title: Catheter-based renal sympathetic denervation: chronic preclinical evidence for renal artery safety.
abstract: BACKGROUND
  Renal sympathetic hyperactivity is associated with hypertension, a leading cause of mortality worldwide. Renal sympathetic denervation via the Symplicity Catheter System has been shown to decrease blood pressure by 33/11 mmHg by 6 months, with no radiofrequency (RF)-related adverse sequelae visible by CT/MR angiography or renal duplex ultrasound 6 months after the procedure. Here, we present preclinical work predating those clinical results. We performed therapeutic renal sympathetic denervation in a swine animal model to characterize the vascular safety and healing response 6 months after renal denervation therapy.
  
  
  METHODS
  In December 2007, seven domestic swine received a total of 32 radiofrequency ablations via the Symplicity Catheter System and were euthanatized 6 months later. Renal angiography was done before, immediately after, and 6 months after procedure. The renal vessels were examined histologically with H&E and Movat pentachrome stains to identify evidence of vascular and neural injury. The kidneys and urinary system were also examined for evidence of gross and microscopic abnormalities.
  
  
  RESULTS
  Renal nerve injury involved primarily nerve fibrosis, replacement of nerve fascicles with fibrous connective tissue, and thickening of the epineurium and perineurium. Renal arterial findings included fibrosis of 10-25% of the total media and underlying adventitia, with mild disruption of the external elastic lamina. No significant smooth muscle hyperplasia or inflammatory components were observed. There was no renal arterial stenosis or thrombosis observed by angiography or histology. No gross or microscopic device-related abnormalities were noted in the kidney, surrounding stroma, or urinary bladder.
  
  
  CONCLUSIONS
  In a swine model, renal denervation via the Symplicity Catheter System resulted in no clinically significant adverse renal artery or renal findings 6 months after the procedure. This is corroborated by the vascular safety profile demonstrated in subsequent human clinical studies.
authors.affiliation: Rippy Pathology Solutions, Woodbury, MN, USA. marian.rippy@comcast.net
authors.forename: Marian K
authors.initials: MK
authors.lastname: Rippy
authors.forename: Denise
authors.initials: D
authors.lastname: Zarins
authors.forename: Neil C
authors.initials: NC
authors.lastname: Barman
authors.forename: Andrew
authors.initials: A
authors.lastname: Wu
authors.forename: Keith L
authors.initials: KL
authors.lastname: Duncan
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Zarins
mesh_terms: D000818:Animals; D017115:Catheter Ablation / Q000009:adverse effects / Q000295:instrumentation; D057785:Catheters; D004867:Equipment Design; D007668:Kidney / Q000294:innervation*; D023421:Models, Animal; D011859:Radiography; D012077:Renal Artery / Q000000981:diagnostic imaging / Q000293:injuries* / Q000473:pathology; D034421:Sus scrofa; D013562:Sympathectomy / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D013564:Sympathetic Nervous System / Q000601:surgery*; D013997:Time Factors; D057772:Vascular System Injuries / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*