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Objectives This study investigates the effect of stellate ganglion (SG) phototherapy in healthy participants and assesses its efficacy in suppressing electrical storm (ES) refractory to an...

ASP7962 is a small molecule inhibitor for the nerve growth factor (NGF) receptor, tropomyosin-related kinase A (TrkA). NGF contributes to the survival of sensory and sympathetic neurons through TrkA receptor activation. Gross, microscopic, and quantitative effects to the nervous system were evaluated following oral ASP7962 administration to Sprague Dawley rats for 4 weeks and 13 weeks and after a recovery period. Histopathological findings included reversible neuronal atrophy but no neuronal death in the sympathetic ganglia (cervicothoracic ganglion, cranial mesenteric ganglion or superior [cranial] cervical ganglion). Stereological analysis showed reversible decreased ganglion volume and/or decreased neuron size in the superior (cranial) cervical ganglion in both the 4-week and the 13-week repeated dose studies. There were no test article related changes in the brain, dorsal root ganglia with spinal nerve roots or trigeminal ganglia and no functional deficits. ASP7962 did not cause any detectable dysfunction of the sympathetic and sensory nervous system in either study.

Objectives This study sought to compare the efficacy and safety of single-injection stellate ganglion block (SGB) with a novel continuous-infusion SGB procedure. Background SGB for ventricular arrhythmia (VA) storm is typically performed with a single injection of local anesthetic agents. Methods Eighteen patients underwent left-sided SGB (9 single injection and 9 continuous infusion). The number of implantable cardioverter-defibrillator therapies and sustained VAs/24 h were compared between the pre-SGB and post-SGB periods. Adverse effects of SGB and in-hospital outcomes were also compared. Results The mean age was 61.1 ± 13.7 years. The presenting arrhythmia was ventricular tachycardia in 13 (72%) patients, ventricular fibrillation in 4 (22%), and both in 1 (6%). Single-injection SGB reduced VA/24 h by a median of 0.3 (interquartile range: 0.2 to 0.9), which was a 45% reduction (p = 0.008), resulting in 5 of 9 patients with no recurrent VA. Continuous-infusion SGB reduced VA/24 h by a median of 2.0 (interquartile range: 1.3 to 3.0), which was a 94% reduction (p = 0.004), resulting in 7 of 9 patients with no recurrent VA (p = 0.006 for comparison with single injection). Transient left arm weakness and voice hoarseness were each noted in 1 patient in both groups. Repeat SGB was required in 4 (44%) patients in the single-injection group. In-hospital outcomes were similar between the groups. Conclusions In patients with VA storm, SGB performed via both continuous-infusion and single-injection approaches provided significant reductions in VA burden. Compared to single-injection SGB, continuous-infusion was associated with a greater reduction in VA burden and similar adverse events, without the need for repeat procedures.

Background More than 640,000 combined in-hospital and out-of-hospital cardiac arrests occur annually in the United States. However, survival rates and meaningful neurologic recovery remain poor. Although “shockable” rhythms (i.e., ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT)) have the best outcomes, many of these ventricular dysrhythmias fail to return to a perfusing rhythm (resistant VF/VT), or recur shortly after they are resolved (recurrent VF/VT). Objective This review discusses 4 emerging therapies in the emergency department for treating these resistant or recurrent ventricular dysrhythmias: beta-blocker therapy, dual simultaneous external defibrillation, stellate ganglion blockade, and extracorporeal cardiopulmonary resuscitation. We discuss the underlying physiology of each therapy, review relevant literature, describe when these approaches should be considered, and provide evidence-based recommendations for these techniques. Discussion Esmolol may mitigate some of epinephrine's negative effects when used during resuscitation, improving both postresuscitation cardiac function and long-term survival. Dual simultaneous external defibrillation targets the region of the heart where ventricular fibrillation typically resumes and may apply a more efficient defibrillation across the heart, leading to higher rates of successful defibrillation. Stellate ganglion blocks, recently described in the emergency medicine literature, have been used to treat patients with recurrent VF/VT, resulting in significant dysrhythmia suppression. Finally, extracorporeal cardiopulmonary resuscitation is used to provide cardiopulmonary support while clinicians correct reversible causes of arrest, potentially resulting in improved survival and good neurologic functional outcomes. Conclusion These emerging therapies do not represent standard practice; however, they may be considered in the appropriate clinical scenario when standard therapies are exhausted without success.

Background The neuropathological mechanism of heart rhythm disorders, following spinal cord pathologies, to our knowledge, has not yet been adequately investigated. In this study, the effect of the ischemic neurodegeneration of the thoracic sympathetic nuclei (TSN) on the heart rate (HR) was examined following a spinal subarachnoid hemorrhage (SSAH). Methods This study was conducted on 22 rabbits. Five rabbits were used as a control group, five as SHAM, and twelve as a study group. The animals’ HRs were recorded via monitoring devices on the first day, and those results were accepted as baseline values. The HRs were remeasured after injecting 0.5 cc of isotonic saline for SHAM and 0.5 cc of autolog arterial blood into the thoracic spinal subarachnoid space at T4–T5 for the study group. After a three-week follow-up with continuous monitoring of their HRs, the rabbit's thoracic spinal cords and stellate ganglia were extracted. The specimens were evaluated by histopathological methods. The densities of degenerated neurons in the TSN and stellate ganglia were compared with the HRs. Results The mean HRs and mean degenerated neuron density of the TSN and stellate ganglia in control group were 251 ± 18/min, 5 ± 2/mm3, and 3 ± 1/mm3, respectively. The mean HRs and the mean degenerated neuron density of the TSN and stellate ganglia were detected as 242 ± 13/min, 6 ± 2/mm3, and 4 ± 2/mm3 in SHAM (P > 0.05 vs. control); 176 ± 19/min, 94 ± 12/mm3, and 28 ± 6/mm3 in the study group (P Conclusions SAH induced TSN neurodegeneration may have been responsible for low HRs following SSAH. To date this has not been mentioned in the literature.

