Vagosympathetic Trunks Research Articles

Роль симпатичних стовбурів в іннервації кровоносних судин заднього середостіння у плодів людини

The purpose of the study was to establish patterns of variation of the branches of the right and left sympathetic trunks in the thoracic aorta azygos and hemiazygos veins during the fetal period of human ontogenesis. Materials and methods. An anatomical study was performed on 47 human fetuses using macromicroscopic preparation of neurovascular branches under the control of binocular magnifier, vascular injection, application contrasting of prepared vessels and nerves, making 3D reconstruction models of the posterior mediastinum structures and morphometry. Results. The anatomical variability of nodes and branches of the thoracic right and left sympathetic trunks involved in the innervation of the thoracic aorta, azygos and hemiazygos veins has been established in the human fetuses of different age groups. The segmental-metameric distribution of the visceral branches of the thoracic sympathetic trunk was revealed, as well as the preservation of the segmental sympathetic innervation of the thoracic aorta, azygos and hemiazygos veins both on the left and on the right. Despite the significant progress in the study of morphological features of innervation of posterior mediastinum organs and structures, the active development of fetal surgery in recent years raises a number of questions related to the sources of sympathetic innervation of the thoracic aorta, azygos and hemiazygos veins. Conclusion. The sources of innervation of the thoracic aorta, azygos and hemiazygos veins in human fetuses are: thoracic nodes and internodal branches of the right and left sympathetic trunks; large visceral nerves; branches of the esophageal, pulmonary and cardiac plexuses; vagosympathetic trunks; collateral trunk. The number of branches to the thoracic aorta from the left sympathetic trunk is 4-16, and from the right sympathetic trunk – 3-14. The largest number of branches that enter the wall of the thoracic aorta, from the left sympathetic trunk skeletotopically determined at the level of III-VI thoracic segments, and from the right sympathetic trunk – at the level of IV-VI thoracic segments. Different skeletotopic levels of the branches of the right and left large visceral nerves are involved in the innervation of the thoracic aorta – from V to X thoracic segments. It is noted that the right and left sympathetic trunks are almost equally involved in the innervation of the azygos and hemiazygos veins. The number of sympathetic branches to the azygos vein ranges from 4 to 7, and the number of sympathetic branches to the hemiazygos vein is usually 2-4

Dispersal and immunohistochemical characteristics of neurons in the stem of the porcine vagus nerve.

The present study investigated the distribution and chemical properties of nerve cell bodies within the trunk of the vagus nerve in juvenile female pigs (n=4) using double-labelling immunofluorescence. The neurons appeared mostly as single cells or formed streaks of cells or small ganglia. Many of the perikarya were cholinergic (VAChT-positive; VAChT+) or adrenergic (DβH+) in nature and no SP+ or CGRP+ neurons were encountered. There were no distinct left-right differences regarding the number and chemical coding of the neuronal somata, however, these characteristics significantly varied between particular nerve segments investigated. The vagosympathetic trunks, and thoracic and abdominal segments of the vagus nerve contained on average (the numerical values represent the means for both the left and right corresponding nerve segments) 142, 236, and 111 PGP 9.5-positive neurons, respectively. Proportions of cholinergic and adrenergic neurons were as follows: 0% and 100%, 54.2% and 33.2%, and 52.8% and 35.4%, respectively. Relatively many neurons in the thoracic and abdominal segments stained also for NOS (39.2% and 39.9%, respectively). It remains to be determined whether the porcine intravagal neurons represent a developmental relic, or whether they have any specific functional significance.

Structural and function organization of intrathoracic extracardiac autonomic projections to the porcine heart: Implications for targeted neuromodulation therapy.

