Autonomic Denervation With Magnetic Nanoparticles

Yu, Lilei; Scherlag, Benjamin J.; Dormer, Kenneth J.; Nguyen, Kytai T.; Pope, Carey; Fung, Kar Ming; Po, Sunny S.

doi:10.1161/circulationaha.110.940288

Cited by 44 publications

(43 citation statements)

References 45 publications

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“…They demonstrated that botulinum neural toxin A selectively injected into the sinoatrial fat pad inhibited a decrease in sinus rate in response to vagus nerve stimulation, and suggested that botulinum toxin can inhibit ganglionic neurotransmission in the dog heart in situ. In a study by Yu et al 32 , a neurotoxic agent (N-isopropylacrylamide monomer) in the anterior right and inferior right GPs reduced GP activity with a subsequent increase in the AF threshold. In a recent study, Oh et al 33 investigated the short-to mid-term effects of GP suppression by botulinum toxin on AF inducibility in the dog.…”

Section: Discussionmentioning

confidence: 98%

“…It is known that autonomic innervation of the heart consists of a large neural network and GP serve as the integration centers in the neural network. 23,[27][28][29][30][31][32] The major atrial GP, targeted by botulinum toxin in this study, contain hundreds to thousands of autonomic neurons, mainly postsynaptic cholinergic neurons activated by presynaptic acetylcholine. The neural network controls the regional electrophysiological functions, such as the refractory period and dispersion of the refractoriness.…”

Section: Discussionmentioning

confidence: 99%

“…[28][29][30][31] Recently, animal studies demonstrated that neurotoxins such as botulinum toxin injected into these fat pads could suppress AF inducibility. 32,33 Botulinum toxin blocks the exocytotic release of acetylcholine stored in synaptic vesicles and thus interferes with cholinergic neurotransmission, which is important in postganglionic neurons. 34 The blocking effects are temporary and recover in 1 to 6 months, depending on the injection site.…”

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confidence: 99%

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Long-Term Suppression of Atrial Fibrillation by Botulinum Toxin Injection Into Epicardial Fat Pads in Patients Undergoing Cardiac Surgery

Pokushalov

Kozlov

Romanov

et al. 2015

Circ: Arrhythmia and Electrophysiology

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102

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Background-Animal models suggest that the neurotransmitter inhibitor, botulinum toxin, when injected into the epicardial fat pads can suppress atrial fibrillation inducibility. The aim of this prospective randomized double-blind study was to compare the efficacy and safety of botulinum toxin injection into epicardial fat pads for preventing atrial tachyarrhythmias. Methods and Results-Patients with history of paroxysmal atrial fibrillation and indication for coronary artery bypass graft surgery were randomized to botulinum toxin (Xeomin, Merz, Germany; 50 U/1 mL at each fat pad; n=30) or placebo (0.9% normal saline, 1 mL at each fat pad; n=30) injection into epicardial fat pads during surgery. Patients were followed for 1 year to assess maintenance of sinus rhythm using an implantable loop recorder. All patients in both groups had successful epicardial fat pad injections without complications. The incidence of early postoperative atrial fibrillation within 30 days after coronary artery bypass graft was 2 of 30 patients (7%) in the botulinum toxin group and 9 of 30 patients (30%) in the placebo group (P=0.024). Between 30 days and up to the 12-month follow-up examination, 7 of the 30 patients in the placebo group (27%) and none of the 30 patients in the botulinum toxin group (0%) had recurrent atrial fibrillation (P=0.002). There were no complications observed during the 1-year follow-up. Conclusions-Botulinum toxin injection into epicardial fat pads during coronary artery bypass graft provided substantial atrial tachyarrhythmia suppression both early as well as during 1-year follow-up, without any serious adverse events. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01842529.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Long-Term Suppression of Atrial Fibrillation by Botulinum Toxin Injection Into Epicardial Fat Pads in Patients Undergoing Cardiac Surgery

Pokushalov

Kozlov

Romanov

et al. 2015

Circ: Arrhythmia and Electrophysiology

Self Cite

102

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“…16,17 In addition, magnetic guidance of nanoparticles has been previously shown as a viable drug delivery system, including its use to direct ganglionic plexus toxicity. 18 Heat-sensitive liposomes can be utilized to systemically administer a pharmacological payload but yet have a localized effect by only releasing that payload on heat activation. Liposomes are biologically inactive and have minimal toxic effects in humans; in our porcine model, animals were pretreated with medications because pigs may have an allergic reaction to the liposomes.…”

Section: Previous Investigations Into Ablation Of Nanoparticle-treatementioning

confidence: 99%

Enhanced Radiofrequency Ablation With Magnetically Directed Metallic Nanoparticles

Nguyen¹,

Tzou²,

Zheng³

et al. 2016

Circ: Arrhythmia and Electrophysiology

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Background-Remote heating of metal located near a radiofrequency ablation source has been previously demonstrated.Therefore, ablation of cardiac tissue treated with metallic nanoparticles may improve local radiofrequency heating and lead to larger ablation lesions. We sought to evaluate the effect of magnetic nanoparticles on tissue sensitivity to radiofrequency energy. Methods and Results-Ablation was performed using an ablation catheter positioned with 10 g of force over prepared ex vivo specimens. Tissue temperatures were measured and lesion volumes were acquired. An in vivo porcine thigh model was used to study systemically delivered magnetically guided iron oxide (FeO) nanoparticles during radiofrequency application. Magnetic resonance imaging and histological staining of ablated tissue were subsequently performed as a part of ablation lesion analysis. Ablation of ex vivo myocardial tissue treated with metallic nanoparticles resulted in significantly larger lesions with greater impedance changes and evidence of increased thermal conductivity within the tissue. Magnet-guided localization of FeO nanoparticles within porcine thigh preps was demonstrated by magnetic resonance imaging and iron staining. Irrigated ablation in the regions with greater FeO, after FeO infusion and magnetic guidance, created larger lesions without a greater incidence of steam pops. Conclusions-Metal nanoparticle infiltration resulted in significantly larger ablation lesions with altered electric and thermal conductivity. In vivo magnetic guidance of FeO nanoparticles allowed for facilitated radiofrequency ablation without direct infiltration into the targeted tissue. Further research is needed to assess the clinical applicability of this ablation strategy using metallic nanoparticles for the treatment of cardiac arrhythmias. (Circ Arrhythm Electrophysiol. 2016;9:e003820.

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“…Interestingly, Yu et al11 have proposed a technique using injected iron-core nanoparticles to target the ganglionated plexi for ablation. The use of magnetic particles has a long history in medicine.…”

mentioning

confidence: 99%

Magnetic Nanoparticles and Neurotoxins for Treating Atrial Fibrillation

Kraitchman

Bulte

2010

Circulation

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Autonomic Denervation With Magnetic Nanoparticles

Abstract: Background-Prior studies indicated that ablation of the 4 major atrial ganglionated plexi (GP) suppressed atrial fibrillation. Methods and Results-Superparamagnetic

Cited by 44 publications

References 45 publications

Long-Term Suppression of Atrial Fibrillation by Botulinum Toxin Injection Into Epicardial Fat Pads in Patients Undergoing Cardiac Surgery

Long-Term Suppression of Atrial Fibrillation by Botulinum Toxin Injection Into Epicardial Fat Pads in Patients Undergoing Cardiac Surgery

Enhanced Radiofrequency Ablation With Magnetically Directed Metallic Nanoparticles

Magnetic Nanoparticles and Neurotoxins for Treating Atrial Fibrillation

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