Background The relationship between the ventricular rate (VR) during atrial fibrillation (AF) and skin sympathetic nerve activity (SKNA) remains unclear. Objective The purpose of this study was to test the hypothesis that SKNA bursts accelerate VR during AF. Methods We simultaneously recorded electrocardiogram and SKNA in 8 patients (median age 66.0 years [interquartile range {IQR} 59.0–77.0 years]; 4 men [50%]) with 30 paroxysmal AF episodes (all >10-minute long) and 12 patients (73.0 years [IQR 60.5–80.0 years]; 6 men [50%]) with persistent AF. The average amplitude of SKNA (aSKNA [μV]) during AF was analyzed in 1-minute windows and binned, showing 2 Gaussian distributions. We used the mean + 3SD of the first Gaussian distribution as the threshold that separates burst from baseline (nonburst) SKNA. All 1-minute aSKNA values above the threshold were detected, and the area between aSKNA and baseline of every 1 minute was calculated and added as burst area. Results VR was higher during SKNA bursts than during the nonburst period (103 beats/min [IQR 83–113 beats/min] vs 88 beats/min [IQR 76–101 beats/min], respectively; P = .003). In the highest quartile of the burst area during persistent AF, the scatterplot of maximal aSKNA and VR during each SKNA burst shows higher aSKNA and VR. The overall estimate of the correlation between maximal VR and aSKNA during bursts show a positive correlation in the highest quartile of the burst area (0.64; 95% confidence interval 0.54–0.74; P Conclusion SKNA bursts are associated with VR acceleration. These SKNA bursts may be new therapeutic targets for rate control during AF.

Stellate ganglion blockade has been previously suggested as a treatment option for intractable ventricular arrhythmia; however, its use in emergency department management of pulseless arrest with shockable rhythm has not been described. We report the case of a 65-year-old man brought in by ambulance who complained of chest pain and received an out-of-hospital ECG suggestive of anterior-wall ST-segment elevation myocardial infarction. Shortly after arrival, the patient became unresponsive, with no palpable pulse, and was found to be in ventricular fibrillation. The patient's ventricular fibrillation persisted despite repeated attempts at standard and double sequential defibrillation, multiple rounds of epinephrine, and amiodarone, magnesium, and bicarbonate. After these interventions were exhausted, a stellate ganglion blockade was conducted after an ultrasonographically guided paratracheal approach. Return of spontaneous circulation was noted after the next defibrillation and pulse check, achieved after a total of 42 minutes of active cardiopulmonary resuscitation. The patient ultimately had both sufficient neurologic activity and hemodynamic recovery for emergency percutaneous coronary intervention of the culprit left anterior descending artery. This positive outcome is multifactorial but suggests sympathetic blockade as a possible adjunctive therapy in the setting of sustained pulseless ventricular storm.

Chronically elevated angiotensin II is a widely-established contributor to hypertension and heart failure via its action on the kidneys and vasculature. It also augments the activity of peripheral sympathetic nerves through activation of presynaptic angiotensin II receptors, thus contributing to sympathetic over-activity. Although some cells can synthesise angiotensin II locally, it is not known if this machinery is present in neurons closely coupled to the heart. Using a combination of RNA sequencing and quantitative real-time polymerase chain reaction, we demonstrate evidence for a renin-angiotensin synthesis pathway within human and rat sympathetic stellate ganglia, where significant alterations were observed in the spontaneously hypertensive rat stellate ganglia compared with Wistar stellates. We also used Förster Resonance Energy Transfer to demonstrate that administration of angiotensin II and angiotensin 1–7 peptides significantly elevate cyclic guanosine monophosphate in the rat stellate ganglia. Whether the release of angiotensin peptides from the sympathetic stellate ganglia alters neurotransmission and/or exacerbates cardiac dysfunction in states associated with sympathetic over activity remains to be established., Highlights • The stellate ganglia may act as a novel source for local angiotensin signaling. • Angiotensin peptides and receptors were identified in human and rat stellates. • Elevations in neuronal cGMP occur in response to angiotensin peptides. • RNA transcript expression was altered in young spontaneously hypertensive rats. • Angiotensin signaling at this site may be linked to dysautonomia in hypertension.

Cardiac sympathetic denervation (CSD) for refractory ventricular tachycardia (VT) has been shown to decrease VT recurrence and defibrillator shocks in patients with ischemic and nonischemic cardiomyopathy. Here and in the accompanying Video, we demonstrate the technique for minimally invasive CSD, highlight important technical points, and report surgical outcomes. CSD is accomplished through bilateral resection of the inferior one-third to one-half of the stellate ganglion en bloc with T2-T4 sympathectomy. Despite the high potential for perioperative risk, most patients do not have serious complications. We find that surgical CSD can be performed safely in an attempt to liberate patients from refractory VT.

Background Subcutaneous nerve stimulation (ScNS) damages the stellate ganglion and improves rhythm control of atrial fibrillation (AF) in ambulatory dogs. Objective The purpose of this study was to test the hypothesis that thoracic ScNS can improve rate control in persistent AF. Methods We created persistent AF in 13 dogs and randomly assigned them to ScNS (n = 6) and sham control (n = 7) groups. 18F-2-Fluoro-2-deoxyglucose positron emission tomography/magnetic resonance imaging of the brain stem was performed at baseline and at the end of the study. Results The average stellate ganglion nerve activity reduced from 4.00 ± 1.68 μV after the induction of persistent AF to 1.72 ± 0.42 μV (P = .032) after ScNS. In contrast, the average stellate ganglion nerve activity increased from 3.01 ± 1.26 μV during AF to 5.52 ± 2.69 μV after sham stimulation (P = .023). The mean ventricular rate during persistent AF reduced from 149 ± 36 to 84 ± 16 beats/min (P = .011) in the ScNS group, but no changes were observed in the sham control group. The left ventricular ejection fraction remained unchanged in the ScNS group but reduced significantly in the sham control group. Immunostaining showed damaged ganglion cells in bilateral stellate ganglia and increased brain stem glial cell reaction in the ScNS group but not in the control group. The 18F-2-fluoro-2-deoxyglucose uptake in the pons and medulla was significantly (P = .011) higher in the ScNS group than the sham control group at the end of the study. Conclusion Thoracic ScNS causes neural remodeling in the brain stem and stellate ganglia, controls the ventricular rate, and preserves the left ventricular ejection fraction in ambulatory dogs with persistent AF.

