Noninvasive Renal Sympathetic Denervation by Extracorporeal High-Intensity Focused Ultrasound in a Pre-Clinical Canine Model

Wang, Qifeng; Guo, Rui; Shu, Rong; Yang, Gang; Zhu, Qingsan; Jiang, Yonghong; Deng, Changming; Liu, Dichuan; Zhou, Qi; Qi, Wenyuan; Wang, Shunhe; Qian, Jun; Wang, Qi; Lv, Han; He, Tong‐Chuan; Wang, Zhibiao; Jing, Huang

doi:10.1016/j.jacc.2013.02.050

Cited by 52 publications

(38 citation statements)

References 21 publications

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“…Wang et al investigated renal denervation with HiFUS in canines using color Doppler flow imaging (CDFI) for guidance [33]. In this study, up to six ablations at three foci of the renal artery led to a significant decrease in plasma NE concentration and in systolic and diastolic blood pressure on days 6 and 28 after the interventions and to degeneration of the targeted nerve fibers.…”

Section: Resultsmentioning

confidence: 89%

MR-guided high-focused ultrasound for renal sympathetic denervation—a feasibility study in pigs

Freyhardt

Heckmann

Beck

et al. 2014

Journal of Therapeutic Ultrasound

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BackgroundRenal sympathetic denervation has recently gained clinical relevance for the treatment of therapy-resistant hypertension. Denervation is currently mainly performed using catheter-based transarterial radiofrequency ablation of periarterial sympathetic nerve fibers. Since this approach has numerous limitations, we conducted a study to evaluate the feasibility, safety, and efficacy of magnetic resonance-guided high-focused ultrasound (MRgHiFUS) for renal sympathetic denervation in pigs as an alternative to catheter-based ablation.MethodsRenal periarterial MRgHiFUS was performed under general anesthesia in ten pigs. Blood pressure measurements and magnetic resonance imaging (MRI) of the kidneys, renal arteries, and surrounding structures were obtained immediately before and after the interventions and after 4 weeks. Histological examinations of periarterial tissues and determination of renal norepinephrine (NE) concentration were performed to assess treatment efficacy.Results and discussionIn each pig, 9.8 ± 2.6 sonications with a mean energy deposition of 2,670 ± 486 J were performed. The procedure was well tolerated by all pigs. No major complications occurred. MRgHiFUS induced periarterial edema in three pigs, but only one pig showed corresponding histological changes. The NE level of the treated kidney was lower in five pigs (-8% to -38%) compared to the untreated side. Overall, there was no significant difference between the NE values of both kidneys in any of the treated pigs. Postinterventional MRI indicated absorption of ultrasound energy at the transverse process and fascia.ConclusionMRgHiFUS had some thermal periarterial effects but failed to induce renal denervation. Insufficient energy deposition is most likely attributable to a small acoustic window with beam path impediment in the porcine model. Since HiFUS treatment in humans is expected to be easier to perform due to better access to renal sympathetic nerves, further studies of this method are desirable to investigate the potential of MRgHiFUS as an alternative for patients not suitable for catheter-based renal sympathicolysis.

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Section: Resultsmentioning

confidence: 89%

MR-guided high-focused ultrasound for renal sympathetic denervation—a feasibility study in pigs

Freyhardt

Heckmann

Beck

et al. 2014

Journal of Therapeutic Ultrasound

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“…Histopathologic examination demonstrated nerve fiber disruption at day 28 after RDN. 162 The WAVE I trial tested Kona Medical's ultrasoundbased Surround Sound® Renal Denervation System (Kona Medical, Menlo Park, CA) in 24 patients with TRH who were taking an average of 4.5 antihypertensive medications and had a mean baseline BP of 190/100 mm Hg. Eighteen focused lesions were applied over 13 minutes to each artery, but for targeting and tracking reasons, a 5F intravascular renal artery catheter by guest on http://circres.ahajournals.org/ Downloaded from had to be used.…”

