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      Autonomic Neuromodulation for Preventing and Treating Ventricular Arrhythmias

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          Abstract

          The cardiac autonomic nervous system (CANS) is associated with modulation of cardiac electrophysiology and arrhythmogenesis. In this mini review, we will briefly introduce cardiac autonomic anatomy and autonomic activity in ventricular arrhythmias (VAs) and discuss novel approaches of CANS modulation for treating VAs. Studies over the decades have provided a better understanding of cardiac autonomic innervation and revealed overwhelming evidence of the relationship between autonomic tone and VAs. A high sympathetic tone and low parasympathetic (vagal) tone are considered as the major triggers of VAs in patients with myocardial ischemia, which can cause sudden cardiac death. In recent years, novel methods of autonomic neuromodulation have been investigated to prevent VAs, and they have been verified as being beneficial for malignant VAs in animal models and humans. The clinical outcome of autonomic neuromodulation depends on the level of cardiac neuraxis, stimulation parameters, and patient’s pathological status. Since autonomic modulation for VA treatment is still in the early stage of clinical application, more basic and clinical studies should be performed to clarify these mechanisms and optimize autonomic neuromodulation therapies for patients with VAs in the future.

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          Most cited references94

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          Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study.

          Renal sympathetic hyperactivity is associated with hypertension and its progression, chronic kidney disease, and heart failure. We did a proof-of-principle trial of therapeutic renal sympathetic denervation in patients with resistant hypertension (ie, systolic blood pressure >/=160 mm Hg on three or more antihypertensive medications, including a diuretic) to assess safety and blood-pressure reduction effectiveness. We enrolled 50 patients at five Australian and European centres; 5 patients were excluded for anatomical reasons (mainly on the basis of dual renal artery systems). Patients received percutaneous radiofrequency catheter-based treatment between June, 2007, and November, 2008, with subsequent follow-up to 1 year. We assessed the effectiveness of renal sympathetic denervation with renal noradrenaline spillover in a subgroup of patients. Primary endpoints were office blood pressure and safety data before and at 1, 3, 6, 9, and 12 months after procedure. Renal angiography was done before, immediately after, and 14-30 days after procedure, and magnetic resonance angiogram 6 months after procedure. We assessed blood-pressure lowering effectiveness by repeated measures ANOVA. This study is registered in Australia and Europe with ClinicalTrials.gov, numbers NCT 00483808 and NCT 00664638. In treated patients, baseline mean office blood pressure was 177/101 mm Hg (SD 20/15), (mean 4.7 antihypertensive medications); estimated glomerular filtration rate was 81 mL/min/1.73m(2) (SD 23); and mean reduction in renal noradrenaline spillover was 47% (95% CI 28-65%). Office blood pressures after procedure were reduced by -14/-10, -21/-10, -22/-11, -24/-11, and -27/-17 mm Hg at 1, 3, 6, 9, and 12 months, respectively. In the five non-treated patients, mean rise in office blood pressure was +3/-2, +2/+3, +14/+9, and +26/+17 mm Hg at 1, 3, 6, and 9 months, respectively. One intraprocedural renal artery dissection occurred before radiofrequency energy delivery, without further sequelae. There were no other renovascular complications. Catheter-based renal denervation causes substantial and sustained blood-pressure reduction, without serious adverse events, in patients with resistant hypertension. Prospective randomised clinical trials are needed to investigate the usefulness of this procedure in the management of this condition.
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            Soft, stretchable, fully implantable miniaturized optoelectronic systems for wireless optogenetics

            Optogenetics allows rapid, temporally specific control of neuronal activity via targeted expression and activation of light-sensitive proteins. Implementation typically requires remote light sources and fiber-optic delivery schemes that impose significant physical constraints on natural behaviors. In this report we bypass these limitations using novel technologies that combine thin, mechanically soft neural interfaces with fully implantable, stretchable wireless radio power and control systems. The resulting devices achieve optogenetic modulation of the spinal cord and peripheral nervous system. This is demonstrated with two form factors; stretchable film appliques that interface directly with peripheral nerves, and flexible filaments that insert into the narrow confines of the spinal epidural space. These soft, thin devices are minimally invasive, and histological tests suggest they can be used in chronic studies. We demonstrate the power of this technology by modulating peripheral and spinal pain circuitry, providing evidence for the potential widespread use of these devices in research and future clinical applications of optogenetics outside the brain.
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              Wirelessly powered, fully internal optogenetics for brain, spinal and peripheral circuits in mice.

              To enable sophisticated optogenetic manipulation of neural circuits throughout the nervous system with limited disruption of animal behavior, light-delivery systems beyond fiber optic tethering and large, head-mounted wireless receivers are desirable. We report the development of an easy-to-construct, implantable wireless optogenetic device. Our smallest version (20 mg, 10 mm(3)) is two orders of magnitude smaller than previously reported wireless optogenetic systems, allowing the entire device to be implanted subcutaneously. With a radio-frequency (RF) power source and controller, this implant produces sufficient light power for optogenetic stimulation with minimal tissue heating (<1 °C). We show how three adaptations of the implant allow for untethered optogenetic control throughout the nervous system (brain, spinal cord and peripheral nerve endings) of behaving mice. This technology opens the door for optogenetic experiments in which animals are able to behave naturally with optogenetic manipulation of both central and peripheral targets.
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                Author and article information

                Contributors
                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                11 March 2019
                2019
                : 10
                : 200
                Affiliations
                [1] 1 Department of Cardiology, Renmin Hospital of Wuhan University , Wuhan, China
                [2] 2 Cardiovascular Research Institute, Wuhan University , Wuhan, China
                [3] 3 Hubei Key Laboratory of Cardiology , Wuhan, China
                Author notes

                Edited by: Maurizio Acampa, Azienda Ospedaliera Universitaria Senese, Italy

                Reviewed by: Antonio Roberto Zamunér, Catholic University of Maule, Chile; Alessandro Tonacci, Institute of Clinical Physiology (IFC), Italy

                *Correspondence: Lilei Yu, whuyulilei@ 123456163.com

                This article was submitted to Autonomic Neuroscience, a section of the journal Frontiers in Physiology

                Article
                10.3389/fphys.2019.00200
                6421499
                30914967
                c2abaf57-e5d5-4550-8c28-d5a85795bf24
                Copyright © 2019 Lai, Yu and Jiang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 December 2018
                : 15 February 2019
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 108, Pages: 9, Words: 7201
                Funding
                Funded by: National Science Foundation of China 10.13039/501100001809
                Award ID: 81530011
                Award ID: 81570463
                Categories
                Physiology
                Review

                Anatomy & Physiology
                cardiac autonomic nervous system,neurocardiology,neuromodulation,neurorebalance,ventricular arrhythmias

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