Prospective study on ultrasound-guided stellate ganglion block improves cerebral blood flow in patients with stroke.

OBJECTIVES: The effect of routine internal medicine and stroke rehabilitation treatment was not good. To confirm that ultrasound-guided stellate ganglion block (SGB) can improve cerebral blood flow in patients with stroke, Transcranial Doppler (TCD) and carotid ultrasound were used to monitor the cerebral blood flow parameters of ultrasound-guided SGB in patients with stroke. METHODS: A prospective study of 40 patients with stroke from January 2021 to October 2022 randomly divided into two groups (group SGB: undergoing ultrasound-guided SGB and standard medical procedures, control group: undergoing standard medical procedures) with 20 cases in each was conducted in People's Hospital of Chongqing Liang Jiang New Area. TCD and carotid artery ultrasound were monitored before and after treatment. There were no significant differences in general data on age, gender, disease course, and stroke type between two groups (P>0.05). RESULTS: After treatment, the bilateral ACA Vm of group SGB was significantly higher, the bilateral internal carotid artery RI and left VA RI were significantly lower than in control group (P<0.05). In group SGB, the Vm of bilateral MCA, bilateral PCA, right ACA, bilateral VA, and BA after treatment were significantly (P<0.05) increased compared to before treatment. PI of bilateral MCA, right ACA, and left VA after treatment were significantly (P<0.05) decreased compared to before treatment. RI of bilateral MCA, bilateral PCA, and bilateral VA after treatment were significantly (P<0.05) decreased compared to before treatment. Right internal carotid artery D after treatment was significantly (P<0.05) higher than before treatment. RI of bilateral internal carotid artery after treatment was significantly (P<0.05) lower than before treatment. CONCLUSIONS: Ultrasound-guided stellate ganglion block could improve local cerebral blood flow and vascular compliance in patients with stroke, and reduce vascular resistance.

Ischemia-reperfusion myocardial infarction induces remodeling of left cardiac-projecting stellate ganglia neurons.

Neurons in the stellate ganglion (SG) provide sympathetic innervation to the heart, brown adipose tissue (BAT), and other organs. Sympathetic innervation to the heart becomes hyperactive following myocardial infarction (MI). The impact of MI on the morphology of cardiac sympathetic neurons is not known, but we hypothesized that MI would stimulate increased cell and dendritic tree size in cardiac neurons. In this study, we examined the effects of ischemia-reperfusion MI on sympathetic neurons using dual retrograde tracing methods to allow detailed characterization of cardiac- and BAT-projecting neurons. Different fluorescently conjugated cholera toxin subunit B (CTb) tracers were injected into the pericardium and the interscapular BAT pads, respectively. Experimental animals received a 45-min occlusion of the left anterior descending coronary artery and controls received sham surgery. One week later, hearts were collected for assessment of MI infarct and SGs were collected for morphological or electrophysiological analysis. Cardiac-projecting SG neurons from MI mice had smaller cell bodies and shorter dendritic trees compared with sham animals, specifically on the left side ipsilateral to the MI. BAT-projecting neurons were not altered by MI, demonstrating the subpopulation specificity of the response. The normal size and distribution differences between BAT- and cardiac-projecting stellate ganglion neurons were not altered by MI. Patch-clamp recordings from cardiac-projecting left SG neurons revealed increased spontaneous excitatory postsynaptic currents despite the decrease in cell and dendritic tree size. Thus, increased dendritic tree size does not contribute to the enhanced sympathetic neural activity seen after MI.NEW & NOTEWORTHY Myocardial infarction (MI) causes structural and functional changes specifically in stellate ganglion neurons that project to the heart, but not in cells that project to brown adipose fat tissue.

Metrics of high cofluctuation and entropy to describe control of cardiac function in the stellate ganglion.