Background Neurogenic stunned myocardium (NSM) is a devastating complication of subarachnoid hemorrhage (SAH). The most widely accepted mechanism in the pathogenesis of NSM and takotsubo cardiomyopathy is catecholamine-mediated direct myocardial injury. The aim of this study is to examine if there is any effect of sympathetic overactivity of the stellate ganglions on myocardial tissues, secondary to vagal complex degeneration in SAH-induced NSM. Materials and Methods This study was conducted on 25 New Zealand female rabbits. After the examination, all animals were assigned into 3 groups randomly: a control group (n = 5), a sham group (n = 5), and a study group (n = 15) that was subjected to experimental SAH with double injection of blood into the cisterna magna. After 7 animals exhibited NSM, all animals were killed. Their brains, vagal complexes, stellate ganglions, and hearts were extracted and examined by histopathologic methods. Degenerated nodose ganglion neurons and stellate ganglion neuron densities were compared with degenerated myocardial tissue/normal myocardial tissue ratios, and the results were analyzed with the Mann-Whitney U test. Results Three rabbits in the study group died immediately after the second injection of blood. NSM developed in 7 animals after 1 to 5 days, which was diagnosed with transthoracic echocardiography. Interestingly, the animals that developed NSM had more stellate ganglia neurons and more degenerated neuron densities of nodose ganglia (P Conclusions NSM and takotsubo cardiomyopathy may be induced by vagal complex degeneration and sympathetic overactivity, which originated from more neurons, including stellate ganglia and more degenerated neuron densities of nodose ganglia.

Background Imbalanced activation of the cardiac autonomic nervous system triggers postoperative atrial fibrillation (POAF). Neuronal calcium overload induces apoptosis. We hypothesize that epicardial injection of timed-release nanoformulated CaCl2 (nCaCl2) into left atrial ganglionic plexi (GP) modulates autonomic function and suppresses POAF. Objective The purpose of this study was to determine whether nCaCl2 GP therapy suppresses POAF. Methods We used a novel canine model of POAF with implanted radiotelemetry to record nerve activity (NA) from the left stellate ganglion (SNA), left cardiac vagus nerve, and GP. At week 3, nCaCl2 (n = 7) or vehicle control (sham; n=3) was injected into left pulmonary vein GP (LGP), followed by right pulmonary vein GP at week 4. Atrial effective refractory period (AERP) and atrial fibrillation vulnerability (AFV) were assessed in vivo. Resting and exercise NA and heart rate (HR) were assessed before and after LGP treatment. Results AERP decreased (P Conclusion Epicardial injection of nCaCl2 into left atrial GP induced neuroapoptosis and modulated autonomic function. This reversed a postoperative reduction in AERP and suppressed POAF.

Background It is reported interleukin (IL)-17A, a classical proinflammatory cytokine, is implicated in neuroimmune-associated remodeling in neural plasticity and pathological conditions. However, the effect of IL-17A on left stellate ganglion (LSG) remodeling remains unclear. Objective This study was performed to determine whether exogenous IL-17A promotes LSG remodeling and destabilize ventricular electrophysiological properties (EPs) in normal canines. Methods 24 beagles were randomly allocated into three groups. In the first group, animals were subjected to 0.1 ml phosphate buffer saline (PBS) microinjection of into LSG (n = 8), an equivalent IL-17A was administrated in the second group (n = 8), and an equivalent anti-IL-17A mAb plus IL-17A was administrated in the third group (n = 8). The ventricular EPs, neural function and activity of the LSG were determined at baseline and 30 min after administration. In the end, LSG tissues were collected. Results Compared with the control group, the experimental group had a significantly shorter effective refractory period (ERP) and action potential duration (APD)90, an increased ERP, APD90, Smax dispersion, and APD alternans cycle length; and steepened APD restitution curves. In addition, IL-17A enhanced the neural function and activity of the LSG, upregulated the expressions of neuropeptides and proinflammatory cytokines and cells. And all these effects were attenuated by anti-IL-17A mAb. Importantly, IL-17 receptor A (IL-17R-A) was detected in sympathetic neurons in the LSG. Conclusion IL-17A promoted LSG remodeling by regulating the neural inflammation response. It did so by binding to IL-17R-A, resulting in unstable ventricular electrophysiology in normal structural hearts.

Stellate ganglion (SG) modification has been investigated for arrhythmia treatment. In this study, transesophageal SG imaging and intervention were explored using a homemade 30F integrated focused ultrasonic catheter in healthy mongrel canines in vivo. Anatomic details of SGs were ultrasonically imaged and evaluated. SG had a heterogeneous echoic structure and characteristic profiles sketched by hyper-echoic outlines in an ultrasonogram. Left SGs in the experimental group were successfully ablated through the esophagus under ultrasonic guidance provided by the catheter itself. Two weeks after the ablation, the QT and QTc of the experimental group decreased compared with those of the sham group and at baseline (both p values < 0.001). Histologic examination revealed that left SGs were destroyed. No major complications were observed. This approach may be further explored as a method for ganglia remodeling evaluation and as a strategy of ganglia modification for arrhythmia and for other diseases.

Greater neuron density, and therefore neuronal remodeling, in the stellate ganglion has been associated with cardiovascular disease, but how this remodeling differs between cardiovascular conditions has not yet been investigated. Here, we have demonstrated a significant increase in neuronal size from individuals with no cardiovascular pathology to those with coronary artery disease or those who have experienced a myocardial infarction; however, this increase was not found to be significant in individuals with heart failure diagnoses. Heat map analysis of neuron nearest-neighbor densities additionally showed clustering, or closeness of neurons, in coronary artery disease and heart failure patients, but this clustering was not noted in individuals who had experienced a myocardial infarction. These observations may allude to differences in the role the sympathetic nervous system plays, and therefore differences in the disease progression, in these cardiovascular conditions.

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.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.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).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.