Mapping the structure/function organization of the cardiac nervous system is foundational for implementation of targeted neuromodulation-based therapeutics for the treatment of cardiac disease. The purpose of this study was to define the spatial organization of intrathoracic parasympathetic and sympathetic efferent projections to the heart. Yucatan mini-pigs (N = 11) were anesthetized and the thoracic cavity exposed. Electrical stimulation of the cervical vagi and stellate ganglia was performed individually, and hemodynamic responses were assessed in the intact state and after progressive debranching of each thoracic vagosympathetic trunk (VST). Subsequently, residual cardiac efferent projections arising from paravertebral chain ganglia (T1-T4) were evaluated by stimulation before and after individual ganglionic debranching. Stimulation of the cervical vagi decreased heart rate and contractility while prolonging the activation-recovery interval (ARI). Stimulation of the stellate ganglia increased heart rate and contractility and decreased ARI. The majority of parasympathetic and sympathetic cardiac-evoked responses were mitigated after debranching of the right VST rostral to heart, whereas the left VST demonstrated a distribution with greater dispersion and caudal intrathoracic shift compared to the right. After complete thoracic VST debranching, stimulation of the T4 paravertebral chain ganglia demonstrated residual cardiac sympathetic efferent innervation to the heart in ∼50% of animals. That response was mitigated by transecting medial ganglionic branches. The nexus point for optimum neuromodulation engagement of parasympathetic efferent projections to the heart is the cervical vagus and the T1-T2 paravertebral chain ganglia for sympathetic control. Removal of principal sympathetic efferent projections to heart requires targeting the T1-T4 regions of the paravertebral chain.

ОСОБЕННОСТИ АНАТОМИИ И ФИЗИОЛОГИИ СЕРДЦА БЕСЧЕЛЮСТНЫХ РЫБООБРАЗНЫХ И ЧЕЛЮСТНЫХ РЫБ

The heart of jawless fish (Cyclostomata; lamprey, hagfish) and jawed fish (Teleostei) is homologous to the heart of higher vertebrates. A study of this organ in archaic Cyclostomata and Teleostei, which are different in their evolutionary “ages”, genetic characteristics and hypoxia tolerance, is of particular interest in the search for the factors that determine myocardial resistance to oxygen deficiency. Cyclostomata and Teleostei share the same branchial type of respiration and the presence of only one circle of blood circulation. The principal contractile organ that provides blood circulation, the branchial heart, consists of two chambers. Hagfish make up the oldest class of extant vertebrates whose circulation is maintained by the non-innervated (aneural) branchial heart and three sets of accessory “hearts”. Lampreys are the first vertebrates whose heart receives innervation from the vagus nerve. In turn, Teleostei are the first to receive sympathetic innervation of the heart from the vagosympathetic trunks. In the heart of Cyclostomata and Teleostei, no signs of the cardiac conduction system similar to that in higher vertebrates were found, which does not negate the existence of a well-coordinated mechanism for the propagation of myocardial excitation−contraction coupling. The mechanism of cardiac rhythm generation links the electrical processes that arise in the myocardium with the expression of hyperpolarization-activated cyclic nucleotide-gated channels (HCN channels). In the heart of hagfish and teleosts, six isoforms of HCN channels are expressed. The regulated distribution density of HCN channels in the myocardium may be a precursor of the cardiac conduction system which characterizes higher vertebrates. The expression of the three cardiac HCN isoforms (HCN2, HCN3 and HCN4) in such a relict taxon as hagfish suggests their presence in the myocardium of the common ancestor of vertebrates before the divergence with Myxiniformes. This may also suggest a particular significance of HCN2, HCN3 and HCN4 in the formation of cardiac activity at the time of the emergence of a multi-chambered myogenic heart. It is assumed that the evolutionary progress in the archaic groups of primitive vertebrates was aimed at the “creation” of a faster effector system for the regulation of cardiac activity and dual (excitatory/inhibitory) control of myocardial functions.

VISUALIZATION OF THE EXCITATION PROCESS IN THE FROG'S NERVES

Aim.Visualization of the excitation process in the frog's nerves.Materials and methods. Observations were carried out on 30 immobilized frogs. Vagosympathetic trunks and sciatic nerve were allocated from the frogs. Ligatures were placed on the right vagosympathetic trunk crossing it. A scanner of the gas discharge visualization camera of the CELSY device, which created a high- frequency electromagnetic field (1024 Hz), was installed above the nerves. The scanner with a highly sensitive camera shot a 60-second video (the frequency of frame-by-frame shooting to 1000 frames per second), during which the edge luminescence (Kirlian effect) and the glow spots were recorded inside the nerve. The electrocardiogram (ECG) was synchronously recorded in the I standard lead. The processing of the obtained results was carried out according to the area of the glow spot, the area of the highest luminescence brightness, the direction of the movement of the foci of the luminescence, and the linear velocity of the movement of the glow foci.Results.Foci of the internal luminescence appeared only in the high-frequency electromagnetic field in the sciatic nerve of the frog when the nerve was stimulated by electrical impulses, which resulted in the contraction of the frog's foot. Glow foci of the brain synchronous to the heart rhythm and preceding the tooth of the V- wave on the frog’s ECG were observed at the central end of the cut of the frog’s vagosympathetic trunk. Conclusion.Visualized foci of luminescence in the nerve reflect the neural activity.

