Left Stellate Ganglion Neural Activity Research Articles

Low-intensity focused ultrasound modulation of the paraventricular nucleus to prevent myocardial infarction–induced ventricular arrhythmia

BackgroundOur previous study showed that light-emitting diode modulation of the hypothalamic paraventricular nucleus (PVN), which is the control center of the sympathetic nervous system, might attenuate neuroinflammation in the PVN and prevent ventricular arrhythmias (VAs) after myocardial infarction (MI). Low-intensity focused ultrasound (LIFU) has deeper penetration than does light-emitting diode, while its effect on the PVN has not been reported. ObjectiveThis study aimed to explore the effect of LIFU modulation of the PVN on the inducibility of post-MI VAs. MethodsFifty-four Sprague-Dawley rats were randomly divided into acute control (n = 12, 22.22%), acute MI (AMI, n = 12, 22.22%), AMI + LIFU (n = 12, 22.22%), chronic control (n = 6, 11.11%), chronic MI (CMI, n = 6, 11.11%), and CMI + LIFU (n = 6, 11.11%) groups. MI was induced by left anterior artery ligation, and electrocardiographic recording for 0.5 hours after MI and programmed electrophysiological stimulation were used to test the vulnerability of VAs. Peripheral sympathetic neural activity was assessed by measuring left stellate ganglion neural activity. Finally, hearts and brains were extracted for Western blotting and histopathological analysis, respectively. ResultsCompared with the AMI group, AMI-induced VAs (P < .05) and left stellate ganglion neural activity (P < .05) were significantly attenuated in the AMI + LIFU group. In addition, LIFU resulted in a significant reduction of microglial activation in the PVN and expression of inflammatory cytokines in the peri-ischemic myocardium. In the CMI + LIFU group, there was no obvious tissue damage in the brain. ConclusionLIFU modulation of the PVN may prevent the incidence of post-MI VAs by attenuating MI-induced sympathetic neural activation and inflammatory response.

Selective chemical ablation of transient receptor potential vanilloid 1 expressing neurons in the left stellate ganglion protects against ischemia-induced ventricular arrhythmias in dogs

ObjectivesFindings from prior investigations show that left stellate ganglion (LSG) inhibitory approaches protect the heart from ventricular arrhythmias (VAs) caused by acute myocardial infarction (AMI), which still remain many side effects. Targeted transient receptor potential vanilloid 1/tyrosine hydroxylase (TRPV-1/TH) expressing sympathetic neurons ablation is a novel neuro-ablative strategy. The aim of this investigation was to explore if targeted molecular neuro-ablative strategy by resiniferatoxin (RTX) stellate microinjection could protect against ischemia-induced VAs. MethodsTwenty-four anesthetized beagles were assigned to a control group (n = 12) and RTX group (n = 12) in a random manner. Targeted molecular neuro-ablative was produced by RTX stellate microinjection and DMSO was microinjected into LSG in the same way as control. Plasma norepinephrine (NE) level, heart rate variability (HRV), Tpeak-Tend interval (Tp-Te), LSG neural activity and function, ventricular effective refractory period (ERP), beat-to-beat variability of repolarization (BVR) and ventricular action potential duration (APD) were measured at baseline and 60 min after RTX or DMSO microinjection. AMI model was established by the ligation of left anterior descending coronary artery and 60-minute electrocardiography was continuously recorded for VAs analysis. Subsequently, HRV, Tp-Te, plasma NE level from jugular vein and coronary sinus, LSG neural activity and function, ventricular ERP, ventricular APD, BVR, action potential duration alternans (APDA) cycle length and ventricular fibrillation threshold (VFT) were evaluated after AMI. Finally, tissue collection of LSG was performed for examining the TRPV-1, nerve growth factor (NGF) protein and c-fos protein. ResultsTRPV-1 was highly expressed in the TH-expressing neurons and RTX injection significantly ablated TRPV-1/TH-positive neurons in LSG. Compared with baseline, RTX stellate microinjection significantly reduced plasma NE level, the sympathetic component of HRV, LSG neural activity and LSG function, shortened Tp-Te, prolonged ventricular ERP and APD, but there were no remarkable differences existed for control group. AMI resulted in the significant raise in plasma NE level from jugular vein and coronary sinus, the sympathetic component of HRV, LSG neural activity and LSG function, the marked prolongation in Tp-Te and BVR, the significant decrease in ERP and APD from ischemia area, and the increase in APDA cycle length in the ischemic region of the control group, which were remarkably attenuated in the RTX group. RTX pretreatment markedly rose the VFT in the RTX group. Furthermore, the AMI-triggered VAs was significantly prevented by RTX injection in the RTX group. RTX microinjection down-regulated significantly TRPV-1, NGF and c-fos expression in the LSG compared with the control group. ConclusionTargeted ablation of TRPV-1/TH positive sympathetic neurons induced by RTX stellate microinjection could suppress ischemia-induced cardiac autonomic imbalances and cardiac electrophysiology instability to protect against AMI-induced VAs.

