Increased Vagal Tone Research Articles

Role of the autonomic nervous system in atrial fibrillation pathogenesis

The aim of this review was to study the role of the autonomic nervous system in the pathogenesis of atrial fibrillation (AF), as well as to establish the relationship of autonomic regulation with other mechanisms underlying the AF At present, the molecular and cellular mechanisms underlying the AF have not been precisely established. There is interest in evidence showing that both sympathetic outflow and an increased vagal tone can initiate and support AF. As modern studies have shown, autonomic cardiac regulation can be an important factor in the pathogenesis of AF.

Heart Rate Variability Parameters During Psychogenic Non-epileptic Seizures: Comparison Between Patients With Pure PNES and Comorbid Epilepsy.

Introduction: Psychogenic non-epileptic seizures (PNES) may resemble epileptic seizures. There are few data about ictal ANS activity alterations induced by PNES in patients with pure PNES (pPNES) compared to PNES with comorbid epilepsy (PNES/ES). We aimed to compare heart rate variability (HRV) parameters and hence autonomic regulation in PNES in epileptic and non-epileptic patients.Methods: We obtained HRV data from video-electroencephalography recordings in 22 patients presenting PNES (11 pPNES and 11 PNES/ES) in awake, and supine states. We calculated HRV parameters in both time and frequency domains including low frequency (LF) power, high frequency power (HF), LF/HF ratio, square root of the mean of the sum of the squares of differences between adjacent R wave intervals (RMSSD) and the standard deviation of all consecutive R wave intervals (SDNN). We also evaluated approximate entropy (ApEn), cardiosympathetic index (CSI), and cardiovagal index (CVI). Four conditions were considered: basal condition (BAS), before PNES (PRE), during PNES (ICT) and after PNES (POST).Results: HRV analysis showed significantly higher ICT LF and LF/HF ratio vs. each condition. We also found higher POST HF vs. PRE and BAS, lower RRI in ICT vs. each condition and PRE vs. BAS. POST RMSSD was significantly higher compared to all other states. ICT CSI was significantly higher compared to all other states, whereas CSI was significantly lower in POST vs. PRE and PRE CVI lower than ICT and higher in POST vs. BAS and PRE. Also, ICT ApEn was lower than in all other states. Higher LF in pPNES vs. PNES/ES was also evident when compared across groups.Significance: A few studies examined HRV alterations in PNES, reporting high sympathetic tone (although less evident than in epileptic seizures). Our data suggest a sympathetic overdrive before and during PNES followed by a post-PNES increase in vagal tone. A sympathovagal imbalance was more evident in pPNES as compared to PNES/ES.

Greater Influence of Aerobic Fitness on Autonomic Support of Blood Pressure in Young Women Than in Older Women.

Aging increases autonomic support of blood pressure; however, the impact of aerobic fitness on autonomic support of blood pressure has not been addressed in women. As such, we hypothesized that aerobic fitness would be related to the change in blood pressure during ganglionic blockade such that women with greater aerobic fitness would have a blunted fall in blood pressure during ganglionic blockade due to increased vagal tone. Thirteen young premenopausal and 13 older postmenopausal women completed a screening visit where aerobic fitness (maximal oxygen consumption, VO2max) was measured. On a separate study day, participants were instrumented for assessment of muscle sympathetic nerve activity, heart rate (electrocardiography), and beat by beat blood pressure (arterial catheter and pressure transducer) and underwent pharmacological blockade of the autonomic ganglia using trimethaphan camyslate. Heart rate, blood pressure, and muscle sympathetic nerve activity were analyzed before and during ganglionic blockade. In young women, there was a significant relationship between aerobic fitness and the change in blood pressure during ganglionic blockade (r=0.761, P=0.003). In older women, there was no relationship between aerobic fitness and the change in blood pressure during ganglionic blockade (r=-0.106, P=0.73). Measures of heart rate variability were related to fitness in young women, but not older women (root mean square of successive differences between normal heartbeats, r=0.713, P=0.006 versus r=-0.172, P=0.575). Our data suggest that in young women, autonomic support of blood pressure is attenuated in those that are highly fit; however, this relationship is not significant in older women.

Man with fever, cough and atypical chest pain.

