Left Stellate Ganglion Stimulation Research Articles

PO-02-152 EFFECTS OF SYMPATHETIC STIMULATION ON REPOLARIZATION AND ARRHYTHMOGENESIS DURING LEFT LATERAL MYOCARDIAL ISCHEMIA

Left stellate ganglion stimulation (LSGS) is arrhythmogenic during acute myocardial ischemia of the anterior wall of the left ventricle. We hypothesized, as a counterpart, that right stellate ganglion stimulation (RSGS) is proarrhythmic when ischemia is produced by occlusion of the circumflex coronary artery. In 7 anesthetized female open-chested pigs, ventricular repolarization was measured in unipolar electrograms from 128 epicardial sites on the left lateral ventricular wall in an electrode grid of 14x30 mm (interelectrode distance 2 mm). Seven subsequent episodes of 5 minutes of acute ischemia (5 minutes occlusion of the circumflex coronary artery with 20 minutes reperfusion). Right atrial pacing was performed throughout the experiment at cycle length of 450 ms. The second occlusion served as a control. During the third and fourth occlusion, left or right stellate ganglion stimulation (LSGS or RSGS), respectively, was initiated after 3 minutes of ischemia for 30 seconds. The protocol was repeated after decentralization of both stellate ganglia and bilateral cervical vagotomy. Between 3 and 5 minutes of ischemia, RSGS caused a median of 9 (interquartile range 3-12), ventricular premature beats and in 2 instances ventricular tachycardia and fibrillation. The number of ventricular premature beats was significantly less during LSGS and control conditions (Figure, panel A), during which no ventricular tachycardia or fibrillation occurred. Following decentralization, RSGS was no longer significantly more arrhythmogenic than LSGS or control conditions (Figure, panel A). Additionally, we found that LSGS-induced changes in repolarization are evident in non-ischemic tissue, but not in ischemic tissue, during coronary occlusion (Figure, panel B, note the overlapping T-waves in the ischemic region). LSGS no longer has an effect on myocardium that has been ischemic for 3 minutes by occlusion of the circumflex coronary artery. RSGS was arrhythmogenic in this setting, while LSGS was not. This supports the clinical findings that bilateral sympathectomy is superior to left sympathectomy alone.

Pulmonary Artery Denervation Inhibits Left Stellate Ganglion Stimulation-Induced Ventricular Arrhythmias Originating From the RVOT

BackgroundElectrical stimulation of the left stellate ganglion (LSG) can evoke ventricular arrhythmias (VAs) that originate from the right ventricular outflow tract (RVOT). The involvement of pulmonary artery innervation is unclear. ObjectivesThis study investigated the effects of selective pulmonary artery denervation (PADN) on blood pressure (BP), sympathetic activity, ventricular effective refractory period (ERP), and the incidence of VAs induced by LSG stimulation in canines. MethodsRadiofrequency ablation with basic anesthetic monitoring was used to induce PADN in canines. In Protocol 1 (n = 11), heart rate variability, serum norepinephrine and angiotensin-II levels, BP changes and ventricular ERP in response to LSG stimulation were measured before and after PADN. In Protocol 2 (n = 8), the incidence of VAs induced by LSG stimulation was calculated before and after PADN in a canine model of complete atrioventricular block. In addition, sympathetic nerves in the excised pulmonary arteries were immunohistochemically stained with tyrosine hydroxylase. ResultsThe low-frequency components of heart rate variability, serum norepinephrine and angiotensin-II levels were remarkably decreased post-PADN. Systolic BP elevation and RVOT ERP shortening induced by LSG stimulation were mitigated by PADN. The number of RVOT-premature ventricular contractions as well as RVOT tachycardia episodes and duration induced by LSG stimulation were significantly reduced after PADN. In addition, a large number of tyrosine hydroxylase-immunoreactive nerve fibers were located in the anterior wall of the pulmonary artery. ConclusionsPADN ameliorated RVOT ERP shortening, and RVOT-VAs induced by LSG stimulation by inhibiting cardiac sympathetic nerve activity.

