Search Results (62)

The intricate relationship between the heart and the brain has transitioned from historical, cardio-centric theories to a modern, circuit-based, bi-directional framework known as neurocardiology. This review provides a comprehensive anatomical, physiological, and clinical synthesis of the bidirectional heart–brain axis, highlighting how disruptions in one organ systematically impact the other. Structurally, the heart–brain axis operates as a closed-loop feedback network. Vagal parasympathetic control dominates at rest, driven by an asymmetrical fiber distribution where sensory afferents actively supply interoceptive data to the brainstem. Hemodynamically, cerebral blood flow delivery is linked to cardiac output in an age-dependent fashion with the related vascular dysfunction. Clinically, brain-to-heart pathologies like acute brain injury trigger life-threatening catecholamine surges, neuroinflammation, and myocardial stunning, including Takotsubo cardiomyopathy. Conversely, heart-to-brain pathways reveal that atrial fibrillation and heart failure can independently trigger cardioembolic stroke, long-term neuroinflammation, and a profound, progressive burden of cognitive decline. The heart and brain are inexorably linked through complex structural, mechanical, and paracrine pathways. Ameliorating clinical outcomes demands integrated cross-specialty diagnostic screening, digital rhythm monitoring, and holistic neurocardioprotective therapeutic strategies. Full article

Historically framed as a behavioral addiction, gambling disorder (GD) has had its somatic dimension neglected by standard clinical evaluation. This is a narrative, hypothesis-generating review focusing on the somatic aspects of GD. Cross-sectional and prospective evidence increasingly shows a somatic phenotype distributed across four axes: cardiovascular (hypertension, angina, stroke, acute stress-induced cardiac events), metabolic (obesity, type 2 diabetes, chronic liver disease), sleep-related (insomnia, poor sleep quality, daytime sleepiness), and—as an emerging and insufficiently characterized dimension—neurological (clustering with seizures and frontal lobe epilepsy). Three candidate biological systems may translate this exposure into multi-system physiology: (i) a hyperreactive mesostriatal reward circuit hypothesized to sustain a behavioral cluster of smoking, hazardous alcohol use, low physical activity, and unhealthy diet; (ii) an integrated stress response postulated to shift from acute hyperreactivity to chronic basal cortisol blunting and reduced vagal tone; and (iii) putative alterations in peripheral neurotrophic signaling and frontal-callosal structure, marked by elevated peripheral brain-derived neurotrophic factor and by frontal-callosal white-matter alterations—with cumulative allostatic load serving as a conceptual integrating frame. We propose that GD can be a behaviorally driven systemic medical condition, warranting internal medicine involvement alongside addiction psychiatry. Within this framework, glucagon-like peptide-1 receptor agonists emerge as an exploratory therapeutic hypothesis warranting dedicated evaluation in GD, given their action on the mesolimbic reward substrate and phase 3 evidence in adjacent cardiometabolic, hepatic, and sleep conditions. Full article

The “athlete’s heart” represents a physiological condition consequent to long-term adaptation to sport-specific training loads. Cardiac imaging is a pivotal tool in the assessment of athletes. The study of the autonomic nervous system (ANS) using heart rate variability is becoming increasingly popular in sports fields, given its fundamental role in cardiovascular adaptation to exercise. Unfortunately, many barriers limit the clinical use of this methodology. In this observational study of 330 elite athletes, we used a composite index of ANS control (ANSI), designed to overcome pitfalls, following the hypothesis that studying the ANS could help address cardiac adaptation to high-volume training. In athletes subdivided into three groups considering the level (LOW/HIGH) of combined static/dynamic exercise and the presence [+]/absence [−] of left ventricular hypertrophy (LVH), we found that ANSI showed a progressive increase (LOW: 38.2 ± 27.6%; HIGH-LVH [−]: 52.1 ± 27.2%; HIGH-LVH [+]: 64.4 ± 24.9%, J-T test p < 0.001), with significant differences between all groups considered (p < 0.001). After adjustment and within the HIGH group, ANSI showed the strongest association with LVH and the highest explanatory power among autonomic variables. In conclusion, ANSI was able to differentiate elite athletes characterized by different cardiac remodeling and workloads (as suggested by different sport disciplines), corroborating the hypothesis for a wider use of ANS evaluation in the sports field. Full article