A 57-year-old Chinese man presented to the emergency department with fever, cough, and atypical chest pain. He had no medical history of note. At triage, his temperature was 101.2°F (38.4°C). His physical examination was unremarkable. His white cell count was normal, but he was both lymphopenic and thrombocytopenic. High sensitivity troponin I was not elevated. The patient's 12-lead electrocardiography (ECG) at triage is shown (Figure 1). The ECG is consistent with a type 1 Brugada ECG pattern. It demonstrates an rSR’ pattern with coved ST-segment elevations both in V1 and V2 (Figure 1). Given a positive contact history with COVID-19 cases, the patient was isolated given the clinical suspicion of COVID-19 pneumonia. His nasopharyngeal swab for COVID-19 RNA polymerase chain reaction testing returned positive. He was managed supportively with supplemental oxygen, and was discharged after 20 days (Figure 2). His ECG showed normalization of ST-segment elevations once afebrile (Figure 3). To the best of our knowledge, this is the first reported case of a type 1 Brugada ECG pattern unmasked by COVID-19 pneumonia. Brugada syndrome is more prevalent within Asia than in Europe or the United States.1 Several factors such as certain drugs, increase in vagal tone, and fever can unmask the type 1 Brugada ECG pattern.2 Our patient's presentation to hospital with COVID-19 pneumonia allowed for opportunistic diagnosis of an asymptomatic type 1 Brugada ECG pattern, and he has since been advised on avoiding specific medications, excessive exercise, and reducing fever.3 The authors have no conflicts of interest to disclose.

Cardiac vagal tone in preschool children: Interrelations and the role of stress exposure

IntroductionCardiac vagal tone has been understood as the biological correlate of emotion regulation and can be divided into emotion regulation (tonic cardiac vagal tone (TCVT)) and the flexibility to adapt to changing conditions (phasic cardiac vagal tone (PCVT)). There is evidence that TCVT influences PCVT dynamics in adults and that stress exposure impacts on cardiac vagal tone in adults and older children. The aim of the study was to investigate the impact of TCVT on PCVT dynamics in preschoolers and to identify the influence of stress exposures on cardiac vagal tone. MethodMeasures of heart rate variability including baseline (TCVT), during an age-adapted stress task (PCVT stress reactivity) and during recovery (PCVT recovery) were assessed in 222 children aged 2–6 years of the SPLASHY study. Further, parents were asked to complete questionnaires on early stress exposure (including pregnancy, birth and early life) and current stress exposure (including family stress and parenting). ResultsPreschool children with high TCVT showed less PCVT reactivity (p < 0.001) and more increase of vagal tone (PCVT) during early recovery (p = 0.016). Further only child's low birth weight was a relevant stress exposure impacting on early and late PCVT recovery (p = 0.03/p = 0.005). None of the other early or late stress exposure conditions, nor the accumulation of stress exposures influenced TCVT or PCVT dynamics in these healthy preschoolers. DiscussionTCVT impacts on PCVT dynamics in a lab-based stress task in healthy preschool children and only low birth weight is related to more change during early and to less late PCVT recovery.

Anti‐inflammatory Effect of Noninvasive Transcutaneous Auricular Vagus Nerve Stimulation and Osteopathic Manipulative Treatment