Defining the neural fulcrum for chronic vagus nerve stimulation: implications for integrated cardiac control.

The evoked cardiac response to bipolar cervical vagus nerve stimulation (VNS) reflects a dynamic interaction between afferent mediated decreases in central parasympathetic drive and suppressive effects evoked by direct stimulation of parasympathetic efferent axons to the heart. The neural fulcrum is defined as the operating point, based on frequency-amplitude-pulse width, where a null heart rate response is reproducibly evoked during the on-phase of VNS. Cardiac control, based on the principal of the neural fulcrum, can be elicited from either vagus. Beta-receptor blockade does not alter the tachycardia phase to low intensity VNS, but can increase the bradycardia to higher intensity VNS. While muscarinic cholinergic blockade prevented the VNS-induced bradycardia, clinically relevant doses of ACE inhibitors, beta-blockade and the funny channel blocker ivabradine did not alter the VNS chronotropic response. While there are qualitative differences in VNS heart control between awake and anaesthetized states, the physiological expression of the neural fulcrum is maintained. Vagus nerve stimulation (VNS) is an emerging therapy for treatment of chronic heart failure and remains a standard of therapy in patients with treatment-resistant epilepsy. The objective of this work was to characterize heart rate (HR) responses (HRRs) during the active phase of chronic VNS over a wide range of stimulation parameters in order to define optimal protocols for bidirectional bioelectronic control of the heart. In normal canines, bipolar electrodes were chronically implanted on the cervical vagosympathetic trunk bilaterally with anode cephalad to cathode (n=8, 'cardiac' configuration) or with electrode positions reversed (n=8, 'epilepsy' configuration). In awake state, HRRs were determined for each combination of pulse frequency (2-20Hz), intensity (0-3.5mA) and pulse widths (130-750μs) over 14months. At low intensities and higher frequency VNS, HR increased during the VNS active phase owing to afferent modulation of parasympathetic central drive. When functional effects of afferent and efferent fibre activation were balanced, a null HRR was evoked (defined as 'neural fulcrum') during which HRR≈0. As intensity increased further, HR was reduced during the active phase of VNS. While qualitatively similar, VNS delivered in the epilepsy configuration resulted in more pronounced HR acceleration and reduced HR deceleration during VNS. At termination, under anaesthesia, transection of the vagi rostral to the stimulation site eliminated the augmenting response to VNS and enhanced the parasympathetic efferent-mediated suppressing effect on electrical and mechanical function of the heart. In conclusion, VNS activates central then peripheral aspects of the cardiac nervous system. VNS control over cardiac function is maintained during chronic therapy.

Developmental Morphology and Topography of the Components of the Cervical Sympathetic Trunk in Sheep (Ovis aries) During the Fetal Period.

The objective of this study was to clarify the typical architecture and morphological variations of cervical sympathetic trunk (CST) in sheep during fetal period. Components of CST were examined on both sides of 40 male and female sheep fetuses aged from 60 to 140 days under a stereomicroscope. Skeletotopy and frequency of presence of cranial cervical ganglion (CCG), syntopy of cervical ganglia, and composition and topography of vagosympathetic trunk were consistent among specimens whereas the shape of cervical ganglia, the skeletotopy and number of three middle cervical ganglia (MG), and the frequency of communicating branches of CCG to the first cervical spinal nerve exhibited differences during fetal period. A reduction in the number of MG and the caudal movement of main MG were noted by increasing fetal age. Based on these detailed findings, comparative and developmental anatomy and evolutionary changes are discussed and compared with previous studies. The number of MG, skeletotopy of CCG and main MG, the number and range of communicating branches of CCG to spinal nerves, and the association of vagus and sympathetic nerves in fetal sheep were fundamentally different from those of mostly reported species. These results suggest that data obtained from CST of fetal sheep are significantly different from those obtained from humans, and it is problematic to apply them to humans because of the more cranial position of CCG, very narrow contribution of CCG to spinal nerve, absence of the vertebral ganglion, existence of multiple MG, and no communicating branches from MG to spinal nerves. Anat Rec, 300:2250-2262, 2017. © 2017 Wiley Periodicals, Inc.

