sex seems to moderate this association. Recently, in human females DS have been associated with greater or similar cardiac vagal activity compared to men in both, clinical and non-clinical samples. A previously validated animal model of behavioral depression was used in the present study to investigate the association of DS and cardiac vagal activity in non-human primates. MethodsThe root mean square of successive differences between adjacent heart beats (RMSSD) was used as an indicator of vagally-mediated heart rate variability in 24h heart rate recordings collected via telemetry in 42 adult female cynomolgus monkeys (Macaca fascicularis). Hierarchical regression models were used to estimate differences in RMSSD comparing monkeys with and without DS. To capture circadian variation patterns of RMSSD, additional quadratic, cubic and quartic terms of hour were added. ResultsMonkeys showing behavioral DS had higher overall 24-h RMSSD. The interaction term of daytime with DS and polynomials of hour contributed significantly to the variance across models. ConclusionsThis is the first study investigating the association of DS and 24h cardiac vagal control in female non-human primates. Results replicate existing human studies showing higher cardiac vagal control in behavioral depressed vs. non-depressed female monkeys.

Mindfulness-Based Relapse Prevention for Substance Use Disorders: Effects on Cardiac Vagal Control and Craving Under Stress.

Mindfulness-based relapse prevention (MBRP) is a therapy for addictive behaviors that incorporates cognitive-behavioral relapse prevention (RP) skills with mindfulness training to increase awareness and skillful action in high-risk situations. Stress is a common reason reported for substance use relapse, and using physiological measures to measure stress engagement may help us identify mechanisms of clinical improvement. Specifically, salutatory changes in HF-HRV post-treatment may serve as a marker of treatment efficacy. We investigated tonic and phasic heart rate variability (HRV) to a cognitive stressor (i.e., arithmetic challenge) following 8 weeks of RP, MBRP, or post-detox treatment known as treatment as usual (TAU; n = 34). MBRP was related to higher levels of tonic and phasic HF-HRV, lower levels of anxiety, and lower heart rate reactivity (than TAU only) compared to RP and TAU. This suggests that those who completed MBRP are engaging with stress, but perhaps in a more adaptive, flexible manner. MBRP is associated with higher cardiac vagal control and lower stress/anxious reactivity. Given that negative emotions are an important component of relapse, these results lend further support to say that mindfulness may be helpful for those with substance use disorders.

Heart rate variability predicts inhibitory control in adults with autism spectrum disorders

Several studies suggest that inhibition difficulties among people with ASD might be related to atypical cardiac vagal control. We examined how low versus high baseline heart rate variability (HRV) influences prepotent response inhibition in 31 males with autism spectrum disorder (ASD; mean age: 32.2; mean IQ: 107.8) compared to 39 typically developing (TD) males (mean age: 30.5; mean IQ: 102.0) by administering a stop signal task. Moreover, we examined whether adding an affective manipulation would alter findings and whether this manipulation affected HRV. Findings indicated that baseline HRV influenced inhibition in ASD males. Specifically, an ASD subgroup with low baseline HRV performed significantly worse compared to an ASD subgroup with high baseline HRV. No influence of baseline HRV was found in TD males. The affective manipulation did negatively influence performance and also altered HRV. Although replication is required, these first findings indicate that baseline cardiac vagal control seems to affect inhibitory control in males with ASD.

Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (−0.74<rg<−0.55) and blood pressure (−0.35<rg<−0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.

Inflexibility as a Vulnerability to Depression: A Systematic Qualitative Review.

The study of vulnerabilities to depression typically identifies factors that are thought to be universally maladaptive or adaptive. In contrast, researchers recently have theorized that the ability to flexibly engage in different thoughts and behaviors that fit situational demands may be most indicative of psychological health. We review empirical evidence from 147 studies reporting associations between five components of flexibility (set-shifting, affective set-shifting, cardiac vagal control, explanatory flexibility, and coping flexibility) and depression and classify studies according to strength of study design. Evidence from correlational and case-controlled studies suggests cross-sectional relationships, but few prospective studies have been conducted. We discuss limitations of existing studies, identify new directions for programmatic research, and discuss implications that flexibility has for the prevention and treatment of depression.

Slow Yogic Breathing and Long-Term Cardiac Autonomic Adaptations: A Pilot Study.

To examine whether long-term practice of yogic breathing alters cardiac autonomic control. Age-sex matched, cross-sectional, physiologic pilot study. Spaulding Rehabilitation Hospital, Cardiovascular Laboratory, Cambridge, MA. Twenty-six (26) long-term yoga practitioners and 26 age- and sex-matched controls, free of cardiovascular disease. Cardiac vagal outflow as assessed by respiratory sinus arrhythmia (RSA). During unpaced (spontaneous) breathing, yoga practitioners exhibited augmented RSA compared to controls (yoga 364.8 ± 75.3 vs. 194.7 ± 46.0 ms2Hz-1, p = 0.03). However, during paced breathing at 0.25 Hz (15 breaths/min), which accounts for inter- and intravariability in breath rate, RSA did not differ between groups (yoga 224.8 ± 48.4 vs. 271.3 ± 59.7 ms2Hz-1, p = 0.98). Furthermore, the relationship between age and RSA, such that RSA declines with age, did not qualitatively differ between groups. Long-term practice of yogic slow breathing does not appear to augment cardiac vagal control nor prevent known age-related declines.

