Vagal Suppression Research Articles

Mothers' responses to children's negative emotions and child emotion regulation: The moderating role of vagal suppression

Mothers' responses to children's negative emotions and child emotion regulation: The moderating role of vagal suppression

Effects of emotion regulation difficulties on the tonic and phasic cardiac autonomic response.

BackgroundEmotion regulation theory aims to explain the interactions between individuals and the environment. In this context, Emotion Regulation Difficulties (ERD) disrupt the physiological component of emotions through the autonomic nervous system and are involved in several psychopathological states.ObjectiveWe were interested in comparing the influence of a film-elicited emotion procedure on the autonomic nervous system activity of two groups with different levels of emotion regulation difficulties.MethodsA total of 63 women (undergraduate students) ranging from 18 to 27 (20.7±1.99) years old were included. Using the upper and lower quartile of a questionnaire assessing the daily difficulties in regulating emotions, two groups, one with low (LERD) and one with high (HERD) levels of emotion regulation difficulties, were constituted and studied during a film-elicited emotion procedure. Cardiac vagal activity (HF-HRV) was analyzed during three periods: baseline, film-elicited emotion, and recovery.ResultsThe cardiovascular results showed a decrease in HF-HRV from baseline to elicitation for both groups. Then, from elicitation to recovery, HF-HRV increased for the LERD group, whereas a low HF-HRV level persisted for the HERD group.ConclusionsThe HERD group exhibited inappropriate cardiac vagal recovery after a negative emotion elicitation had ended. Cardiac vagal tone took longer to return to its initial state in the HERD group than in the LERD group. Prolonged cardiac vagal suppression might constitute an early marker of emotion regulation difficulties leading to lower cardiac vagal tone.

Experimental Evaluation of the Cardiac Rhythm Originating in Myocardial Sleeves of Pulmonary Veins Using a Monophasic Action Potential

Spontaneous depolarization similar to that from the sinus node was documented from the myocardial sleeves of pulmonary veins (PV) after isolation procedures. It was then hypothesized that sinus node-like tissue is present in the PVs of humans. Based on a number of features, the myocardium of myocardial sleeves (MS) is highly arrhythmogenic. Membrane potentials originating from MS are invariably recordable at the PVs ostia in patients with atrial fibrillation (AF) and delayed conduction around the PVs ostia may play a role in re-entry process responsible for the initiation and maintenance of AF. Diagnostic and therapeutic evidence of premature atrial beats induced in MS of PVs and resulting in launch of AF was detected by 3D electroanatomic method of monophasic action potential (MAP). MAP recording plays an important role in a direct view of human myocardial electrophysiology under both physiological and pathological conditions. Its crucial importance lies in the fact that it enables the study of the action potential of myocardial cell in vivo and, therefore, the study of the dynamic relation of this potential with all the organism variables. The knowledge of pathological MAPs from PV myocardial sleeves can help us to confirm a diagnosis when finding the similar action potential morphology. MAP can be also used to evaluate the therapeutic efficiency of vagal nerves suppression, radiofrequency ablation or other treatment procedures in PVs myocardial sleeves as well as for post-treatment following up.

Links between adolescent sympathetic and parasympathetic nervous system functioning and interpersonal behavior over time

Extensive research has investigated links between individual differences in youths' autonomic nervous system (ANS) functioning and psychological outcomes related to emotion regulation, yet little of this research has examined developmental change. The study tested whether individual differences in youths' tonic and stress-induced ANS functioning, assessed at age 14, and changes in ANS functioning from age 14 to 16 predicted corresponding changes in youths' behavioral warmth, as displayed during videotaped mother-child conflict interactions conducted at age 14 and 16. Increased behavioral warmth was predicted by increased baseline respiratory sinus arrhythmia (RSA), increased SCL stress reactivity, decreased RSA stress reactivity (i.e., greater vagal suppression), and decreased baseline SCL. There was also an interaction between RSA stress reactivity at age 14 and changes in maternal warmth from age 14 to 16, such that increased maternal warmth was only associated with increased adolescent warmth for adolescents with lower RSA stress reactivity at age 14.

