Angiotensin II and the Cardiac Parasympathetic Nervous System in Hypertension.

The renin-angiotensin-aldosterone system (RAAS) impacts cardiovascular homeostasis via direct actions on peripheral blood vessels and via modulation of the autonomic nervous system. To date, research has primarily focused on the actions of the RAAS on the sympathetic nervous system. Here, we review the critical role of the RAAS on parasympathetic nerve function during normal physiology and its role in cardiovascular disease, focusing on hypertension. Angiotensin (Ang) II receptors are present throughout the parasympathetic nerves and can modulate vagal activity via actions at the level of the nerve endings as well as via the circumventricular organs and as a neuromodulator acting within brain regions. There is tonic inhibition of cardiac vagal tone by endogenous Ang II. We review the actions of Ang II via peripheral nerve endings as well as via central actions on brain regions. We review the evidence that Ang II modulates arterial baroreflex function and examine the pathways via which Ang II can modulate baroreflex control of cardiac vagal drive. Although there is evidence that Ang II can modulate parasympathetic activity and has the potential to contribute to impaired baseline levels and impaired baroreflex control during hypertension, the exact central regions where Ang II acts need further investigation. The beneficial actions of angiotensin receptor blockers in hypertension may be mediated in part via actions on the parasympathetic nervous system. We highlight important unknown questions about the interaction between the RAAS and the parasympathetic nervous system and conclude that this remains an important area where future research is needed.

Age-related decrease of cholinergic parasympathetic reflex vasodilation in the rat masseter muscle.

Skeletal muscle hemodynamics, including that in jaw muscles, is an important in their functions and is modulated by aging. Marked blood flow increases mediated by parasympathetic vasodilation may be important for blood flow in the masseter muscle (MBF); however, the relationship between parasympathetic vasodilation and aging is unclear. We examined the effect of aging on parasympathetic vasodilation evoked by trigeminal afferent inputs and their mechanisms by investigating the MBF during stimulation of the lingual nerve (LN) in young and old urethane-anesthetized and vago-sympathectomized rats. Electrical stimulation of the central cut end of the LN elicited intensity- and frequency-dependent increases in MBF in young rats, while these increases were significantly reduced in old rats. Increases in the MBF evoked by LN stimulation in the young rats were greatly reduced by hexamethonium and atropine administration. Increases in MBF in young rats were produced by exogenous acetylcholine in a dose-dependent manner, whereas acetylcholine did not influence the MBF in old rats. Significant levels of muscarinic acetylcholine receptor type 1 (MR1) and type 3 (MR3) mRNA were observed in the masseter muscle in young rats, but not in old rats. Our results indicate that cholinergic parasympathetic reflex vasodilation evoked by trigeminal afferent inputs to the masseter muscle is reduced by aging and that this reduction may be mediated by suppression of the expression of MR1 and MR3 in the masseter muscle with age.

Intestinal Cetobacterium and acetate modify glucose homeostasis via parasympathetic activation in zebrafish.

The capability of carbohydrate utilization in fish is limited compared to mammals. It has scientific and practical significance to improve the ability of fish to use carbohydrates. The efficiency of dietary carbohydrate utilization varies among fish with different feeding habits, which are associated with differential intestinal microbiota. In this study, we found that zebrafish fed with omnivorous diet (OD) and herbivorous diet (HD) showed better glucose homeostasis compared with carnivorous diet (CD) fed counterpart and the differential glucose utilization efficiency was attributable to the intestinal microbiota. The commensal bacterium Cetobacterium somerae, an acetate producer, was enriched in OD and HD groups, and administration of C. somerae in both adult zebrafish and gnotobiotic larval zebrafish models resulted in improved glucose homeostasis and increased insulin expression, supporting a causative role of C. somerae enrichment in glucose homeostasis in fish. The enrichment of C. somerae was constantly associated with higher acetate levels, and dietary supplementation of acetate promotes glucose utilization in zebrafish, suggesting a contribution of acetate in the function of C. somerae. Furthermore, we found that the beneficial effect of both acetate and C. somerae on glucose homeostasis was mediated through parasympathetic activation. Overall, this work highlights the existence of a C. somerae-brain axis in the regulation of glucose homeostasis in fish and suggests a role of acetate in mediating the axis function. Our results suggest potential strategies for improvement of fish carbohydrate utilization.