Stellate ganglia within the intrathoracic cardiac control system receive and integrate central, peripheral, and cardiopulmonary information to produce postganglionic cardiac sympathetic inputs. Pathological anatomical and structural remodeling occurs within the neurons of the stellate ganglion (SG) in the setting of heart failure (HF). A large proportion of SG neurons function as interneurons whose networking capabilities are largely unknown. Current therapies are limited to targeting sympathetic activity at the cardiac level or surgical interventions such as stellectomy, to treat HF. Future therapies that target the SG will require understanding of their networking capabilities to modify any pathological remodeling. We observe SG networking by examining cofluctuation and specificity of SG networked activity to cardiac cycle phases. We investigate network processing of cardiopulmonary transduction by SG neuronal populations in porcine with chronic pacing-induced HF and control subjects during extended in-vivo extracellular microelectrode recordings. We find that information processing and cardiac control in chronic HF by the SG, relative to controls, exhibits: (i) more frequent, short-lived, high magnitude cofluctuations, (ii) greater variation in neural specificity to cardiac cycles, and (iii) neural network activity and cardiac control linkage that depends on disease state and cofluctuation magnitude.

Distinct morphology of cardiac- and brown adipose tissue-projecting neurons in the stellate ganglia of mice.

Sympathetic neurons that innervate the heart are located primarily in the stellate ganglia (SG), which also contains neurons that project to brown adipose tissue (BAT). These studies were designed to examine the morphology of these two populations (cardiac- and BAT-projecting) and their target connectivity. We examined SG neurons in C57BL/6J mice following injections of the retrograde tracer cholera toxin B (CTb) conjugated to Alexa Fluor 488 and Alexa Fluor 555, into cardiac tissue and intrascapular BAT. BAT-projecting SG neurons were widely dispersed in SG, while cardiac-projecting SG neurons were localized primarily near the inferior cardiac nerve base. SG neurons were not dual-labeled, suggesting that sympathetic innervation is specific to the heart and BAT, supporting the idea of "labeled lines" of efferents. Morphologically, cardiac-projecting SG somata had more volume and were less abundant than BAT-projecting neurons using our tracer-labeling paradigm. We found a positive correlation between the number of primary dendrites per neuron and soma volume in cardiac-projecting SG neurons, though not in BAT-projecting neurons. In both SG subpopulations, the number of cholinergic inputs marked with vesicular acetylcholine transporter (VAChT) puncta contacting the soma was positively correlated to soma volume, suggesting scaling of inputs across a range of neuronal sizes. In separate studies using dual tracing from left and right BAT, we found that BAT-projecting SG neurons were located predominately ipsilateral to the injection, but a small subset of SG neurons project bilaterally to BAT. This tracing approach will allow the assessment of cell-specific mechanisms of plasticity within subpopulations of SG neurons.

Impact of Stellate Ganglion Block on Tissue Blood Flow/Oxygenation and Postoperative Mandibular Nerve Hypoesthesia: A Cohort Study.

PURPOSE: Although a stellate ganglion block (SGB) increases tissue blood flow in the mandibular region, the change in tissue oxygenation after SGB and therapeutic effect of SGB for postoperative mandibular nerve hypoesthesia remain to be established. The study aim was to measure the change in tissue oxygenation in the mandibular region after SGB. METHODS: To determine the variation in tissue oxygenation in the mandibular region, the tissue oxygen index (TOI; percentage of oxygenated hemoglobin in the total hemoglobin) was measured at the skin near the mental foramen bilaterally, at the primary site of unilateral SGB, achieved using 6 mL of 1% lidocaine hydrochloride, for the treatment of bilateral postoperative mandibular nerve injury. The primary outcome of this study is the temporal variation in TOI after SGB (0.5, 1, 5, 10, 15, 20, and 25 minutes after SGB), and the control group in this study is the TOI at the end of SGB injection (0 minute). All data are expressed as the mean ± standard deviation and 95% confidence interval (CI). Repeated-measures analysis of variance with Dunnett's test was used to determine parametric statistical significance. A P-value <.05 was considered statistically significant. RESULTS: Thirteen patients were enrolled in this study. On both the blocked and contralateral side, the TOI was significantly increased compared to that before SGB (ΔTOI at 15 minute after SGB, 5.87 ± 2.89%, P < .001, 95% CI: 4.122 to 7.617% in the blocked side, 1.88 ± 2.73%, P = .005, 95% CI: 1.877 to 2.725% in the contralateral side). CONCLUSIONS: Unilateral SGB using 6 mL of 1% lidocaine hydrochloride results in an increase in tissue oxygenation in the mandibular region. Based on these findings, we hypothesize that a series of SGBs may contribute to a more rapid recovery of postoperative trigeminal nerve injury.