Mothers' responses to children's negative emotions and child emotion regulation: the moderating role of vagal suppression.

The current study examined the moderating effect of children's cardiac vagal suppression on the association between maternal socialization of negative emotions (supportive and nonsupportive responses) and children's emotion regulation behaviors. One hundred and ninety-seven 4-year-olds and their mothers participated. Mothers reported on their reactions to children's negative emotions and children's regulatory behaviors. Observed distraction, an adaptive self-regulatory strategy, and vagal suppression were assessed during a laboratory task designed to elicit frustration. Results indicated that children's vagal suppression moderated the association between mothers' nonsupportive emotion socialization and children's emotion regulation behaviors such that nonsupportive reactions to negative emotions predicted lower observed distraction and lower reported emotion regulation behaviors when children displayed lower levels of vagal suppression. No interaction was found between supportive maternal emotion socialization and vagal suppression for children's emotion regulation behaviors. Results suggest physiological regulation may serve as a buffer against nonsupportive emotion socialization.

Preschool Children’s Cardiac Reactivity Moderates Relations Between Exposure to Family Violence and Emotional Adjustment

This study examined relations between cardiac reactivity, family violence exposure (i.e., child maltreatment [CM] and inter-partner violence [IPV]), and preschool children's emotional adjustment. A sample of 92 mother-preschooler dyads was drawn from predominantly low-income, rural communities. Dyads participated in a laboratory session in which children's Electrocardiograph (ECG) monitoring occurred during a resting baseline, joint-challenge, and individual emotional and cognitive tasks. Mothers consented to review of Children & Youth Services (CYS) records for CM and completed an IPV measure. Mothers rated children's emotional adjustment, and observers rated children on their frustration and positive affect. Children's vagal suppression was shown to moderate relations between family violence exposure and emotional adjustment. Findings indicated that children greater in vagal suppression showed better emotional adjustment when from families low in violence. However, regardless of children's level of vagal suppression, all children showed poorer emotional adjustment when from families high in violence.

Acute effects of ganglionated plexi ablation on sinoatrial nodal and atrioventricular nodal functions

Ganglionated plexus (GP) ablation has been shown effective for eliminating atrial fibrillation (AF), the most common clinical tachyarrhythmia. However, the safety of destroying the main cardiac autonomic structures remains unclear. This study investigated the acute effects of GP ablation on the sinoatrial nodal (SAN) and atrioventricular nodal (AVN) functions in a canine model. In 10 open-chest dogs, multiple electrode catheters were sutured at both atria for recording and pacing. SAN and AVN function were evaluated. GP ablation caused no significant change of sinus rate immediately after GP ablation compared with the baseline state. After GP ablation, the sinus node recovery time (SNRT) and corrected SNRT did not show significant changes at long pacing cycle lengths (CLs), and only showed significant decrease at shorter pacing CLs. The AH interval at different pacing CLs, the Wenckebach atrioventricular block (AVB) CL, 2:1 AVB CL or the ventricular rate during AF were not significantly altered by GP ablations. Vagal suppression of SAN and AVN functions was eliminated by GP ablation. GP staining showed abundant choline acetyl transferase or tyrosine hydroxylase positive neurons. These findings suggest the functions of the SAN and AVN are mainly retained after GP ablation. These results may be partially related to destroying both parasympathetic and sympathetic elements in the GP by ablation.

Rationale for faster oral delivery to overcome the pathophysiology associated with dental pain — Biopharmaceutic and pharmacokinetic challenges

Recent published evidences on ibuprofen and meloxicam confirm the need of faster oral drug absorption to overcome the pathophysiological conditions associated with dental pain (due to excessive vagal nerve suppression) in order to provide relief in acute pain management. While the communication provides relevant case studies to support the hypothesis in both dental pain and migraine attacks, it also provides biopharmaceutical and pharmacokinetic challenges of developing such a strategy for faster oral drug absorption. It is envisaged that the unmet need in this area, to overcome the pathophsiological barriers, should provide impetus for further research exploration in formulation strategies and biopharmaceutical/pharmacokinetic integration.