BackgroundThe anti‐inflammatory reflex inhibits excessive pro‐inflammatory cytokine production through the parasympathetic nervous system. It has been demonstrated that non‐invasive transcutaneous auricular vagus nerve stimulation (taVNS) increases various heart rate variability (HRV)‐derived parameters that are associated with parasympathetic modulation of cardiac function. Likewise, osteopathic occipito‐atlantal decompression (OA‐D) has been demonstrated to increase HRV, consistent with increased vagal tone. However, it is not known if these interventions also inhibit inflammation. Thus, the hypothesis of this study was that noninvasive taVNS and osteopathic OA‐D decrease synthesis and/or release of pro‐inflammatory cytokines through an increase in parasympathetic nervous system activity.MethodsAdult healthy participants received OA‐D (5 min, n=7), taVNS (15 min, n=8), or no intervention (15 min, control group, n=8) on three consecutive days. Before and after these interventions, noninvasive arterial blood pressure (Finapres Finometer Pro) and the ECG were recorded continuously for 30 min. Before and after each daily experiment, saliva samples were collected for determination of salivary interleukin‐1β (IL‐1β) and tumor necrosis factor α (TNF‐α) by ELISA.ResultsOnly in the OA‐D group, mean blood pressure decreased from the first (100±8 mmHg) to the third (93±8 mmHg, P&lt;0.05) study day. Low frequency blood pressure variability, a marker of sympathetic modulation of vascular tone, declined only in response to OA‐D (− 8.6±3.5 mmHg2, P&lt;0.05 vs. +3.8±2.9 mmHg2 in taVNS and +1.0±2.9 mmHg2 in control). RMSSD, a time domain HRV parameter that reflects parasympathetic modulation of cardiac function, increased only in response to taVNS (+5.0±1.6 ms, P&lt;0.05 vs. +2.4±4.8 ms in OA‐D and +3.1±3.8 ms in control). In control subjects the 2‐hour experimental procedure increased salivary IL‐1β (+288±84 pg/mL, P&lt;0.05) and TNF‐α (+2.5±0.3 pg/mL, P&lt;0.05). As illustrated in Fig. 1, noninvasive taVNS blunted both, the IL‐1β (+54±18 pg/mL, P&lt;0.05 vs. control) and TNF‐α (+1.5±0.3 pg/mL, P&lt;0.05 vs. control) responses, while OA‐D reduced only the IL‐1β response (+104±43 pg/mL, P&lt;0.05 vs. control).Summary/ConclusionOA‐D reduces arterial blood pressure, possibly through inhibition of sympathetic modulation of vascular function. The experimental protocol was associated with a pro‐inflammatory response as indicated by the marked increase in salivary IL‐1β and TNF‐α in the control group. This pro‐inflammatory response was inhibited by OA‐D and taVNS, although this anti‐inflammatory effect was more pronounced by taVNS that blunted both, the IL‐1β and TNF‐α responses, while OA‐D only reduced the IL‐1β response. The increase in RMSSD associated with taVNS suggests that taVNS inhibits inflammation through the parasympathetic anti‐inflammatory reflex.Support or Funding InformationSupported by the American Osteopathic Association (Grant #19137759) and generous funding by the Research Office at Burrell College of Osteopathic Medicine.Differences (⊗) in the salivary concentrations of the pro‐inflammatory cytokines interleukin‐1β (IL‐1β, left) and tumor necrosis factor‐α (TNF‐α, right) before and after the experimental protocol. The cytokine concentrations from days 1 to 3 were averaged. CTR: control group; OMT: osteopathic occipito‐atlantal decompression (OA‐D) group; taVNS: transcutaneous auricular vagus nerve stimulation group; *: P&lt;0.05 vs control.Figure 1

The Association Between Pain Relief Using Video Games and an Increase in Vagal Tone in Children With Cancer: Analytic Observational Study With a Quasi-Experimental Pre/Posttest Methodology.

BackgroundPatients with secondary pain due to mucositis after chemotherapy require treatment with morphine. Use of electronic video games (EVGs) has been shown to be an effective method of analgesia in other clinical settings.ObjectiveThe main objective of this study was to assess the association between the use of EVGs and the intensity of pain caused by chemotherapy-induced mucositis in pediatric patients with cancer. The secondary objective was to assess the association between changes in pain intensity and sympathetic-parasympathetic balance in this sample of pediatric patients.MethodsClinical records were compared between the day prior to the use of EVGs and the day after the use of EVGs. The variables were variations in pupil size measured using the AlgiScan video pupilometer (IDMed, Marseille, France), heart rate variability measured using the Analgesia Nociception Index (ANI) monitor (Mdoloris Medical Systems, Loos, France), intensity of pain measured using the Numerical Rating Scale (score 0-10), and self-administered morphine pump parameters.ResultsTwenty patients (11 girls and nine boys; mean age 11.5 years, SD 4.5 years; mean weight 41.5 kg, SD 20.7 kg) who met all the inclusion criteria were recruited. EVGs were played for a mean of 2.3 (SD 1.3) hours per day, resulting in statistically significant changes. After playing EVGs, there was significantly lower daily morphine use (before vs after playing EVGs: 35.9 vs 28.6 µg/kg/day, P=.003), lower demand for additional pain relief medication (17 vs 9.6 boluses in 24 hours, P=.001), lower scores of incidental pain intensity (7.7 vs 5.4, P=.001), lower scores of resting pain (4.8 vs 3.2, P=.01), and higher basal parasympathetic tone as measured using the ANI monitor (61.8 vs 71.9, P=.009). No variation in pupil size was observed with the use of EVGs.ConclusionsThe use of EVGs in pediatric patients with chemotherapy-induced mucositis has a considerable analgesic effect, which is associated physiologically with an increase in parasympathetic vagal tone despite lower consumption of morphine.

Comparison of symptomatic and functional responses to vagus nerve stimulation in ANTHEM-HF, INOVATE-HF, and NECTAR-HF.