Diabetic cardiac autonomic neuropathy (DCAN) is a common and serious complication of diabetes mellitus (DM), is manifested by nerve fiber injury in the sympathetic and parasympathetic nerve of the autonomic nervous system, and causes hypertension, cardiac arrhythmias, silent myocardial infarction, and sudden death. Our previous study observed that P2X3 receptor in superior cervical ganglia in rat was associated with sympathetic neuropathy caused by myocardial ischemia. However, whether the P2X3 receptor is involved in the diabetic cardiac autonomic neuropathy and the underlying mechanisms remain unclear. The aim of this research was explored the effect of P2X3 short hairpin RNA (shRNA) on information transmission of sympathetic nerve induced by DCAN. Sprague-Dawley (SD) male rats were randomly divided into four groups: Control, DM, DM treated with P2X3 shRNA and DM treated with scramble shRNA. Blood pressure, heart rate and heart rate variability were measured in each group. The expression of P2X3 in stellate ganglion (SG) was detected by immunohistochemistry, western blotting and QPCR. Results showed that P2X3 shRNA alleviated blood pressure and heart rate, improved heart rate variability, decreased the up-regulated expression levels of P2X3, interleukin-1beta and tumor necrosis factor alpha in stellate ganglion (SG) of diabetic rats. P2X3 shRNA also reduced the incremental concentration of serum epinephrine and the phosphorylation level of extracellular regulated protein kinases1/2 in diabetic rats. These results indicated that P2X3 shRNA could decrease sympathetic activity via inhibiting P2X3 receptor in the SG to alleviate DCAN.

Background Stellate ganglion nerve activity (SGNA) precedes paroxysmal atrial tachyarrhythmia (PAT) episodes in dogs with intermittent rapid left atrial (LA) pacing. The left dorsal branch of the thoracic nerve (LDTN) contains sympathetic nerves originating from the stellate ganglia. Objective The purpose of this study was to test the hypothesis that high-frequency electrical stimulation of the LDTN can cause stellate ganglia damage and suppress PATs. Methods We performed long-term LDTN stimulation in 6 dogs with and 2 dogs without intermittent rapid LA pacing while monitoring SGNA. Results LDTN stimulation reduced average SGNA from 4.36 μV (95% confidence interval [CI] 4.10–4.62 μV) at baseline to 3.22 μV (95% CI 3.04–3.40 μV) after 2 weeks (P = .028) and completely suppressed all PAT episodes in all dogs studied. Tyrosine hydroxylase staining showed large damaged regions in both stellate ganglia, with increased percentages of tyrosine hydroxylase–negative cells. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that 23.36% (95% CI 18.74%–27.98%) of ganglion cells in the left stellate ganglia and 11.15% (95% CI 9.34%–12.96%) ganglion cells in the right stellate ganglia were positive, indicating extensive cell death. A reduction of both SGNA and heart rate was also observed in dogs with LDTN stimulation but without rapid LA pacing. Histological studies in the 2 dogs without intermittent rapid LA pacing confirmed the presence of extensive stellate ganglia damage, along with a high percentage of terminal deoxynucleotidyl transferase dUTP nick end labeling–positive cells. Conclusion LDTN stimulation damages both left and right stellate ganglia, reduces left SGNA, and is antiarrhythmic in this canine model of PAT.

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., Graphical abstract, Highlights • RNA Seq showed shifts in neuronal gene expression following browning of white fat. • Gene expression in ganglia projecting to white fat became brown-like with beiging. • Bioinformatics analyses revealed neuronal gene candidates associated with beiging. • Prominent gene candidates associated with beiging included POMC and CGRP. • POMC cleavage product α-MSH caused beiging of cultured fat cells.

Background Reducing sympathetic efferent outflow from the stellate ganglia (SG) may be antiarrhythmic. Objective The purpose of this study was to test the hypothesis that chronic thoracic subcutaneous nerve stimulation (ScNS) could reduce SG nerve activity (SGNA) and control paroxysmal atrial tachycardia (PAT). Methods Thoracic ScNS was performed in 8 dogs while SGNA, vagal nerve activity (VNA), and subcutaneous nerve activity (ScNA) were monitored. An additional 3 dogs were used for sham stimulation as controls. Results Xinshu ScNS and left lateral thoracic nerve ScNS reduced heart rate (HR). Xinshu ScNS at 3.5 mA for 2 weeks reduced mean average SGNA from 5.32 μV (95% confidence interval [CI] 3.89-6.75) at baseline to 3.24 μV (95% CI 2.16-4.31; P = .015) and mean HR from 89 bpm (95% CI 80-98) at baseline to 83 bpm (95% CI 76-90; P = .007). Bilateral SG showed regions of decreased tyrosine hydroxylase staining with increased terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive nuclei in 18.47% (95% CI 9.68-46.62) of all ganglion cells, indicating cell death. Spontaneous PAT episodes were reduced from 9.83 per day (95% CI 5.77-13.89) in controls to 3.00 per day (95% CI 0.11-5.89) after ScNS (P = .027). Left lateral thoracic nerve ScNS also led to significant bilateral SG neuronal death and significantly reduced average SGNA and HR in dogs. Conclusion ScNS at 2 different sites in the thorax led to SG cell death, reduced SGNA, and suppressed PAT in ambulatory dogs.

High-resolution ultrasound (US) enables prompt depiction of muscles, tendons, ligaments, and peripheral nerves. It seems to be the best imaging modality for guiding perineural injections. The most complicated neurovascular network of the musculoskeletal system surrounds the cervical spine; so injection to that region is never an easy task. This article elaborates the regional anatomy and the use of US scanning and guidance for cervical interventions; for example, cervical root, superficial cervical plexus, stellate ganglion, cervical medial branch, greater occipital nerve, and third occipital nerve. The article aims to lead readers to practice US-guided cervical injections precisely and safely.

Tanezumab, a humanized monoclonal anti-NGF antibody, has demonstrated efficacy and safety profiles in Phase III clinical trials of chronic pain. In a 24-week study in non-human primates, morphological observations of sympathetic ganglia showed decreased ganglia volume, decreased neuronal size, and increased glial cell density compared with controls after 3 tanezumab treatments. Using stereological techniques to quantify glial cells, the present 26-week study found no significant difference after weekly treatments in total cervicothoracic ganglia satellite glial cell number between placebo- or tanezumab-treated cynomolgus monkeys. These findings suggest that tanezumab treatment does not result in a true gliosis in sympathetic ganglia.