Obstructive sleep apnea (OSA) constitutes a chronic disorder characterized by recurrent upper airway collapse during sleep. This condition is prevalent among patients with cardiac rhythm disturbances and represents a potent independent risk factor for arrhythmia. Although most studies have concentrated on the association between OSA and atrial fibrillation (AF), numerous investigations have established connections with ventricular and supraventricular arrhythmias. Arrhythmogenesis in OSA represents a complex multifactorial phenomenon. Acute mechanisms involve induction of negative intrathoracic pressure during the effort to breathe, which triggers recurrent episodes of hypoxia, hypercapnia, alterations in carbon dioxide and acid–base equilibrium, as well as surges in sympathetic nervous system activity. Chronic intermittent hypoxia (CIH) and negative thoracic pressure (NTP) induce atrial stretch, chronic structural remodeling, and elevated vagal tone, thereby heightening susceptibility to bradycardic and conduction arrhythmias. Intermediate pathways through which OSA may precipitate arrhythmia encompass heightened systemic inflammation, oxidative stress, a prothrombotic state, and vascular dysfunction. Long-term OSA is linked with atrial enlargement and fibrosis, ventricular hypertrophy, hypertension, and coronary artery disease. These factors predispose to cardiac arrhythmias through the following mechanisms: shortening of the atrial effective refractory period, abnormal automaticity, promotion of slowed and heterogeneous conduction, enhancement of reentrant arrhythmia persistence, and prolongation of the QT interval. In this paper, we aim to present the pathophysiological mechanisms underpinning the association between obstructive sleep apnea and cardiac arrhythmias. Understanding the precise pathophysiological pathways by which obstructive sleep apnea contributes to arrhythmogenesis will enable targeted preventive stratification of patients at risk for cardiovascular events and promote the development of innovative therapies to attenuate OSA-induced arrhythmogenicity. Full article

Precise respiration assessment is crucial for heart rate variability (HRV) interpretation as respiratory components—particularly respiratory sinus arrhythmia (RSA)—provide essential information on vagally mediated regulation. Conventional single-lead electrocardiogram-derived respiration (EDR) methods measure the amplitude modulation of the QRS-waveform caused by respiratory chest movements. This causes a displacement of the electrical heart axis in relation to the ECG lead axis, typically within the 2D frontal plane of the Einthoven electrode montage. Another approach is based on heartbeat acceleration and deceleration during respective inspiration and expiration causing RR interval modulation. However, interval-based methods depend on the complexity of sympathovagal factors that affect RSA. The present feasibility study accounts for the 3D rotational movement of the electrical heart axis during the respiratory cycle and avoids non-respiratory neuromodulatory confounds. The beat-to-beat cardiac rotation was extracted from Frank-XYZ coordinates reconstructed via a four-electrode EASI device. In a pilot study with data from 19 healthy adults performing acoustically paced breathing (6–18 bpm), three surrogates (${\mathrm{RR-Interval}}_{\mathrm{EDR}}$, ${\mathrm{R-Amplitude}}_{\mathrm{EDR}}$, ${\mathrm{Heartmovement}}_{\mathrm{EDR}}$) were compared using a unified Python 3.11.13 pipeline (3D VCG R-peak detection, multivariate Mahalanobis artifact correction, wavelet-based analysis) against a synthetic reference derived from the instructed breathing schedule. The results demonstrated a consistently lower estimation error and higher reference-based signal-to-noise ratio (refSNR), measuring spectral alignment with the paced-breathing trajectory for ${\mathrm{Heartmovement}}_{\mathrm{EDR}}$ and achieving a mean refSNR of 6.01 dB (vs. 4.62 dB for ${\mathrm{RR-Interval}}_{\mathrm{EDR}}$ and 3.20 dB for ${\mathrm{R-Amplitude}}_{\mathrm{EDR}}$) and a mean absolute estimation error of 0.016 Hz (vs. 0.050 Hz and 0.032 Hz, respectively). Notably, ${\mathrm{Heartmovement}}_{\mathrm{EDR}}$ and ${\mathrm{R-Amplitude}}_{\mathrm{EDR}}$ performance slightly improved at higher heart rates, consistent with the interpretation that higher cardiac sampling density benefits spectral resolution for chest movement-based methods, whereas ${\mathrm{RR-Interval}}_{\mathrm{EDR}}$ showed no significant heart rate dependence. Furthermore, ${\mathrm{Heartmovement}}_{\mathrm{EDR}}$ was compared with the EDR results obtained by applying the Kubios-HRV Premium software (version 3.5.0). Kubios-EDR yielded higher precision at elevated breathing frequencies, whereas ${\mathrm{Heartmovement}}_{\mathrm{EDR}}$ outperformed Kubios-EDR at breathing rates below 10 bpm—a range that is particularly relevant for vagally activating slow breathing protocols or treatments. Future work should validate this method using a direct respiration measurement under spontaneous natural breathing conditions. Full article

