Autonomic Modulation Research Articles

Does a single oral administration of amiloride affect spontaneous arterial baroreflex sensitivity and blood pressure variability in healthy young adults?

Preclinical models indicate that amiloride (AMD) reduces baroreflex sensitivity and perturbs homeostatic blood pressure (BP) regulation. However, it remains unclear whether these findings translate to humans. This study investigated whether oral administration of AMD reduces spontaneous cardiac and sympathetic baroreflex sensitivity and perturbs BP regulation in healthy young humans. Heart rate (HR; electrocardiography), beat-to-beat BP (photoplethysmography), and muscle sympathetic activity (MSNA, microneurography) were continuously measured in 10 young subjects (4 females) during rest across two randomized experimental visits: 1) after 3 h of oral administration of placebo (PLA, 10 mg of methylcellulose within a gelatin capsule) and 2) after 3 h of oral administration of AMD (10 mg). Visits were separated for at least 48 h. We calculated the standard deviation and other indices of BP variability. Spontaneous cardiac baroreflex was assessed via the sequence technique and cardiac autonomic modulation through time- and frequency-domain HR variability. The sensitivity (gain) of the sympathetic baroreflex was determined via weighted linear regression analysis between MSNA and diastolic BP. AMD did not affect HR, BP, and MSNA compared with PLA. Indexes of cardiac autonomic modulation (time- and frequency-domain HR variability) and BP variability were also unchanged after AMD ingestion. Likewise, AMD did not modify the gain of both spontaneous cardiac and sympathetic arterial baroreflex. A single oral dose of AMD does not affect spontaneous arterial baroreflex sensitivity and BP variability in healthy young adults.NEW & NOTEWORTHY Preclinical models indicate that amiloride (AMD), a nonselective antagonist of the acid-sensing ion channels (ASICs), impairs baroreflex sensitivity and perturbs blood pressure regulation. We translated these findings into humans, investigating the impact of acute oral ingestion of AMD on blood pressure variability and spontaneous cardiac and sympathetic baroreflex sensitivity in healthy young humans. In contrast to preclinical evidence, AMD does not impair spontaneous arterial baroreflex sensitivity and blood pressure variability in healthy young adults.

Mitigation of Subsequent Ovariectomy Responses through Prior Exercise Training in Rats.

It is well known that cardiometabolic dysfunction gradually increases after menopause, and the sedentary lifestyle can aggravate this condition. Therefore, we compared the effects of aerobic exercise training during the premenopausal period and after ovariectomy (OVX) on metabolic, hemodynamic, and autonomic parameters in an experimental rat model of menopause. The female rats were divided into four groups: control (C), sedentary OVX (SO), trained OVX (TO), and previously trained OVX (PTO). The PTO group was trained for 4 weeks prior to+8 weeks after OVX, and the TO group trained only after OVX on a motor treadmill. Autonomic modulation was evaluated, white adipose tissue (WAT) was removed and weighed, and lipolysis was assessed. The citrate synthase activity in the soleus muscle was analyzed. The trained groups prevented the impairment of baroreceptor reflex sensitivity in relation to SO; however, only PTO reduced the low-frequency band of the pulse interval compared to SO. PTO reduced the weight of WAT compared to the other groups; lipolysis in PTO was similar to that in C. PTO preserved muscle metabolic injury in all types of fibers analyzed. In conclusion, this study suggests that exercise training should be recommended in a premenopausal model to prevent cardiometabolic and autonomic menopause-induced deleterious effects.

Short-term heart rate variability: A potential approach to frailty assessment in older adults.