A novel metric linking stellate ganglion neuronal population dynamics to cardiopulmonary physiology.

Cardiopulmonary sympathetic control is exerted via stellate ganglia (SG); however, little is known about how neuronal firing patterns in the stellate ganglion relate to dynamic physiological function in the heart and lungs. We performed continuous extracellular recordings from SG neurons using multielectrode arrays in chloralose-anesthetized pigs (n = 6) for 8-9 h. Respiratory and left ventricular pressures (RP and LVP, respectively) and the electrocardiogram (ECG) were recorded concomitantly. Linkages between sampled spikes and LVP or RP were determined using a novel metric to evaluate specificity in neural activity for phases of the cardiac and pulmonary cycles during resting conditions and under various cardiopulmonary stressors. Firing frequency (mean 4.6 ± 1.2 Hz) varied spatially across the stellate ganglion, suggesting regional processing. The firing pattern of most neurons was synchronized with both cardiac (LVP) and pulmonary (RP) activity indicative of cardiopulmonary integration. Using the novel metric to determine cardiac phase specificity of neuronal activity, we found that spike density was highest during diastole and near-peak systole. This specificity was independent of the actual LVP or population firing frequency as revealed by perturbations to the LVP. The observed specificity was weaker for RP. Stellate ganglion neuronal populations exhibit cardiopulmonary integration and profound specificity toward the near-peak systolic phase of the cardiac cycle. This novel approach provides practically deployable tools to probe stellate ganglion function and its relationship to cardiopulmonary pathophysiology.NEW & NOTEWORTHY Activity of stellate ganglion neurons is often linking indirectly to cardiac function. Using novel approaches coupled with extended period of recordings in large animals, we link neuronal population dynamics to mechanical events occurring at near-peak systole. This metric can be deployed to probe stellate ganglion neuronal control of cardiopulmonary function in normal and disease states.

Recording Intrinsic Nerve Activity at the Sinoatrial Node in Normal Dogs With High-Density Mapping.

BACKGROUND: It is known that autonomic nerve activity controls the sinus rate. However, the coupling between local nerve activity and electrical activation at the sinoatrial node (SAN) remains unclear. We hypothesized that we would be able to record nerve activity at the SAN to investigate if right stellate ganglion (RSG) activation can increase the local intrinsic nerve activity, accelerate sinus rate, and change the earliest activation sites. METHODS: High-density mapping of the epicardial surface of the right atrium including the SAN was performed in 6 dogs during stimulation of the RSG and after RSG stellectomy. A radio transmitter was implanted into 3 additional dogs to record RSG and local nerve activity at the SAN. RESULTS: Heart rate accelerated from 108±4 bpm at baseline to 125±7 bpm after RSG stimulation (P=0.001), and to 132±7 bpm after apamin injection (P<0.001). Both electrical RSG stimulation and apamin injection induced local nerve activity at the SAN with the average amplitudes of 3.60±0.72 and 3.86±0.56 µV, respectively. RSG stellectomy eliminated the local nerve activity and decreased the heart rate. In ambulatory dogs, local nerve activity at the SAN had a significantly higher average Pearson correlation to heart rate (0.72±0.02, P=0.001) than RSG nerve activity to HR (0.45±0.04, P=0.001). CONCLUSIONS: Local intrinsic nerve activity can be recorded at the SAN. Short bursts of these local nerve activities are present before each atrial activation during heart rate acceleration induced by stimulation of the RSG.

Stellate ganglion ischemia on the prevention of pulmonary vasospasm during bilateral carotid artery ligation: The first experimental study.