Selective intracardiac sympathetic denervation acutely modulates left ventricular control

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): German Centre for Cardiovascular Research (DZHK) Background The sympathetic nervous system plays an integral role in cardiac physiology. Neuromodulation is emerging as a treatment option for ventricular arrhythmias, but selective intracardiac approaches are rare. Sympathetic nerve fibers innervating the left ventricle have been demonstrated to be amenable to transvenous catheter stimulation along the coronary sinus (CS). Purpose The aim of the present study was to modulate left ventricular control by selective sympathetic denervation using epicardial or standard catheter ablation for intracardiac axotomy at the level of the CS. Methods First, the impact of epicardial CS ablation on cardiac electrophysiology was studied in a Langendorff model of murine hearts (n=10 each, ablation and control). Second, the impact of transvenous, anatomically-driven axotomy by catheter-based radiofrequency ablation along the CS was evaluated in a healthy ovine in vivo model (n=8) before and during left stellate ganglion stimulation (LSGS). Results CS ablation for intracardiac sympathetic axotomy prolonged epicardial ventricular refractory period (VRP) without (41.8±8.4 ms vs. 53.0±13.5 ms; P=0.0487) and with beta1-2-adrenergic receptor blockade (47.8±2.8 ms vs. 73.1±5.0 ms; P=0.0009) and enhanced the increasing effect of beta1-2-adrenergic receptor blockade on epicardial VRP (∆VRP 6.3±7.0 ms vs. 20.0±7.5 ms; P=0.0045) in mice (Figure, A). Mean epicardial wave propagation velocity in the left ventricle was faster in ablated hearts than in controls (1.13±0.05 m/s vs. 1.00±0.02 m/s; P=0.0463), but did not differ in the right ventricle (1.15±0.05 m/s vs. 1.20±0.08 m/s; P=0.7938). Transvenous catheter ablation of the CS reduced systolic (SBP, 57.7±5.0 mmHg vs. 46.9±3.6 mmHg; P=0.0428) and diastolic blood pressure (DBP, 35.5±3.0 mmHg vs. 26.7±1.8 mmHg; P=0.0106) and diminished the blood pressure increase during LSGS in sheep (∆SBP 21.9±3.8 mmHg vs. 10.5±4.2 mmHg; P=0.0234; ∆DBP 9.0±1.9 mmHg vs. 3.0±1.2 mmHg; P=0.0391) (Figure, B, C). Cycle length remained unchanged by LSGS, both before (baseline 653.2±20.6 ms vs. LSGS 627.8±27.5 ms; P=0.2309) and after CS ablation (baseline 734.8±24.2 ms vs. LSGS 746.2±37.3 ms; P=0.7145). Conclusions Anatomically-driven axotomy targeting nerve fibers along the CS enables selective intracardiac sympathetic denervation resulting in acute modulation of left ventricular control.

CE-521-01 STELLATE GANGLION INSTRUMENTATION FOR RECORDING AND STIMULATION IN PATIENTS WITH VENTRICULAR ARRHYTHMIAS. PRELIMINARY EXPERIENCE

Stellate Ganglion (SG) blockade is used for controlling ventricular arrhythmias (VA). In animal models, SG instrumentation with electrode catheters can allow stimulation and recording cardiac sympathetic activity. Studies on direct modulation and recording of the sympathetic nervous system in human are lacking. To assess the feasibility of SG stimulation (SGS) and recording in humans undergoing VA ablation Patients (n=11) undergoing ablation procedures for VAs underwent bilateral SG recording and stimulation. Under ultrasound guidance, a 2F octapolar catheter was advanced in the SG at the C7 level. Signals were recorded at 30 kHz and filtered at 0.5-2kHz bandpass. Nerve activities were defined as a 3-fold increase in the amplitude over baseline. Stimulation was performed up to 80 mA output (50 Hz, 2 ms pulse width) for 20-30 s. Eleven patients (age 63 ± 12.7 years; 82.7% men) with ischemic ventricular tachycardia (VT) (4, 36%), nonischemic VT (5, 45%), and PVCs (2, 18.2%) were included. Stimulation catheter placement was successful without complications in all patients. SGS caused significant increase in the systolic blood pressure (Fig A-B). More after right than left SGS. SGS induced PVCs in 2 patients and VF in 1. We were able to record SG firings preceding VF in a patient with primary VF in the context of ischemic cardiomyopathy (Fig C-E), and left SG firing preceding the arrhythmia after SD stimulation (Fig F-G) in a patient with PVCs induced VF. SG recording and stimulation are feasible in humans. SGS leads to blood pressure increases, more pronounced after right SGS. SG firing can precede VA onset in humans. Technical refinements are needed to improve reliability of SG recordings.

Enhanced atrial internal-external neural remodeling facilitates atrial fibrillation in the chronic obstructive sleep apnea model.