Detection of flashing areas attributed to the frog cardiac function in the vagosympathetic trunk placed into a high frequency electric field.

In a high frequency electric field, two flashing areas were observed during each contraction of the heart in the vagosympathetic trunk of a paralyzed frog with an intact brain. One area with a higher diameter was moving along the nerve from the heart at a speed of 16.6 ± 0.2 m/s. It was identified as afferent. Another area with a smaller diameter was spreading along the nerve towards the venous sinus of the frog heart at a speed of 5.6 ± 0.3 m/s, and it was efferent.

Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function.

Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy.

Detailed Anatomy of the Cranial Cervical Ganglion in the Dromedary Camel (Camelus dromedarius).

The detailed morphology and topography of the cranial cervical ganglion (CCG) with its surrounding structures were studied in 10 sides of five heads of adult one-humped camel to determine its general arrangement as well as its differences and similarities to other animals. The following detailed descriptions were obtained: (1) the bilateral CCG was constantly present caudal to cranial base at the rostroventral border of the occipital condyle over the caudolateral part of nasopharynx; (2) the CCG was always in close relations medially with the longus capitis muscle, rostrolaterally with the internal carotid artery, and caudally with the vagus nerve; and (3) the branches of the CCG were the internal carotid and external carotid nerves, jugular nerve, cervical interganglionic branch, laryngopharyngeal branch, carotid sinus branch and communicating branches to the vagus, and first spinal nerves. In conclusion, there was no variation regarding topography of dromedary CCG among the specimens, in spite of typical variations in number, and mainly in origin of nerve branches ramifying from the CCG. In comparative anatomy aspect, the close constant relations, and presence of major nerves (internal/external carotid and jugular nerves) of dromedary CCG exhibited a typical reported animal's pattern. However, the shape, structures lateral to the CCG, the origin and course pattern of external carotid and jugular nerves, the number of the major nerves branches, the communicating branches of the CCG to the spinal and cranial nerves, and the separation of most rostral parts of vagosympathetic trunk of dromedary were different from those of most reported animals.

Intrinsic and extrinsic innervation of the heart in zebrafish (Danio rerio).

In the vertebrate heart the intracardiac nervous system is the final common pathway for autonomic control of cardiac output, but the neuroanatomy of this system is not well understood. In this study we investigated the innervation of the heart in a model vertebrate, the zebrafish. We used antibodies against acetylated tubulin, human neuronal protein C/D, choline acetyltransferase, tyrosine hydroxylase, neuronal nitric oxide synthase, and vasoactive intestinal polypeptide to visualize neural elements and their neurotransmitter content. Most neurons were located at the venous pole in a plexus around the sinoatrial valve; mean total number of cells was 197 ± 23, and 92% were choline acetyltransferase positive, implying a cholinergic role. The plexus contained cholinergic, adrenergic, and nitrergic axons and vasoactive intestinal polypeptide-positive terminals, some innervating somata. Putative pacemaker cells near the plexus showed immunoreactivity for hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) and the transcription factor Islet-1 (Isl1). The neurotracer neurobiotin showed that extrinsic axons from the left and right vagosympathetic trunks innervated the sinoatrial plexus proximal to their entry into the heart; some extrinsic axons from each trunk also projected into the medial dorsal plexus region. Extrinsic axons also innervated the atrial and ventricular walls. An extracardiac nerve trunk innervated the bulbus arteriosus and entered the arterial pole of the heart to innervate the proximal ventricle. We have shown that the intracardiac nervous system in the zebrafish is anatomically and neurochemically complex, providing a substrate for autonomic control of cardiac effectors in all chambers.