Pharmacokinetics of meloxicam administered as regular and fast dissolving formulations to the rat: Influence of gastrointestinal dysfunction on the relative bioavailability of two formulations

It is believed that acute pain suppresses nervus vagus, thereby, influencing gastrointestinal secretion and motility, which are the two factors that are necessary for disintegration and dissolution of solid dosage forms. We studied the pharmacokinetics of meloxicam and the effect of vagal suppression on the oral bioavailability and bioequivalence using a marketed (Brand) and a fast dissolving (FD) formulation. In simulated gastric juice, FD was disintegrated in 30 s and released 30% of its meloxicam in 15 min and 60% in 2 h. Brand was disintegrated in 4.5 min with a dissolution rate of 5.6% in 30 min that stayed plateau for the 2 h experiment time. To suppress the vagus nerve, intraperitoneal injection of 20 mg/kg propantheline 1 and 2 h before meloxicam administration was used. Meloxicam (0.9 mg/kg) was administered to both control and vagally suppressed rats i.v. ( n = 4–6/group) as well as orally in a paired random fashion as broken pieces of Brand or FD tablets ( n = 7/ group). Serial (0–48 h) blood samples were collected for pharmacokinetic and bioavailability studies. Relative bioavailability was measured according to a method in use for bioequivalence assessments. Systemic pharmacokinetics of meloxicam was not affected by vagal suppression. Absolute bioavailability of meloxicam, based on 0–48 h measurement, was >0.68 regardless of the type of formulation and treatment. Vagal suppression, however, significantly reduced AUC 0–24 (μg h mL −1) for Brand (control, 58.8 ± 22.0 vs treated, 22.1 ± 9.7) but not for FD (control, 63.5 ± 17.9 vs treated, 64.6 ± 8.9) indicating a reduced absorption rate for the former. The peak time for Brand was also significantly delayed by over 20 h for Brand and not for FD. Relative bioavailability was confirmed between FD and Brand that were in control but not in the vagally suppressed rats, indicating a disease-dependent bioequivalence. The effect of vagal suppression on the drug absorption rate can be obviated if the disintegration and dissolution become independent of gastrointestinal motility and secretion.

Heart rate and arterial pressure variability in the experimental renovascular hypertension model in rats

This study was conducted in one kidney, one clip (1K1C) Goldblatt hypertensive rats to evaluate vascular and cardiac autonomic control using different approaches: 1) evaluation of the autonomic modulation of heart rate (HR) and systolic arterial pressure (SAP) by means of autoregressive power spectral analysis 2) assessment of the cardiac baroreflex sensitivity; and 3) double blockade with methylatropine and propranolol.The 1K1C group developed hypertension and tachycardia. The 1K1C group also presented reduction in variance as well as in LF (0.23±0.1 vs. 1.32±0.2 ms2) and HF (6.6±0.49 vs. 15.1±0.61 ms2) oscillations of pulse interval. Autoregressive spectral analysis of SAP showed that 1K1C rats had an increase in variance and LF band (13.3±2.7 vs. 7.4±1.01 mmHg2) in comparison with the sham group. The baroreflex gain was attenuated in the hypertensive 1K1C (−1.83±0.05 bpm/mmHg) rats in comparison with normotensive sham (−3.23±0.06 bpm/mmHg) rats. The autonomic blockade caused an increase in the intrinsic HR and sympathetic predominance on the basal HR of 1K1C rats. Overall, these data indicate that the tachycardia observed in the 1K1C group may be attributed to intrinsic cardiac mechanisms (increased intrinsic heart rate) and to a shift in the sympathovagal balance towards cardiac sympathetic over-activity and vagal suppression associated to depressed baroreflex sensitivity. Finally, the increase in the LF components of SAP also suggests an increase in sympathetic activity to peripheral vessels.