AimsClinical studies of vagal nerve stimulation (VNS) for heart failure with reduced ejection fraction have had mixed results to date. We sought to compare VNS delivery and associated changes in symptoms and function in autonomic regulation therapy via left or right cervical vagus nerve stimulation in patients with chronic heart failure (ANTHEM‐HF), increase of vagal tone in heart failure (INOVATE‐HF), and neural cardiac therapy for heart failure (NECTAR‐HF) for hypothesis generation.Methods and resultsDescriptive statistics were used to analyse data from the public domain for differences in proportions using Pearson's chi‐square test, differences in mean values using Student's unpaired t‐test, and differences in changes of mean values using two‐sample t‐tests.Guideline‐directed medical therapy recommendations were similar across studies. Fewer patients were in New York Heart Association 3, and baseline heart rate (HR) was higher in ANTHEM‐HF. In INOVATE‐HF, VNS was aimed at peripheral neural targets, using closed‐loop delivery that required synchronization of VNS to R‐wave sensing by an intracardiac lead. Pulse frequency was low (1–2 Hz) because of a timing schedule allowing ≤3 pulses of VNS following at most 25% of detected R waves. NECTAR‐HF and ANTHEM‐HF used open‐loop VNS delivery (i.e. independent of any external signal) aimed at both central and peripheral targets. In NECTAR‐HF, VNS delivery at 20 Hz caused off‐target effects that limited VNS up‐titration in a majority of patients. In ANTHEM‐HF, VNS delivery at 10 Hz allowed up‐titration until changes in HR dynamics were confirmed. Six months after VNS titration, significant improvements in both HR and HR variability occurred only in ANTHEM‐HF. When ANTHEM‐HF and NECTAR‐HF were compared, greater improvements from baseline were observed in ANTHEM‐HF in standard deviation in normal‐to‐normal R‐R intervals (94 ± 26 to 111 ± 50 vs. 146 ± 48 to 130 ± 52 ms; P < 0.001), left ventricular ejection fraction (32 ± 7 to 37 ± 0.4 vs. 31 ± 6 to 33 ± 6; P < 0.05), and Minnesota Living with Heart Failure mean score (40 ± 14 to 21 ± 10 vs. 44 ± 22 to 36 ± 21; P < 0.002). When compared with INOVATE‐HF, greater improvement in 6‐min walk distance was observed in ANTHEM‐HF (287 ± 66 to 346 ± 78 vs. 304 ± 111 to 334 ± 111 m; P < 0.04).ConclusionsIn this post‐hoc analysis, differences in patient demographics were seen and may have caused the differential responses in symptoms and function observed in association with VNS. Major differences in technology platforms, neural targets, VNS delivery, and HR and HR variability responses could have also potentially played a very important role. Further study is underway in a randomized controlled trial with these considerations in mind.

Combined femoral and sciatic nerve block with Levobupivacaine in Brugada syndrome patient: A case report

Introduction: Brugada syndrome is a rare arrhythmic disorder associated to ventricular fibrillation and sudden cardiac death. General recommendations in Brugada syndrome patient are focused on avoiding increases in vagal tone and precipitating agents such as electrolyte disorders, hypo/hyperthermia and drugs. Anesthetic management in Brugada syndrome patient has been described in many case reports, however it is still unknown which anesthesia is the safest. Local anesthetic may have a theoretical arrhythmogenic risk, but currently there is no clear evidence and their risk is still debated. Peripheral nerve block avoids autonomic nervous system changes that occur with other anesthetic techniques and it is associated to a lower level in the plasma concentration of the local anesthetic compared with neuraxial anesthesia. Case Report: We report a case of a 38-year-old man patient with Brugada syndrome who underwent urgent orthopedic surgery which was managed with a combined femoral and sciatic nerve blocks using levobupivacaine without any complications. Conclusions: Peripheral nerve block with levobupivacaine provided good analgesia, hemodynamic and cardiac stability in Brugada syndrome patient. Keywords: Brugada syndrome, Anesthesia, Levobupivacaine, Peripheral nerve block, Regional anesthesia

Sacral nerve stimulation prompts vagally-mediated amelioration of rodent colitis.

Neuromodulation based on the vagal anti‐inflammatory reflex has emerged as an exciting therapeutic approach for chronic inflammatory diseases. However, it is unclear whether direct stimulation of the vagus or of pelvic nerves coming from sacral roots, providing the bulk of colonic parasympathetic innervation, is the best approach. We hypothesized that sacral nerve stimulation (SNS) would be an effective treatment for colitis. Age and sex‐matched Sprague‐Dawley rats were administered 5% dextran sulphate sodium (DSS) in drinking water ad libitum for 7 days. A group of rats was sacrificed after DSS treatment, and the remaining rats were randomized to either sham‐SNS or SNS groups, which were performed for 1 hr daily for 10 days. Stimulations were delivered via chronically implanted electrodes using an 8‐channel universal pulse generator. Sacral nerve stimulation promoted recovery of colitis demonstrated by decreased disease activity index, myeloperoxidase activity, tissue TNF‐alpha, and histological scores as well as an increased colonic M2 macrophage population. Heart rate variability analysis demonstrated a decrease in low frequency and increase in high frequency with SNS, corresponding to increased vagal tone. Additionally, plasma pancreatic peptide was increased and norepinephrine was decreased after SNS in colitis while colon tissue acetylcholine was increased with SNS. This is the first study to the best of our knowledge that demonstrates the benefit of SNS with autonomic mediation. SNS alters the expression of inflammatory cytokines and macrophages as well as modulates neurotransmitters involved in systemic inflammation.