Neuronally released vasoactive intestinal polypeptide alters atrial electrophysiological properties and may promote atrial fibrillation.

Vagal hyperactivity promotes atrial fibrillation (AF), which has been almost exclusively attributed to acetylcholine. Vasoactive intestinal polypeptide (VIP) and acetylcholine are neurotransmitters co-released during vagal stimulation. Exogenous VIP has been shown to promote AF by shortening action potential duration (APD), increasing APD spatial heterogeneity, and causing intra-atrial conduction block. The purpose of this study was to investigate the effects of neuronally released VIP on atrial electrophysiologic properties during vagal stimulation. We used a specific VIP antagonist (H9935) to uncover the effects of endogenous VIP released during vagal stimulation in canine hearts. H9935 significantly attenuated (1) the vagally induced shortening of atrial effective refractory period and widening of atrial vulnerability window during stimulation of cervical vagosympathetic trunks (VCNS) and (2) vagal effects on APD during stimulation through fat-pad ganglion plexus (VGPS). Atropine completely abolished these vagal effects during VCNS and VGPS. In contrast, VGPS-induced slowing of local conduction velocity was completely abolished by either VIP antagonist or atropine. In pacing-induced AF during VGPS, maximal dominant frequencies and their spatial gradients were reduced significantly by H9935 and, more pronouncedly, by atropine. Furthermore, VIP release in the atria during vagal stimulation was inhibited by atropine, which may account for the concealment of VIP effects with muscarinic blockade. Neuronally released VIP contributes to vagal effects on atrial electrophysiologic properties and affects the pathophysiology of vagally induced AF. Neuronal release of VIP in the atria is inhibited by muscarinic blockade, a novel mechanism by which VIP effects are concealed by atropine during vagal stimulation.

Low-level vagosympathetic trunk stimulation inhibits atrial fibrillation in a rabbit model of obstructive sleep apnea.

Atrial fibrillation (AF) is highly associated with obstructive sleep apnea (OSA) in which AF is triggered by hyperactivity of the cardiac autonomic nervous system. Previous studies showed that low-level vagosympathetic trunk stimulation (LLVS), at voltages not slowing sinus rate or AV conduction, inhibits AF by suppressing the cardiac autonomic nervous system. The purpose of this study was to investigate whether LLVS delivered at the right vagosympathetic trunk suppresses AF in a rabbit model of OSA. Eleven rabbits received a tracheostomy under general anesthesia. The endotracheal tube was clamped at end expiration for 1 minute to simulate OSA. Over a period of 4 hours, OSA was delivered every 6 minutes. Effective refractory period (ERP), blood pressure, intraesophageal pressure, and blood gases (O2, CO2, pH) were measured before and after each episode of OSA. AF duration and ERP were measured by programmed stimulation. Group 1 rabbits (n = 6) received LLVS (50% below that which slowed the sinus rate) in the first 3 hours. Group 2 rabbits (n = 5) only received OSA. Group 1 ERP began to lengthen progressively from the second hour compared to group 2. AF duration increased in the first hour for both groups but began to shorten progressively after the first hour in group 1 rabbits. Blood pH, O2 or CO2 level, intraesophageal pressure, and hypertensive response during OSA were not different between the 2 groups. LLVS is capable of suppressing ERP shortening and AF induced by OSA. LLVS may serve as a new therapeutic approach to treat OSA-induced AF.

GW25-e2220 Impact of cervical vagosympathetic trunks stimulation on TNF and CRP in dogs with rapid atrial pacing

GW25-e2220 Impact of cervical vagosympathetic trunks stimulation on TNF and CRP in dogs with rapid atrial pacing

ASSA13-02-5 Impact of Cervical Vagosympathetic Trunks Stimulation on Interleukin-1 and Interleukin-6 in Dogs with Rapid Atrial Pacing

BackgroundAtrial fibrillation (AF) lead to calcium overload and Myocardial cell death, which could have inflammatory response in body. The autonomic nervous system (ANS) plays an important role in AF and...