This study aimed to evaluate cardiac autonomic modulation using short-term heart rate variability (HRV) and compare it among frailty statuses in older Indian adults. A total of 210 subjects aged 60 years and above were recruited into three groups: frail (n = 70), pre-frail (n = 70), and non-frail (n = 70) from the outpatient department of Geriatric Medicine at a tertiary care hospital in India. Frailty status was assessed using the Rockwood frailty index (FI) criteria. HRV was derived from a 5-min ECG recording of standard limb leads and assessed using time domain, frequency domain, and nonlinear analysis of cardiac interval variability. The HRV parameters indicative of parasympathetic modulation such as SDNN, SDSD, rMSSD, NN50, pNN50, absolute HF power, and SD1 were significantly lower in frail subjects compared with both pre-frail and non-frail subjects (P < 0.05). Absolute LF power and SD2 were also lower in frail subjects compared with pre-frail and non-frail subjects (P < 0.05). Measures of sympatho-vagal balance (LF/HF and SD1/SD2 ratios) did not show statistical significance. The FI demonstrated negative correlations with all HRV parameters. Frail individuals exhibit decreased sympathetic and parasympathetic modulation compared with pre-frail and non-frail individuals, although maintaining a balanced sympatho-vagal state. Furthermore, autonomic modulation declines progressively with increasing frailty.

Heart rate variability measurement and influencing factors: Towards the standardization of methodology.

Heart rate variability (HRV) is widely recognized as an effective and valuable tool for evaluating cardiac autonomic modulation. However, various factors can influence HRV before and during assessment, complicating the interpretation and comparability of results. This review outlines the different factors affecting HRV and underscores the importance of considering them to ensure consistent and reliable HRV outcomes. Key influencing factors are categorized into physiological (e.g., age, gender, genetics), lifestyle (e.g., physical activity, alcohol use, smoking, drugs, diet), environmental (e.g., time of day, temperature, noise), and methodological (e.g., body position, recording duration, and respiration) domains. Knowing these factors can help researchers and physicians gain a better understanding of HRV and improve the interpretation of their findings. Consequently, this can lead to the development of standardized methods for consistently assessing and interpreting HRV measures in clinical practice.

Autonomic modulation by SGLT2i or DPP4i in patients with diabetes favors cardiovascular outcomes as revealed by skin sympathetic nerve activity.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP4i) are important second-line treatments for patients with type 2 diabetes mellitus (T2DM). Patients taking SGLT2i have favorable cardiovascular outcomes via various mechanisms, including autonomic nervous system (ANS) modulation. This study aimed to use neuro-electrocardiography (neuECG) to test the effects of SGLT2i or DPP4i on the ANS. Patients with T2DM, who did not reach target hemoglobin (Hb)A1C levels despite metformin treatment, were enrolled. SGLT2i or DPP4i were prescribed randomly unless a compelling indication was present. NeuECG and heart rate were recorded for 10min before and after a 3-month treatment. The patients were treated according to standard practice and the obtained data for skin sympathetic nerve activity (SKNA) and ANS entropy were analyzed offline. We enrolled 96 patients, of which 49 received SGLT2i and 47 received DPP4i. The baseline parameters were similar between the groups. No adverse event was seen during the study period. In the burst analysis of SKNA at baseline, all parameters were similar. After the 3-month treatment, the firing frequency was higher in SGLT2i group (0.104 ± 0.045 vs 0.083 ± 0.033 burst/min, p < 0.05), with increased long firing duration (7.34 ± 3.66 vs 5.906 ± 2.921, p < 0.05) in 3-s aSKNA scale; the other parameters did not show any significant change. By symbolic entropy, the most complex patterns (Rank 3) were found to be significantly higher in SGLT2i-treated patients than in DDP4i-treated group (0.084 ± 0.028 vs 0.07 ± 0.024, p = 0.01) and the direction of change in Rank 3, after SGLT2i treatment, was opposite to that observed in the DDP4i group (0.012 ± 0.036 vs. -0.005 ± 0.037, p = 0.024). Our findings demonstrated the favorable autonomic modulation by SGLTi and the detrimental effects of DPP4i on ANS. We demonstrated the autonomic modulation by SGLTi and DPP4i using SKNA in patients with DM, which might provide insights into the favorable outcomes of SGLT2i. Furthermore, we refined the analytical methods of neuECG, which uses SKNA to evaluate autonomic function.

Sinoatrial node heterogeneity and fibroblasts increase atrial driving capability in a two-dimensional human computational model.