Background Heart failure (HF) is associated with autonomic dysfunction. Vagus nerve stimulation has been shown to improve cardiac function both in HF patients and animal models of HF. The purpose of this present study is to investigate the effects of ganglionated plexus stimulation (GPS) on HF progression and autonomic remodeling in a canine model of acute HF post-myocardial infarction. Methods and results Eighteen adult mongrel male dogs were randomized into the control (n = 8) and GPS (n = 10) groups. All dogs underwent left anterior descending artery ligation followed by 6-hour high-rate (180–220 bpm) ventricular pacing to induce acute HF. Transthoracic 2-dimensional echocardiography was performed at different time points. The plasma levels of norepinephrine, B-type natriuretic peptide (BNP) and Ang-II were measured using ELISA kits. C-fos and nerve growth factor (NGF) proteins expressed in the left stellate ganglion as well as GAP43 and TH proteins expressed in the peri-infarct zone were measured using western blot. After 6 h of GPS, the left ventricular end-diastolic volume, end-systolic volume and ejection fraction showed no significant differences between the 2 groups, but the interventricular septal thickness at end-systole in the GPS group was significantly higher than that in the control group. The plasma levels of norepinephrine, BNP, Ang-II were increased 1 h after myocardial infarction while the increase was attenuated by GPS. The expression of c-fos and NGF proteins in the left stellate ganglion as well as GAP43 and TH proteins in cardiac peri-infarct zone in GPS group were significantly lower than that in control group. Conclusions GPS inhibits cardiac sympathetic remodeling and attenuates HF progression in canines with acute HF induced by myocardial infarction and ventricular pacing.

Background Increased inflammation was found in the left stellate ganglion (LSG) in patients with malignant ventricular arrhythmia (VA). However, the role of inflammation in LSG remodeling is unknown. This study aimed to investigate whether exogenous interleukin-1β (IL-1β) could aggravate VA through regulating LSG remodeling. Methods Twenty-four canines who received saline (Control, n=8), IL-1β injection into the LSG (n=8) or IL-1 receptor antagonist (IL-Ra) pre-injection plus IL-1β injection (n=8) were included. Ventricular electrophysiology parameters, heart rate variability (HRV), LSG activity were measured at different time points. VA was recorded for 60min after ischemia and then LSG tissues were collected for molecular detection. Results Compared with the control group, IL-1β injection decreased the effective refractory period, action potential duration (APD) 90 and increased the maximal slope of the restitution curve in normal hearts. Besides, the occurrence of VA was significantly increased in the IL-1β group. Additionally, IL-1β injection increased the sympathetic indices of HRV and LSG activity in normal and ischemic hearts. Mechanically, the mRNA expression of pro-inflammatory cytokines and protein expression of c-fos, nerve growth factor and neuropeptide Y in LSG were increased, whereas the expression of neuronal nitric oxide synthase was decreased in the IL-1β group. More importantly, all these effects induced by IL-1β were attenuated by IL-1Ra pre-injection. Conclusion Increased inflammation induced by IL-1β injection aggravates ischemia induced VA through regulating the neuronal remodeling of the LSG. Inflammation induced neuroplasticity may be a novel mechanism and therapeutic target for VA.

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.

The pathophysiology of takotsubo syndrome (TTS) is still elusive; many hypotheses of its cause have been proposed with a heightened activity of the peripheral autonomic sympathetic nervous system (PASNS) via local norepinephrine release, and direct cardiomyocyte toxicity mediated by blood-borne catecholamines, being among the most currently entertained. Monitoring of PASNS during hospitalization will provide a metric which could be of immense value in unraveling of the pathophysiology and aiding in the management of the patients with TTS by predicting in-hospital complications, long-term outcome, and its recurrence. Recent work with noninvasive monitoring of skin sympathetic nerve activity (SKNA), via conventional electrodes used for the recording of the electrocardiogram have shown that the filtered signals >500 Hz originate in the cervical and stellate ganglia, which also innervate the heart, and thus they provide an estimate of stellate ganglion nerve activity. Such information may prove invaluable for the management of patients with TTS.

Objectives The study sought to characterize the efficacy of stellate ganglion block (SGB) as a treatment for electrical storm (ES). Background The efficacy of percutaneous SGB for managing ES is not well understood. Methods The authors conducted published data 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, ventricular fibrillation, electrical storm. Inclusion criteria were presentation with guideline-defined ES and treatment with SGB. Exclusion criteria were 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 (52.0 ± 19.1 years of age, 11 women, 17 with ischemic cardiomyopathy). Antiarrhythmics 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% to 0.50%). SGB resulted in a significant decrease in VA burden (12.40 ± 8.80 episodes/day vs. 1.04 ± 2.12 episodes/day; p Conclusions 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.

The literature is littered with variable and scant reports of the vertebral nerve. The present paper reviews the literature regarding this nervous structure of the neck and attempts to clarify a number of issues surrounding its form, function, and implications of surgical manipulation. The nerve may arise from the stellate ganglion or the ansa subclavia, amongst a number of other structures. Additionally, the terminal insertion of the vertebral nerve varies in the reported literature, with authors observing various terminations. Animal models of the vertebral nerve have limited value, as variations between species and with species have been observed. This review also indicates that contradictory evidence exists regarding the clinical implications of vertebral nerve damage. Although irritation may result in ocular disturbance, hearing loss, headaches, and dizziness, a high degree of incongruity exists around whether or not any clinical findings will actually be observed. Based on our review of the available literature and recent cadaveric research, it appears it may be more logical to classify the vertebral nerve as a variable ramus communicans that connects the stellate or inferior cervical ganglia to the lower cervical spinal nerves and not a structure that ascends entirely with the vertebral artery to enter the cranium.

Background Renal sympathetic denervation (RD) is a promising method of neuromodulation for the management of cardiac arrhythmia. Objective We tested the hypothesis that RD is antiarrhythmic in ambulatory dogs because it reduces the stellate ganglion nerve activity (SGNA) by remodeling the stellate ganglion (SG) and brain stem. Methods We implanted a radiotransmitter to record SGNA and electrocardiogram in 9 ambulatory dogs for 2 weeks, followed by a second surgery for RD and 2 months SGNA recording. Cell death was probed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Results Integrated SGNA at baseline and 1 and 2 months after RD were 14.0 ± 4.0, 9.3 ± 2.8, and 9.6 ± 2.0 μV, respectively ( P = .042). The SG from RD but not normal control dogs (n = 5) showed confluent damage. An average of 41% ± 10% and 40% ± 16% of ganglion cells in the left and right SG, respectively, were TUNEL positive in RD dogs compared with 0% in controls dogs ( P = .005 for both). The left and right SG from RD dogs had more tyrosine hydroxylase–negative ganglion cells than did the left SG of control dogs ( P = .028 and P = .047, respectively). Extensive TUNEL-positive neurons and glial cells were also noted in the medulla, associated with strongly positive glial fibrillary acidic protein staining. The distribution was heterogeneous, with more cell death in the medial than lateral aspects of the medulla. Conclusion Bilateral RD caused significant central and peripheral sympathetic nerve remodeling and reduced SGNA in ambulatory dogs. These findings may in part explain the antiarrhythmic effects of RD.

