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      Ultrasound: The Potential Power for Cardiovascular Disease Therapy

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          Abstract

          Ultrasound can be considered a mechanical wave for both clinical diagnostic and therapeutic purposes on the basis of its good penetrability and directivity while spreading in solid organs or tissues without any ionizing radiation. As a powerful form of energy, ultrasound, is used for deep-tissue therapy with different sonication parameters. The feasibility of minimally invasive or noninvasive acoustic treatment of a variety of diseases, such as hypertension, arrhythmia, hypertrophic cardiomyopathy, and myocardial infraction, is being explored in animal experiments and clinical trials. In this review, we summarize the biomedical effects of acoustic intervention in experimental and clinical studies, current challenges, and the potential of ultrasound for cardiovascular disease therapy.

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          Most cited references 61

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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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            Transcranial pulsed ultrasound stimulates intact brain circuits.

            Electromagnetic-based methods of stimulating brain activity require invasive procedures or have other limitations. Deep-brain stimulation requires surgically implanted electrodes. Transcranial magnetic stimulation does not require surgery, but suffers from low spatial resolution. Optogenetic-based approaches have unrivaled spatial precision, but require genetic manipulation. In search of a potential solution to these limitations, we began investigating the influence of transcranial pulsed ultrasound on neuronal activity in the intact mouse brain. In motor cortex, ultrasound-stimulated neuronal activity was sufficient to evoke motor behaviors. Deeper in subcortical circuits, we used targeted transcranial ultrasound to stimulate neuronal activity and synchronous oscillations in the intact hippocampus. We found that ultrasound triggers TTX-sensitive neuronal activity in the absence of a rise in brain temperature (<0.01 degrees C). Here, we also report that transcranial pulsed ultrasound for intact brain circuit stimulation has a lateral spatial resolution of approximately 2 mm and does not require exogenous factors or surgical invasion. Copyright 2010 Elsevier Inc. All rights reserved.
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              Remote Excitation of Neuronal Circuits Using Low-Intensity, Low-Frequency Ultrasound

              Possessing the ability to noninvasively elicit brain circuit activity yields immense experimental and therapeutic power. Most currently employed neurostimulation methods rely on the somewhat invasive use of stimulating electrodes or photon-emitting devices. Due to its ability to noninvasively propagate through bone and other tissues in a focused manner, the implementation of ultrasound (US) represents a compelling alternative approach to current neuromodulation strategies. Here, we investigated the influence of low-intensity, low-frequency ultrasound (LILFU) on neuronal activity. By transmitting US waveforms through hippocampal slice cultures and ex vivo mouse brains, we determined LILFU is capable of remotely and noninvasively exciting neurons and network activity. Our results illustrate that LILFU can stimulate electrical activity in neurons by activating voltage-gated sodium channels, as well as voltage-gated calcium channels. The LILFU-induced changes in neuronal activity were sufficient to trigger SNARE-mediated exocytosis and synaptic transmission in hippocampal circuits. Because LILFU can stimulate electrical activity and calcium signaling in neurons as well as central synaptic transmission we conclude US provides a powerful tool for remotely modulating brain circuit activity.
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                Author and article information

                Journal
                CVIA
                Cardiovascular Innovations and Applications
                CVIA
                Compuscript (Ireland )
                2009-8782
                2009-8618
                July 2019
                August 2019
                : 4
                : 2
                : 125-134
                Affiliations
                1Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, No. 76 Linjiang Road, Chongqing 400010, China
                2Institute of Acoustics, Chinese Academy of Sciences, No. 21 North 4th Ring Road, Haidian District, Beijing 100190, China
                Author notes
                Correspondence: Jing Huang, MD, Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, No. 76, Linjiang Road, Chongqing 400010, China, E-mail: huangjingcqmu@ 123456cqmu.edu.cn
                Article
                cvia20190013
                10.15212/CVIA.2019.0013
                Copyright © 2019 Cardiovascular Innovations and Applications

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 Unported License (CC BY-NC 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See https://creativecommons.org/licenses/by-nc/4.0/.

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