Background: Cardiac pacemaking remains an unsolved matter from many perspectives. Extensive experimental and computational studies have been performed to describe the sinoatrial physiology across different scales, from the molecular to clinical levels. Nevertheless, the mechanism by which a heartbeat is generated inside the sinoatrial node and propagated to the working myocardium is not fully understood at present. This work aims to provide quantitative information about this fascinating phenomenon, especially regarding the contributions of cellular heterogeneity and fibroblasts to sinoatrial node automaticity and atrial driving. Methods: We developed a bidimensional computational model of the human right atrial tissue, including the sinoatrial node. State-of-the-art knowledge of the anatomical and physiological aspects was adopted during the design of the baseline tissue model. The novelty of this study is the consideration of cellular heterogeneity and fibroblasts inside the sinoatrial node for investigating the manner by which they tune the robustness of stimulus formation and conduction under different conditions (baseline, ionic current blocks, autonomic modulation, and external high-frequency pacing). Results: The simulations show that both heterogeneity and fibroblasts significantly increase the safety factor for conduction by more than 10% in almost all the conditions tested and shorten the sinus node recovery time after overdrive suppression by up to 60%. In the human model, especially under challenging conditions, the fibroblasts help the heterogeneous myocytes to synchronise their rate (e.g. -82% in under 25 nM of acetylcholine administration) and capture the atrium (with 25% L-type calcium current block). However, the anatomical and gap junctional coupling aspects remain the most important model parameters that allow effective atrial excitations. Conclusion: Despite the limitations to the proposed model, this work suggests a quantitative explanation to the astonishing overall heterogeneity shown by the sinoatrial node.

Pt nanoshells with a high NIR-II photothermal conversion efficiency mediates multimodal neuromodulation against ventricular arrhythmias

Autonomic nervous system disorders play a pivotal role in the pathophysiology of cardiovascular diseases. Regulating it is essential for preventing and treating acute ventricular arrhythmias (VAs). Photothermal neuromodulation is a nonimplanted technique, but the response temperature ranges of transient receptor potential vanilloid 1 (TRPV1) and TWIK-related K+ Channel 1 (TREK1) exhibit differences while being closely aligned, and the acute nature of VAs require that it must be rapid and precise. However, the low photothermal conversion efficiency (PCE) still poses limitations in achieving rapid and precise treatment. Here, we achieve a nearly perfect blackbody absorption and a high PCE in the second near infrared (NIR-II) window (73.7% at 1064 nm) via a Pt nanoparticle shell (PtNP-shell). By precisely manipulating the photothermal effect, we successfully achieve rapid and precise multimodal neuromodulation encompassing neural activation (41.0–42.9 °C) and inhibition (45.0–46.9 °C) in a male canine model. The NIR-II photothermal modulation additionally achieves multimodal reversible autonomic modulation and confers protection against acute VAs associated with myocardial ischemia and reperfusion injury in interventional therapy.

The Effect of In-Ear and Behind-Ear Transcutaneous Auricular Vagus Nerve Stimulation on Autonomic Function: A Randomized, Single-Blind, Sham-Controlled Study.

Background/Objectives: Transcutaneous auricular vagus nerve stimulation (TaVNS) is a non-invasive method of electrical stimulation used to autonomic neuromodulation. Position and form of the electrodes are important for the effectiveness of autonomic modulation. This study was aimed to investigate the effect of TaVNS in-ear and behind-ear on autonomic variables. Methods: A total of 76 healthy participants (male: 40, female: 36) were randomized into four groups as in-ear TaVNS, behind-ear TaVNS, in-ear sham, and behind-ear sham. The TaVNS protocol included bilateral auricular stimulation for 20 min, 25 hertz frequency, a pulse width of 250 μs, and a suprathreshold current (0.13-50 mA). Heart rate (HR), systolic and diastolic blood pressure (SBP and DBP), and heart rate variability (HRV) were measured baseline and after stimulation. The parameters RMSSD (root mean square of consecutive differences between normal heartbeats), LF power (low-frequency), and HF power (high-frequency) were assessed in the HRV analysis. Results: HR decreased in the in-ear TaVNS after intervention (p < 0.05), but did not change in behind-ear TaVNS and sham groups compared to baseline (p > 0.05). SBP and DBP decreased and RMSSD increased in the in-ear and behind-ear TaVNS groups (p < 0.05), but did not change in sham groups compared to baseline (p > 0.05). There was no significant difference in LF and HF power after TaVNS compared to baseline in all groups (p > 0.05). SBP was lower and RMSSD was higher in-ear TaVNS than behind-ear TaVNS after intervention (p < 0.05). Conclusions: In-ear TaVNS appears to be more effective than behind-ear TaVNS in modulating SBP and RMSSD, but this needs to be studied in larger populations.