Electroacupuncture ameliorates intestinal inflammation by activating α7nAChR-mediated JAK2/STAT3 signaling pathway in postoperative ileus.

Inflammatory cytokines produced by muscularis macrophages largely contribute to the pathological signs of postoperative ileus (POI). Electroacupuncture (EA) can suppress inflammation, mainly or partly via activation of vagal efferent. The goal of this study was to investigate the mechanisms by which EA stimulation at an hindlimb region ameliorates inflammation in POI. Methods: Intestinal motility and inflammation were examined after 24 h after intestinal manipulation (IM)-induced POI in mice. Local immune response in the intestinal muscularis, expression of macrophages, α7 nicotinic acetylcholine receptor (α7nAChR), Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) were determined by flow cytometry, Western Blot, qPCR and immunofluorescence. The effects of α7nAChR antagonists (methyllycaconitine and α-bungarotoxin) and JAK2/STAT3 inhibitors (AG490 and WP1066) were also administered in a subset of mice prior to EA. In the parasympathetic pathways, intestinal motility and inflammation were determined after cervical vagotomy and sub-diaphragmatic vagotomy. The expression of gamma absorptiometry aminobutyric acid (GABAA) receptor in dorsal motor nucleus of vagal (DMV) cholinergic neurons was assessed by immunofluorescence and the response to DMV microinjection of bicuculine (antagonist of GABAA receptor) or muscimol (agonist of GABAA receptor) were assessed. Results: EA suppressed intestinal inflammation and promoted gastrointestinal motility. Mechanistically, EA activated the α7nAChR-mediated JAK2/STAT3 signaling pathway in macrophages which reduced the production of inflammatory cytokines. Furthermore, we also demonstrated that hindlimb region stimulation drove vagal efferent output by inhibiting the expression of GABAA receptor in DMV to ameliorate inflammation. Conclusions: The present study revealed that EA of hindlimb regions inhibited the expression of GABAA receptor in DMV neurons, whose excited vagal nerve, in turn suppressed IM-induced inflammation via activation of α7nAChR-mediated JAK2/STAT3 signaling pathway.

Mini review: Neural mechanisms underlying airway hyperresponsiveness.

Neural changes underly hyperresponsiveness in asthma and other airway diseases. Afferent sensory nerves, nerves within the brainstem, and efferent parasympathetic nerves all contribute to airway hyperresponsiveness. Inflammation plays a critical role in these nerve changes. Chronic inflammation and pre-natal exposures lead to increased airway innervation and structural changes. Acute inflammation leads to shifts in neurotransmitter expression of afferent nerves and dysfunction of M2 muscarinic receptors on efferent nerve endings. Eosinophils and macrophages drive these changes through release of inflammatory mediators. Novel tools, including optogenetics, two photon microscopy, and optical clearing and whole mount microscopy, allow for improved studies of the structure and function of airway nerves and airway hyperresponsiveness.

Changes Induced by Mind-Body Intervention Including Epigenetic Marks and Its Effects on Diabetes.

Studies have evidenced that epigenetic marks associated with type 2 diabetes (T2D) can be inherited from parents or acquired through fetal and early-life events, as well as through lifelong environments or lifestyles, which can increase the risk of diabetes in adulthood. However, epigenetic modifications are reversible, and can be altered through proper intervention, thus mitigating the risk factors of T2D. Mind-body intervention (MBI) refers to interventions like meditation, yoga, and qigong, which deal with both physical and mental well-being. MBI not only induces psychological changes, such as alleviation of depression, anxiety, and stress, but also physiological changes like parasympathetic activation, lower cortisol secretion, reduced inflammation, and aging rate delay, which are all risk factors for T2D. Notably, MBI has been reported to reduce blood glucose in patients with T2D. Herein, based on recent findings, we review the effects of MBI on diabetes and the mechanisms involved, including epigenetic modifications.

Characteristic Effects of the Cardiac Non-Neuronal Acetylcholine System Augmentation on Brain Functions.