Fatal pulmonary edema and hemorrhage are significant complications of endovascular treatment in steno-occlusive carotid artery disease; a rational mechanism has not been adequately examined in the literature so far. We investigated if cervical sympathetic ganglia ischemia prevents pulmonary vasospasm on the prognosis of bilateral common carotid artery ligation (BCCAL). Twenty-three adult New Zealand rabbits (4.2 ± 0.3 kg) were randomly divided into three groups: the control group (G1, n = 5), the sham group (G2, n = 6), and the BCCAL group (G3, n = 12). Common carotid arteries were dissected bilaterally in G2/G3, and permanent BCCAL was applied to only in G3. All animals were followed for 3 weeks and decapitated under general anesthesia. Histopathological changes in stellate ganglia and severity of pulmonary vasospasm-related lung edema and hemorrhage were investigated. Results were analyzed by the Kruskal-Wallis test. Two animals of G3 dead within three weeks and the remainder were sacrificed three weeks later. Subpleural petechial foci and an endotracheal bloody fluid collection were grossly observed in the lungs. Histopathologically, pulmonary artery vasospasm, perivascular and subintimal edema, interalveolar hemorrhage, and alveolar wall destructions were observed with less ischemic-degenerated neuron density-determined stellate ganglia animals. Neurodegeneration of stellate ganglia may have a beneficial effect on the prevention of lung injury during steno-occlusive carotid artery disease.

Effects of Vagal Nerve Stimulation on Ganglionated Plexi Nerve Activity and Ventricular Rate in Ambulatory Dogs With Persistent Atrial Fibrillation.

OBJECTIVES: This study was designed to test the hypothesis that low-level vagal nerve stimulation (VNS) reduces the ventricular rate (VR) during atrial fibrillation (AF) through the activation of the inferior vena cava (IVC)-inferior atrial ganglionated plexus nerve activity (IAGPNA). BACKGROUND: Increased IVC-IAGPNA can suppress atrioventricular node conduction and slow VR in canine models of AF. METHODS: Persistent AF was induced in 6 dogs and the IVC-IAGPNA, right vagal nerve activity, left vagal nerve activity, and an electrocardiogram were recorded. After persistent AF was documented, VNS was programed to 14 s "on" and 1.1 min "off." After 1 week, the VNS was reprogramed to 3 min off and stimulation continued for another week. Neural remodeling of the stellate ganglion (SG) was assessed with tyrosine hydroxylase staining and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining. RESULTS: Average IVC-IAGPNA was increased during both VNS 1.1 min off (8.20 ± 2.25 µV [95% confidence interval (CI): 6.33 to 9.53 µV]; p = 0.002) and 3 min off (7.96 ± 2.03 µV [95% CI: 6.30 to 9.27 µV]; p = 0.001) versus baseline (7.14 ± 2.20 µV [95% CI: 5.35 to 8.52 µV]). VR was reduced during both VNS 1.1 min off (123.29 ± 6.29 beats/min [95% CI: 116.69 to 129.89 beats/min]; p = 0.001) and 3 min off (120.01 ± 4.93 beats/min [95% CI: 114.84 to 125.18 beats/min]; p = 0.001) compared to baseline (142.04 ± 7.93 bpm [95% CI: 133.72 to 150.37]). Abnormal regions were observed in the left SG, but not in the right SG. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling-positive neurons were found in 22.2 ± 17.2% [95% CI: 0.9% to 43.5%] of left SG cells and 12.8 ± 8.4% [95% CI: 2.4% to 23.2%] of right SG cells. CONCLUSIONS: Chronic low-level VNS increases IVC-IAGPNA and damages bilateral stellate ganglia. Both mechanisms could contribute to the underlying mechanism of VR control during AF.

Transcriptional profiling of stellate ganglia from normotensive and spontaneously hypertensive rat strains.

The course of hypertension remains poorly understood, although impairment of the sympathetic nervous systems is thought to play a role in its aetiology. In this study, RNA-sequencing (RNAseq) was used to identify transcriptomal differences in the sympathetic stellate ganglia between 16-week-old normotensive Wistar rats and spontaneously hypertensive rats (SHR). Sequencing quality was assessed by FastQC and quasi-mapping rate by Salmon. Differential expression results were confirmed by real time reverse transcriptase Quantitative Polymerase Chain Reaction (qRT-PCR). RNAseq analysis was found to be predictive and representative of transcriptomal changes when compared to qRT-PCR by correlation analysis. Whether these changes underpin physiological sympathetic phenotypes associated with hypertension remains to be established, however this dataset identifies lead transcripts as a priori targets for further investigation.

Insights into the neurochemical signature of the Innervation of Beige Fat.