Background: Long COVID, or post-COVID-19 condition (PCC), affects around 36% of individuals following SARS-CoV-2 infection, manifesting as persistent fatigue, cognitive dysfunction, and dysautonomia among its hallmark features. Affecting an estimated 400 million individuals globally, it imposes an annual economic burden exceeding $1 trillion, yet no pharmacological therapy has demonstrated consistent efficacy in adequately powered randomized controlled trials. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a candidate intervention targeting the autonomic dysfunction and neuroinflammation responsible for PCC pathophysiology. Methods: We conducted a PRISMA 2020-compliant systematic review (PROSPERO: CRD420261287286) searching PubMed, Scopus, Cochrane, and Web of Science databases from inception to January 2026 for studies evaluating any form of VNS in adults with Long COVID. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, the JADAD scale, and the PEDro scale. Certainty of evidence was evaluated using the GRADE framework. Narrative synthesis followed SWiM guidelines. Results: Five studies (n = 154 participants) (three randomized controlled trials (RCTs) and two single-arm studies) met inclusion criteria. Three of five studies (60%) were rated high overall risk of bias; only two RCTs achieved “some concerns.” The only adequately double-blinded RCT found no significant between-group differences across all outcomes. Paradoxically, in the best-powered RCT (Percin et al.), sham stimulation produced significantly greater fatigue improvement than active taVNS, despite active taVNS producing significant HRV increases consistent with cardiac autonomic modulation. All efficacy outcomes were rated “very low” certainty (GRADE); safety was rated “low” certainty. Conclusions: Currently available evidence supporting the use of taVNS for Long COVID remains limited, and the absence of reliable target engagement markers in the included studies constrains confidence in this approach. Nonetheless, the physiological rationale remains sound, and the favorable safety profile across all included studies supports the feasibility of future investigation. However, given that positive findings were confined to inadequately controlled studies, enthusiasm for further research should be directed first toward mechanistic clarification and rigorous dose-finding work. Large-scale, double-blind, sham-controlled trials incorporating validated markers of vagal engagement are required before taVNS can be firmly recommended for COVID-19 sequelae management. Full article

Background: Metabolic syndrome (MetS) leads to alterations in cardiac autonomic control that can be detected from electrocardiogram (ECG)-derived markers, particularly when the cardiovascular system is challenged during an oral glucose tolerance test (OGTT). Methods: In this paper, we present an automated framework for MetS identification using RR intervals and heart rate variability (HRV) features extracted from 12-lead ECG recordings acquired during the five OGTT stages in 40 male participants (15 with MetS, 10 controls, and 15 endurance-trained marathon runners). RR intervals were first derived using a multilead Pan-Tompkins approach with fusion-based validation. From these RR series, HRV descriptors were computed from time-domain statistics (RR mean, SDNN, rMSSD, pNN50), spectral indices (VLF, LF, HF, LF/HF), and nonlinear measures (SD1, SD2, SampEn, DFA-${\alpha }_1$). Conventional HRV analysis revealed pronounced physiological differences between groups: MetS subjects exhibited reduced parasympathetic activity, reflected by lower rMSSD and SD1, lower HF power, and higher LF/HF ratios, whereas marathoners showed greater vagal modulation, higher HF power, and increased signal complexity. Healthy controls showed an intermediate autonomic profile. Using RR sequences and HRV descriptors (256 samples per stage), we trained three multimodal classifiers: a CNN-MLP model with a softmax output, a CNN-MLP model with an SVM head, and a CNN + LSTM-MLP + SVM architecture. Results: All models achieved strong discriminative performance, with accuracies ranging from 0.92 to 0.95, F1-macro values from 0.92 to 0.95, and macro-AUC values from 0.96 to 0.97. The CNN-MLP model achieved the best overall performance, whereas the CNN + LSTM-MLP + SVM model showed strong class discrimination, particularly for endurance athletes, while maintaining competitive recall for MetS. Conclusions: These findings support the feasibility of ECG-based autonomic assessment as a complementary non-invasive approach for early metabolic risk detection in clinical and preventive cardiometabolic screening settings. Full article