Morphology of sympathetic chain in Saguinus niger

Saguinus niger popularly known as Sauim, is a Brazilian North primate. Sympathetic chain investigation would support traumatic and/or cancer diagnosis which are little described in wild animals. The aim of this study was to describe the morphology and distribution of sympathetic chain in order to supply knowledge for neurocomparative research. Three female young animals that came death by natural causes were investigated. Animals were fixed in formaldehyde 10% and dissected along the sympathetic chain in neck, thorax and abdomen. Cranial cervical ganglion was located at the level of carotid bifurcation, related to carotid internal artery. In neck basis the vagosympathetic trunk divides into the sympathetic trunk and the parasympathetic vagal nerve. Sympathetic trunk ran in dorsal position and originated the stellate ganglia, formed by the fusion of caudal cervical and first thoracic ganglia. Vagal trunk laid ventrally to heart and formed the cardiac plexus. In abdomen, on the right side, were found the celiac ganglion and cranial mesenteric ganglion; in the left side these ganglia were fusioned into the celiac-mesenteric ganglion displaced closely to the celiac artery. In both sides, the caudal mesenteric ganglion was located near to the caudal mesenteric artery.

Effects of Low-Level Autonomic Stimulation on Prevention of Atrial Fibrillation Induced by Acute Electrical Remodeling

Background. Rapid atrial pacing (RAP) can induce electrical and autonomic remodeling and facilitate atrial fibrillation (AF). Recent reports showed that low-level vagosympathetic nerve stimulation (LLVNS) can suppress AF, as an antiarrhythmic effect. We hypothesized that LLVNS can reverse substrate heterogeneity induced by RAP. Methods and Results. Mongrel dogs were divided into (LLVNS+RAP) and RAP groups. Electrode catheters were sutured to multiple atrial sites, and LLVNS was applied to cervical vagosympathetic trunks with voltage 50% below the threshold slowing sinus rate by ⩽30 msec. RAP induced a significant decrease in effective refractory period (ERP) and increase in the window of vulnerability at all sites, characterized by descending and elevated gradient differences towards the ganglionic plexi (GP) sites, respectively. The ERP dispersion was obviously enlarged by RAP and more significant when the ERP of GP-related sites was considered. Recovery time from AF was also prolonged significantly as a result of RAP. LLVNS could reverse all these changes induced by RAP and recover the heterogeneous substrate to baseline. Conclusions. LLVNS can reverse the electrical and autonomic remodeling and abolish the GP-central gradient differences induced by RAP, and thus it can recover the homogeneous substrate, which may be the underlying mechanism of its antiarrhythmic effect.

Effect of left superior pulmonary vein fat pad on atrial fibrillation in dogs

Objective To explore the effect of ablation of left superior pulmonary vein fat pad(LSPV-FP) on atrial fibrillation(AF).Methods Twelve healthy adult mongrel dogs were anesthetized and ventilated;both cervical vagosympathetic trunks were exposed for stimulation.Thoracotomies at the 4th intercostal space of left and right chest were performed to expose the LSPV-FP.The effective refractory period(ERP)/ERP-dispersion(dERP) of atrium and LSPV,AF inducibility,and the ventricular rate of AF were measured in the following statuses: baseline,vagosympathetic trunk stimulation(VTS),LSPV-FP ablation,and VTS post LSPV-FP ablation.Results At baseline status,stimulation of the left or right vagosympathetic trunks significantly shortened the ERP of atrial([84.44±29.50] ms vs [129.7±15.83] ms,[85.42±26.11] ms vs [129.7±15.83] ms,P0.05),increased the dERP of atrial([71.67±14.03] ms vs [34.17±18.32] ms,[57.5±24.17] ms vs [34.17±18.32] ms,P0.05),the difference of ERP between proximal and distal of LSPV(P0.05),AF inducibility([5.33±1.231] times vs [0.75±0.96] times,[4.67±1.155] times vs [0.75±0.96] times,P0.05),and deceased the ventricular rate of AF([143.6±22.42] beats/min vs [226.3±28.50] beats/min,[146.4±30.72] times/min vs [226.3±28.50] times/min,P0.05).LSPV-FP ablation significantly attenuated all the above electrophysiological changes induced by left VTS(P0.05),but showed no effects on those induced by right VTS.Conclusion Left vagosympathetic trunk plays an important role in the development and maintenance of AF partially through LSPV-FP.