OBJECTIVE: The potential for brown adipose tissue (BAT) to be targeted as a therapeutic option to combat obesity has been heightened by the discovery of a brown-like form of inducible "beige" adipose tissue in white fat which has overlapping structural and functional properties to "classical" BAT. The likelihood that both beige and brown fat are recruited functionally by neural mechanisms, taken together with the lack of a detailed understanding of the nature of changes in the nervous system when white adipose tissue (WAT) is transformed to brown, provides the impetus for this study. Here, we aim to identify whether there is a shift in the gene expression profile in neurons directly innervating inguinal white adipose tissue (iWAT) that has undergone "beiging" to a signature that is more similar to neurons projecting to BAT. METHODS: Two groups of rats, one housed at thermoneutrality (27 °C) and the other exposed to cold (8 °C) for 7 days, were killed, and their T13/L1 ganglia, stellate ganglion (T1/T2), or superior cervical ganglion (SCG, C2/3) removed. This approach yielded ganglia containing neurons that innervate either beiged white fat (8 °C for 7 days), inguinal WAT (27 °C for 7 days), BAT (both 27 °C and 8 °C for 7 days) or non-WAT (8 °C for 7 days), the latter included to isolate changes in gene expression that were more aligned with a response to cold exposure than the transformation of white to beige adipocytes. Bioinformatics analyses of RNA sequencing data was performed followed by Ingenuity Pathway Analysis (IPA) to determine differential gene expression and recruitment of biosynthetic pathways. RESULTS: When iWAT is "beiged" there is a significant shift in the gene expression profile of neurons in sympathetic ganglia (T13/L1) innervating this depot toward a gene neurochemical signature that is similar to the stellate ganglion projecting to BAT. Bioinformatics analyses of "beiging" related genes revealed upregulation of genes encoding neuropeptides proopiomelanocortin (POMC) and calcitonin-gene related peptide (CGRP) within ganglionic neurons. Treatment of differentiated 3T3L1 adipocytes with αMSH, one of the products cleaved from POMC, results in an elevation in lipolysis and the beiging of these cells as indicated by changes in gene expression markers of browning (Ucp1 and Ppargc1a). CONCLUSION: These data indicate that, coincident with beiging, there is a shift toward a "brown-like" neurochemical signature of postganglionic neurons projecting to inguinal white fat, an increased expression of POMC, and, consistent with a causative role for this prohormone in beiging, an αMSH-mediated increase in beige gene markers in isolated adipocytes.

Effect of Stellate Ganglion Block on the Regional Hemodynamics of the Upper Extremity: A Randomized Controlled Trial.

BACKGROUND: The success of stellate ganglion block (SGB) is traditionally determined on the basis of findings such as Horner's syndrome, temperature rise in the face, hyperemia of the tympanic membrane, and nasal congestion. However, decreases in vascular resistance and increases in blood flow in the arm may be more meaningful findings. To date, the effect of SGB on the regional hemodynamics of the arm has not been evaluated using pulsed-wave Doppler ultrasound. METHODS: A total of 52 patients who were to undergo orthopedic surgery of the forearm were randomly assigned to either the mepivacaine group (SGB with 5 mL of 0.5% mepivacaine) or the saline group (SGB with 5 mL of normal saline). Before surgery, a single anesthesiologist performed a SGB under ultrasound guidance. The temperature of the upper extremity and the resistance index and blood flow in the brachial artery were measured before SGB, 15 and 30 minutes after SGB, and 1 hour after surgery. The severity of pain, requirement for rescue analgesics, and side effects of the local anesthetic agent were all documented. RESULTS: After SGB, the resistance index decreased significantly and the blood flow increased significantly in the brachial artery of members of the mepivacaine group (15 minutes: P = .004 and P < .001, respectively; 30 minutes: P < .001 and P < .001, respectively). However, these values normalized after surgery. The severity of pain, need for rescue analgesics, and incidence of adverse effects were not significantly different between the 2 groups. CONCLUSIONS: Although SGB did not decrease the pain associated with forearm surgery, ultrasound-guided SGB did increase blood flow and decrease vascular resistance in the arm. Therefore, pulsed-wave Doppler may be used to monitor the success of SGB.