Maintaining cardiovascular stability during anesthesia is essential, yet the routine use of atropine to prevent vagally induced low heart rate may impose additional stress on the heart. This randomized, controlled, observer-blinded, clinical study aimed to evaluate whether ondansetron, a selective 5-HT₃ receptor antagonist, could serve as an alternative anesthetic adjuvant to modulate autonomic activity while maintaining cardiovascular stability in dogs. A total of 66 female dogs, with a mean age of 1.5 years and a mean weight of 16–18 kg ASA I, undergoing elective surgery were assigned to three study groups to receive atropine, ondansetron, or no autonomic-modulating drug. Heart rate, arterial pressure, respiratory rate, and NT-proBNP were recorded before, during, and after anesthesia. Dogs treated with ondansetron maintained stable cardiovascular values throughout the procedure, with no episodes of low heart rate or excessive increases in heart rate. In contrast, atropine induced marked and sustained elevation in heart rate and higher arterial pressures. Concentrations of the cardiac biomarker NT-proBNP increased significantly 48 h after surgery in the atropine group but remained unchanged in the ondansetron group, indicating the absence of additional myocardial stress. These findings suggest that ondansetron may help preserve autonomic balance during anesthesia while minimizing myocardial stress. Ondansetron could represent a useful component of multimodal anesthetic protocols, particularly in dogs in which excessive cardiac stimulation should be avoided. Full article

Non-invasive vagus nerve stimulation (nVNS) is gaining attention as a promising approach to modulate emotional, cognitive, and autonomic processes. This exploratory study analyzed the short-term effects of manual vagal maneuver (MVM), applied to the left or the right side of the neck (carotid region), on emotional regulation, cognitive performance, and cardiac autonomic activity in healthy young females. Sixty participants, divided equally into three groups (left MVM, right MVM, and control), completed attentional tasks under their respective conditions. Heart rate variability (HRV), cardiac coherence, self-reported emotional states, and task performance were measured. The preliminary findings of this pilot study offer mixed evidence: while both stimulation groups seem to show significant improvements in attentional performance, only left-sided MVM was associated with increased cardiac coherence and elevated perceived emotional dominance. No significant changes were observed in HRV indices across groups, highlighting potential limitations of current physiological markers in capturing subtle autonomic modulation. These preliminary findings from a pilot study suggest that, in young healthy women, stimulation—particularly on the left side—may have a potential to enhance cognitive and affective functioning, even though no detectable changes were observed in conventional HRV metrics. Given the small sample size and other important methodological limitations, such as the single-session design, these results should be interpreted with caution, and replication in larger, more rigorous studies is necessary. Full article

The gut microbiota is crucial for metabolic homeostasis and cardiovascular health. Dysbiosis triggers a gut–brain–heart axis dysfunction: vagal signaling promotes neuroinflammation and cerebral damage, which in turn impairs cardiac function. This bidirectional cycle is further exacerbated by reduced cerebral perfusion. Trimethylamine-N-oxide (TMAO), a metabolite of dietary choline and L-carnitine, acts as a primary mediator in this network. Elevated TMAO levels—resulting from bacterial conversion and hepatic oxidation—are linked to atherosclerosis and heart failure. Mechanistically, TMAO activates the NLRP3 inflammasome, inhibits the SIRT3-SOD2 pathway, and promotes platelet hyperreactivity. Furthermore, it modulates the autonomic nervous system, enhancing sympathetic activity and cardiac arrhythmias. Clinical evidence suggests TMAO is a potent predictor of mortality in HF. While current HF therapies focus on end-organ response (beta-blockers) or humoral pathways (ACE inhibitors), directly targeting the microbiota and TMAO offers a novel therapeutic frontier. Integrating TMAO assessment into risk models and utilizing advanced in vitro gut–brain models will be essential for developing personalized, groundbreaking cardiovascular interventions. Within this framework, the main aim of the present review is to describe how cardiac autonomic control can be directly modulated by the microbiota and its byproducts like TMAO. This latter is a leading target candidate for novel HF prevention and therapy interventions. Full article