Comparative Efficacy of Neuromodulation and Structured Exercise Program on Autonomic Modulation in Fibromyalgia Patients: Pilot Study.

Background: Fibromyalgia is a chronic disorder marked by widespread muscle and joint pain, persistent fatigue, sleep disturbances, and irregularities in the autonomic nervous system (ANS). Methods: This study compared the effectiveness of neuromodulation using the EXOPULSE Mollii suit with a structured exercise program in regulating ANS function in fibromyalgia patients. In this randomized, longitudinal crossover study, 10 female patients were randomly assigned to either the Suit + Exercise group or the Exercise + Suit group. Each group participated in two sessions per week for eight weeks, followed by a two-week washout period before switching to the other intervention. We measured cortical arousal, microcirculation, and heart rate variability (HRV) before and after the 1st, 8th, and 16th sessions. Results: The results showed significant improvements in cortical arousal, HRV, and microcirculation with the neuromodulation treatment whereas the exercise program only produced short-term improvements in cortical arousal. Conclusion: The EXOPULSE Mollii suit exhibited cumulative benefits on ANS modulation over time, suggesting potential long-term advantages for managing fibromyalgia. However, further research is needed to explore the delayed effects of both treatments on ANS modulation.

Cardiovascular Autonomic Modulation in Chronic Coronary Syndrome Following Percutaneous Coronary Intervention.

Introduction The risk of sudden death in patients with chronic coronary syndrome (CCS) is increased by unbalanced cardiovascular autonomic function. Since myocardial ischemia appears to be the causeof this condition of autonomic dysregulation, treating this condition should improve and correct the autonomic functions. Improving myocardial perfusion by PCI might have beneficial effects on the recovery of autonomic balance in ischemia-triggered autonomic dysregulation. Objective In the present study, autonomic modulation in patients with CCS was evaluated before and after percutaneous coronary intervention (PCI) using cardiovascular reflex tests. Methods A total of 30CCS patients were recruited from the cardiology outpatient department. The patients were tested withcardiovascular reflex tests (lying to standing, 30:15 ratio, Valsalva ratio, isometric handgrip test, and deep breathing test) before and after PCI. The licensed statistical software SPSS version 21.0 was used to compile and analyse the data. Results Out of 30 patients, parasympathetic reactivity tests conducted post-PCI were significantly higher as compared to pre-PCI patients: (1) lying to standing - 30:15 ratio (1.17± 0.102 versus 1.03± 0.064, p=0.000); (2) Valsalva ratio (1.42±0.276 versus 1.02±0.133, p=0.000), (3) delta heart rate in deep breathing test (17.23± 3.004 bpm versus 7.85± 4.076 bpm, p=0.000), and (4) expiration to inspiration (E:I) ratio (1.25± 0.050 versus 1.11± 0.064, p=0.000. Among sympathetic reactivity tests, lying to standing test for fall in systolic blood pressure was significantly higher in the pre-PCI state than post-PCI (-20.73± 10.29 versus -2.33± 7.67, p=0.000). The rise in DBP of the isometric handgrip test was significantly higher in post-PCI compared to pre-PCI patients (36.73±8.39 mm Hg versus 16.63±8.47 mm Hg, p=0.000). Conclusion Resting autonomic tone as determined by cardiovascular reflex testing reveals an increase in both parasympathetic and sympathetic reactivity following PCI in CCS, according to the findings of this preliminary study. As a result, we propose that noninvasive procedures like cardiovascular reflex tests be used to stratify the likelihood of illness development in the future.