Stellate ganglion block ameliorates vascular calcification by inhibiting endoplasmic reticulum stress.

AIMS: Vascular calcification (VC) underlies substantial cardiovascular morbidity and mortality. No clinically therapies have emerged presently. Stellate ganglion block (SGB) is one of the most often used sympathetic blockade procedure, and regulates vascular dilation. However, the effect of SGB on VC is still unknown. Therefore, we aimed to identify the ameliorative effect of SGB on VC. KEY FINDING: In vivo VC was induced in rats by administering vitamin D3 plus nicotine (VDN), and in vitro calcification of rat aortic vascular smooth muscle cells (VSMC) was induced by ß-glycerophosphate. In VDN rats, alkaline phosphatase (ALP) activity and Calcium contents were higher than that in control rats. The transformation of VSMC from contractile to osteoblast-like phenotype was observed in calcified aorta. SGB ameliorated the increase of ALP activity and Calcium content, and the transformation of VSMC in calcified aorta. The stimulation of endoplasmic reticulum stress (ERS) in calcified aorta was also attenuated by SGB treatment. The inducer of ERS, tunicamycin could block the beneficial effect of SGB on VC, and the ERS inhibitor, 4-PBA could mimic the amelioration of SGB. Furthermore, SGB attenuated the increased plasma levels of norepinephrine in VDN rats. In vitro experiments, norepinephrine exaggerated VSMC calcification, phenotype transformation and ERS. SIGNIFICANCE: These results demonstrate that SGB could inhibit sympathetic nervous activity, and then prevent the activation of ERS followed by ameliorating VC. Sympathetic over-activation might play critical role in the pathogenesis of VC, which provides new strategy and target for therapy and prevention of VC.

Optogenetic Modulation of Cardiac Sympathetic Nerve Activity to Prevent Ventricular Arrhythmias.

BACKGROUND: Studies have shown that left stellate ganglion (LSG) suppression protects against ventricular arrhythmias (VAs). Optogenetics is a novel technique to reversibly regulate the activity of the targeted neurons. OBJECTIVES: This study aimed to investigate whether an optogenetically silenced LSG could protect against VAs induced by myocardial ischemia. METHODS: Adeno-associated virus (AAV) was used as the vector to deliver ArchT, an inhibitory light-sensitive opsin, to the LSG neurons. Twenty male beagles were randomized into the optogenetics group (n = 10, AAV2/9-CAG-ArchT-GFP microinjected into LSG) and control group (n = 10, AAV2/9-CAG-GFP microinjected into LSG). After 4 weeks, the LSG function and neural activity, heart rate variability, ventricular action potential duration, and effective refractory period were measured in the absence or presence of a light-emitting diode illumination (565 nm). Myocardial ischemia was induced by left anterior coronary artery ligation and 1 h of electrocardiography was recorded for VAs analysis. RESULTS: ArchT was successfully expressed in all dogs. Transient light-emitting diode illumination significantly suppressed the LSG function, LSG neural activity, and sympathetic nerve indices of heart rate variability as well as prolonged left ventricular effective refractory period and APD90 only in the optogenetics group. Thirty-minute illumination further enhanced these changes in the optogenetics group. Importantly, all of these changes returned to baseline within 2 h after illumination was turned off. Moreover, the ischemia-induced VAs were significantly suppressed by illumination only in the optogenetics group. CONCLUSIONS: Optogenetic modulation could reversibly inhibit the neural activity of LSG, thereby increasing electrophysiological stability and protecting against myocardial ischemia-induced VAs.

Efficacy of Stellate Ganglion Blockade in Managing Electrical Storm: A Systematic Review.