Could affect regulation via vagal nerve self- stimulation be a maintaining factor in non-suicidal self-harm?

BackgroundNon-suicidal self-injury (NSSI) is a serious and common phenomenon which has been linked with emotion or affect regulation. The capacity for top-down emotion regulation has also been linked to vagal tone. Vagal tone is known to be low in groups with a propensity to engage in NSSI. HypothesisSome forms of NSSI, both direct and indirect, may result in vagal stimulation. The resulting increase in vagal tone may be linked to activation of prefrontal areas and improved top-down emotion regulation. This may be a maintaining factor in NSSI. EvaluationCutting with the sight of blood, the use of ligatures, eating disorders and risky sexual behaviour, behaviours that could be considered direct or indirect forms of NSSI, are all plausible methods of vagal self-stimulation. ConclusionNSSI may increase vagal tone. This may result in improved top down emotion regulation and result in a calmer emotional state. These vagal effects may be important maintaining factors in self-harm. This has important implications for the study and possible management of a common and serious issue.

P4423Extreme bradycardia in athletes is due to intrinsic changes within the heart

Abstract Background It is well known that athletes and in particular endurance athletes have lower resting heart rates than non-athletes. This has generally been considered a healthy adaptation. Traditionally this was thought be due to increased vagal tone. Several studies have shown that endurance athletes continue to have lower heart rates in the absence of autonomic influence suggesting bradycardia is due to intrinsic changes within the heart. A subset of endurance athletes have very low heart rates with Tour de France cyclists having described heart rates in the 30s. It is unclear whether in these elite athletes with very low heart rates the profound bradycardia is due to autonomic influence or intrinsic changes within the heart. Aim The aim of this study was to determine if extreme bradycardia in athletes is due to excess vagal tone or more profound intrinsic changes within the heart. Methods We recruited three cohorts for this study: non-athlete controls (NA), endurance athletes with a documented resting heart rate &gt;40 (EA) and endurance athletes with a resting heart rate &lt;40 (BA). All participants underwent baseline testing including ECG, echocardiography and VO2 max testing. All participants came back on a second occasion for treatment with dual autonomic blockade (DAB) to determine intrinsic heart rate in the following manner. After resting supine for five minutes resting heart rate was measured. Participants were then administered 0.04mg/kg of intravenous atropine. After five minutes participants were then administered 0.05mg/kg of intravenous metoprolol. This was repeated every five minutes until there was no further drop in heart rate or 0.2mg/kg had been administered. The resting heart rate at this stage was recorded as the intrinsic heart rate. Parasympathetic blockade was confirmed by lack of response to Valsalva manoeuvre and sympathetic blockade was confirmed by lack of response to metoprolol. VO2 max testing was then performed to determine maximum heart rate. Results 9 NA (7 male), 10 EA (8 male) and 5 BA (4 male) participated in this study. The average age was similar in all groups (NA 32.9y, EA 32.4y, BA 31.4y). The average resting heart rate was 71.7 in the NA group, 48.3 in the EA group and 41.6 in the BA group (p&lt;0.05 for comparisons between all three groups). Following dual autonomic blockade resting heart rate was 86.0 in the NA group, 76.9 in the EA group and 64.4 in the BA group (p&lt;0.05 for comparisons between all three groups). Maximum heart rate under DAB was 140.1 in the NA group, 138.0 in the EA group and 140.4 in the BA group. These differences were not significant. Conclusion In athletes with very low heart rates, bradycardia is due to more profound intrinsic changes within the heart. Acknowledgement/Funding NHMRC Project Grant

Heart Rate Variability, Cortisol and Attention Focus During Shamatha Quiescence Meditation.