Intake of Dark and Milk Chocolate Differently Affects Autonomic Nervous Control of the Heart During Rest and Mental Stress

Objective Chocolate is a popular food that may affect the activity of the autonomic nervous system (ANS). The aim of this study was to determine the effect of a single dose of dark or milk chocolate on ANS cardiac control during rest and mental stress induced by the Stroop test (ST). Methods Healthy participants, divided into DARK or MILK chocolate groups, ingested corresponding type of chocolate (1 g/kg body weight). They underwent measurement of ANS during relaxation and ST before and 2 h after chocolate consumption. ANS control was assessed by determination of heart rate (HR) and heart rate variability using parameters related to complex autonomic modulation (TP, SDNN) or primary vagal modulation (HFnu, RMSSD). Results HR was always increased during ST in both groups. Relaxation HR values after chocolate ingestion were higher only in the DARK chocolate group. During ST, values of TP, SDNN and HFnu decreased before and after chocolate ingestion in the DARK group, but only before chocolate ingestion in the MILK group. RMSSD values decreased during ST before and after chocolate ingestion in both groups. Relaxation TP, RMSSD and HFnu values after chocolate ingestion were lower in the DARK but not in the MILK group. Conclusion The results suggest that even a single dose of milk chocolate attenuates changes in ANS cardiac control induced by mental stress, whereas a single dose of dark chocolate has an activating effect on the heart via modification of ANS cardiac control at rest. Different levels of sugars and cocoa biologically active compounds in the two types of chocolate could explain the observed effects.

Influence of heart failure (HF) comorbidity in chronic obstructive pulmonary disease (COPD) and isolated forms of HF and COPD on cardiovascular function during hospitalization

IntroductionCoexistence of chronic obstructive pulmonary disease(COPD) and heart failure(HF) is associated with systemic inflammation, myocardial injury, and arterial stiffening, impacting cardiovascular risk and prognosis in patients. Arterial stiffness, reduced nitric oxide synthesis, and altered cardiac autonomic control further link COPD and HF pathophysiology, emphasizing the need for comprehensive cardiovascular assessment. ObjectiveTo investigate a cardiovascular profile in patients hospitalized with exacerbation COPD(ECOPD) in coexistence with HF compared with isolated diseases. MethodsA cross-sectional study including patients diagnosed with ECOPD and decompensated HF, approached between 24 and 48 h after hospital admission. Assessments included: endothelial function by brachial artery flow-mediated vasodilation(FMD); hemodynamic through analysis of pulse wave and arterial stiffness by carotid-femoral pulse wave velocity(cfPWV) and cardiac autonomic modulation(CAM) by heart rate variability(HRV). ResultsThe mean FMD was 4.45 %, indicating endothelial dysfunction in all patients. Date is present in mean(confidence interval) sequency COPD(n = 12), COPD-HF(n = 21) and HF(n = 21). FMD: 5.47(3.96–6.91); 2.66(0.09–3.48); 4.60(2.30–6.43) p < 0.01. However, COPD-HF had worse FMD. Arterial stiffens (AIx: 29.0(19.0–42.6); 34.6(24.3–43.2); 14.5(8.0–24.0)p < 0.01; cfPWV: (6.5(5.4–7.2); 7.7(7.0–8.5); 6.0(5.0–6.5)); COPD-HF also showed greater activation of the sympathetic nervous system compared to patients with isolated diseases (PNS: 1.32(-2.53 to −0.62); −2.33(-2.60 to −2.12); −1.32(-1.42 to −1.01) p < 0.01; SNS: 3.50(1.40–8.55); 7.11(5.70–8.29); 2.32(1.78–5.01) p < 0.01). In addition, rMSSD, NN50, pNN50, and TINN also indicate worse CAM in the COPD-HF group compared to isolated diseases. ConclusionDuring hospitalization, the worst impairment in vascular function and cardiac autonomic modulation were found in patients with COPD and HF comorbidity compared to the isolated diseases(HF or COPD).

