Optogenetic Modulation of Cardiac Sympathetic Nerve Activity to Prevent Ventricular Arrhythmias

Yu, Lilei; Zhou, Liping; Cui, Gang; Po, Sunny S.; Huang, Bing; Zhou, Xin; Wang, Menglong; Yuan, Shaopeng; Wang, Zhuo; Wang, Songyun; Jiang, Hong

doi:10.1016/j.jacc.2017.09.1107

Cited by 88 publications

(80 citation statements)

References 37 publications

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“…A canine study found reduced incidence of ischemic‐induced VAs when low‐frequency EMF was applied to the LSG area at 1 Hz, with 8 s “on”, 10 s “off” and intensity at about 90% of motor threshold . A similar result was observed using optogenetic techniques, which combines optical stimulation and genetic modification of target cells, to suppress genetically modified LSG neuronal activity in canines . In the clinic setting, bilateral CSD has been successful in prevention of HF‐associated VT or VF storm and may have more prolonged and durable effect on VA suppression when compared to a left sided only procedure alone .…”

Section: Effects Of Neuromodulation On Ventricular Arrhythmiasmentioning

confidence: 75%

“…89 A similar result was observed using optogenetic techniques, which combines optical stimulation and genetic modification of target cells, to suppress genetically modified LSG neuronal activity in canines. 90 In the clinic setting, bilateral CSD has been successful in prevention of HF-associated VT or VF storm and may have more prolonged and durable effect on VA suppression when compared to a left sided only procedure alone. 91 In a study of 121 patients from five international sites with structural heart disease and recurrent VT, CSD decreased sustained VT and ICD shock recurrence and approximately one-third of patients no longer took antiarrhythmic medications on follow up.…”

Section: Blockade Of Sympathetic Neurotransmissionmentioning

confidence: 99%

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The autonomic nervous system and ventricular arrhythmias in myocardial infarction and heart failure

Wu¹,

Vaseghi²

2020

Pacing Clinical Electrophis

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Ventricular arrhythmias (VA) can range in presentation from asymptomatic to cardiac arrest and sudden cardiac death (SCD). Sustained ventricular tachycardias/ventricular fibrillation (VT/VF) are a common cause of SCD in the setting of myocardial infarction (MI) and heart failure. A particularly arrhythmogenic cardiac syncytia in these conditions can be attributed to both sympathetic activation and parasympathetic dysfunction, while appropriate neuromodulation has the potential to reduce occurrence of VT/VF. In this review, we outline the components of the autonomic nervous system that play an important role in normal cardiac electrophysiology and function. In addition, we discuss changes that occur in the setting of cardiac disease including adverse neural remodeling and neurohormonal activation which significantly contribute to propensity for VT/VF. Finally, we review neuromodulation strategies to mitigate VT/VF which predominantly rely on increasing parasympathetic drive and blockade of sympathetic neurotransmission.

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Section: Effects Of Neuromodulation On Ventricular Arrhythmiasmentioning

confidence: 75%

Section: Blockade Of Sympathetic Neurotransmissionmentioning

confidence: 99%

The autonomic nervous system and ventricular arrhythmias in myocardial infarction and heart failure

Wu¹,

Vaseghi²

2020

Pacing Clinical Electrophis

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“…LSG function was defined as the maximal change in systolic blood pressure (SBP) in response to direct electrical stimulation of the LSG . Briefly, high‐frequency stimulation (HFS) released by a stimulator was applied to the LSG.…”

Section: Resultsmentioning

confidence: 99%

“…The neural activity of the LSG was recorded for 1 min at three time points (baseline, after the LSG intervention and after acute myocardial infarction) and analyzed as described in our previous studies . Figure f shows representative recordings of LSG neural activity at different time points in the two groups.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, we hypothesized that neuromodulation might become an optimized strategy for treating autonomic activity‐related diseases rather than complete ablation. Our previous study has found that optogenetics, combining gene modified LSG neurons with light stimuli, could reversely inhibit the LSG activity and protect against ischemia‐induced VAs in dogs with myocardial ischemia (MI) . Although optogenetics enables precise control of neural activity, adeno‐associated viral (AAV) transfection might induce potential toxic effects or immune response and light‐mediated neuromodulation for deep tissue has yet to be achieved .…”

Section: Introductionmentioning

confidence: 99%

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Precise Modulation of Gold Nanorods for Protecting against Malignant Ventricular Arrhythmias via Near‐Infrared Neuromodulation

Lai

Wang

et al. 2019

Adv Funct Materials

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Hyperactivity of the left stellate ganglion (LSG) contributes to the occurrence of ventricular arrhythmias (VAs). Recently, advances in neuromodulation have been achieved with near-infrared (NIR)-sensitive gold nanorods (AuNRs). Here, AuNRs are precisely regulated and applied to inhibit LSG function as well as neural activity, thus ameliorating myocardial ischemia-induced VAs in a canine model. Specifically, the optimized AuNRs are synthesized and microinjected into the LSG of anesthetized dogs, and then followed by 5 min of NIR laser irradiation at a wavelength of 808 nm. The results demonstrate that 5 min NIR laser irradiation on the PEG-AuNR-treated LSG can reversely inhibit LSG function and neural activity, thereby ameliorating myocardial ischemia-induced VAs. With the tissue-penetrating NIR and excellent photothermal effect of AuNRs, this method may become a promising and noninvasive therapeutic strategy for suppressing hyperactivity of the cardiac sympathetic nerves, therefore benefiting patients with VAs in the future.

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AIEgen‐Based Covalent Organic Frameworks for Preventing Malignant Ventricular Arrhythmias Via Local Hyperthermia Therapy

Zhang

Guo

et al. 2023

Advanced Materials

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We report the engineering of aggregation‐induced emission luminogens (AIEgen) based covalent organic frameworks (COFs), TDTA‐COF, BTDTA‐COF, and BTDBETA‐COF, as hyperthermia agents for inhibiting the occurrence of malignant ventricular arrhythmias (VAs). These AIE COFs exhibit dual functionality, as they not only directly modulate the function and neural activity of stellate ganglion (SG) through local hyperthermia therapy (LHT) but also induce the browning of white fat and improve the neuro‐inflammation peri‐SG microenvironment, which is favorable for inhibiting ischemia‐induced VAs. In vivo studies have confirmed that BTDBETA‐COF‐mediated LHT enhances thermogenesis and browning‐related gene expression, thereby serving a synergistic role in combating VAs. Transcriptome analysis of peri‐SG adipose tissue reveals a substantial downregulation of inflammatory cytokines, highlighting the potency of BTDBETA‐COF‐mediated LHT in ameliorating the neuro‐inflammation peri‐SG microenvironment and offering myocardial and arrhythmia protection. Our work on AIE COF‐based hyperthermia agent for VAs inhibition providing a new avenue for mitigating cardiac sympathetic nerve hyperactivity.AIEgen; covalent organic frameworks; hyperthermia agent; malignant ventricular arrhythmias; neuromodulationThis article is protected by copyright. All rights reserved

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Optogenetic Modulation of Cardiac Sympathetic Nerve Activity to Prevent Ventricular Arrhythmias

Cited by 88 publications

References 37 publications

The autonomic nervous system and ventricular arrhythmias in myocardial infarction and heart failure

The autonomic nervous system and ventricular arrhythmias in myocardial infarction and heart failure

Precise Modulation of Gold Nanorods for Protecting against Malignant Ventricular Arrhythmias via Near‐Infrared Neuromodulation

AIEgen‐Based Covalent Organic Frameworks for Preventing Malignant Ventricular Arrhythmias Via Local Hyperthermia Therapy

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