BACKGROUND: The efficacy of percutaneous stellate ganglion block (SGB) for managing electrical storm (ES) is not well understood. OBJECTIVE: To characterize the efficacy of SGB as a treatment for ES. METHODS: We conducted literature searches using PubMed/Medline and Google Scholar, for mixed combinations of terms including "stellate ganglion block", *ganglion block (ade)", "sympathetic block (ade)" and "arrhythmia", "ventricular arrhythmia (VA)" or "tachycardia" (VT), "ventricular fibrillation" (VF), "electrical storm". Inclusion criteria were presentation with guideline-defined ES and treatment with SGB. Exclusion criteria: presentation with any supraventricular arrhythmia, VA without ES, or surgical sympathectomy. Studies lacking basic demographic data, arrhythmia description, and outcomes were excluded. RESULTS: Of 3,374 publications reviewed, 38 patients from 23 studies met study criteria (52 ± 19.1 years, 11 F, 17 with ischemic cardiomyopathy). Anti-arrhythmics were used in all patients. Mean Left ventricular ejection fraction was 31 ± 10%. ES was triggered by acute myocardial infarction in 15 patients and QT prolongation in 7 patients. The most common local anesthetic used for SGB was bupivacaine (0.25-0.5%). SGB resulted in a significant decrease in VA burden (12.4±8.8 vs. 1.04±2.12 episodes/day, p< 0.001) and number of external and ICD shocks (10.0±9.1 vs. 0.05±0.22 shocks/day, p< 0.01). Following SGB, 80.6% of patients survived to discharge. CONCLUSION: SGB is an effective acute treatment for ES. However, larger prospective randomized studies are needed to better understand the role of SGB in ES and other VAs.

Inflammation, oxidative stress, and glial cell activation characterize stellate ganglia from humans with electrical storm.

BACKGROUND: Neuronal remodeling in human heart disease is not well understood. METHODS: Stellate ganglia from patients with cardiomyopathy (CMY) and refractory ventricular arrhythmias undergoing cardiac sympathetic denervation (n = 8), and from organ donors with normal hearts (n = 8) collected at the time of organ procurement were compared. Clinical data on all subjects were reviewed. Electron microscopy (EM), histologic, and immunohistochemical assessments of neurotransmitter profiles, glial activation and distribution, and lipofuscin deposition, a marker of oxidative stress, were quantified. RESULTS: In CMY specimens, lipofuscin deposits were larger, and present in more neurons (26.3% ± 6.3% vs. 16.7% ± 7.6%, P < 0.043), than age-matched controls. EM analysis revealed extensive mitochondrial degeneration in CMY specimens. T cell (CD3+) infiltration was identified in 60% of the CMY samples, with one case having large inflammatory nodules, while none were identified in controls. Myeloperoxidase-immunoreactive neutrophils were also identified at parenchymal sites distinct from inflammatory foci in CMY ganglia, but not in controls. The adrenergic phenotype of pathologic samples revealed a decrease in tyrosine hydroxylase staining intensity compared with controls. Evaluation of cholinergic phenotype by staining for the vesicular acetylcholine transporter revealed a low but comparable number of cholinergic neurons in ganglia from both groups and demonstrated that preganglionic cholinergic innervation was maintained in CMY ganglia. S100 staining (a glial cell marker) demonstrated no differences in glial distribution and relationship to neurons; however, glial activation demonstrated by glial fibrillary acidic protein (GFAP) staining was substantially increased in pathologic specimens compared with controls. CONCLUSIONS: Stellate ganglia from patients with CMY and arrhythmias demonstrate inflammation, neurochemical remodeling, oxidative stress, and satellite glial cell activation. These changes likely contribute to excessive and dysfunctional efferent sympathetic tone, and provide a rationale for sympathectomy as a treatment for arrhythmias in this population. FUNDING: This work was made possible by support from NIH grants HL125730 to OAA, GM107949 to DBH, and HL084261 and OT2OD023848 to KS.

Possible Reversal of PTSD-Related DNA Methylation by Sympathetic Blockade.