A 75-year-old man presented with dizziness and fatigue secondary to ventricular and supraventricular arrhythmias. He underwent an elective ablation but continued to suffer from ventricular tachycardia with cardiovascular instability despite antiarrhythmic therapy with multiple agents. The patient continued to develop episodes of ventricular tachycardia and an episode of ventricular fibrillation. Electrical storm encompasses a situation of cardiac instability which may present as several episodes of ventricular tachycardia or ventricular fibrillation in a short period. We performed an ultrasound-guided left stellate ganglion block at the bedside which resulted in abolition of electrical storm. The patient demonstrated sinus rhythm with episodes of sinus tachycardia. Left stellate ganglion block has proven to be a successful mode of treatment for those patients with ventricular tachyarrhythmia resistant to medical management or those who fail atrioventricular node ablation. Ultrasound-guided left stellate ganglion block is a valuable and effective means to providing sympathectomy in the management of electrical storm or ventricular tachyarrhythmias.

Study objective Elderly patients undergoing elective laparoscopic cholecystectomy (LC) were given right stellate ganglion block (RSGB) to observe its effects on the hemodynamics and stress response during carbon dioxide (CO 2 )-pneumoperitoneum. Design A randomized, single-blinded, and placebo-controlled study. Setting University-affiliated teaching hospital. Participants Sixty patients (aged 65–78years; weight, 45–75kg; American Society of Anesthesiologists (ASA) physical status classification, class I or II) undergoing elective LC. Interventions Right stellate ganglion block was performed via C7 access using 10mL of 1% lidocaine in all patients. Measurements The patients' heart rate (HR) and mean arterial pressure (MAP) were recorded before the block (T 0 ), 5min following pneumoperitoneum (T 1 ), 30min following pneumoperitoneum (T 2 ), 5min following the deflation of pneumoperitoneum (T 3 ), and upon completion of the surgery (T 4 ). Additionally, the concentrations of epinephrine (E), norepinephrine (NE) and cortisol (COR) were detected in arterial blood at each time point by enzyme-linked immunosorbent assay. Main results For control group, the MAP and RPP (RPP=SBP×HR) were significantly elevated at T 1~3 ( P 0 . Inter-group comparison showed that the MAP, HR and RPP were significantly lower at T 1~4 in RSGB group ( P 0 , the E, NE and COR levels significantly rose at T 1~4 in control group ( P 2, 3 in RSGB group ( P 1~4 were significantly lower in RSGB group as compared to control group ( P Conclusion Right stellate ganglion block can reduce blood catecholamines during CO 2 -pneumoperitoneum to maintain perioperative hemodynamic stability and prevent adverse cardiovascular events in elderly patients.

BackgroundSympathetic nerve activity is important to cardiac arrhythmogenesis.ObjectiveThe purpose of this study was to develop a method for simultaneous noninvasive recording of skin sympathetic nerve activity (SKNA) and electrocardiogram (ECG) using conventional ECG electrodes. This method (neuECG) can be used to adequately estimate sympathetic tone.MethodsWe recorded neuECG signals from the skin of 56 human subjects. The signals were low-pass filtered to show the ECG and high-pass filtered to show nerve activity. Protocol 1 included 12 healthy volunteers who underwent cold water pressor test and Valsalva maneuver. Protocol 2 included 19 inpatients with epilepsy but without known heart diseases monitored for 24 hours. Protocol 3 included 22 patients admitted with electrical storm and monitored for 39.0 ± 28.2 hours. Protocol 4 included 3 patients who underwent bilateral stellate ganglion blockade with lidocaine injection.ResultsIn patients without heart diseases, spontaneous nerve discharges were frequently observed at baseline and were associated with heart rate acceleration. SKNA recorded from chest leads (V1-V6) during cold water pressor test and Valsalva maneuver (protocol 1) was invariably higher than during baseline and recovery periods (P < .001). In protocol 2, the average SKNA correlated with heart rate acceleration (r = 0.73 ± 0.14, P < .05) and shortening of QT interval (P < .001). Among 146 spontaneous ventricular tachycardia episodes recorded in 9 patients of protocol 3, 106 episodes (73%) were preceded by SKNA within 30 seconds of onset. Protocol 4 showed that bilateral stellate ganglia blockade by lidocaine inhibited SKNA.ConclusionSKNA is detectable using conventional ECG electrodes in humans and may be useful in estimating sympathetic tone.

Introduction The Chronic Chagasic Cardiomyopathy is one important cause of arrhythmias in Brazil. The usual anti-arrhythmic treatment involves the use of medication, placement of implantable cardioverter defibrillator (ICD) and catheter ablation therapy. Some patients with ICD develop electrical storms (ES), 3 or more episodes of ventricular arrhythmia followed by electrical therapy in 24h. Under these circumstances is believed that the sympathetic tone is heightened. There has been a growing evidence showing that the modulation of neural activity with the Stellate Ganglion Blockade (SGB) can be an adjuvant treatment for patients with ES. Methods Case Report: A 50-year-old male patient with medical history of arrhythmogenic chagasic cardiomyopathy with previous ICD presented several episodes of chest pain, dizziness and Sustained Ventricular Tachycardia frequently leading him to the emergency room (ER). After cardioversion from the ICD and drug optimization he presented better control of the arrhythmia. A month later, a new episode of chest pain, dyspnea, abdominal pain, Sustained Ventricular Tachycardia with a heart rate of 130bpm - below the ICD trigger – brought him to the ER again. In addition to the pharmacological therapy, the stellate ganglion blockade was chosen (SGB). It was performed in sterile conditions and ultrasound-guided. From cricoid cartilage, the probe was moved caudad and laterally to visualize C7’s transverse process. We used a Quincke 22G needle to perform the SG . The tip of the needle was placed on the anterior fascia of the longus coli muscle. Through ultrasound imaging the dispersion of the 10ml of anesthetic solution with lidocaine 1% and bupivacaine 0,25% was seen throughout the stellate ganglion pathway. Results Procedure was performed without any complications.On the 24-hour follow up the patient presented a slow ventricular tachycardia, treated with ATP and sent to cardiac ablation, with satisfactory outcome. Discussion Conclusion: The SGB can be a bedside and efficient option as a treatment for ES, it improves cardiac autonomic modulation decreasing the occurrence of ES and can be used as a bridge for cardiac ablation.