ObjectiveAutonomic imbalance plays a crucial role in obstructive sleep apnea (OSA) associated atrial fibrillation (AF). Here, we investigated the potential neural mechanism of AF induced by OSA.MethodsTen dogs were divided into control group (n = 5) and OSA group (n = 5). The chronic OSA model was established by repeat apnea-ventilation cycles for 4 hours a day for 12 weeks. During the process of model establishment, arterial blood gases, atrial effective refractory period (AERP), AF inducibility, normalized low-frequency power (LFnu), normalized high-frequency power (HFnu), and LFnu/ HFnu were evaluated at baseline, 4th week, 8th week, and 12th week. Nerve activities of left stellate ganglion (LSG) and left vagal nerve(LVN) were recorded. Tyrosine hydroxylase(TH), choline acetyltransferase(CHAT), PGP9.5, nerve growth factor(NGF), and c-Fos were detected in the left atrium, LSG, and LVN by immunohistochemistry and western blot. Moreover, high-frequency stimulations of LSG and LVN were conducted to observe the AF inducibility.ResultsCompared with the control group, the OSA group showed significantly enhanced neural activity of the LSG, increased AF inducibility, and shortened AERP. LFnu and LFnu/HFnu were markedly increased in the OSA group, while no significant difference in HFnu was observed. TH-positive and PGP9.5-positive nerve densities were significantly increased in the LSG and left atrium. Additionally, the protein levels of NGF, c-Fos, and PGP9.5 were upregulated both in the LSG and left atrium. AF inducibility was markedly increased under LSG stimulation without a stimulus threshold change in the OSA group.ConclusionsOSA significantly enhanced LSG and left atrial neural remodeling, and hyperactivity of LSG may accelerate left atrial neural remodeling to increase AF inducibility.

Mechanism of ventricular premature beats elicited by left stellate ganglion stimulation during acute ischaemia of the anterior left ventricle.

AimsEnhanced sympathetic activity during acute ischaemia is arrhythmogenic, but the underlying mechanism is unknown. During ischaemia, a diastolic current flows from the ischaemic to the non-ischaemic myocardium. This ‘injury’ current can cause ventricular premature beats (VPBs) originating in the non-ischaemic myocardium, especially during a deeply negative T wave in the ischaemic zone. We reasoned that shortening of repolarization in myocardium adjacent to ischaemic myocardium increases the ‘injury’ current and causes earlier deeply negative T waves in the ischaemic zone, and re-excitation of the normal myocardium. We tested this hypothesis by activation and repolarization mapping during stimulation of the left stellate ganglion (LSG) during left anterior descending coronary artery (LAD) occlusion.Methods and resultsIn nine pigs, five subsequent episodes of acute ischaemia, separated by 20 min of reperfusion, were produced by occlusion of the LAD and 121 epicardial local unipolar electrograms were recorded. During the third occlusion, left stellate ganglion stimulation (LSGS) was initiated after 3 min for a 30-s period, causing a shortening of repolarization in the normal myocardium by about 100 ms. This resulted in more negative T waves in the ischaemic zone and more VPBs than during the second, control, occlusion. Following the decentralization of the LSG (including removal of the right stellate ganglion and bilateral cervical vagotomy), fewer VPBs occurred during ischaemia without LSGS. During LSGS, the number of VPBs was similar to that recorded before decentralization.ConclusionLSGS, by virtue of shortening of repolarization in the non-ischaemic myocardium by about 100 ms, causes deeply negative T waves in the ischaemic tissue and VPBs originating from the normal tissue adjacent to the ischaemic border.

Stellate ganglion stimulation causes spatiotemporal changes in ventricular repolarization in pig

Dispersion in ventricular repolarization is relevant for arrhythmogenesis. The purpose of this study was to determine the spatiotemporal effects of sympathetic stimulation on ventricular repolarization. In 5 anesthetized female open-chest pigs, ventricular repolarization was measured from the anterior, lateral, and posterior walls of the left ventricle (LV) and right ventricle using up to 40 transmural plunge needles (4 electrodes each) before and after left stellate ganglion stimulation (LSGS) and right stellate ganglion stimulation. In addition, LSGS was performed in 3 pigs (2 male, 1 female) before and after verapamil (5-10 mg/h) administration. LSGS yielded a biphasic response in repolarization in the lateral and posterior walls of the LV, with prolongation at ∼5 seconds (10 ± 1.5 ms) and shortening at 20-30 seconds of stimulation (-28.9 ± 4.4 ms) during a monotonic pressure increase. While the initial prolongation was abolished by verapamil, late shortening was augmented. Sequential transections of the vagal nerve and stellate ganglia augmented repolarization dispersion responses to LSGS in 2of 5 hearts. An equal pressure increase by aortic occlusion resulted in a homogeneous shortening of repolarization in the LV, and the effects were smaller than those during LSGS. Right stellate stimulation shortened repolarization mainly in the anterior LV wall, but the effects were smaller than those of LSGS. LSGS first prolongs (through the L-type calcium current) and then shortens repolarization. The effect of LSGS was prominent in the posterior and lateral, not the anterior, LV walls.