Since the discovery of non-neuronal acetylcholine in the heart, this specific system has drawn scientific interest from many research fields, including cardiology, immunology, and pharmacology. This system, acquired by cardiomyocytes independent of the parasympathetic nervous system of the autonomic nervous system, helps us to understand unsolved issues in cardiac physiology and to realize that the system may be more pivotal for cardiac homeostasis than expected. However, it has been shown that the effects of this system may not be restricted to the heart, but rather extended to cover extra-cardiac organs. To this end, this system intriguingly influences brain function, specifically potentiating blood brain barrier function. Although the results reported appear to be unusual, this novel characteristic can provide us with another research interest and therapeutic application mode for central nervous system diseases. In this review, we discuss our recent studies and raise the possibility of application of this system as an adjunctive therapeutic modality.

Interactions of Eosinophils with Nerves.

Eosinophils affect nerve structure and function in organs such as lungs and skin, which contributes to disease pathogenesis. We have developed methods for culturing primary sensory and parasympathetic neurons in multiple species and have refined these techniques for coculture with eosinophils. Eosinophil-nerve coculture has been an essential tool for testing interactions between these cell types. Here we describe methods for coculturing primary parasympathetic ganglia, vagal sensory nerves, and dorsal root sensory nerves with eosinophils.

Significance of vagus nerve function in terms of pathogenesis of psychosocial disorders.

The vagus nerve (VN) belongs to the parasympathetic nervous system, which is well known to be involved in the regulation of the functions of organs in the body. The neurotransmitter acetylcholine, released from the cholinergic system including VN, has been known to play an anti-inflammatory role through the efferent pathways in regulating peripheral inflammatory responses profoundly involved in the pathogenesis of diseases. In contrast, anatomically, it connects the central nervous system (CNS) and peripheral organs, including the heart and gastrointestinal (GI) tract. Therefore, it has been recently reported that the VN also plays an important role in the pathogenesis of psychological disorders since it confers varied signals from the GI tract to the CNS, and alteration of microbiota residing in GI definitely influences the condition of neuropsychiatric disorders. Furthermore, the CNS includes microglia, a neuroinflammatory effector in the brain, which is also influenced by the VN to modulate its inflammatory status. Based on significant findings of the VN, the VN stimulation (VNS) has recently drawn attention from many scientific fields. VNS was initially applied to patients with refractory epilepsy, followed by patients with refractory depression. Subsequently, VNS was also attempted to be introduced to other diseases. However, against whichever disease, central or peripheral, detailed underlying mechanisms of VNS involved in neuropsychiatric disorders as well as VNS target molecules in the GI tract and the CNS remains to be studied. In this review, we discuss the mechanisms and predicted responsible factors of VNS in terms of neuropsychiatric disorders.

Galantamine in rheumatoid arthritis: A cross talk of parasympathetic and sympathetic system regulates synovium-derived microRNAs and related pathogenic pathways.

The acetylcholinesterase inhibitor, galantamine, has shown therapeutic effect in rat model of rheumatoid arthritis. Hence, the current study aims at determining the mode of action of galantamine by examining different synovium-derived microRNAs (miRs) and their related pathogenic pathways. The study also focuses on how parasympathetic and sympathetic pathways in the synovial tissue could affect the mode of action and anti-arthritic effect of galantamine. Chemical sympathectomy was initiated in 12 adjuvant arthritic rats by exposure to 6-hydroxydopamine (6-OHDA; 2 × 50 mg/kg) on day 9 after adjuvant injection and again (2 × 100 mg/kg) one week later. Six rats were treated with galantamine (2.5 mg/kg/day) to explore the influence of sympathetic impairment on galantamine effect. Another twelve additional adjuvant arthritic rats were exposed to the selective α7 nicotinic acetylcholine receptor blocker methylcaconitine citrate (MLA; 5.6 mg/kg/day), 15 min before galantamine treatment. As control, six adjuvant arthritic rats were treated with galantamine alone. Treatment proceeded for 5 days, from day 14 till day 18 post-adjuvant injection. Different miRs and their related pathogenic pathways were examined. Tyrosine hydroxylase (TH) expression was also measured in joint tissue. Galantamine affected the expression of the different miRs and their related parameters. Both, 6-OHDA and MLA, interrupted the anti-inflammatory/anti-arthritic effect of galantamine to different extent. Additionally, TH expression in the synovium was affected by galantamine, suggesting a novel pathogenic target in the treatment of rheumatoid arthritis.