Cardiac autonomic modulation and exercise capacity in older adults with intellectual disability: A 6-month randomised control trial.

Despite reported physical and functional improvements with aerobic and sprint interval training (SIT) protocols in individuals with intellectual disability (ID), it is not known if these interventions' effectivity would promote improvements in cardiac autonomic modulation. This study aimed to investigate if a 6-month SIT or a continuous aerobic programme could enhance physical performance and cardiac autonomic modulation at rest, during physical activity (PA) and after it in older adults with an ID. This is a randomised control trial. Participants with ID (age: 50.58±7.25) were allocated to one of three groups [multicomponent aerobic training group (MATG), multicomponent interval sprint training group (MISTG) and control group (CG)]. The programmes lasted 24weeks, with three sessions/week, 75-90min per session. The HRV was analysed at rest and recovery, the delta of heart rate (HR) was analysed during 6MWT, and the HR t-off kinetics was analysed in recovery after 6MWT. There were not found differences between groups, moments, or interaction for cardiac autonomic modulation at rest and recovery. During exercise, only MSITG showed a significant increase of HR between rest and the first 30s of exercise (P<0.05). Physical performance increased only in MSITG (P<0.05), while CG showed a significant reduction (P<0.01). The MSITG improved the physical performance and the vagal withdrawal at the beginning of the submaximal exercise. These findings suggest that high-intensity exercise may positively impact baroreflex function, mitigating the decline in autonomic reflex response capacity associated with aging in individuals with ID.

Impact of Concurrent Exercise Training on Cardiac Autonomic Modulation, Metabolic Profile, Body Composition, Cardiorespiratory Fitness, and Quality of Life in Type 2 Diabetes with Cardiac Autonomic Neuropathy: A Randomized Controlled Trial.

Background: Type 2 diabetes mellitus (T2DM) often leads to cardiac autonomic neuropathy (CAN), a severe complication affecting cardiovascular health. Exercise training is a proven intervention for improving metabolic control and cardiovascular health in T2DM, but the effects of concurrent exercise training (CET), combining aerobic and resistance exercises, on CAN are not fully understood. Objective: This randomized controlled trial investigates the impact of a structured CET program on cardiac autonomic modulation, metabolic profile, body composition, cardiorespiratory fitness (CRF), and quality of life (QoL) in individuals with T2DM and CAN. Methods: A total of 96 participants, aged 35-70 years, with T2DM and CAN, were randomized into CET (n = 48) and control (n = 48) groups. The CET group engaged in combined aerobic and resistance training three times per week for 13 weeks, while the control group received standard care. Primary outcomes included heart rate variability (HRV) and heart rate recovery (HRR). Secondary outcomes were metabolic profile, body composition, CRF, and QoL, which were assessed using standardized protocols and validated questionnaires. The trial was registered with the Clinical Trials Registry-India (CTRI/2021/09/036711). Results: Significant improvements were noted in the CET group compared to controls. HRV metrics (SDNN, RMSSD, pNN50, TP, LF power, HF power, and LF/HF ratio) and HRR metrics (HRR30s, HRR1, HRR2, and HRR3) all showed significant enhancements (p < 0.01). The CET group also exhibited substantial reductions in fasting blood glucose, postprandial blood glucose, HbA1c, waist circumference, hip circumference, and percentage body fat (p < 0.01). Improvements were observed in lipid profile markers and CRF (VO2max) (p < 0.01). QoL scores improved significantly in the CET group as per the ADDQoL-19 (p < 0.01). Conclusions: CET significantly enhances cardiac autonomic modulation, metabolic profile, body composition, CRF, and QoL in individuals with T2DM and CAN. These findings support the integration of CET into standard T2DM management to improve clinical outcomes and QoL. Further research is needed to explore the long-term benefits and broader applicability of CET in diverse diabetic populations.