We describe the novel use of bilateral cardiac sympathectomy in a woman with end-stage heart failure caused by ventricular tachycardia refractory to standard medical therapy who was under consideration for heart transplantation. Postoperatively, our patient has not experienced any symptoms of ventricular tachycardia, has returned to normal physical activity, and is no longer under consideration for transplantation as a result of the improvement in her cardiac function. Bilateral sympathectomy can be more effective than unilateral sympathectomy or percutaneous stellate ganglion blockade in patients with refractory ventricular tachycardia. Careful patient selection is necessary to identify patients who will benefit most from the procedure.

Neuraxial modulation therapies, such as stellate ganglion block, thoracic epidural anaesthesia, and cardiac sympathetic denervation, are effective for ventricular arrhythmias. However, these treatments can increase the risk of bleeding and infection. In this case report, stellate ganglion phototherapy was safely and effectively performed for refractory ventricular tachycardias in a patient with a history of left ventricular assist device implantation. Stellate ganglion phototherapy may have the potential to treat refractory ventricular arrhythmias as an additive therapy or bridge therapy.

Low-level carotid baroreflex stimulation (LL-CBS) appears to have a potential antiarrhythmogenic effect.The purpose of this study was to investigate effects of short-term LL-CBS on an atrial fibrillation (AF) canine model.Group 1 (LL-CBS in the 6 hour-rapid atrial pacing model): Anesthetized dogs underwent 6 hours of rapid atrial pacing (RAP) with concomitant LL-CBS in last 3 hours (LL-CBS group; n = 7) or without (control group; n = 6). Effective refractory period (ERP), ERP dispersion, and window of vulnerability to AF were determined. Left stellate ganglion (LSG) neural activity and heart rate variability were analyzed. Group 2 (LL-CBS on electrically or mechanically induced AF with acetylcholine): In subgroup 1, sustained AF was induced by injecting acetylcholine (Ach; 10 mM) into the anterior right ganglionated plexus at baseline and after 3-hour LL-CBS (n = 7) or sham operation (n = 6). In subgroup 2, Ach was applied onto the right atrial appendage. The time of duration of AF and the average AF cycle length were determined in both subgroups.Group 1: LL-CBS reversed the RAP-induced ERP shortening and increase in ERP dispersion and window of vulnerability (P.05). The activation of LSG, decrease in high frequency, and increase in low frequency and low frequency/high frequency ratio induced by RAP were also reversed by LL-CBS (P.05). After 6-hour RAP, plasma norepinephrine and angiotensin II concentrations were significantly lower in the LL-CBS group than in the control group (P.05). Group 2: The AF duration was shortened and the average AF cycle length was prolonged markedly in both subgroups (P.01) by LL-CBS.LL-CBS can reverse RAP-induced atrial electrical remodeling and suppress electrically or mechanically induced AF with Ach, and the anti-AF effect is attributed to attenuation of autonomic nerve remodeling, including inhibition of the LSG activity.

In a pilot randomized clinical trial of active stellate ganglion blockade (SGB) versus sham control, SGB significantly reduced the frequency of reported moderate to severe vasomotor symptoms (VMS) and the frequency of physiologic VMS measured using ambulatory skin conductance monitors. Here we examine secondary effects of SGB on verbal learning and memory.In a randomized, sham-controlled study, 36 women met eligibility criteria for cognitive assessments, of whom 17 were randomized to receive fluoroscopy-guided SGB and 19 to sham control.At baseline and three months post-treatment, women completed tests of verbal learning and memory (primary outcome) and other cognitive measures and also wore an ambulatory monitor for 24h to measure physiologic VMS and VMS reported in real time.Verbal learning improved following active SGB (p0.05) but not sham treatment; however, the interaction between group and time was not significant (p values 0.13-0.20). Two secondary cognitive measures improved only in the sham group. Improvements in physiologic VMS correlated significantly with improvements in verbal learning (r=0.51, p0.05).SGB might confer benefits to memory in relation to the magnitude of improvement in physiologic VMS. Broadly these findings suggest a possible link between physiologic VMS and memory problems in midlife women.

Background CO 2 -pneumoperitoneum can cause sympathetic nerve activity increased and is likely to causes severe stress-related homeostatic disorders. Objective Patients undergoing elective laparoscopic cholecystectomy were administered type-B ultrasound-guided stellate ganglion block (SGB) to observe the effects on autonomic nervous system during CO 2 - pneumoperitoneum. Design A randomized, double-blinded, and placebo-controlled study. Setting University-affiliated teaching hospital. Patients Eighty patients (aged 32-75 years; weight, 45-80 kg; American Society of Anesthesiologists (ASA) physical status classification, class I or II) undergoing elective laparoscopic cholecystectomy. Interventions The RSGB group was administered lidocaine 1% 7 ml under ultrasound guidance. Main outcome measures The low frequency (LF), high frequency (HF), total power (TP) and LF/HF ratio were recorded before the block (T 0 ), 5 min (T 1 ) and 30 min (T 2 ) following pneumoperitoneum, 5 min after deflation of pneumoperitoneum (T 3 ) and after surgery (T 4 ). The low-frequency normalized unit (LFnu) and high-frequency normalized units (HFnu) were calculated. Results Compared with T 0 , LF, LFnu and LF/HF ratio were significantly elevated at T 1 - 4 (all P 2 - 4 in control group ( P P P 1 - 4 in RSGB group. Compared with control group, the LF, LFnu and LF/HF ratio were significantly decreased ( P P 1 - 4 in RSGB group. Conclusion Ultrasound-guided RSGB inhibited CO 2 -pneumoperitoneum-induced sympathetic neural excitation, upregulated vagal nerve stimulation and maintained stable autonomic nervous function.