Selective Induction of Human Autonomic Neurons Enables Precise Control of Cardiomyocyte Beating.

The autonomic nervous system (ANS) regulates tissue homeostasis and remodelling through antagonistic effects of noradrenergic sympathetic and cholinergic parasympathetic signalling. Despite numerous reports on the induction of sympathetic neurons from human pluripotent stem cells (hPSCs), no induction methods have effectively derived cholinergic parasympathetic neurons from hPSCs. Considering the antagonistic effects of noradrenergic and cholinergic inputs on target organs, both sympathetic and parasympathetic neurons are expected to be induced. This study aimed to develop a stepwise chemical induction method to induce sympathetic-like and parasympathetic-like ANS neurons. Autonomic specification was achieved through restricting signals inducing sensory or enteric neurogenesis and activating bone morphogenetic protein (BMP) signals. Global mRNA expression analyses after stepwise induction, including single-cell RNA-seq analysis of induced neurons and functional assays revealed that each induced sympathetic-like or parasympathetic-like neuron acquired pharmacological and electrophysiological functional properties with distinct marker expression. Further, we identified selective induction methods using appropriate seeding cell densities and neurotrophic factor concentrations. Neurons were individually induced, facilitating the regulation of the beating rates of hiPSC-derived cardiomyocytes in an antagonistic manner. The induction methods yield specific neuron types, and their influence on various tissues can be studied by co-cultured assays.

Gut microbiota and neuroinflammation in pathogenesis of hypertension: A potential role for hydrogen sulfide.

Inflammation and gut dysbiosis are hallmarks of hypertension (HTN). Hydrogen sulfide (H2S) is an important freely diffusing molecule that modulates the function of neural, cardiovascular and immune systems, and circulating levels of H2S are reduced in animals and humans with HTN. While most research to date has focused on H2S produced endogenously by the host, H2S is also produced by the gut bacteria and may affect the host homeostasis. Here, we review an association between neuroinflammation and gut dysbiosis in HTN, with special emphasis on a potential role of H2S in this interplay.

Usefulness of cardiac parasympathetic index in CPAP-treated patients with obstructive sleep apnea: A preliminary study.

Cardiac autonomic indexes, including cardiac parasympathetic index and cardiac sympathetic index, have been reported to accurately identify patients with sleep disorders such as obstructive sleep apnea. Our study aimed to assess cardiac autonomic indexes in patients with obstructive sleep apnea before and during a single full-night continuous positive airway pressure therapy using a combined approach. Our simultaneous heart rate variability-polysomnographic study included 16 never-treated obstructive sleep apnea patients. Two patients dropped out. Patients underwent combined recordings in two consecutive days, at baseline and during a single full-night of acute continuous positive airway pressure treatment. We calculated cardiac parasympathetic index and cardiac sympathetic index as night/day ratio for high-frequency and low-frequency heart rate variability spectral components, respectively. Continuous positive airway pressure treatment significantly reduced cardiac autonomic indexes values in comparison with baseline values (cardiac parasympathetic index: p < .0001; cardiac sympathetic index: p = .001). After acute continuous positive airway pressure treatment, the percentage of decrease of cardiac parasympathetic index was greater than that of cardiac sympathetic index (51.02 ± 15.72 versus 34.64 ± 26.93). A positive statistical correlation was also found between decrease of cardiac parasympathetic index and decrease of apnea-hypopnea index after continuous positive airway pressure (p < .001). This study improves the knowledge on cardiac autonomic modulation during acute continuous positive airway pressure therapy in obstructive sleep apnea. Our results demonstrate that both autonomic indexes decreased significantly after a single-night of acute continuous positive airway pressure therapy. Cardiac parasympathetic index more than cardiac sympathetic index was related to decrease of apnea-hypopnea index after continuous positive airway pressure therapy, thus representing a potential help in everyday clinical practice.

