{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:00:22Z","timestamp":1792612822220,"version":"4.5.0"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:00:00Z","timestamp":1634169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> The association between the treatment efficacy and safety of high-intensity focused ultrasound (HIFU)-based renal sympathetic denervation (RDN) and the acoustic energy dose applied has not been fully studied and may provide important understanding of the mechanism that led to failure of the WAVE IV trial. The objective of this study was to externally deliver different HIFU doses to canines for RDN treatment and to investigate the optimal energy dose for HIFU-based RDN.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Thirty canines were divided into five RDN groups according to dose of acoustic energy applied, and a sham control group that consisted of four canines was used for comparisons. All animals in the RDN groups underwent the RDN procedure with different acoustic energy doses, while in the sham control group, renal arteries were harvested without being subjected to acoustic energy delivery and were imaged using color Doppler flow imaging (CDFI). Blood pressure (BP) was recorded, and blood samples were collected before the RDN procedure and at 28 days after the RDN procedure. Histological examinations and measurement of renal tissue norepinephrine concentration were performed in all retrieved samples.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Suppression of BP was significant in the 300 W (15.17\/8.33 \u00b1 1.47\/1.21 mmHg), 250 W (14.67\/9.33 \u00b1 1.21\/1.37 mmHg), and 200 W (13.17\/9.17 \u00b1 2.32\/1.84 mmHg) groups. Semiquantitative histological assessment of periarterial nerves around the kidney revealed that target nerves in the 300 W (9.77 \u00b1 0.63), 250 W (9.42 \u00b1 0.67), and 200 W (9.58 \u00b1 0.54) groups had the highest nerve injury scores, followed by the 150 W group (5.29 \u00b1 0.62). Furthermore, decreased renal tissue norepinephrine concentration, together with decreased expression of tyrosine hydroxylase in the 300, 250, and 200 W groups demonstrated effective sympathetic depression following sufficient acoustic energy deposition. However, the renal artery injury score in the 300 W group (0.93 \u00b1 0.13) was significantly higher than in the other groups (<jats:italic>p<\/jats:italic> &amp;lt; 0.001).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> This study provides evidence that RDN effectiveness is based on the energy dose delivered and that 200\u2013250 W is effective and safe in normal-sized canines.<\/jats:p>","DOI":"10.3389\/fcvm.2021.739560","type":"journal-article","created":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T05:51:46Z","timestamp":1634190706000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Optimal Strategy for HIFU-Based Renal Sympathetic Denervation in Canines"],"prefix":"10.3389","volume":"8","author":[{"given":"Qingyao","family":"Liao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1016\/S0140-6736(09)60566-3","article-title":"Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study","volume":"373","author":"Krum","year":"2009","journal-title":"Lancet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1903","DOI":"10.1016\/S0140-6736(10)62039-9","article-title":"Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial","volume":"376","author":"Esler","year":"2010","journal-title":"Lancet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2160","DOI":"10.1016\/S0140-6736(17)32281-X","article-title":"Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial","volume":"390","author":"Townsend","year":"2017","journal-title":"Lancet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2346","DOI":"10.1016\/S0140-6736(18)30951-6","article-title":"Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial","volume":"391","author":"Kandzari","year":"2018","journal-title":"Lancet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1097\/HJH.0000000000001301","article-title":"Ultrasound-based renal sympathetic denervation for the treatment of therapy-resistant hypertension: a single-center experience","volume":"35","author":"Fengler","year":"2017","journal-title":"J Hypertens."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2335","DOI":"10.1016\/S0140-6736(18)31082-1","article-title":"Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial","volume":"391","author":"Azizi","year":"2018","journal-title":"Lancet."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2476","DOI":"10.1016\/S0140-6736(21)00788-1","article-title":"Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial","volume":"397","author":"Azizi","year":"2021","journal-title":"Lancet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"460","DOI":"10.3390\/jcm9020460","article-title":"An introduction to high intensity focused ultrasound: systematic review on principles, devices, and clinical applications","volume":"9","author":"Izadifar","year":"2020","journal-title":"J Clin Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1097\/SLA.0b013e3182128a8b","article-title":"High-intensity focused ultrasound for hepatocellular carcinoma: a single-center experience","volume":"253","author":"Ng","year":"2011","journal-title":"Ann Surg."},{"key":"B10","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1038\/sj.bjc.6602803","article-title":"The safety and feasibility of extracorporeal high-intensity focused ultrasound (HIFU) for the treatment of liver and kidney tumours in a Western population","volume":"93","author":"Illing","year":"2005","journal-title":"Br J Cancer."