Effect of electroacupuncture on porcine cardiac excitability induced by left stellate ganglion stimulation

Augmentation of cardiac sympathetic tone has been shown to induce ventricular arrhythmias. Acupuncture has been clinically used to treat hypertension, angina pectoris, and atrial arrhythmias. However, the effects of acupuncture on ventricular electrophysiology and autonomic tone remain unknown. We hypothesized that acupuncture attenuates cardiac excitability and corrects the imbalance of autonomic tone during sympathetic hyperactivity. Fourteen Yorkshire pigs were randomized to electroacupuncture (EA, 2 Hz, 0.3-0.5 mA, 0.5 ms duration) or control (without EA) groups. Animals were sedated with terazol. General anesthesia consisted of isoflurane and fentanyl during surgical preparation and was transitioned to α-chloralose during experimental protocols. Through a median sternotomy, the heart was exposed and fitted with an elastic epicardial 56-electrode sock. Cardiac excitability was measured via activation recovery interval (ARI) and dispersion of repolarization (DOR) while autonomic balance was evaluated by heart rate variability (HRV) power spectrum analysis at baseline and during left stellate ganglion stimulation (LSS) with and without EA delivered at P 5-6 acupoints. 30-min of EA did not alter the baseline ARI and DOR, but significantly suppressed cardiac excitability during LSS through attenuation of ARI shortening (EA 2.1 ± 0.3% vs. control 5.2 ± 0.7%, P < 0.05) and DOR (EA 74.3 ± 26.9% vs., control 110.1 ± 22.9%, P < 0.05). EA significantly attenuated the increase in LF/HF (EA 0.6 ± 0.1 vs. control 1.1 ± 0.2, P < 0.05). In conclusion, EA reduces the cardiac excitability induced by LSS through correction of cardiac sympathovagal balance. This study provides mechanistic insights underlying cardiac neuromodulation of EA during sympathoexcitation.

Effects of extrinsic cardiac nerve stimulation on atrial fibrillation inducibility: The regulatory role of the spinal cord.

To investigate the effect of the mutual regulation of the extrinsic cardiac nerves on atrial electrophysiology and atrial fibrillation (AF) vulnerability. Fourteen dogs were randomly divided into two groups: spinal cord stimulation (SCS) group (n = 7) and spinal cord block (SCB) group (n = 7). SCS was performed with 90% of the threshold voltage stimulating the T1 -T2 spinal level, while SCB was performed by injecting 2% lidocaine into the epidural space at the T2-3 level. The effective refractory period (ERP), ERP dispersion, and AF inducibility were measured during atrial pacing combined with different extrinsic cardiac nerve stimulation. ERPs were decreased in the atrium and pulmonary veins and ERP dispersion was increased from baseline during left cervical vagus nerve stimulation (VNS) or left stellate ganglion stimulation (SGS) in the two groups. When combined with SCS, VNS resulted in diminished ERPs at all recording sites, longer ERP dispersion and more episodes of AF than were observed during VNS, whereas ERPs were greater and correspondingly fewer episodes of AF occurred during SCS combined with SGS than SGS. In the SCB group, ERPs were shortened, ERP dispersion was lengthened, and episodes of AF were increased during SGS after SCB. SCS enhanced the activity of the left vagus nerve but attenuated the left stellate ganglion and superior left ganglionated plexus. SCS modulates extrinsic and intrinsic cardiac nerve activity among the vagus nerve, stellate ganglion, and ganglionated plexus. SCS facilitates the effect of VNS and attenuates the effect of SGS on atrial electrophysiology.

Effect of Thoracic Epidural Anesthesia on Ventricular Excitability in a Porcine Model.

Imbalances in the autonomic nervous system, namely, excessive sympathoexcitation, contribute to ventricular tachyarrhythmias. While thoracic epidural anesthesia clinically suppresses ventricular tachyarrhythmias, its effects on global and regional ventricular electrophysiology and electrical wave stability have not been fully characterized. The authors hypothesized that thoracic epidural anesthesia attenuates myocardial excitability and the proarrhythmic effects of sympathetic hyperactivity. Yorkshire pigs (n = 15) had an epidural catheter inserted (T1 to T4) and a 56-electrode sock placed on the heart. Myocardial excitability was measured by activation recovery interval, dispersion of repolarization, and action potential duration restitution at baseline and during programed ventricular extrastimulation or left stellate ganglion stimulation, before and 30 min after thoracic epidural anesthesia (0.25% bupivacaine). After thoracic epidural anesthesia infusion, there was no change in baseline activation recovery interval or dispersion of repolarization. During programmed ventricular extrastimulation, thoracic epidural anesthesia decreased the maximum slope of ventricular electrical restitution (0.70 ± 0.24 vs. 0.89 ± 0.24; P = 0.021) reflecting improved electrical wave stability. Thoracic epidural anesthesia also reduced myocardial excitability during left stellate ganglion stimulation-induced sympathoexcitation through attenuated shortening of activation recovery interval (-7 ± 4% vs. -4 ± 3%; P = 0.001), suppression of the increase in dispersion of repolarization (313 ± 293% vs. 185 ± 234%; P = 0.029), and reduction in sympathovagal imbalance as measured by heart rate variability. Our study describes the electrophysiologic mechanisms underlying antiarrhythmic effects of thoracic epidural anesthesia during sympathetic hyperactivity. Thoracic epidural anesthesia attenuates ventricular myocardial excitability and induces electrical wave stability through its effects on activation recovery interval, dispersion of repolarization, and the action potential duration restitution slope.