Cardiac vagal tone can be seen as a stable marker for the ability to sustain attention and regulate emotion, two factors associated with the quality of meditation. In this study, heart rate variability (HRV) has been monitored in different forms of Shamatha quiescence meditation: three breath meditations, Settling the Mind in its natural state, Awareness of Awareness, Loving-kindness and Tonglen. Establish and test a practical means of monitoring neurobiological effects of meditation. Over 6 weeks, two experimental groups practiced Shamatha meditation on a daily basis (n = 20). HRV patterns and cortisol tests were monitored at three measuring points during these weeks, and an attention focus test was performed at the start and after 6 weeks. Six weeks of regular practice in Shamatha meditation were associated with HRV indices suggesting improvements in the homeostatic regulation of the autonomic nervous system (ANS) in 85% of the HRV recordings (tachogram and frequency specter) of all 20 subjects. Further, a substantial decrease in cortisol levels was also noted. The attention focus test showed a significant increase of 18.7% in sustained attention, moving from medium to high attention focus, with a significant result of t(20) = - 8.764 and p < 0.001. Participants reported positive subjective changes in attention focus, sense of happiness and calmness and increased abilities in emotional regulation and attunement. Six weeks of regular practice in Shamatha meditation contributes to a substantial increase of attention focus and a decrease in stress levels evidenced in changes in diurnal cortisol measures. HRV biofeedback shows that the sympathetic nervous system is counterbalanced by increased vagal tone, and autonomic balance is enhanced by all Shamatha meditations, not only breath meditations, but also mind meditations: Settling the Mind in its natural state, Awareness of Awareness, Loving-kindness and Tonglen. Although these results are promising, further research is recommended with HRV biofeedback instruments to report statistical analysis and to understand unique HRV patterns in Shamatha mind meditation.

Primary oesophageal squamous cell carcinoma in a cat with bradycardia and ionised hypercalcaemia

An adult male domestic shorthair cat was presented for vomiting and anorexia, with a three-month history of weight loss. Bradycardia was documented during physical examination and was diagnosed as sinusal...

Cardiovascular outcomes related to social defeat stress: New insights from resilient and susceptible rats

Stress exposure is an important risk factor for psychiatric and cardiovascular disorders. Two phenotypes related to coping with stress can be observed in rodents that experience chronic social defeat stress (SDS): susceptible, showing social avoidance and behavioral changes related to depression, and resilient, showing none of these alterations. Moreover, a strong correlation exists between depression and the development of or mortality due to cardiovascular diseases. Nevertheless, little is known about cardiovascular alterations related to SDS exposure in those phenotypes or their correlation with depressive-like behaviors. Using a chronic SDS protocol followed by the social interaction test, we identified Wistar rats as resilient or susceptible to SDS. Susceptible animals showed increased depressive-like behaviors with resting tachycardia and decreased heart rate variability (HRV) due to increased sympathetic tone in the heart and a less effective baroreflex. In contrast, resilient rats were protected from these alterations by increased vagal tone, resulting in greater HRV values. To our knowledge, our study is the first to indicate that harmful cardiovascular outcomes are related to depressive-like behaviors in susceptible rats and to suggest a mechanism by which resilient rats are protected from these changes. Also, our results suggest that enhanced HRV and vagal tone may be an important trait in resilient individuals.

Changes in Heart Rate Variability During Heartfulness Meditation: A Power Spectral Analysis Including the Residual Spectrum.

Background: Meditation refers to a group of practices commonly proposed to treat stress-related conditions and improve overall wellness. In particular, meditation might exert beneficial actions on heart rate variability (HRV) by acting on autonomic tone with an increase in the vagal activity. The effects of heartfulness meditation (HM) on HRV remain poorly defined.Methods: We investigated the effects of HM on HRV in a group of 26 healthy subjects. Subjects were regularly practicing this form of meditation on a daily basis. We assessed the HRV and residual HRV (rHRV) at rest and during meditation. We also used as control a period of respiratory rhythm imposed by an auditory signal, with the imposed breathing rhythm being identical to the spontaneous rhythm recorded during meditation.Results: During deep meditation period, the standard deviation of RR intervals (SDRR), coefficient of variation of RR intervals (CVRR), and total power (TP) were decreased while the low-frequency power (LFP), normalized LFP (nLFP), and normalized residual LFP (nrLFP) were increased as compared with those at rest, suggesting that the global vagal modulation was suppressed while the baroreflex was increased during deep medication. At the end of meditation, the LFP, residual LFP (rLFP), nLFP, nrLFP, low-/high-frequency power ratio (LHR), and residual LHR (rLHR) were increased while the residual very low-frequency power (rVLFP), normalized high-frequency power (nHFP), and normalized residual HFP (nrHFP) were decreased, as compared with those during paced breathing, suggesting that the vagal modulation was decreased while the sympathetic modulation was increased by deep meditation. During paced breathing period, the SDRR, CVRR, TP, LFP, rLFP, nLFP, nrLFP, LHR, and rLHR were decreased while nHFP and nrHFP were increased as compared with at rest, suggesting that paced breathing could suppress the sympathetic modulation and enhance the vagal modulation.Conclusion: HM can induce a suppression of global vagal modulation and increased the sympathetic modulation and baroreflex. In addition, paced breathing can suppress the sympathetic modulation and enhance the vagal modulation. Unlike studies using other types of meditation, we did not identify evidence of increased vagal tone during HM.