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1016\/j.jcin.2016.04.013","article-title":"Externally delivered focused ultrasound for renal denervation","volume":"9","author":"Neuzil","year":"2016","journal-title":"JACC Cardiovasc Interv."},{"key":"B12","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1097\/HJH.0000000000001584","article-title":"Phase II randomized sham-controlled study of renal denervation for individuals with uncontrolled hypertension - WAVE IV","volume":"36","author":"Schmieder","year":"2018","journal-title":"J Hypertens."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e22","DOI":"10.1161\/HYPERTENSIONAHA.115.05754","article-title":"Noninvasive renal denervation for resistant hypertension using high-intensity focused ultrasound","volume":"66","author":"Rong","year":"2015","journal-title":"Hypertension."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2185","DOI":"10.1016\/j.jacc.2013.02.050","article-title":"Noninvasive renal sympathetic denervation by extracorporeal high-intensity focused ultrasound in a pre-clinical canine model","volume":"61","author":"Wang","year":"2013","journal-title":"J Am Coll Cardiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1016\/j.jcin.2014.04.024","article-title":"Methodological standardization for the pre-clinical evaluation of renal sympathetic denervation","volume":"7","author":"Sakakura","year":"2014","journal-title":"JACC Cardiovasc Interv"},{"key":"B16","doi-asserted-by":"publisher","first-page":"601","DOI":"10.33549\/physiolres.933503","article-title":"Early morphologic alterations in renal artery wall and renal nerves in response to catheter-based renal denervation procedure in sheep: difference between single-point and multiple-point ablation catheters","volume":"66","author":"T\u00e1borsk\u00fd","year":"2017","journal-title":"Physiol Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1056\/NEJMoa1402670","article-title":"A controlled trial of renal denervation for resistant hypertension","volume":"370","author":"Bhatt","year":"2014","journal-title":"N Engl J Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1161\/HYPERTENSIONAHA.115.06604","article-title":"Persistent increase in blood pressure after renal nerve stimulation in accessory renal arteries after sympathetic renal denervation","volume":"67","author":"de Jong","year":"2016","journal-title":"Hypertension."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.4244\/EIJV9I9A175","article-title":"What the interventionalist should know about renal denervation in hypertensive patients: a position paper by the ESH WG on the interventional treatment of hypertension","volume":"9","author":"Tsioufis","year":"2014","journal-title":"EuroIntervention."},{"key":"B20","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1007\/s11906-016-0653-6","article-title":"Non-invasive renal denervation: update on external ultrasound approaches","volume":"18","author":"Schmieder","year":"2016","journal-title":"Curr Hypertens Rep."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1161\/HYPERTENSIONAHA.116.06715","article-title":"Residual sympathetic responsiveness after catheter-based renal denervation: lessons from renal nerve stimulation","volume":"67","author":"Schlaich","year":"2016","journal-title":"Hypertension."},{"key":"B22","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s40349-017-0094-y","article-title":"Effect of applied energy in renal sympathetic denervation with magnetic resonance guided focused ultrasound in a porcine model","volume":"5","author":"Shea","year":"2017","journal-title":"J Ther Ultrasound."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e001813","DOI":"10.1161\/CIRCINTERVENTIONS.114.001813","article-title":"Comparison of histopathologic analysis following renal sympathetic denervation over multiple time points","volume":"8","author":"Sakakura","year":"2015","journal-title":"Circ Cardiovasc Interv."},{"key":"B24","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/2050-5736-2-12","article-title":"MR-guided high-focused ultrasound for renal sympathetic denervation-a feasibility study in pigs","volume":"2","author":"Freyhardt","year":"2014","journal-title":"J Ther Ultrasound."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1016\/0002-9149(94)90560-6","article-title":"Study of the mechanism of ultrasound angioplasty from human thrombi and bovine aorta","volume":"74","author":"Rosenschein","year":"1994","journal-title":"Am J Cardiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1002\/mus.20932","article-title":"Effects of high-intensity focused ultrasound on nerve conduction","volume":"37","author":"Foley","year":"2008","journal-title":"Muscle Nerve."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1016\/j.ultrasmedbio.2004.07.004","article-title":"Image-guided HIFU neurolysis of peripheral nerves to treat spasticity and pain","volume":"30","author":"Foley","year":"2004","journal-title":"Ultrasound Med Biol."}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2021.739560\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T05:51:49Z","timestamp":1634190709000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2021.739560\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,14]]},"references-count":27,"alternative-id":["10.3389\/fcvm.2021.739560"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2021.739560","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,14]]},"article-number":"739560"}}