Effect of thoracic epidural anesthesia on heart rate variability in a porcine model.

Heart rate variability (HRV) is increasingly recognized as a means of evaluating autonomic tone. Thoracic epidural anesthesia (TEA) has been previously demonstrated to suppress the electrical storms in patients. However, the effect of TEA on HRV during sympathoexcitation remains unknown. In this study, we aimed to determine the effects of TEA on HRV response to left stellate ganglion stimulation (LSS) in a porcine model. In 12 anesthetized pigs after insertion of an epidural catheter to T1 level, a median sternotomy was performed to expose the heart and the left stellate ganglion. A 56‐electrode sock was used for obtaining epicardial activation recovery interval (ARI). Animal received LSS at 4 Hz for 30 sec. After 30 min of bupivacaine epidural injection, LSS was performed in the same way as the baseline condition. LSS significantly increased low‐frequency normalized units (LF: 44.9 ± 6.7 vs. 13.6 ± 3.1 msec2 baseline, P < 0.05) and decreased high‐frequency normalized units (HF: 11.5 ± 4.6 vs. 41.9 ± 5.1 msec2 baseline, P < 0.05). As a result, LF/HF significantly increased from 0.3 ± 0.2 to 3.9 ± 1.4 during LSS. TEA significantly attenuated the LF/HF from 3.9 ± 1.4 to 1.6 ± 0.8 with increased HF components from 11.5 ± 4.6 to 26.5 ± 3.2 msec2. LF component significantly correlates with global ARI (r = −0.81) and dispersion of repolarization (r = 0.85). HRV can precisely reflect the cardiac autonomic tone and TEA modulates the HRV by enhancing the HF components probably through a parasympathetic nerve system.

Sympathetic modulation of electrical activation in normal and infarcted myocardium: implications for arrhythmogenesis.

The influence of cardiac sympathetic innervation on electrical activation in normal and chronically infarcted ventricular myocardium is not understood. Yorkshire pigs with normal hearts (NL, n = 12) or anterior myocardial infarction (MI, n = 9) underwent high-resolution mapping of the anteroapical left ventricle at baseline and during left and right stellate ganglion stimulation (LSGS and RSGS, respectively). Conduction velocity (CV), activation times (ATs), and directionality of propagation were measured. Myocardial fiber orientation was determined using diffusion tensor imaging and histology. Longitudinal CV (CVL) was increased by RSGS (0.98 ± 0.11 vs. 1.2 ± 0.14m/s, P < 0.001) but not transverse CV (CVT). This increase was abrogated by β-adrenergic receptor and gap junction (GJ) blockade. Neither CVL nor CVT was increased by LSGS. In the peri-infarct region, both RSGS and LSGS shortened ARIs in sinus rhythm (423 ± 37 vs. 322 ± 30 ms, P < 0.001, and 423 ± 36 vs. 398 ± 36 ms, P = 0.035, respectively) and altered activation patterns in all animals. CV, as estimated by mean ATs, increased in a directionally dependent manner by RSGS (14.6 ± 1.2 vs. 17.3 ± 1.6 ms, P = 0.015), associated with GJ lateralization. RSGS and LSGS inhomogeneously modulated AT and induced relative or absolute functional activation delay in parts of the mapped regions in 75 and 67%, respectively, in MI animals, and in 0 and 15%, respectively, in control animals (P < 0.001 for both). In conclusion, sympathoexcitation increases CV in normal myocardium and modulates activation propagation in peri-infarcted ventricular myocardium. These data demonstrate functional control of arrhythmogenic peri-infarct substrates by sympathetic nerves and in part explain the temporal nature of arrhythmogenesis.NEW & NOTEWORTHY This study demonstrates regional control of conduction velocity in normal hearts by sympathetic nerves. In infarcted hearts, however, not only is modulation of propagation heterogeneous, some regions showed paradoxical conduction slowing. Sympathoexcitation altered propagation in all infarcted hearts studied, and we describe the temporal arrhythmogenic potential of these findings.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/sympathetic-nerves-and-cardiac-propagation/.