Rapidly dissolving formulations for quick absorption during pain episodes: Ibuprofen

Pain or its associated trauma impairs oral absorption of drugs due, perhaps, to a diminished disintegration and dissolution rate secondary to suppression of the vagal nervous system. We first examined whether ibuprofen absorption is impaired on suppressing vagus nerve activity in a rat model. Secondly, we examined if ibuprofen absorption in rats during vagal suppression and in humans experiencing dental pain is improved by enhancing disintegration and dissolution rate of the administered formulation. Vagal suppression was achieved in rats by administering 20 mg/kg propantheline i.p. 2 h and 1 h before gastric gavage of 20 mg/kg ibuprofen as small crushed pieces of a regular release and a fast-dissolving ibuprofen caplets. In humans, after surgical removal of wisdom teeth and emergence of pain, 2 A 200 mg ibuprofen as regular released (n = 14) and fast-dissolving (n = 12) caplets were administered. Serial blood sample were collected for bioavailability studies. Vagal suppression resulted in significantly decreased absorption rate of ibuprofen enantiomers following administration of the regular release but not after fast-dissolving formulation. Human dental pain was associated with significantly slower absorption of ibuprofen enantiomers from the regular released as compared with the fast-dissolving caplets. Within the first hour post-dose the area under the plasma drug concentration-time curve was raised to 2.7-fold (p < 0.05) after the fast-dissolving as compared with the regular release formulations. There was a 1-h difference in the peak concentration time (tmax) between the two caplets. Impaired drug absorption appears to be due to slow disintegration and dissolution encountered during pain episodes.

Parental Socialization, Vagal Regulation, and Preschoolers’ Anxious Difficulties: Direct Mothers and Moderated Fathers

Parental supportiveness and protective overcontrol and preschoolers' parasympathetic regulation were examined as predictors of temperamental inhibition, social wariness, and internalizing problems. Lower baseline vagal tone and weaker vagal suppression were expected to mark poorer dispositional self-regulatory capacity, leaving children more susceptible to the influence of parental socialization. Less supportive mothers had preschoolers with more internalizing problems. One interaction between baseline vagal tone and maternal protective overcontrol, predicting social wariness, conformed to the moderation hypothesis. Conversely, vagal suppression moderated several links between paternal socialization and children's anxious difficulties in the expected pattern. There were more links between mothers' self-reported parenting and child outcomes than were noted for direct observations of maternal behavior, whereas the opposite tended to be true for fathers.

Children’s sleep and adjustment: the moderating role of vagal regulation

Children's vagal tone and vagal suppression were examined as moderators of associations between children's sleep disruptions and adjustment problems. A relatively large sample (n = 167) of boys and girls who ranged in age between 8 and 9 years participated with their parents. Sleep was examined via actigraphy in the child's home for seven consecutive days. Children's vagal tone was examined during baseline conditions, and their vagal suppression was assessed in response to an inter-adult argument. In comparison with children exhibiting higher levels of vagal tone, those with lower vagal tone were at increased risk of externalizing problems, depression symptoms and higher body mass index associated with increased sleep disruptions (i.e. lower Sleep Efficiency, increased Wake Minutes and fewer Sleep Minutes). Thus, lower vagal tone functioned as a vulnerability factor for adjustment problems in the context of sleep problems. A higher level of vagal suppression to the inter-adult argument functioned as a protective factor against externalizing behaviors otherwise associated with increased Wake Minutes and reduced Sleep Efficiency. Findings demonstrating the moderating role of vagal functioning in the context of sleep disruptions are novel, and highlight the importance of individual differences in children's physiological regulation for sleep and adjustment.