Social-evaluative threat: Stress response stages and influences of biological sex and neuroticism.

Social-evaluative threat (SET) - when the self could be negatively judged by others - can cause pronounced responses in the different stress systems: threat/challenge appraisal, the sympathetic (SNS) and parasympathetic (PNS) nervous systems, experienced motivation and affect, and the hypothalamus-pituitary-adrenal (HPA) axis. Here, we utilize a four-stage stress response model to shed light on the complex associations between different stress responses, where earlier stages are hypothesized to predict later stages. Additionally, we take into account important moderators, such as biological sex (controlling for menstrual cycle phase), personality traits (neuroticism and extraversion), and baseline stress levels. Thirty-seven men and 30 women in their luteal phase participated in an impromptu public speaking task to induce SET. Stress responses in four different stages were measured using: self-reported appraisal (threat or challenge, stage 1: S1), cardiovascular measures (pre-ejection period as SNS index, respiratory sinus arrhythmia as PNS index, S2), self-reported motivation and affect (state approach motivation, state anxiety, S3) and endocrine measures (cortisol as HPA index, S4). Stress reactivity was calculated by subtracting individual peaks from baseline. Results showed that SET induced pronounced stress reactivity in stages two to four. Against expectations, self-reported appraisal (S1) or motivation and affect (S3) did not predict later stress reactivity. As hypothesized, increased SNS (but not PNS) reactivity (S2) predicted increased HPA reactivity (S4). Bayesian model comparison confirmed the absence of sex differences in stress reactivity, likely due to controlling for menstrual cycle phase and sex differences in neuroticism levels. Higher trait neuroticism predicted blunted SNS (S2) and HPA (S4) reactivity, while higher baseline stress levels predicted blunted stages two and three reactivity overall. In conclusion, this rigorously controlled experiment partly supports and partly contradicts previous findings regarding associations between stress response stages, and offers new insight into the causes of blunted HPA responses in women.

Higher nicotinic receptor availability in the cingulo-insular network is associated with lower cardiac parasympathetic tone.

The dorsal anterior cingulate cortex (dACC) and the anterior insula (AI) constitute the salience network and form as well the major cortical components of the central autonomic nervous system. These two cortical regions have the highest density in α4ß2 nicotinic acetylcholine receptors (nAChRs) within the whole cortex.The aim of the study was to test the association between nAChRs density/availability in the salience network and the heart rate variability in humans. We selected subjects from a previous positron emission tomography (PET) imaging study in epilepsy with 18F-FA-85380, a specific marker for α4ß2 nAChRs, including 10 healthy controls, 10 patients with nonlesional focal epilepsy and 8 patients with idiopathic generalized epilepsy. Participants underwent a 10 min-resting electrocardiogram as they were lying still in a semi-supine position while watching an emotionally neutral video. We tested the association between parasympathetic tone and the regional brain nAChR availability, as measured by 18F-F-A-85380 binding potential (BP), using linear regression. We observed an association between higher nAChRs availability in the bilateral dACC and the right dorsal AI/frontal operculum and a lower parasympathetic tone, without significant effect of the clinical group on this relation. Our study is the first one to show a neurochemical correlate to the parasympathetic role of the anterior cingulate cortex and the AI. The nicotinic system, which plays a major role in the peripheral autonomic nervous system intervening both in the parasympathetic and sympathetic chains, seems also to play a role in the central autonomic nervous system.

Age-specific associations among functional COMT Val158Met polymorphism, resting parasympathetic nervous control and generalized anxiety disorder.