Noninvasive low-frequency electromagnetic stimulation of the left stellate ganglion reduces myocardial infarction-induced ventricular arrhythmia.

Noninvasive magnetic stimulation has been widely used in autonomic disorders in the past few decades, but few studies has been done in cardiac diseases. Recently, studies showed that low-frequency electromagnetic field (LF-EMF) might suppress atrial fibrillation by mediating the cardiac autonomic nervous system. In the present study, the effect of LF-EMF stimulation of left stellate ganglion (LSG) on LSG neural activity and ventricular arrhythmia has been studied in an acute myocardium infarction canine model. It is shown that LF-EMF stimulation leads to a reduction both in the neural activity of LSG and in the incidence of ventricular arrhythmia. The obtained results suggested that inhibition of the LSG neural activity might be the causal of the reduction of ventricular arrhythmia since previous studies have shown that LSG hyperactivity may facilitate the incidence of ventricular arrhythmia. LF-EMF stimulation might be a novel noninvasive substitute for the existing implant device-based electrical stimulation or sympathectomy in the treatment of cardiac disorders.

Effect of electroacupuncture on cardiac excitability during sympathoexcitation induced by acute ischemia and left stellate ganglion stimulation in a porcine model

Augmentation of cardiac sympathetic tone during myocardial ischemia has been shown to increase myocardial O2 demand and infarct size as well as induce arrhythmias. We have previously demonstrated that electroacupuncture (EA) mitigates myocardial ischemia‐reperfusion injury by modulation of cardiac norepinephrine release. The purpose of this study is to determine the effects of EA on cardiac excitability evaluated by measurement of activation recovery interval (ARI) and heart rate variability (HRV) by using power spectral analysis. A median sternotomy was performed to expose the heart and the left stellate ganglion (LSG). Acute myocardial ischemia (AMI) was induced by ligation of left descending coronary artery. A 56‐electrode was placed on the heart to record ARI, a surrogate measure of action potential duration. AMI with LSG stimulation significantly shortened ARI by 5.4% and increased dispersion by 160% as well as increased LF/HF from 0.31 to 1.18 (n.u.). 30 min of EA significantly attenuated the ARI shortening (1.7% vs. 5.4%) and dispersion (104% vs. 160%) as well as decreased the LF/HF from 1.18 to 0.70 (n.u.) with decreased LF components from 46.5±3.5 to 27.2±4.1(n.u.) and increased HF components from 38.5 to 49.2 (n.u.). In conclusion, EA modulates the cardiac excitability through inhibition of sympathetic nerve system and activation of parasympathetic nerve system.Support or Funding InformationDepartment Fund

Central vs. peripheral neuraxial sympathetic control of porcine ventricular electrophysiology

Sympathoexcitation is associated with ventricular arrhythmogenesis. The aim of this study was to determine the role of thoracic dorsal root afferent neural inputs to the spinal cord in modulating ventricular sympathetic control of normal heart electrophysiology. We hypothesize that dorsal root afferent input tonically modulates basal and evoked efferent sympathetic control of the heart. A 56-electrode sock placed on the epicardial ventricle in anesthetized Yorkshire pigs (n = 17) recorded electrophysiological function, as well as activation recovery interval (ARI) and dispersion in ARI, at baseline conditions and during stellate ganglion electrical stimulation. Measures were compared between intact states and sequential unilateral T1-T4 dorsal root transection (DRTx), ipsilateral ventral root transection (VRTx), and contralateral dorsal and ventral root transections (DVRTx). Left or right DRTx decreased global basal ARI [Lt.DRTx: 369 ± 12 to 319 ± 13 ms (P < 0.01) and Rt.DRTx: 388 ± 19 to 356 ± 15 ms (P < 0.01)]. Subsequent unilateral VRTx followed by contralateral DRx+VRTx induced no further change. In intact states, left and right stellate ganglion stimulation shortened ARIs (6 ± 2% vs. 17 ± 3%), while increasing dispersion (+139% vs. +88%). There was no difference in magnitude of ARI or dispersion change with stellate stimulation following spinal root transections. Interruption of thoracic spinal afferent signaling results in enhanced basal cardiac sympathoexcitability without diminishing the sympathetic response to stellate ganglion stimulation. This suggests spinal dorsal root transection releases spinal cord-mediated tonic inhibitory control of efferent sympathetic tone, while maintaining intrathoracic cardiocentric neural networks.

Selective Ablation of the Ligament of Marshall Reduces the Prevalence of Ventricular Arrhythmias Through Autonomic Modulation in a Cesium-Induced Long QT Canine Model.