Section: Renal Denervationmentioning

confidence: 99%

New Approaches in the Treatment of Hypertension

Oparil

Schmieder

2015

Circulation Research

231

137

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Hypertension is the most common modifiable risk factor for cardiovascular disease and death, and lowering blood pressure with antihypertensive drugs reduces target organ damage and prevents cardiovascular disease outcomes. Despite a plethora of available treatment options, a substantial portion of the hypertensive population has uncontrolled blood pressure. The unmet need of controlling blood pressure in this population may be addressed, in part, by developing new drugs and devices/procedures to treat hypertension and its comorbidities. In this Compendium Review, we discuss new drugs and interventional treatments that are undergoing preclinical or clinical testing for hypertension treatment. New drug classes, eg, inhibitors of vasopeptidases, aldosterone synthase and soluble epoxide hydrolase, agonists of natriuretic peptide A and vasoactive intestinal peptide receptor 2, and a novel mineralocorticoid receptor antagonist are in phase II/III of development, while inhibitors of aminopeptidase A, dopamine β-hydroxylase, and the intestinal Na + /H + exchanger 3, agonists of components of the angiotensin-converting enzyme 2/angiotensin(1–7)/Mas receptor axis and vaccines directed toward angiotensin II and its type 1 receptor are in phase I or preclinical development. The two main interventional approaches, transcatheter renal denervation and baroreflex activation therapy, are used in clinical practice for severe treatment resistant hypertension in some countries. Renal denervation is also being evaluated for treatment of various comorbidities, eg, chronic heart failure, cardiac arrhythmias and chronic renal failure. Novel interventional approaches in early development include carotid body ablation and arteriovenous fistula placement. Importantly, none of these novel drug or device treatments has been shown to prevent cardiovascular disease outcomes or death in hypertensive patients.

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“…Outside the United States, HIFU is being explored in several conditions such as cancer of the prostate (4), the breast (5), the pancreas (6), the liver (7) and also in nononcologic applications, e.g., the management of back pain, neuromodulation for essential tremor, or Parkinson's disease (8). Preliminary trials are also being conducted to use HIFU to treat hypertension by selective renal denervation (9).…”

Section: Introductionmentioning

confidence: 99%

High intensity focused ultrasound (HIFU) applied to hepato-bilio-pancreatic and the digestive system—current state of the art and future perspectives

Diana¹,

Schiraldi²,

Liu³

et al. 2016

Hepatobiliary Surg. Nutr.

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Background: High intensity focused ultrasound (HIFU) is emerging as a valid minimally-invasive imageguided treatment of malignancies. We aimed to review to current state of the art of HIFU therapy applied to the digestive system and discuss some promising avenues of the technology.Methods: Pertinent studies were identified through PubMed and Embase search engines using the following keywords, combined in different ways: HIFU, esophagus, stomach, liver, pancreas, gallbladder, colon, rectum, and cancer. Experimental proof of the concept of endoluminal HIFU mucosa/submucosa ablation using a custom-made transducer has been obtained in vivo in the porcine model. Results:Forty-four studies reported on the clinical use of HIFU to treat liver lesions, while 19 series were found on HIFU treatment of pancreatic cancers and four studies included patients suffering from both liver and pancreatic cancers, reporting on a total of 1,682 and 823 cases for liver and pancreas, respectively. Only very limited comparative prospective studies have been reported. Conclusions:Digestive system clinical applications of HIFU are limited to pancreatic and liver cancer. It is safe and well tolerated. The exact place in the hepatocellular carcinoma (HCC) management algorithm remains to be defined. HIFU seems to add clear survival advantages over trans arterial chemo embolization (TACE) alone and similar results when compared to radio frequency (RF). For pancreatic cancer, HIFU achieves consistent cancer-related pain relief. Further research is warranted to improve targeting accuracy and efficacy monitoring. Furthermore, additional work is required to transfer this technology on appealing treatments such as endoscopic HIFU-based therapies.Keywords: High intensity focused ultrasound (HIFU); liver cancer; pancreatic cancer; miniature HIFU delivery system; endoluminal applications of HIFU; mucosa and submucosal ablations using HIFU

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Noninvasive Renal Sympathetic Denervation by Extracorporeal High-Intensity Focused Ultrasound in a Pre-Clinical Canine Model

Cited by 52 publications

References 21 publications

MR-guided high-focused ultrasound for renal sympathetic denervation—a feasibility study in pigs

MR-guided high-focused ultrasound for renal sympathetic denervation—a feasibility study in pigs

New Approaches in the Treatment of Hypertension

High intensity focused ultrasound (HIFU) applied to hepato-bilio-pancreatic and the digestive system—current state of the art and future perspectives

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