Vasopressor Use in the Critical Care Unit for Treatment of Persistent Post-carotid Artery Stent Induced Hypotension

Hypotension is common following carotid artery stenting (CAS), and may be mediated by vagal stimulation and/or suppression of spinal sympathetic outflow. Both mixed alpha/beta agonists (dopamine (DA)), and more selective alpha- agonists (norepinephrine (NE) and phenylephrine (PE)), have been used, but the most effective treatment of post-CAS hypotension is unknown. We analyzed data for consecutive patients requiring vasopressor treatment of post-CAS hypotension. The treating physician made choice of vasopressor. Endpoints included infusion duration, coronary care unit (CCU) length of stay (LOS), and any major adverse events (death, stroke, myocardial infarction, arrhythmia). During the study period, CAS stenting was performed in 623 patients. CCU admission in atropine non-responders for vasopressor treatment was required in 42 patients (6.7%). DA was used in 20 patients (48%), NE in 13 patients (31%), and PE in nine patients (21%). Vasopressor infusion time was 31.8 +/- 10.6 h for DA, compared with 23.8 +/- 8.1 h for NE (P = 0.052) and 22.1 +/- 6.1 h (P = 0.028) for PE. CCU LOS was 46.5 +/- 14.1 h for DA compared with 36.9 +/- 9.1 h for the NE and PE groups combined (P = 0.056). Major adverse events were more common in patients receiving DA than among patients receiving NE or PE (P = 0.04). Compared with DA, treatment of post-CAS hypotension with a selective alpha-agonist (NE or PE) is associated with shorter drug infusion time, shorter CCU LOS, and fewer major adverse events.

Acute psychosocial challenge and cardiac autonomic response in women: The role of estrogens, corticosteroids, and behavioral coping styles

Theoretical statements, as well as clinical and experimental data, suggest that the amplitude of cardiovascular reactivity to acute stressors can be a good predictor of preclinical and clinical cardiovascular states. The aim of the present study is to investigate the role of estrogens, the hypothalamic-pituitary-adrenocortical activity, and the behavioral profile in individual cardiac autonomic reactivity to brief laboratory stressors in women. Thirty-six adult, healthy women were exposed to a stress interview and a mental task test, each lasting 5 min. They were assigned to two experimental groups: D4, i.e. 4 days after menses beginning (follicular phase, n=18), and D14, i.e. 14 days after menses beginning (ovulatory phase, n=18). The cardiac measurements in the baseline, stress and recovery periods consisted in heart rate (average R-R interval) and parasympathetic tone (r-MSSD) quantification, while the HPA axis activity and stress reactivity were assessed via plasma cortisol and dehydroepiandrosterone concentrations. The ethological profile during the interview was drawn by means of non-verbal behavior analysis. The cardiac, adrenocortical and behavioral responses to the two stressors were similar in groups D4 and D14, despite significantly higher estradiol levels in the latter. Subjects with higher pre-stress cortisol levels had higher heart rate and lower vagal activity in the baseline, stress and recovery phases. Women showing higher level of submission were characterized by higher heart rate acceleration and vagal withdrawal during both the interview and the recovery phase. In addition, the subjects that exhibited greater displacement during the interview were also characterized by lower heart rate increments and less pronounced vagal suppression during post-stress recovery. In conclusion, the present results do not support a clear buffering role of estrogens in cardiovascular response to acute stressors. However, they confirm that baseline HPA axis activity can be predictive of cardiac autonomic activity and stress responsiveness. They also highlight the modulating role of the individual style of behavioral coping in cardiac sympathovagal stress reactivity. Therefore, the objective assessment of the individual behavioral profile via the analysis of non-verbal communication patterns might represent a powerful tool for identifying subjects with higher risk of cardiac events.

RSA fluctuation in major depressive disorder

Cardiac vagal control, as measured by indices of respiratory sinus arrhythmia (RSA), has been investigated as a marker of impaired self-regulation in mental disorders, including depression. Past work in depressed samples has focused on deficits in resting RSA levels, with mixed results. This study tested the hypothesis that depression involves abnormal RSA fluctuation. RSA was measured in depressed and healthy control participants during rest and during two reactivity tasks, each followed by a recovery period. Relative to controls, depressed persons exhibited lower resting RSA levels as well as less RSA fluctuation, primarily evidenced by a lack of task-related vagal suppression. Group differences in RSA fluctuation were not accounted for by differences in physical health or respiration, whereas group differences in resting RSA level did not survive covariate analyses. Depression may involve multiple deficits in cardiac vagal control.

