title: Renal Sympathetic Denervation System via Intraluminal Ultrasonic Ablation: Therapeutic Intravascular Ultrasound Design and Preclinical Evaluation.
abstract: OBJECTIVE
  To assess the safety and performance of a nonfocused and nonballooned ultrasonic (US) catheter-based renal sympathetic denervation (RDN) system in normotensive swine.
  
  
  METHODS
  RDN with the therapeutic intravascular US catheter was evaluated in 3 experiments: (i) therapeutic intravascular US RDN vs a control group of untreated animals with follow-up of 30, 45, and 90 days (n = 6; n = 12 renal arteries for each group); (ii) therapeutic intravascular US RDN vs radiofrequency (RF) RDN in the contralateral artery in the same animal (n = 2; n = 4 renal arteries); and (iii) therapeutic intravascular US RDN in a recently stent-implanted renal artery (n = 2; n = 4 renal arteries).
  
  
  RESULTS
  In the first experiment, therapeutic intravascular US RDN was safe, without angiographic evidence of dissection or renal artery stenosis. Neuronal tissue vacuolization, nuclei pyknosis, and perineuronal inflammation were evident after RDN, without renal artery wall damage. Norepinephrine levels were significantly lower after therapeutic intravascular US RDN after 30, 45, and 90 days compared with the control group (200.17 pg/mg ± 63.35, 184.75 pg/mg ± 44.51, and 203.43 pg/mg ± 58.54, respectively, vs 342.42 pg/mg ± 79.97). In the second experiment, deeper neuronal ablation penetrance was found with therapeutic intravascular US RDN vs RF RDN (maximal penetrance from endothelium of 7.0 mm vs 3.5 mm, respectively). There was less damage to the artery wall after therapeutic intravascular US RDN than with RF RDN, after which edema and injured endothelium were seen. In the third experiment, denervation inside the stent-implanted segments was feasible without damage to the renal artery wall or stent.
  
  
  CONCLUSIONS
  The therapeutic intravascular US system performed safely and reduced norepinephrine levels. Deeper penetrance and better preservation of vessel wall were observed with therapeutic intravascular US RDN vs RF RDN. Neuronal ablations were observed in stent-implanted renal arteries.
authors.affiliation: Departments of Nephrology and Hypertension, Kaplan Medical Center, Hebrew University School of Medicine, Rehovot, Israel. Electronic address: gilch@clalit.org.il.
authors.forename: Gil
authors.initials: G
authors.lastname: Chernin
authors.affiliation: Cardiosonic, Tel Aviv, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Szwarcfiter
authors.affiliation: Division of Interventional Angiology, Department of Internal Medicine, Neurology and Dermatology, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Bausback
authors.affiliation: Department of Cardiology, Kaplan Medical Center, Hebrew University School of Medicine, Rehovot, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Jonas
mesh_terms: D000818:Animals; D057086:High-Intensity Focused Ultrasound Ablation; D007668:Kidney / Q000098:blood supply* / Q000294:innervation*; D023421:Models, Animal; D009638:Norepinephrine / Q000378:metabolism; D012077:Renal Artery / Q000294:innervation*; D015607:Stents; D013552:Swine; D013562:Sympathectomy / Q000379:methods*
chemical_list: D009638:Norepinephrine