The functional Val158Met polymorphism (rs4680) of the Catechol-O-Methyltransferase (COMT) gene has been implicated in generalized anxiety disorder (GAD); however, the underlying neural mechanisms remain unexamined. Recent evidence reveals that low resting parasympathetic (vagal) control is an endophenotypic predictor of anxiety, while the effect of COMT rs4680 differs at different ages. Thus, we examined whether the COMT Val158Met variant could increase the risk of GAD through decreased resting parasympathetic nervous control in an age-specific manner. COMT rs4680 polymorphism was genotyped in 1,655 Han Chinese adults (1,142 healthy subjects and 513 patients with GAD; age: 20-65). High-frequency power (HF) of heart rate variability (HRV) was used to measure resting state parasympathetic nervous regulation. Non-genetic factors, such as gender, smoking status, medication use and comorbidity conditions, were treated as covariates. After adjusting for relevant covariates, there was a significant age x COMT genotype interaction on resting HF of HRV. In younger adults, Met allele carriers had a significantly lower HF index; however, older adults exhibited the opposite pattern, with Val/Val homozygotes exhibiting decreased HF values. Moreover, reduced HF-HRV is associated with increased risk of GAD. Finally, pathway analysis revealed a significant indirect effect of COMT on the risk of GAD via reduced resting HF-HRV, in the aforementioned age-dependent manner. Our findings are the first to demonstrate that COMT Val158Met polymorphism is associated with risk of GAD via reduced resting parasympathetic nervous control, an age-specific risk pathway.

The Neurochemical Characterization of Parasympathetic Nerve Fibers in the Porcine Uterine Wall Under Physiological Conditions and After Exposure to Bisphenol A (BPA).

Bisphenol A, a substance commonly used in plastic manufacturing, is relatively well known as an endocrine disruptor, which may bind to estrogen receptors and has multidirectional negative effects on both human and animal organisms. Previous studies have reported that BPA may act on the reproductive organs, but knowledge concerning BPA-induced changes within the nerves located in the uterine wall is extremely scant. The aim of this study was to investigate the impact of various doses of BPA on the parasympathetic nerves located in the corpus and horns of the uterus using a single and double immunofluorescence method. The obtained results have shown that BPA may change not only the expression of vesicular acetylcholine transporter (VAChT-a marker of parasympathetic nervous structures) in the uterine intramural nerve fibers, but also the degree of colocalization of this substance with other neuronal factors, including substance P (SP), vasoactive intestinal polypeptide (VIP), galanin (GAL), and calcitonin gene-related peptide (CGRP). Moreover, BPA caused changes in the density of the overall populations of fibers immunoreactive to the particular neuropeptides mentioned above. The characteristics of the changes clearly depended on the part of the uterus, the neuronal factors studied, and the dosage of BPA. The mechanisms of the observed fluctuations are probably connected with the neurotoxic and/or pro-inflammatory activity of BPA. Moreover, the results have shown that even low doses of BPA are not neutral to living organisms. Changes in the neurochemical characterization of nerves supplying the uterine wall may be the first subclinical sign of intoxication with this substance.

Inhibition of Nigrostriatal Dopamine Release by Striatal GABAA and GABAB Receptors.

Nigrostriatal dopamine (DA) is critical to action selection and learning. Axonal DA release is locally influenced by striatal neurotransmitters. Striatal neurons are principally GABAergic projection neurons and interneurons, and a small minority of other neurons are cholinergic interneurons (ChIs). ChIs strongly gate striatal DA release via nicotinic receptors (nAChRs) identified on DA axons. Striatal GABA is thought to modulate DA, but GABA receptors have not been documented conclusively on DA axons. However, ChIs express GABA receptors and are therefore candidates for potential mediators of GABA regulation of DA. We addressed whether striatal GABA and its receptors can modulate DA release directly, independently from ChI regulation, by detecting DA in striatal slices from male mice using fast-scan cyclic voltammetry in the absence of nAChR activation. DA release evoked by single electrical pulses in the presence of the nAChR antagonist dihydro-ß-erythroidine was reduced by GABA or agonists of GABAA or GABAB receptors, with effects prevented by selective GABA receptor antagonists. GABA agonists slightly modified the frequency sensitivity of DA release during short stimulus trains. GABA agonists also suppressed DA release evoked by optogenetic stimulation of DA axons. Furthermore, antagonists of GABAA and GABAB receptors together, or GABAB receptors alone, significantly enhanced DA release evoked by either optogenetic or electrical stimuli. These results indicate that striatal GABA can inhibit DA release through GABAA and GABAB receptors and that these actions are not mediated by cholinergic circuits. Furthermore, these data reveal that there is a tonic inhibition of DA release by striatal GABA operating through predominantly GABAB receptors.SIGNIFICANCE STATEMENT The principal inhibitory transmitter in the mammalian striatum, GABA, is thought to modulate striatal dopamine (DA) release, but definitive evidence for GABA receptors on DA axons is lacking. Striatal cholinergic interneurons regulate DA release via axonal nicotinic receptors (nAChRs) and also express GABA receptors, but they have not been eliminated as potentially critical mediators of DA regulation by GABA. Here, we found that GABAA and GABAB receptors inhibit DA release without requiring cholinergic interneurons. Furthermore, ambient levels of GABA inhibited DA release predominantly through GABAB receptors. These findings provide further support for direct inhibition of DA release by GABA receptors and reveal that striatal GABA operates a tonic inhibition on DA output that could critically influence striatal output.