Background Autonomous innervations of the lungs are maintained by cervical sympathetic and vagal nerves. Sympathetic overactivity-induced neurogenic pulmonary edema (NPE) is known as a serious complication of subarachnoid hemorrhage, but the rational neuronal mechanism of that overactivity has not yet been clarified fully. The aim of this study was to examine whether there is a relationship between vagal nerve ischemia related sympathetic overactivity and neurogenic pulmonary edema in subarachnoid hemorrhage. Methods This study was conducted on 27 rabbits. A control group was formed of 5 animals, a sham group of 7 to which saline was administered, and a study group of 15 animals that were injected with homologous arterial blood into the cisterna magna. Electrocardiography and respiratory rhythm parameters were monitored for 3 weeks and the animals were then decapitated. Statistical analysis was made of the numbers of degenerated axons in the pulmonary branches of the vagal nerves, the neuron density of stellate ganglions and the vasospasm index of the pulmonary arteries. Results In the control group, the normal respiration rate was 34 ± 6 bpm, total axon number was 1600 ± 270/mm 2 , degenerated axon number was 10 ± 3/mm 2 , and vasospasm index was 1.34 ± 0.25. The sham group values were 30 ± 3 bpm, 163 ± 47/mm 2 , and 1.95 ± 0.45 and the study group values were 45 ± 8 bpm, 530 ± 92/mm 2 , and 2.76 ± 0.83. The mean stellate ganglion neuron density was evaluated as 8.112 ± 1.230/mm 3 in all animals, as 7.420 ± 4.10/mm 3 in animals with slight NPE, and as 12.512 ± 1.236/mm 3 in animals that developed severe NPE. Conclusion High neuron density of stellate ganglion may have important roots in sympathetic overactivity-related NPE development in subarachnoid hemorrhage.

The nociceptin/orphanin FQ peptide (NOP) opioid receptors regulate neurotransmitter release via inhibition of voltage-gated Ca(2+) channels (CaV2.2) in sympathetic and sensory neurons. Stimulation of NOP receptors by its endogenous agonist, nociception (Noc), leads to membrane-delimited, voltage-dependent (VD) block of CaV2.2 channel currents mediated by Gβγ protein subunits. Previously we reported that the pertussis toxin-sensitive Gαi1 and Gβ2/β4 isoforms mediate the functional coupling of NOP opioid receptors with CaV channels in rat stellate ganglion (SG) sympathetic neurons. In the present report we extended our studies by identifying the Gγ subunit that forms the heterotrimer within this signaling pathway. Small interference RNA (or siRNA) was employed to silence the expression of the natively expressed Gγ subunits. Initial PCR assays indicated that SG neurons expressed seven Gγ subunits. Silencing Gγ3 subunits did not alter signaling between NOP receptors and Ca(2+) channels. However, after Gγ7 isoforms were silenced, the Noc-mediated inhibition of CaV channels was significantly decreased when compared to SG neurons transfected with scrambled siRNA. We observed that Gγ10 and Gγ11 mRNA levels increased 2.5- and 2.7-fold, respectively, after Gγ7 subunits were silenced. However, this compensatory increase in mRNA expression did not appear to fully rescue the NOP receptor coupling efficiency. Additionally, both Gγ2 and Gγ5 levels increased 50 and 75%, respectively, while Gγ3 and Gγ4 expression levels remained relatively unchanged. Taken together, our findings suggest that the Gαi1/Gβ2(β4)/Gγ7 heterotrimeric G protein complex determines the NOP receptor-mediated modulation of CaV channels in SG neurons.

Background Hyperhidrosis is secondary to over activation of the sympathetic nervous system and surgical sympathectomy is the treatment of choice when other modalities have failed. This study investigated anatomic variation in the upper thoracic sympathetic chain and associated rami communicantes among cadaveric specimens. It considers the implications of these findings on surgical techniques to treat hyperhidrosis. Methods The upper 4 thoracic sympathetic ganglia, intercostal nerves, and connecting rami were dissected, measured and mapped in 40 sides of 20 adult human cadavers. Ganglia location was recorded. The incidence, orientation, and distance travelled by rami communicantes was compared across different ganglionic levels and between sides. Results The percentage of ganglia located below their associated intercostal space was 6.25% with stellate ganglions present in 70% of specimens and Kuntz fibers noted in 40%. There was a stepwise reduction in incidence of rami from superior to inferior placed ganglia. The number of rami identified across all levels was significantly greater on the right (P = 0.03). The horizontal distance between the sympathetic chain and union of the rami on the intercostal nerves was significantly greater on the right across all levels (P = 0.04). Conclusions There was substantial variation in the rami communicantes across the upper 4 ganglia and between right and left sides. Consideration of this variation should be given when planning surgical sympathectomy for hyperhidrosis particularly to avoid symptom recurrence.

There is increasing interest in interventional therapies targeting the cardiac sympathetic nervous system to suppress ventricular arrhythmias. In this case report, we describe an 80-year-old patient with ischemic cardiomyopathy and multiple implantable cardioverter-defibrillator shocks due to refractory ventricular tachycardia and ventricular fibrillation who was unable to continue biweekly stellate ganglion block procedures using bupivacaine 0.25% for suppression of his arrhythmias. He had previously failed antiarrhythmic drug therapy with amiodarone, catheter ablation, and attempted surgical autonomic denervation. He underwent pulsed radiofrequency treatment (3 lesions, 2 minutes each, temperature 42°C, 2-Hz frequency, 20-millisecond pulse width) of the left stellate ganglion resulting in persistent arrhythmia suppression for more than 12 months duration. This represents the first report of a pulsed radiofrequency stellate ganglion lesion providing long-term suppression of ventricular arrhythmias. Further study of this technique in patients with refractory ventricular tachycardia or ventricular fibrillation is warranted.

Harlequin syndrome (HS) is a rare autonomic disorder due to a hemifacial cutaneous sympathetic denervation. It is characterized by unilateral diminished sweating and flushing of the face even though after heat or prolonged exercise. It is typically acquired. Congenital cases only represent a 6% of all individuals with HS. All congenital HS cases reported so far showed a concomitant Horner syndrome, probably due to a stellate ganglion involvement. HS represents an uncommon autonomic disorder due to a hemifacial cutaneous sympathetic denervation. It is clinically characterized by a dramatic alteration in facial appearance: ipsilateral denervated pale and dry half from the other intact red and moist half. Conclusion : We present, to the best of our knowledge, the first case of a patient with a congenital HS as an isolated phenomenon.