Light-emitting diode therapy protects against ventricular arrhythmias by neuro-immune modulation in myocardial ischemia and reperfusion rat model

BackgroundSympathetic overactivation and inflammation are two major mediators to post-myocardial ischemia-reperfusion (I/R)-induced ventricular arrhythmia (VA). The vicious cycle between microglia and sympathetic activation plays an important role in sympathetic hyperactivity related to cardiovascular diseases. Recently, studies have shown that microglial activation might be attenuated by light-emitting diode (LED) therapy. Therefore, we hypothesized that LED therapy might protect against myocardial I/R-induced VAs by attenuating microglial and sympathetic activation.MethodsThirty-six male anesthetized rats were randomized into four groups: control group (n = 6), LED group (n = 6), I/R group (n = 12), and LED+I/R group (n = 12). I/R was generated by left anterior descending artery occlusion for 30 min followed by 3 h reperfusion. ECG and left stellate ganglion (LSG) neural activity were recorded continuously. After 3 h reperfusion, a programmed stimulation protocol was conducted to test the inducibility of VA. Furthermore, we extracted the brain tissue to examine the microglial activation, and the peri-ischemic myocardium to examine the expression of NGF and inflammatory cytokines (IL-1β, IL-18, IL-6, and TNF-α).ResultsAs compared to the I/R group, LED illumination significantly inhibited the LSG neural activity (P < 0.01) and reduced the inducibility of VAs (arrhythmia score 4.417 ± 0.358 vs. 3 ± 0.3257, P < 0.01) in the LED+I/R group. Furthermore, LED significantly attenuated microglial activation and downregulated the expression of inflammatory cytokines and NGF in the peri-infarct myocardium.ConclusionsLED therapy may protect against myocardial I/R-induced VAs by central and peripheral neuro-immune regulation.

Noninvasive light emitting diode therapy: A novel approach for postinfarction ventricular arrhythmias and neuroimmune modulation.

Sympathetic neural activation plays a key role in the incidence and maintenance of acute myocardial infarction (AMI) induced ventricular arrhythmia (VA). Furthermore, previous studies showed that AMI might induce microglia and sympathetic activation and that microglial activation might contribute to sympathetic activation. Recently, studies showed that light emitting diode (LED) therapy might attenuate microglial activation. Therefore, we hypothesized that LED therapy might reduce AMI-induced VA by attenuating microglia and sympathetic activation. Thirty anesthetized rats were randomly divided into three groups: the Control group (n = 6), AMI group (n = 12), and AMI + LED group (n = 12). Electrocardiogram (ECG) and left stellate ganglion (LSG) neural activity were continuously recorded. The incidence of VAs was recorded during the first hour after AMI. Furthermore, we sampled the brain and myocardium tissue of the different groups to examine the microglial activation and expression of nerve growth factor (NGF), interleukin-18 (IL-18), and IL-1β, respectively. Compared to the AMI group, LED therapy significantly reduced the incidence of AMI-induced VAs (ventricular premature beats [VPB] number: 85.08 ± 13.91 vs 27.5 ± 9.168, P < .01; nonsustained ventricular tachycardia (nSVT) duration: 34.39 ± 8.562 vs 9.005 ± 3.442, P < .05; nSVT number: 18.92 ± 4.52 vs 7.583 ± 3.019, P < .05; incidence rate of SVT/VF: 58.33% vs. 8.33%, P < .05) and reduced the LSG neural activity (P < .01) in the AMI + LED group. Furthermore, LED significantly attenuated microglial activation and reduced IL-18, IL-1β, and NGF expression in the peri-infarct myocardium. LED therapy may protect against AMI-induced VAs by suppressing sympathetic neural activity and the inflammatory response.

Cardiac Sympathetic Afferent Denervation Protects Against Ventricular Arrhythmias by Modulating Cardiac Sympathetic Nerve Activity During Acute Myocardial Infarction.