Vagal Stimulation Promotes Atrial Electrical Remodeling Induced by Rapid Atrial Pacing in Dogs: Evidence of a Noncholinergic Effect

Atrial electrical remodeling (AER) is one of the mechanisms by which atrial fibrillation (AF) begets AF. It is known that vagal activity increases the propensity for AF. However, vagal effects on AER have not been fully investigated. Adult mongrel dogs were divided in four groups: group I, rapid atria pacing (RAP); group II, RAP plus vagal nerve stimulation (VNS); group III, RAP and VNS with atropine (0.2 mg/kg/h, intravenous), and group IV, group III plus vasoactive intestinal polypeptide (VIP) antagonist ([D-p-Cl-Phe(6), Leu(17)]-VIP, 0.125 μg/kg/h). VNS was performed bilaterally through vagosympathetic trunks to achieve second-degree AV block or sinus rate slowing of >30 beats per minute. Atrial effective refractory periods (AERPs) were determined in the coronary sinus and right atrial appendage every hour at drive cycle lengths (DCLs) 350 ms, 300 ms, and 250 ms. During 5 hours RAP with or without VNS, AERP shortened progressively from baseline at both pacing sites and at all DCLs (P < 0.01). Furthermore, RAP-induced AERP shortening was more pronounced with VNS (P < 0.01). With atropine, the AERP shortening during VNS was blunted (P < 0.01), but was still significantly more pronounced than that in group I (P < 0.05). However, VNS effect on AERP shortening was eliminated completely with the combination of atropine and VIP antagonist (P = 0.15 vs group I). Increased vagal activity promotes RAP-induced AER, which could not be totally accounted for by cholinergic effect but could be blocked by the combination of atropine and VIP antagonist. Vagally released VIP may have important role in the vagal promotion of AER.

Prevention and Reversal of Atrial Fibrillation Inducibility and Autonomic Remodeling by Low-Level Vagosympathetic Nerve Stimulation

We hypothesized that autonomic atrial remodeling can be reversed by low-level (LL) vagosympathetic nerve stimulation (VNS). Previously, we showed that VNS can be antiarrhythmogenic. Thirty-three dogs were subjected to electrical stimulation (20 Hz) applied to both vagosympathetic trunks at voltages 10% to 50% below the threshold that slowed sinus rate or AV conduction. Group 1 (n = 7): Programmed stimulation (PS) was performed at baseline and during 6-h rapid atrial pacing (RAP). PS allowed determination of effective refractory period (ERP) and AF inducibility measured by window of vulnerability (WOV). LL-VNS was continuously applied from the 4th to 6th hours. Group 2 (n = 4): After baseline ERP and WOV determinations, 6-h concomitant RAP+LL-VNS was applied. Sustained AF was induced by injecting acetylcholine (ACh) 10 mM into the anterior right ganglionated plexus (Group 3, n = 10) or applying ACh 10 mM to right atrial appendage (Group 4, n = 9). Group 1: The ERP progressively shortened and the ΣWOV (sum of WOV from all tested sites) progressively increased (p < 0.05) during 3-h RAP then returned toward baseline during 3-h RAP+LL-VNS (p < 0.05). Group 2: 6-h concomitant RAP+LL-VNS did not induce any significant change in ERP and ΣWOV. Group 3 and Group 4: AF duration (AF-D) and cycle length (AF-CL) were markedly altered by 3-h LL-VNS (Group 3: baseline: AF-D = 389 ± 90 s, AF-CL = 45.1 ± 7.8 ms; LL-VNS: AF-D = 50 ± 15 s, AF-CL = 82.0 ± 13.7 ms [both p < 0.001]; Group 4: baseline: AF-D = 505 ± 162 s, AF-CL = 48.8 ± 6.6 ms; LL-VNS: AF-D = 71 ± 21 s, AF-CL = 101.3 ± 20.9 ms [both p < 0.001]). LL-VNS can prevent and reverse atrial remodeling induced by RAP as well as suppress AF induced by strong cholinergic stimulation. Inhibition of the intrinsic cardiac autonomic nervous system by LL-VNS may be responsible for these salutary results.