Effect of Experience and Professional Role on Psychophysiological Stress Response in an Underwater Evacuation Training

Background: This research aimed to analyze the effect of experience and professional role on psychophysiological stress response in underwater evacuation training. Methods: We analyzed 36 participants (39.06±9.01 years), divided into two different groups; 17 crew members (38.6±7.2 years) and 19 medical members (39.5±10.5 years). modifications in the rating of perceived exertion, subjective stress perception, heart rate, blood oxygen saturation, cortical arousal, heart rate variability, spirometry, isometric hand strength, and short-term memory before and after underwater evacuation training were analyzed. Results: The maneuver produced a significant increase in SSP, RPE, IHS, FVC, and SatO2 at different moments of the intervention, being higher in crew members. Conclusions: We found that the underwater evacuation training produced an anticipatory anxiety response, and an increase in autonomous sympathetic nervous system modulation not affecting strength capacities, cortical arousal, and memory independently of the aircraft role (medical or crew).

When the Clock Strikes A-fib.

Within the broad spectrum of atrial fibrillation (AF) symptomatology, there is a striking subset of patients with predominant or even solitary nocturnal onset of the arrhythmia. This review covers AF with nocturnal onset, with the aim of defining this distinctive subgroup among patients with AF. A periodicity analysis is provided showing a clear increased onset between 10:00 pm and 7:00 am. Multiple interacting mechanisms are discussed, such as circadian modulation of electrophysiological properties, vagal tone, and sleep disorders, as well as the potential interaction and synergism between these factors, to provide a better understanding of this clinical entity. Lastly, potential therapeutic targets for AF with nocturnal onset are addressed such as upstream therapy for underlying comorbidities, type of drug and timing of drug administration and pulmonary vein isolation, ablation of the ganglionated plexus, and autonomic nervous system modulation. Understanding the underlying AF mechanisms in the individual patient with nocturnal onset will contribute to patient-specific therapy.

Development of autonomic heart rate modulations during childhood and adolescence

Autonomic control of heart rate is well known in adult subjects, but limited data are available on the development of the heart rate control during childhood and adolescence. Continuous 12-lead electrocardiograms were recorded in 1045 healthy children and adolescents (550 females) aged 4 to 19 years during postural manoeuvres involving repeated 10-min supine, unsupported sitting, and unsupported standing positions. In each position, heart rate was measured, and heart rate variability indices were evaluated (SDNN, RMSSD, and high (HF) and low (LF) frequency components were obtained). Quasi-normalized HF frequency components were defined as qnHF = HF/(HF + LF). These measurements were, among others, related to age using linear regressions. In supine position, heart rate decreases per year of age were significant in both sexes but lower in females than in males. In standing position, these decreases per year of age were substantially lowered. RMSSD and qnHF indices were independent of age in supine position but significantly decreased with age in sitting and standing positions. Correspondingly, LF/HF proportions showed steep increases with age in sitting and standing positions but not in the supine position. The study suggests that baseline supine parasympathetic influence shows little developmental changes during childhood and adolescence but that in young children, sympathetic branch is less responsive to vagal influence. While vagal influences modulate cardiac periods in young and older children equally, they are less able to suppress the sympathetic influence in younger children.

Early detection of cardiac autonomic dysfunction using the respiratory sinus arrhythmia accentuation maneuver in patients with stage B1 of Chagas Disease

Introduction: The maneuver to accentuate respiratory sinus arrhythmia (RSA) demonstrates to be a convenient instrument to evaluate the autonomic modulation of individuals with chronic Chagas disease cardiomyopathy (CCC), even with medication influence, as T-cruzi causes an inflammatory process creating lesions in the cardiac nerve endings of patients affected by Chagas disease. Objective: To evaluate the autonomic modulation of heart rate (HR) at rest and during the respiratory sinus arrhythmia accentuation maneuver (RSA-M) in patients with CCC in stage B1. Methods: thirty-six individuals were evaluated, divided into the CCC group, composed of 18 patients with Chagas heart disease, and the control group, formed by 18 healthy individuals. Heart rate variability (HRV) was collected beat by beat using the electrocardiography system Wincardio USB, supine for 10 minutes, and during the RSA-M for 6 minutes. Results: We observed higher values of statistical significance in Control group for mean HR (p = 0.005), IRR (p = 0.007), and worse autonomic adjustments related to SD2 / SD1 (p = 0.001) concerning CCC group in a supine position. However, evaluating the RSA-M, we observed a statistical difference in the delta I-E (p = 0,039) and the E / I rate (p = 0.045) of the Control group in relation to the CCC group. Conclusion: Patients with CCC showed better cardiovascular condition and HR control compared to the group of healthy individuals at rest. However, when subjected to RSA-M, the results showed a reduction in vagal balance in the autonomic control of individuals with CCC. Keywords: respiration; heart rate; chagas cardiomyopathy; autonomic nervous system diseases.