BackgroundAugmented cardiac sympathetic afferent reflex (CSAR) plays a role in enhanced sympathetic activity. Given that a strategy for abolishing augmented CSAR-induced sympathetic activation may be beneficial for protecting against ventricular arrhythmias (VAs) triggered by acute myocardial infarction (AMI), we investigated whether cardiac sympathetic afferent denervation (CSAD) could protect against VAs by modulating cardiac sympathetic nerve activity in an AMI dog model.Material/MethodsTwenty-two anesthetized dogs were assigned to the CSAD group (n=9) and the sham group (n=13) randomly. CSAD was produced by epicardial application of resiniferatoxin. Heart rate variability (HRV), ventricular action potential duration (APD), APD dispersion, beat-to-beat variability of repolarization (BVR), effective refractory period (ERP) of ventricles, ERP dispersion, plasma norepinephrine (NE) concentration, and left stellate ganglion (LSG) neural activity were determined at baseline and after CSAD. We designed an AMI model by occluding the left anterior coronary artery, and performed analysis of VAs for 60 minutes using electrocardiography. Then, levels of c-fos and nerve growth factor (NGF) were determined.ResultsRelative to baseline values, CSAD prolonged ERP and APD of ventricles, increased HRV, decreased APD dispersion, BVR, ERP dispersion and serum NE concentration, and attenuated LSG activity in the CSAD group. AMI triggered a remarkable increase in LSG activity and function but decreased the HRV of the sham group animals relative to the CSAD group. Moreover, the CSAD group had higher levels of VAs relative to the sham group. This was accompanied by a corresponding decrease in proteins quantities of NGF and c-fos in the CSAD group in the LSG after AMI compared to the sham group.ConclusionsCSAD can suppress LSG neural activity, hence enhance the electrophysiological stability and protect the heart from AMI-triggered VAs.

Electrical stimulation-based renal nerve mapping exacerbates ventricular arrhythmias during acute myocardial ischaemia.

Blood pressure elevation in response to transient renal nerve stimulation (RNS) has been used to determine the ablation target and endpoint of renal denervation. This study aimed to evaluate the safety of transient RNS in canines with normal or ischaemic hearts. In ten normal (Group 1) and six healed myocardial infarction (HMI) (Group 2) canines, a large-tip catheter was inserted into the left or right renal artery to perform transient RNS. The left stellate ganglion neural activity (LSGNA) and ventricular electrophysiological parameters were measured at baseline and during transient RNS. In another 20 acute myocardial infarction (AMI) canines, RNS (Group 3, n = 10) or sham RNS (Group 4, n = 10) was intermittently (1 min ON and 4 min OFF) performed for 1 h following AMI induction. The LSGNA and AMI-induced ventricular arrhythmias were analysed. In normal and HMI canines, although transient RNS significantly increased the LSGNA and facilitated the action potential duration (APD) alternans, it did not induce any ventricular arrhythmias and did not change the ventricular effective refractory period, APD or maximum slope of the APD restitution curve. In AMI canines, transient RNS significantly exacerbated LSG activation and promoted the incidence of ventricular arrhythmias. Transient RNS did not increase the risk of ventricular arrhythmias in normal or HMI hearts, but it significantly promoted the occurrence of ventricular arrhythmias in AMI hearts. Therefore, electrical stimulation-based renal nerve mapping may be unsafe in AMI patients and in patients with a high risk for malignant ventricular arrhythmias.

Optogenetic Modulation of Cardiac Sympathetic Nerve Activity to Prevent Ventricular Arrhythmias

BackgroundStudies 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. ObjectivesThis study aimed to investigate whether an optogenetically silenced LSG could protect against VAs induced by myocardial ischemia. MethodsAdeno-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. ResultsArchT 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. ConclusionsOptogenetic modulation could reversibly inhibit the neural activity of LSG, thereby increasing electrophysiological stability and protecting against myocardial ischemia–induced VAs.

Renal sympathetic stimulation and ablation affect ventricular arrhythmia by modulating autonomic activity in a cesium-induced long QT canine model

Our previous studies showed that renal sympathetic stimulation (RS) may facilitate ischemic ventricular arrhythmia (VA) by increasing left stellate ganglion (LSG) nerve activity, whereas renal sympathetic ablation (RA) may suppress VA. The purpose of this study was to investigate whether renal sympathetic interventions also can affect VA by modulating LSG activity in a cesium-induced long QT canine model. Twenty-four dogs were randomly divided into RS group (n = 8), RA group (n = 8), or control group (n = 8). Serum norepinephrine, LSG function, and LSG neural activity were measured before and 3 hours after RS or RA. Increasing doses of cesium chloride then were administered until a "threshold dose" produced sustained ventricular tachycardia or ventricular fibrillation. Early afterdepolarization amplitude, VA prevalence, and tachycardia threshold dose were compared among these groups. Nerve growth factor and c-fos protein expressed in the LSG also were examined. Serum norepinephrine, LSG function, and LSG neural activity were all significantly increased after 3 hours of RS and all were decreased 3 hours after RA. In addition, RS significantly decreased the tachycardia threshold dose, increased the early afterdepolarization amplitude, facilitated the incidence of VAs, and increased the expression of nerve growth factor and c-fos protein. In contrast, RA induced the opposite effects. RS promotes, whereas RA suppresses, the incidence of VAs in a canine model of cesium-induced long QT. Modulation of LSG neural activity by RS and RA may be responsible for these different effects.

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

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

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

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