Cardiac vagal control in a knock-in mouse model of dilated cardiomyopathy with a troponin mutation.

The aim of this study was to evaluate cardiac vagal nerve activity and identify the abnormality of cardiac vagal control in heart failure caused by dilated cardiomyopathy (DCM) using a knock-in mouse model with a ΔK210 mutation in the cardiac troponin T gene. The effects of electrical stimulation of the cervical vagal nerve at 5 and 10Hz (peripheral vagal control) and α2-adrennoceptor stimulation by intravenous medetomidine at 0.1mg/kg (central vagal control) were examined in wild-type (WT) mice and DCM mice. Microdialysis technique was applied to the left ventricular myocardium of anesthetized mice and myocardial interstitial acetylcholine (ACh) levels were measured by HPLC as an index of ACh release from cardiac vagal nerve endings. Electrical vagal nerve stimulation increased cardiac interval and myocardial interstitial ACh level in both WT and DCM mice, and these responses did not differ between WT and DCM mice. In contrast, intravenous medetomidine increased cardiac interval and myocardial interstitial ACh level in both WT and DCM mice, but the responses of cardiac interval and myocardial interstitial ACh level were significantly suppressed in DCM mice compared to WT mice. Medetomidine did not affect the myocardial interstitial ACh response induced by vagal nerve stimulation in WT mice. In this mouse model of DCM, peripheral vagal control including ACh release from vagal nerve endings and the postsynaptic response of pacemaker cells was preserved, but central vagal control through α2-adrenoceptors was impaired.

Police work stressors and cardiac vagal control.

This study examines relationships between the frequency and intensity of police work stressors and cardiac vagal control, estimated using the high frequency component of heart rate variability (HRV). This is a cross-sectional study of 360 officers from the Buffalo New York Police Department. Police stress was measured using the Spielberger police stress survey, which includes exposure indices created as the product of the self-evaluation of how stressful certain events were and the self-reported frequency with which they occurred. Vagal control was estimated using the high frequency component of resting HRV calculated in units of milliseconds squared and reported in natural log scale. Associations between police work stressors and vagal control were examined using linear regression for significance testing and analysis of covariance for descriptive purposes, stratified by gender, and adjusted for age and race/ethnicity. There were no significant associations between police work stressor exposure indices and vagal control among men. Among women, the inverse associations between the lack of support stressor exposure and vagal control were statistically significant in adjusted models for indices of exposure over the past year (lowest stressor quartile: M = 5.57, 95% CI 5.07 to 6.08, and highest stressor quartile: M = 5.02, 95% CI 4.54 to 5.51, test of association from continuous linear regression of vagal control on lack of support stressor β = -0.273, P = .04). This study supports an inverse association between lack of organizational support and vagal control among female but not male police officers.

A Little Goes a Long Way: Low Working Memory Load Is Associated with Optimal Distractor Inhibition and Increased Vagal Control under Anxiety.

Anxiety impairs both inhibition of distraction and attentional focus. It is unclear whether these impairments are reduced or exacerbated when loading working memory with non-affective information. Cardiac vagal control has been related to top–down regulation of anxiety; therefore, vagal control may reflect load-related inhibition of distraction under anxiety. The present study examined whether: (1) the enhancing and impairing effects of load on inhibition exist together in a non-linear function, (2) there is a similar association between inhibition and concurrent vagal control under anxiety. During anxiogenic threat-of-noise, 116 subjects maintained a digit series of varying lengths (0, 2, 4, and 6 digits) while completing a visual flanker task. The task was broken into four blocks, with a baseline period preceding each. Electrocardiography was acquired throughout to quantify vagal control as high-frequency heart rate variability (HRV). There were significant quadratic relations of working memory load to flanker performance and to HRV, but no associations between HRV and performance. Results indicate that low load was associated with relatively better inhibition and increased HRV. These findings suggest that attentional performance under anxiety depends on the availability of working memory resources, which might be reflected by vagal control. These results have implications for treating anxiety disorders, in which regulation of anxiety can be optimized for attentional focus.

Vagally-mediated heart rate variability and indices of well-being: Results of a nationally representative study.

High frequency (HF) heart rate variability (HRV) has long been accepted as an index of cardiac vagal control. Recent studies report relationships between HF-HRV and indices of positive and negative affect, personality traits and well-being but these studies generally are based on small and selective samples. These relationships were examined using data from 967 participants in the second Midlife in the U.S. (MIDUS II) study. Participants completed survey questionnaires on well-being and affect. HF-HRV was measured at rest. A hierarchical series of regression analyses examined relationships between these various indices and HF-HRV before and after adjustment for relevant demographic and biomedical factors. Significant inverse relationships were found only between indices of negative affect and HF-HRV. Relationships between indices of psychological and hedonic well-being and positive affect failed to reach significance. These findings raise questions about relationships between cardiac parasympathetic modulation, emotion regulation, and indices of well-being. (PsycINFO Database Record