Chronic Atrioventricular Nodal Vagal Stimulation

Zhang, Youhua; Yamada, Hirotoshi; Bibevski, Steve; Zhuang, Shaowei; Mowrey, Kent A.; Wallick, Don W.; Oh, Seil; Mazgalev, Todor N.

doi:10.1161/circulationaha.105.568832

Cited by 39 publications

(11 citation statements)

References 56 publications

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“…A first clinical application might be chronic selective parasympathetic stimulation of the RIGP for ventricular rate control during AF. 9,10 Neurotrophic effects in addition to the acute release of neurotransmitters by electric stimulation might increase neurostimulation efficacy and potentially decrease energy consumption and thereby device longevity.…”

Section: Discussionmentioning

confidence: 99%

“…It contains abundant parasympathetic fibers that affect AV node conduction. 6,7 After proof of concept in humans, we and others developed a technique for chronic endocardial 8,9 and epicardial 10 neurostimulation of the RIGP for ventricular rate control during atrial fibrillation (AF) in dogs. Of note, the negative dromotropic effect during endocardial HFES could be maintained throughout the entire neurostimulation period of 2 years.…”

mentioning

confidence: 99%

“…9 The same observation was made by Zhang et al when epicardial HFES of the RIGP was delivered for 5 weeks. 10 We thus hypothesized that, besides acute transmitter release, HFES might elicit neurotrophic effects on cardiac neurons, which in turn might increase baseline parasympathetic tone of the AV node. Therefore, the present study aimed to investigate the impact of HFES on neural growth and morphology of intrinsic cardiac neurons and to elucidate the underlying molecular mechanisms.…”

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confidence: 99%

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Chronic Electrical Neuronal Stimulation Increases Cardiac Parasympathetic Tone by Eliciting Neurotrophic Effects

Rana

Saygili

Gemein

et al. 2011

Circulation Research

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Rationale: Recently, we provided a technique of chronic high-frequency electric stimulation (HFES) of the right inferior ganglionated plexus for ventricular rate control during atrial fibrillation in dogs and humans. In these experiments, we observed a decrease of the intrinsic ventricular rate during the first 4 to 5 months when HFES was intermittently shut off.Objective: We thus hypothesized that HFES might elicit trophic effects on cardiac neurons, which in turn increase baseline parasympathetic tone of the atrioventricular node. Methods and Results:In mongrel dogs atrial fibrillation was induced by rapid atrial pacing. Endocardial HFES of the right inferior ganglionated plexus, which contains abundant fibers to the atrioventricular node, was performed for 2 years. Sham-operated nonstimulated dogs served as control. In chronic neurostimulated dogs, we found an increased neuronal cell size accompanied by an increase of choline acetyltransferase and unchanged tyrosine hydroxylase protein expression as compared with unstimulated dogs. Moreover, ␤-nerve growth factor (NGF) and neurotrophin (NT)-3 were upregulated in chronically neurostimulated dogs. In vitro, HFES of cultured neurons of interatrial ganglionated plexus from adult rats increased neuronal growth accompanied by upregulation of NGF, NT-3, glial-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) expression. NGF was identified as the main growth-inducing factor, whereas NT-3 did not affect HFES-induced growth. However, NT-3 could be identified as an important acetylcholine-upregulating factor. Key Words: atrial fibrillation Ⅲ tachyarrhythmias Ⅲ acetylcholine Ⅲ nervous system D uring the last 10 years, techniques have been developed to directly and selectively interfere with the intrinsic cardiac neural system via electric stimulation catheters or leads in animals and patients. [1][2][3][4][5] The baseline observation for these applications was that depolarization of intracardiac neural fibers by high-frequency electric stimulation (HFES) delivers neurotransmitters that subsequently act locally on cardiac structures (eg, stimulation of sympathetic fibers along the coronary sinus selectively increases left ventricle inotropy). 5 Furthermore, acute, short-term endocardial HFES of the right inferior ganglionated plexus (RIGP) elicits selective negative dromotropic effects in awake patients and slows atrioventricular (AV) conduction during atrial fibrillation. 3 The RIGP is located between the inferior caval vein, the left atrium and the ostium of the coronary sinus. It contains abundant parasympathetic fibers that affect AV node conduction. 6,7 After proof of concept in humans, we and others developed a technique for chronic endocardial 8,9 and epicardial 10 neurostimulation of the RIGP for ventricular rate control during atrial fibrillation (AF) in dogs. Of note, the negative dromotropic effect during endocardial HFES could be maintained throughout the entire neurostimulation period of 2 year...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Chronic Electrical Neuronal Stimulation Increases Cardiac Parasympathetic Tone by Eliciting Neurotrophic Effects

