title: Next generation renal denervation: chemical "perivascular" renal denervation with alcohol using a novel drug infusion catheter.
abstract: OBJECTIVE
  We update the pre-clinical and early clinical results using a novel endovascular approach, to perform chemical renal denervation, via peri-adventitial injection of micro-doses of dehydrated alcohol (ethanol-EtOH).
  
  
  METHODS
  A novel, three-needle delivery device (Peregrine™) was used to denervate the renal arteries of adult swine (n = 17) and in a first-in-man feasibility study (n = 18). In the pre-clinical testing EtOH was infused bilaterally with one infusion per renal artery into to the perivascular space, using EtOH doses of 0.3 ml/artery (n = 8), and 0.6 ml/artery (n = 9), and with saline sham control (0.4 ml/artery n = 3). Renal parenchymal norepinephrine (NE) concentration (performed blindly), and safety were the primary endpoints. Data from the first-in-man study (n = 18) to evaluate device performance, safety and peri-procedural pain are reported.
  
  
  RESULTS
  In the pre-clinical testing renal function was unchanged at 3-month follow-up. Angiography at 90 days (n = 34 arteries) demonstrated normal appearing renal arteries, unchanged from baseline, and without stenosis or other abnormalities. The reductions in mean renal parenchymal NE reductions at 3 months were 68% and 88% at doses of 0.3 and 0.6 ml, respectively (p < 0.001 vs. controls). In the first-in-man study, there was 100% device success, no complications, a mean treatment time of 4.3 ± 3 minutes/artery, and minimal or no patient discomfort during treatment. Angiography at 6-months showed no evidence of renal artery stenosis, and evidence of a reduction of blood pressure from baseline.
  
  
  CONCLUSIONS
  Perivascular RDN using micro-doses of alcohol is a promising alternative to energy-based systems to achieve dose-dependent, predictable, safe and essentially painless renal denervation. Further clinical evaluation is warranted.
  
  
  CONCLUSIONS
  (For annotated table of contents) This paper describes the preclinical results, in a porcine model, and the early first-in-man results, using the Peregrine™ chemical renal denervation catheter to perform renal sympathetic denervation using micro-doses of alcohol.
authors.affiliation: Borgess Heart Institute, 1521 Gull Road, Kalamazoo, MI, 49008, USA; Ablative Solutions, 801 Hermosa Way, Menlo Park, CA, 94025, USA.
authors.forename: Tim A
authors.initials: TA
authors.lastname: Fischell
authors.affiliation: Ablative Solutions, 801 Hermosa Way, Menlo Park, CA, 94025, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Fischell
authors.affiliation: Ablative Solutions, 801 Hermosa Way, Menlo Park, CA, 94025, USA.
authors.forename: Vartan E
authors.initials: VE
authors.lastname: Ghazarossian
authors.affiliation: Preclinical Consultation, San Francisco, CA.
authors.forename: Félix
authors.initials: F
authors.lastname: Vega
authors.affiliation: Clinics, Ascension, Paraguay.
authors.forename: Adrian
authors.initials: A
authors.lastname: Ebner
mesh_terms: D000328:Adult; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D017115:Catheter Ablation / Q000295:instrumentation / Q000379:methods; D003714:Denervation; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D007668:Kidney / Q000473:pathology / Q000601:surgery*; D012077:Renal Artery / Q000473:pathology* / Q000601:surgery; D012078:Renal Artery Obstruction / Q000473:pathology / Q000628:therapy*; D013552:Swine; D013562:Sympathectomy / Q000295:instrumentation / Q000379:methods
chemical_list: D000431:Ethanol
keywords: Adventitial; Alcohol; Hypertension; Renal denervation