The goal of this study was to investigate the effect of selective ablation of the ligament of Marshall (LOM) on ventricular arrhythmias (VAs). Previous studies have shown that selective stimulation of sympathetic elements of the LOM, the distalsegment of the ligament of Marshall that extends beyond the left superior pulmonary vein (LOMLSPV), might induceVAs. In protocol 1, the blood pressure and ventricular effective refractory period changes as a response to LOMLSPV stimulation and left stellate ganglion (LSG) stimulation were measured before and after LOMLSPV ablation in 8anesthetized dogs. In protocol 2, a total of 24 dogs were randomly divided into group 1 (cesium alone, n= 8), group 2 (cesium combined with LSG stimulation, n= 8), and group 3 (cesium combined with LSG stimulation after LOMLSPV ablation, n= 8). Early afterdepolarization amplitude, VA prevalence, and the tachycardia threshold (measured according to the dose of cesium administered) were compared among the groups. In protocol 1, both LOMLSPV stimulation and LSG stimulation significantly increased blood pressure and shortened the ventricular effective refractory period, both of which were significantly attenuated by LOMLSPV ablation. Inprotocol 2, compared with group 1, the prevalence of VAs and the early afterdepolarization amplitudes were significantly augmented in group 2 and were maintained at a comparable level in group 3. Furthermore, the tachycardia threshold in group 2 (0.625 mmol/kg) was significantly lower than that noted in groups 1 and 3 (both 1.000 mmol/kg; p< 0.05). LOMLSPV ablation reduced the prevalence of the VAs induced by cesium in combination with LSG stimulation, and the antiarrhythmic effect may involve the blockade of the sympathetic conduit between the LSG and the ventricles.

Abstract 328: Effects of Sympatho-excitation on Directional Anisotropy in Ventricular Myocardium

Introduction: Control of electrical propagation exerted by the sympathetic nervous system is has not been quantified in-depth. Methods: High-resolution mapping (64-electrode plaque, 8x8, 1.96cm 2 ) of the anterior LV myocardium in porcine model (n=6) was performed before &amp; during left stellate ganglion stimulation (LSGS). Activation times (AT), activation recovery intervals (ARIs), conduction velocities (CV), and CV anisotropy were obtained during pacing. Ex vivo diffusion tensor MRI and histology were performed to define myocardial fiber orientation in the mapped regions. Results: LSGS shortened ARI (314.3±7.8ms vs. 287.8±6.6ms, p&lt;0.001). At baseline, longitudinal CV (CV L ) was greater than transverse CV (CV T ) (1.2±0.2m/s vs 0.7±0.1m/s, p&lt;0.001). LSGS did not increase CV L (1.16±0.16m/s vs 1.17±0.15m/s, p=0.2), or CV T (0.67±0.07m/s vs 0.7±0.04m/s, p=0.2). However, CV in the retrograde direction along fiber orientation was significantly increased by LSGS (0.7±0.05m/s vs 0.9±0.06m/s, p&lt;0.01). This resulted in a significant reduction in directional anisotropy (CV antegrade /CV retrograde ) along fiber direction (1.6±0.3 vs 1.3±0.3, p&lt;0.001), but not CV L /CV T (1.78±0.2 vs. 1.66±0.2 for BL and LSGS, respectively, p&gt;0.2). Heterogeneity of activation (AT disp ) was greater in the transverse than longitudinal direction (20±2ms 2 /cm 2 vs. 13±1.5ms 2 /cm 2 , p= 0.022). LSGS decreased transverse AT disp to 18±1.8 ms 2 /cm 2 (p=0.015), but not longitudinal AT disp . Conclusion: Cardiac sympatho-excitation modulates CV and AT disp in a fiber orientation-dependent manner. These uneven changes may contribute to arrhythmogenic mechanisms seen during sympatho-excitation.

Spinal cord stimulation protects against ventricular arrhythmias by suppressing left stellate ganglion neural activity in an acute myocardial infarction canine model.

Previous studies have shown that spinal cord stimulation (SCS) may reduce ventricular arrhythmias (VAs) induced by acute myocardial infarction (AMI). Furthermore, activation of left stellate ganglion (LSG) appears to facilitate VAs after AMI. The purpose of this study was to investigate whether pretreatment with SCS could protect against VAs by reducing LSG neural activity in an AMI canine model. Thirty dogs were anesthetized and randomly divided into SCS group (with SCS, n = 15) and sham group (sham operation without SCS, n = 15). SCS was performed for 1 hour before AMI. Heart rate variability (HRV), ventricular effective refractory period (ERP), serum norepinephrine level, LSG function measured by blood pressure increases in response to LSG stimulation, and LSG neural activity were measured for 1 minute at baseline and 1 hour after SCS. AMI was induced by left anterior descending coronary artery ligation, and then HRV, LSG neural activity, and VAs were measured. Compared to baseline, SCS for 1 hour significantly prolonged ventricular ERP, increased HRV, and attenuated LSG function and LSG activity in the SCS group, whereas no significant change was shown in the sham group. AMI resulted in a significant decrease in HRV and increase in LSG neural activity in the sham group, which were attenuated in the SCS group (frequency: 99 ± 34 impulses/min vs 62 ± 22 impulses/min; amplitude: 0.41 ± 0.12 mV vs 0.18 ± 0.05 mV; both P <.05). The incidence of VAs was significantly lower in the SCS group than in the sham group. SCS may prevent AMI-induced VAs, possibly by suppressing LSG activity.