Early-life feeding strategies are known to affect growth, behavior, and stress physiology in dairy calves. This study examined the effects of different milk feeding regimes on heart rate (HR) and heart rate variability (HRV) during feeding and rehousing as indicators of autonomic activity. Dairy calves were fed either a restrictive milk allowance twice per day (6 L/d; RES; n = 21) or an unlimited amount of milk (ad libitum; ADL; n = 24) during the first three weeks of life. All calves were housed in individual straw bedded hutches from d 1 to 23 of life and were moved to a group pen on d 23 ± 2 of life. Starting at least one day before rehousing until one hour after the rehousing process HR, HRV, and variables in the time and frequency domain were measured continuously using a portable recording system. To study the cardiac response to the feeding process, six time windows of 5 min each were chosen as follows: resting time at 5.00 a.m., start of personnel activity in the barn, 15 min before feeding, during feeding, 15 min after feeding, and 1 h after feeding. For the evaluation of cardiac response to an unknown stressor such as rehousing, four time windows of 5 min each were selected as follows: resting time at 5.00 a.m., during rehousing, 30 min after rehousing, and 1 h after rehousing. During resting as well as before feeding and rehousing, HR was higher in ADL calves compared with RES calves. During feeding and rehousing, HR reached peak values which were comparable in both groups. HRV variables of the time and frequency domain indicated a shift towards a sympathetic dominance in the balance of the autonomic nervous system during feeding time, particularly in RES calves. Differences between resting and feeding values were demonstrated in RES calves at low-frequency and high-frequency power, whereas no differences were observed in ADL calves which did not react to the feeding process. The cardiac response of calves to rehousing was inconsistent in both groups. An increase in RMSSD and SD1 in ADL calves indicated that the vagal component in the vegetative neurological control was increased in these calves during rehousing. In conclusion, our findings indicate that restrictive milk feeding alters autonomic regulation and may increase physiological stress responses in calves. Full article

Adverse cardiovascular events and increased mortality are associated with cardiac autonomic nervous system dysfunction in the early stages of the systemic sclerosis (SSc), even prior to the development of cardiac fibrosis. The objective of the study was to evaluate the impact of a three-month exercise training regimen and a subsequent comparable period of detraining on the activity of the cardiac autonomic nervous system in patients with SSc. A total of forty patients with SSc were randomized to either the control group (Group COΝ) or the exercise training group (Group ET). Cardiopulmonary exercise testing was performed at baseline, three months later, and six months later to assess peak oxygen uptake (VO₂peak). They also had 24 h electrocardiogram monitoring for heart rate variability (HRV) and heart rate turbulence analysis. The following time-domain indices were evaluated in the context of HRV analysis: the standard deviation of NN intervals (SDNN), the root mean square of successive RR interval differences (rMSSD), and the percentage of successive RR intervals that differ by more than 50 ms (pNN50). Additionally, regarding the frequency-domain indicators, the low-frequency (LF) and high-frequency (HF) components, as well as the LF/HF ratio, were evaluated. Independent t-tests and Chi-square tests were used for baseline comparisons, while two-way repeated measures ANOVA with Bonferroni post hoc tests assessed changes over time and between groups. Linear and multiple regression analyses were conducted to explore relationships among variables and identify predictors of HRV indices and VO₂peak. Group ET implemented a three-month mixed-type exercise training program, while Group COΝ received standard care. Group ET improved indices of vagal activity [rMSSD by 32.6% (p = 0.017), pNN50 by 57.1% (p = 0.01) and HF by 20.1% (p = 0.01)] and sympathovagal activity [SDNN by 15.5% (p = 0.002) and LF/HF by 12.03% (p = 0.004)] after three months. Exercising patients also increased their VO₂peak by 20.8% (p = 0.001). A robust positive correlation was observed between ΔVO₂peak and ΔSDNN (r = 0.754, p < 0.001). After three months, there was no statistically significant difference in the VO₂peak or any HRV index in the group COΝ. Compared to the baseline values, there was no statistically significant difference in group ET at 6 months, whereas the control group exhibited a decline. In summary, a three-month mixed-type exercise training program can enhance the cardiorespiratory efficiency and cardiac autonomic nervous system function of patients with SSc, as well as alleviate the deterioration that arises following the detraining period. Full article