The Effects of High‐Intensity Treadmill‐Running on Gastric Emptying and Heart Rate Variability in a Rodent Model

PURPOSEExercise is well known for the beneficial effects it provides to organs and systems of the body. Proper and consistent exercise has been shown to improve cardiovascular and neural function, reduce adipose tissue, and lower the risk of developing certain metabolic disorders. Patients suffering from gastrointestinal (GI) dysfunction are frequently prescribed exercise to improve their symptoms. Yet, exercise has also been shown to provoke GI disturbances including diarrhea, abdominal pain, and gastroesophageal reflux. These GI disturbances commonly occur after bouts of prolonged or high‐intensity exercise, and the GI disturbance frequency is twice as high during running compared to other endurance sports. The effect of exercise on the upper‐GI tract remains controversial; studies have reported increases, decreases, and no changes in gastric emptying (GE) rate following running. We evaluated the effects of high‐intensity treadmill‐training on GE rate in rats. We hypothesized that exercise will contribute to increased vagal tone leading to an increase in GE rate. By developing an understanding of the relationship between exercise and GI function, exercise may be medicine in treating a number of GI health dysfunctions (e.g. gastroparesis).METHODSIn this study, we evaluated the effects of high‐intensity treadmill‐running on GE rate and heart rate variability (HRV) in Male Wistar rats. Rats (n = 8) ran on a treadmill at 23.0m/min, five days/week, for 4‐weeks; control rat (n = 8) were placed on the powered off treadmill. For GE measurements, fasted rats were placed in collection chambers, baseline air measurements collected, and rats received 1g of pancake containing 5μL of the stable isotope [13C]‐octanoic acid. Exhaled breath was collected and analyzed to determine the [13C]‐ to [12C]‐CO2 ratio. HRV was assessed at baseline and at the conclusion of the study to compare pre‐exercise to post‐exercise differences between exercise and control rats' autonomic activity.RESULTSAfter 4‐weeks, anthropometric factors remained similar between exercise and control: mean energy intake (29.92 ± 0.44 vs 29.59 ± 0.53kcal/100g/day; p&gt;0.05), body mass (85% increase; 325.83 ± 3.30 vs. 330.28 ± 3.48g; p&gt;0.05), food intake (24.38 ± 0.29 vs. 24.48 ± 0.35g; p&gt;0.05). Cumulative percent recovery of the administered [13C]‐octanoic acid dose was reduced in exercise vs control 6‐hours following GE testing (11.70 ± 0.83 vs 13.29 ± 0.60; p&gt;0.05). Peak fractional dose per hour of 13CO2 during the breath test was the same between groups (6.96 ± 0.89 vs 7.61 ± 0.40; p&gt;0.05), but there was a rapid reduction of [13C] values following peak over several time points of the exercise group. HRV data is inconclusive.CONCLUSIONWe previously validated moderate‐intensity treadmill running has no significant effect on gastric emptying. By increasing the intensity of running, we found no significant difference in GE rate in the exercise vs control groups. We believe the duration of the exercise was too acute to elicit physiological changes to gastric emptying. However, further investigation may reveal neuronal changes prior to the physiological alterations.Support or Funding InformationGettysburg College Start‐up FundsThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Ophthalmic Insert versus Eye Drops for Mydriasis in Neonates: A Randomized Clinical Trial