Relation between cardiac vagal tone and performance in male military personnel exposed to high stress: Three prospective studies

Vagal tone has been proposed both as an index of emotion regulation and cognitive ability. To assess the relation between vagal tone and emotion regulation and cognitive ability, the present research prospectively measured vagal tone (measured either as high-frequency spectral power or respiratory sinus arrhythmia) in healthy participants exposed to high stress. The participants were active duty military personnel (men) enrolled in high intensity military training: Survival School (Experiments 1 and 3) and Combat Diver Qualification Course (Experiment 2). We consistently observed a significant relationship between low vagal tone and superior performance. The data suggest that vagal suppression is associated with enhanced performance under conditions of high stress and that this enhanced performance may be related to emotion regulation and cognitive functioning.

Domestic violence and vagal reactivity to peer provocation

This paper examined whether individual differences in children's vagal reactivity to peer provocation were related to domestic violence within the family. It also examined the question of whether conduct-problem children who show vagal augmentation to peer provocation come from families with high levels of domestic violence. During the peer provocation, children were expecting to interact with a difficult peer while vagal reactivity was assessed. Groups were divided into children who showed vagal augmentation and vagal suppression to the stressful peer interaction. Findings indicated that conduct-problem children who showed vagal augmentation to interpersonal challenge came from families with the highest levels of domestic violence. Vagal augmentation was also associated with a greater number of conduct-related problems for those children exposed to high levels of domestic violence. Discussion highlights the role of individual differences in physiological reactivity in understanding children's behavior problems in relation to domestic violence.

Longitudinal relations between marital conflict and child adjustment: Vagal regulation as a protective factor.

Although associations between marital conflict and children's adjustment problems are established, less is known about child individual differences that can have an impact on these relations. The authors examined longitudinal relations between marital conflict and children's adjustment using a community sample of elementary school-age children and young adolescents and assessed the role of children's vagal regulation in moderating the conflict-child problems link. Elevated marital conflict was predictive of negative child outcomes, and greater vagal suppression to a simulated argument was protective against internalizing problems associated with marital conflict. Findings are supportive of the value of a biopsychosocial perspective and illustrate that child vagal regulation can contribute to the aggregation or amelioration of risk for maladjustment in the context of exposure to marital conflict.

Letter Regarding the Article by Xue et al, “Functional Integration of Electrically Active Cardiac Derivatives From Genetically Engineered Human Embryonic Stem Cells With Quiescent Recipient Ventricular Cardiomyocytes”

To the Editor: The article by Xue et al1 on human embryonic stem cell-derived pacemakers illustrates that embryonic stem cells differentiated into spontaneously beating cardiocytes may function as biological pacemakers and mentions a potential limitation: The intrinsic pacemaker rate was slower than desirable. They suggest that incorporating HCN pacemaker channel genes might achieve more desirable rates, an idea consistent with our published results using HCN2 in gene- and adult human mesenchymal stem cell (hMSC)-based therapies.2–4 However, certain of the comments by Xue et al misinterpret our own work on HCN-loaded hMSCs. They state that “…these modified, undifferentiated, human mesenchymal stem cells are incapable of pacing quiescent cells because the former are neither electrically active nor genuine cardiac cells” (p 19). This statement suggests a misunderstanding of the rationale and underlying biophysics of the hMSC experiments. In fact, generation of pacemaker activity does not require delivery of an “excitable differentiated cardiac cell,” but only that the delivered cell (1) carry sufficient pacemaker current and (2) make gap junctions; thus, the hMSC-myocyte pair should behave as a pacemaker unit entirely equivalent to a single heart cell with substantial if. We clearly demonstrated both …