We examined heart rate (HR) and heart rate variability (HRV) in young and middle-aged men after a period of detraining that immediately followed the completion of an exercise training program. Eight young (27.8 ± 3.8 years) and ten middle-aged (41.9 ± 3.8 years) men were randomly assigned to complete an 8-week exercise training program that included either aerobic (young: n = 3; middle-aged: n = 2), resistance (young: n = 3; middle-aged: n = 3), or combined (aerobic/resistance) (young: n = 2; middle-aged: n = 5) exercise. Thereafter, participants ceased all planned exercise training activities during an 8-week detraining period. Resting HR and HRV were assessed at baseline, after exercise training, and after detraining. An analysis of mean differences between age groups at each time-point revealed a significantly higher standard deviation of normal RR intervals (SDNN), square root of the mean of squared differences between successive RR intervals (RMSSD), high-frequency (HF) band (0.15–0.40 Hz), and cardiac vagal index (CVI) in young participants when compared to middle-aged participants at baseline (p ≤ 0.019) and after detraining (p ≤ 0.045), but not after the 8-week exercise training intervention (p ≥ 0.057). Additionally, in middle-aged participants, we observed a significant negative association between the percent change in HRV indices (RMSSD, HF, and CVI) and systolic blood pressure in response to detraining (p < 0.05). In conclusion, young participants had higher levels of HRV indices at baseline, reflecting greater cardiac vagal modulation when compared to middle-aged participants. We showed that these age-related differences in HRV are diminished following exercise training but are reestablished following 8 weeks of detraining. Given that age-related attenuations in HRV may reflect changes in cardiovascular health, it is important to further investigate the relationships between HRV, exercise training and detraining, aging, and the risk of poor health outcomes. Full article

The imbalance in the interaction between the autonomic nervous system and the immune system serves as a central mechanism in the onset and progression of cardiovascular diseases. The excessive activation of the sympathetic nervous system and suppression of vagal function contribute to chronic inflammation and cardiac remodeling. Precision medicine, by integrating multidimensional data such as genomics and metabolomics, offers a novel perspective for the personalized design of exercise interventions. This systematic review explores the bidirectional regulatory mechanisms of exercise interventions on the autonomic nervous system–immune axis and examines the potential applications of precision medicine in optimizing exercise prescriptions and clinical translation. Exercise significantly improves cardiovascular function through immunometabolic reprogramming, which includes suppressing sympathetic overactivity, enhancing vagal tone, and modulating the IL-6/IL-10 balance, as well as activating the short-chain fatty acid (SCFA)–Treg axis. Moreover, precision-medicine-driven ACE I/D gene typing provides a basis for selecting tailored exercise prescriptions, thereby significantly enhancing the efficacy of exercise interventions. By leveraging a multi-tiered “neuro–immune–metabolic” regulatory framework, exercise interventions contribute to improved cardiovascular health. The application of precision medicine technology overcomes individual variability constraints, advancing exercise prescription design from generalized recommendations toward personalized and dynamically adaptive strategies. Full article

Diabetes mellitus, especially type 2 diabetes mellitus (T2DM), is a major health problem worldwide and has become a leading cause of mortality. As a common complication of patients with T2DM, cardiac autonomic dysfunction (including sympathetic overactivation and reduced vagal tone) is associated with a higher risk of arrhythmia-related sudden cardiac death. Our previous study found that T2DM-elevated hydrogen peroxide (H₂O₂) levels in atrioventricular ganglion (AVG) neurons contribute to the decrease in cardiac vagal function and ventricular arrhythmogenesis through inhibition of N-type Ca²⁺ channels (Ca_v2.2). In the present study, treatment with exogenous H₂O₂ in differentiated NG108-15 cells increased REST expression and decreased Ca_v2.2-α expression. Adenoviral catalase gene transfection into the AVG neurons significantly reduced the REST levels elevated by a high-fat diet plus streptozotocin-induced T2DM. Lentiviral REST shRNA transfection markedly increased Ca_v2.2-α expression in the AVG neurons from T2DM rats. REST shRNA also activated N-type Ca²⁺ channels and increased cell excitability of AVG neurons in T2DM rats. Additionally, REST shRNA markedly improved cardiac vagal activation in T2DM rats. The present study suggests that the H₂O₂-REST-Ca_v2.2 channel signaling axis could be a potential therapeutic target to normalize cardiac vagal dysfunction and its related cardiac complications in T2DM. Full article