Augmentation of cardiac sympathetic tone by percutaneous low-level stellate ganglion stimulation in humans: a feasibility study.

Modulation of human cardiac mechanical and electrophysiologic function by direct stellate ganglion stimulation has not been performed. Our aim was to assess the effect of low-level left stellate ganglion (LSG) stimulation (SGS) on arrhythmias, hemodynamic, and cardiac electrophysiological indices. Patients undergoing ablation procedures for arrhythmias were recruited for SGS. A stimulating electrode was placed next to the LSG under fluoroscopy and ultrasound imaging; and SGS (5–10 Hz, 10–20 mA) was performed. We measured hemodynamic, intracardiac and ECG parameters, and activation recovery intervals (ARIs) (surrogate for action potential duration) from a duodecapolar catheter in the right ventricular outflow tract. Five patients underwent SGS (3 males, 45 ± 20 years). Stimulating catheter placement was successful, and without complication in all patients. SGS did not change heart rate, but increased mean arterial blood pressure (78 ± 3 mmHg to 98 ± 5 mmHg, P < 0.001) and dP/dt max (1148 ± 244 mmHg/sec to 1645 ± 493 mmHg/sec, P = 0.03). SGS shortened mean ARI from 304 ± 23 msec to 283 ± 17 msec (P < 0.001), although one patient required parasympathetic blockade. Dispersion of repolarization (DOR) increased in four patients and decreased in one, consistent with animal models. QT interval, T-wave duration and amplitude at baseline and with SGS were 415 ± 15 msec versus 399 ± 15 msec (P < 0.001); 201 ± 12 msec versus 230 ± 28 msec; and 0.2 ± 0.09 mV versus 0.22 ± 0.08 mV, respectively. At the level of SGS performed, no increase in arrhythmias was seen. Percutaneous low-level SGS shortens ARI in the RVOT, and increases blood pressure and LV contractility. These observations demonstrate feasibility of percutaneous SGS in humans.

Vagus nerve stimulation reverses ventricular electrophysiological changes induced by hypersympathetic nerve activity.

What is the central question of this study? Previous studies have shown that hypersympathetic nerve activity results in ventricular electrophysiological changes and facilitates the occurrence of ventricular arrhythmias. Vagus nerve stimulation has shown therapeutic potential for myocardial infarction-induced ventricular arrhythmias. However, the actions of vagus nerve stimulation on hypersympathetic nerve activity-induced ventricular electrophysiological changes are still unknown. What is the main finding and its importance? We show that vagus nerve stimulation is able to reverse hypersympathetic nerve activity-induced ventricular electrophysiological changes and suppress the occurrence of ventricular fibrillation. These findings further suggest that vagus nerve stimulation may be an effective treatment option for ventricular arrhythmias, especially in patients with myocardial infarction or heart failure. Vagus nerve stimulation (VNS) has shown therapeutic potential for myocardial infarction-induced ventricular arrhythmias. This study aimed to investigate the effects of VNS on ventricular electrophysiological changes induced by hypersympathetic nerve activity. Seventeen open-chest dogs were subjected to left stellate ganglion stimulation (LSGS) for 4h to simulate hypersympathetic tone. All animals were randomly assigned to the VNS group (n=9) or the control group (n=8). In the VNS group, VNS was performed at the voltage causing a 10% decrease in heart rate for hours3-4 during 4h of LSGS. During the first 2h of LSGS, the ventricular effective refractory period (ERP) and action potential duration (APD) were both progressively and significantly decreased; the spatial dispersion of ERP, maximal slope of the restitution curve and pacing cycle length of APD alternans were all increased. With LSGS+VNS during the next 2h, there was a significant return of all the altered electrophysiological parameters towards baseline levels. In the eight control dogs that received 4h of LSGS without VNS, all the parameters changed progressively, but without any reversals. The ventricular fibrillation threshold was higher in the VNS group than in the control group (17.3±3.4 versus 11.3±3.8V, P<0.05). The present study demonstrated that VNS was able to reverse LSGS-induced ventricular electrophysiological changes and suppress the occurrence of ventricular fibrillation.