Rana

Saygili

Gemein

et al. 2011

Circulation Research

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“…20 Animals were given a 2-week recovery period after device implantation. Standard postoperative care was performed daily until the incisions were healed.…”

Section: Implantation Of Devicesmentioning

confidence: 99%

Chronic Vagus Nerve Stimulation Improves Autonomic Control and Attenuates Systemic Inflammation and Heart Failure Progression in a Canine High-Rate Pacing Model

Zhang

Popović

Bibevski

et al. 2009

Circ: Heart Failure

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323

269

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Background-Autonomic dysfunction, characterized by sympathetic activation and vagal withdrawal, contributes to the progression of heart failure (HF). Although the therapeutic benefits of sympathetic inhibition with ␤-blockers in HF are clear, the role of increased vagal tone in this setting has been less studied. We have investigated the impact of enhancing vagal tone (achieved through chronic cervical vagus nerve stimulation, [VNS]) on HF development in a canine high-rate ventricular pacing model. Methods and Results-Fifteen dogs were randomized into control (nϭ7) and VNS (nϭ8) groups. All dogs underwent 8 weeks of high-rate ventricular pacing (at 220 bpm for the first 4 weeks to develop HF and another 4 weeks at 180 bpm to maintain HF). Concomitant VNS, at an intensity reducing sinus rate Ϸ20 bpm, was delivered together with the ventricular pacing in the VNS group. At 4 and 8 weeks of ventricular pacing, both left ventricular end-diastolic and -systolic volumes were lower and left ventricular ejection fraction was higher in the VNS group than in the control group. Heart rate variability and baroreflex sensitivity improved in the VNS dogs. Rises in plasma norepinephrine, angiotensin II, and C-reactive protein levels, ordinarily expected in this model, were markedly attenuated with VNS treatment. Conclusions-Chronic VNS improves cardiac autonomic control and significantly attenuates HF development in the canine high-rate ventricular pacing model. The therapeutic benefit of VNS is associated with pronounced antiinflammatory effects. VNS is a novel and potentially useful therapy for treating HF. (Circ Heart Fail. 2009;2:692-699.)

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“…A pioneering proof of concept, this study was the first to apply a purely biological strategy (gene therapy) toward rate control in AF, although its practical translation is limited by unsustained transgene expression and safety concerns associated with viral infection. Zhang and colleagues 20 recently demonstrated the feasibility of selective vagal stimulation of the epicardial AV nodal fat pad to achieve sustained (up to 6 weeks) and reversible lowering of the ventricular response in a chronic, ambulatory canine model of AF. Although this approach circumvents the need for chronic ventricular pacing and theoretically may offer the potential to "titrate" the level of rate control, it requires permanent surgical implantation of a nerve stimulator.…”

Section: Article P 2485mentioning

confidence: 99%

Cell Therapy for Rate Control in Atrial Fibrillation

Kwaku¹

2006

Circulation

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Chronic Atrioventricular Nodal Vagal Stimulation

Cited by 39 publications

References 56 publications

Chronic Electrical Neuronal Stimulation Increases Cardiac Parasympathetic Tone by Eliciting Neurotrophic Effects

Chronic Electrical Neuronal Stimulation Increases Cardiac Parasympathetic Tone by Eliciting Neurotrophic Effects

Chronic Vagus Nerve Stimulation Improves Autonomic Control and Attenuates Systemic Inflammation and Heart Failure Progression in a Canine High-Rate Pacing Model

Cell Therapy for Rate Control in Atrial Fibrillation

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