Selective ablation of the ligament of Marshall reduces ischemia and reperfusion-induced ventricular arrhythmias.

Cardiac sympathetic tone overdrive is a key mechanism of arrhythmia. Cardiac sympathetic nerves denervation, such as LSG ablation or renal sympathetic denervation, suppressed both the prevalence of VAs and the incidence of SCD. Accumulating evidence demonstrates the ligament of Marshall (LOM) is a key component of the sympathetic conduit between the left stellate ganglion (LSG) and the ventricles. The present study aimed to investigate the roles of the distal segment of LOM (LOMLSPV) denervation in ischemia and reperfusion (IR)-induced VAs, and compared that LSG denervation. Thirty-three canines were randomly divided into group 1 (IR group, n = 11), group 2 (LOMLSPV Denervation + IR, n = 9), and group 3 (LSG Denervation + IR, n = 13). Hematoxylin-Eosin (HE) and Immunohistochemistry staining revealed that LOMLSPV contained bundles of sympathetic but not parasympathetic nerves. IR increased the cardiac sympathetic tone [serum concentrations of noradrenaline (NE) and epinephrine (E)] and induced the prevalence of VAs [ventricular premature beat (VPB), salvo of VPB, ventricular tachycardia (VT), VT duration (VTD) and ventricular fibrillation (VF)]. Both LOMLSPV denervation and LSG denervation could reduce the cardiac sympathetic tone in Baseline (BS) [heart rate variability (HRV)]. Compared with group 1, LOMLSPV denervation and LSG denervation similarly reduced sympathetic tone [NE (1.39±0.068 ng/ml in group 2, 1.29±0.081 ng/ml in group 3 vs 2.32±0.17 ng/ml in group 1, P<0.05) and E (114.64±9.22 pg/ml in group 2, 112.60±9.69 pg/ml in group 3 vs 166.18±15.78 pg/ml in group 1, P<0.05),] and VAs [VT (0±3.00 in group 2, 0±1.75 in group 3 vs 8.00±11.00 in group 1, P<0.05) and VTD (0 ± 4 s in group 2, 0±0.88s in group 3 vs 10.0 ± 22.00s in group 1, P<0.05)] after 2h reperfusion. These findings indicated LOMLSPV denervation reduced the prevalence of VT by suppressing SNS activity. These effects are comparable to those of LSG denervation. In myocardial IR, the anti-arrhythmic effects of LOMLSPV Denervation may be related to the inhibition of the expression of NE and E.

A systematic review of parent-child synchrony: It is more than skin deep.

This manuscript provides a critical review of the literature on parent-child physiological synchrony-the matching of biological states between parents and children. All eligible studies found some evidence of physiological synchrony, though the magnitude and direction of synchrony varied according to methodological factors, including the physiological system examined (i.e., parasympathetic or sympathetic nervous system activity, adrenocortical functioning) and the statistical approach used (e.g., multilevel modeling, correlation). The review underscores the need to consider the context in which physiological synchrony occurs (e.g., family risk) to best understand its significance. Furthermore, the review delineates vital avenues for future research, including the need to assess synchrony across multiple physiological systems and the importance of documenting continuity/change in physiological synchrony across developmental periods. Such research is crucial for understanding how the parent-child relationship unfolds at a physiological level and, in turn, how this relationship can facilitate or hinder parent, child, and family adjustment.