Proof of mechanism investigation of Transcutaneous auricular vagus nerve stimulation through simultaneous measurement of autonomic functions: a randomized controlled trial protocol

BackgroundThe autonomic nervous system plays a vital role in regulating physiological functions. Transcutaneous auricular vagus nerve stimulation (taVNS) is a method that provides insights into autonomic nerve modulation. This paper presents a research protocol investigating proof of mechanism for the impact of taVNS on autonomic functions and aims to both deepen theoretical understanding and pave the way for clinically relevant applications.MethodsThis protocol employs a single-blind, randomized cross-over design involving 10 healthy male participants. Simultaneous assessment of both the afferent and efferent aspects of the vagus nerve will be performed by integrating physiological measures, magnetic resonance imaging, and a questionnaire survey. Electrocardiogram will be measured to assess changes in heart rate, as a primary outcome, and heart rate variability. Active taVNS and sham stimulation will be compared, which ensures precision and blinding. Electrical stimulation will be applied to the left concha cymba and the left lobule for the active and sham conditions, respectively. The specific parameters of taVNS involve a pulse width of 250 µs, a frequency of 25 Hz, and a current adjusted to the perception threshold (0.1 mA ≤ 5 mA), delivered in cycles of 32 s on and 28 s off.ConclusionsThis research investigates proof of mechanism for taVNS to elucidate its modulatory effects on the central and peripheral components of the autonomic nervous system. Beyond theoretical insights, the findings will provide a foundation for designing targeted neuromodulation strategies, potentially benefiting diverse patient populations experiencing autonomic dysregulation. By elucidating the neural mechanisms, this study contributes to the evolution of personalized and effective clinical interventions in the field of neuromodulation.Trial RegistrationJRCT, jRCTs032220332, Registered 13 September 2022; https://jrct.niph.go.jp/latest-detail/jRCTs032220332.

Effects of Exercise Training on Heart Rate Variability in Healthy Adults: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

This meta-analysis was conducted to investigate the effects of exercise training on heart rate variability (HRV) parameters associated with the autonomic nervous system (ANS) activity. Randomized controlled trials (RCTs) involving healthy adults (aged ≥ 18 years) were included. We searched PubMed, Scopus, Web of Science, and EBSCO databases to identify relevant studies. A random-effects meta-analysis was performed using the standardized mean difference (SMD) and 95% confidence interval (CI). Sixteen RCTs with a total of 623participants were selected for the final analysis. The analysis showed that exercise training improved the standard deviation of normal-to-normal intervals (SDNN) (SMD: 0.58 (0.16, 1.00); p = 0.007), the root mean square of successive differences in heart period series (RMSSD) (SMD: 0.84 (0.36, 1.31); p = 0.0005), and the absolute power of high-frequency band (HF) (SMD: 0.89 (0.27, 1.51); p = 0.005) parameters compared to the control group. Analysis of the moderator variables showed that the effect of exercise on HRV indices may be influenced by sex, age, and type of exercise used, specifically in HF band, absolute power of low-frequency band (LF), and LF/HF ratio parameters. Despite the limited number of existing RCTs related to the subject, the results suggest that exercise training enhances HRV parameters associated with vagal-related activity (RMSSD and HF) and both sympathetic and parasympathetic activities (SDNN). This study overcomes the lack of meta-analyses on the effects of exercise training on autonomic modulation among healthy adults and may bridge the gap in understanding the potential physiological underpinnings of the acknowledged positive health benefits of exercise.