Studies have shown that brain-derived neurotrophic factor (BDNF) level increase is associated with post-traumatic stress disorder (PTSD) risk. BDNF may be a "missing-link" that mediates the interaction between genetics, environment, and the sympathetic system. Trauma has been shown to induce DNA methylation that in turn can increase BDNF concentration due to increased gene expression. Therapies that focus on the reduction of beta-NGF (BNGF) levels may impact PTSD symptoms. The focus of this paper is to discuss possible effect of stellate ganglion block (SGB) on epigenetic changes noted with PTSD mediated by BDNF and NGF. Stellate ganglion block has recently shown significant therapeutic efficacy for treatment of PTSD symptoms. Previously reported theoretical mechanisms of SGB impact on PTSD have focused on likely reduction of NGF, leading to eventual loss of extraneous sympathetic nerve growth, eventually leading to reduction of secondary norepinephrine level, which in turn is hypothesized to reduce PTSD symptoms. We used PUBMED to obtain available data following a search for the following: DNA, neurotrophic factors, post-traumatic stress disorder, and demethylation following local anesthetic application. A number of articles meeting criteria were found and reviewed. Based on the evidence summarized, trauma can lead to DNA methylation, as well as BNGF/NGF level increase, which in turn starts a cascade of sympathetic sprouting, leading to increased brain norepinephrine, and finally symptomatic PTSD. Cascade reversal may occur in part by demethylation of DNA caused by application of local anesthetic to the stellate ganglion.

Bioelectronic neuromodulation of the paravertebral cardiac efferent sympathetic outflow and its effect on ventricular electrical indices.

BACKGROUND: Neuromodulation of the paravertebral ganglia by using symmetric voltage controlled kilohertz frequency alternating current (KHFAC) has the potential to be a reversible alternative to surgical intervention in patients with refractory ventricular arrhythmias. KHFAC creates scalable focal inhibition of action potential conduction. OBJECTIVE: The purpose of this article was to evaluate the efficacy of KHFAC when applied to the T1-T2 paravertebral chain to mitigate sympathetic outflow to the heart. METHODS: In anesthetized, vagotomized, porcine subjects, the heart was exposed via a midline sternotomy along with paravertebral chain ganglia. The T3 paravertebral ganglion was electrically stimulated, and activation recovery intervals (ARIs) were obtained from a 56-electrode sock placed over both ventricles. A bipolar Ag electrode was wrapped around the paravertebral chain between T1 and T2 and connected to a symmetric voltage controlled KHFAC generator. A comparison of cardiac indices during T3 stimulation conditions, with and without KHFAC, provided a measure of block efficacy. RESULTS: Right-sided T3 stimulation (at 4 Hz) was titrated to produce reproducible ARI changes from baseline (52 ± 30 ms). KHFAC resulted in a 67% mitigation of T3 electrical stimulation effects on ARI (18.5 ± 22 ms; P < .005). T3 stimulation repeated after KHFAC produced equivalent ARI changes as control. KHFAC evoked a transient functional sympathoexcitation at onset that was inversely related to frequency and directly related to intensity. The optimum block threshold was 15 kHz and 15 V. CONCLUSION: KHFAC applied to nexus (convergence) points of the cardiac nervous system produces a graded and reversible block of underlying axons. As such, KHFAC has the therapeutic potential for on-demand and reversible mitigation of sympathoexcitation.

Effects of Linearly Polarized Near-Infrared Irradiation Near the Stellate Ganglion Region on Pain and Heart Rate Variability in Patients with Neuropathic Pain.

Background: Neuropathic pain associated with sympathetic overactivity can be effectively relieved by light irradiating the region near stellate ganglion (SGI), applied as an alternative to a conventional sympathetic blockade. The clinical effect of SGI on heart rate variability (HRV) and its association with pain outcomes require investigation. Objective: This study attempted to identify the effects of SGI on pain outcomes and HRV indices and to determine the association between pain and HRV outcomes. Design: A prospective double-blind, randomized study. Setting: An outpatient pain medicine clinic. Subjects and Methods: A total of 44 patients were enrolled and randomized into the experimental group ( n = 22) and control group ( n = 22). The experimental group received 12 sessions (twice weekly) of standard SGI, whereas the control group received the same protocol with sham irradiation. Pain and HRV were measured before and after each irradiation session. All outcome measures used in the first- and second-half treatment courses were analyzed. Results: Pain and HRV outcome measures of the experimental group significantly improved after SGI when compared with the control group in both courses. Considering time and frequency domains, the changes in HRV in the second-half treatment course exceeded those in the first-half treatment course. Pain was significantly associated with postirradiated HRV indices ( P < 0.001). Conclusions: Twelve sessions of SGI exerted time-dependent positive effects on pain and sympathovagal imbalance. HRV outcomes, including time and frequency domains, were an independent indicator of the clinical efficiency of SGI for treating pain in patients with neuropathic pain.