Background: Eye drop treatment routinely used to obtain mydriasis prior to fundoscopy in neonates requires repeated instillations of mydriatic agents that can lead to systemic side effects. Objectives: The aim of this study was to compare the mydriatic efficacy and tolerance of administration of phenylephrine and tropicamide via the ophthalmic insert Mydriasert® versus standard eye drop treatment in neonates. Methods: In this prospective, single-blinded, noninferiority study, 80 hospitalized neonates (age < 18 months) requiring bilateral fundus examination were randomized to receive eye drops (repeated instillations of 2.5% phenylephrine and 0.5% tropicamide) or the insert. The primary outcome was mydriasis suitable for fundoscopy 75 min after mydriatic agent introduction (T75). Results: Mydriasis was successfully achieved in both eyes at T75 in 97.5% (n = 39/40) of the insert group patients versus 90% (n = 36/40) receiving eye drops (between-group difference 7.5%, demonstrating noninferiority). Mydriasis remained stable in 60.0% of patients (n = 24/40) in the insert group versus 15% (n = 6/40) in the eye drop group (p < 0.0001). The insert group required fewer nursing interventions than the eye drop group (p = 0.0001). Mean blood pressure were significantly higher in the insert versus the eye drop group (p < 0.0001 and p = 0.0003, respectively); mean heart rate was not significantly different between the groups (p = 0.37). In the insert group, 2 patients reported an adverse event (bradycardia, n = 1, and gastroesophageal reflux, n = 1; both appeared to be related to neonate pathology). Conclusions: The degree of mydriasis achieved with Mydriasert® was noninferior to that obtained with eye drops. The insert appears to be safe to use in neonates without a history of increased vagal tone or gastrointestinal reflux.

Characteristics of psychological and physiological responses while anger experiencing in individuals with depression

The purpose of this study was to assess the interrelation between cortical, cardiovascular, behavioural, and psychological responses to acute stressors in a large sample of healthy individuals. To date, there are only preliminary evidences for a significant association among these psychophysiological indexes during a stress task.65 participants completed psychological questionnaires (Beck Depression Inventory and State-Trait Anxiety Inventory) and underwent a psychosocial math stress task, consisting of a control and an experimental (i.e. stressful) condition. Prefrontal and autonomic activities were recorded using respectively a 2-channel near-infrared spectroscopy (NIRS) device and a portable ECG monitoring system.Results evidenced an increased activation of both frontal areas assessed by NIRS, and a positive association between the right NIRS channel and heart rate changes from baseline, during both control and experimental conditions. Subjective stress increased during the procedure, reaching its maximum during the experimental condition. Behavioural performances during the task (e.g. response time) did not correlate with anxiety or depression. Autonomic data evidenced, as expected, an overall reduction of vagal tone during the experimental condition. Finally, severity of depressive and anxious symptoms predicted an increase in parasympathetic activity both at rest and during the task, even when controlling for respiration rate.Results support the hypothesis of an integration between right sectors of frontopolar or dorsolateral PFC and cardiac regulation. Trait anxiety and depression predicted an increase in vagal tone during the entire procedure. The implication of these findings is discussed.

Pharmacological Modulation of Right Ventricular Endocardial-Epicardial Gradients in Brugada Syndrome.

Background We explored the hypothesis that increased cholinergic tone exerts its proarrhythmic effects in Brugada syndrome (BrS) through increasing dispersion of transmural repolarization in patients with spontaneous and drug-induced BrS. Methods BrS and supraventricular tachycardia patients were studied after deploying an Ensite Array in the right ventricular outflow tract and a Cardima catheter in the great cardiac vein to record endo and epicardial signals, respectively. S1-S2 restitution curves from the right ventricular apex were conducted at baseline and after edrophonium challenge to promote increased cholinergic tone. The local unipolar electrograms were then analyzed to study transmural conduction and repolarization dynamics. Results The study included 8 BrS patients (5 men:3 women; mean age, 56 years) and 8 controls patients with supraventricular tachycardia (5 men:3 women; mean age, 48 years). Electrophysiological studies in controls demonstrated shorter endocardial than epicardial right ventricular activation times (mean difference: 26 ms; P<0.001). In contrast, patients with BrS showed longer endocardial than epicardial activation time (mean difference: -15 ms; P=0.001). BrS hearts, compared with controls, showed significantly larger transmural gradients in their activation recovery intervals (mean intervals, 20.5 versus 3.5 ms; P<0.01), with longer endocardial than epicardial activation recovery intervals. Edrophonium challenge increased such gradients in both controls (to a mean of 16 ms [ P<0.001]) and BrS (to 29.7 ms; P<0.001). However, these were attributable to epicardial and endocardial activation recovery interval prolongations in control and BrS hearts, respectively. Dynamic changes in repolarization gradients were also observed across the BrS right ventricular wall in BrS. Conclusions Differential contributions of conduction and repolarization were identified in BrS which critically modulated transmural dispersion of repolarization with significant cholinergic effects only identified in the patients with BrS. This has important implications for explaining the proarrhythmic effects of increased vagal tone in BrS, as well as evaluating autonomic modulation and epicardial ablation as therapeutic strategies.