title: Nitric oxide delivery via a permeable balloon catheter inhibits neointimal growth after arterial injury.
abstract: BACKGROUND
  Neointimal hyperplasia limits the longevity of vascular interventions. Nitric oxide (NO) is well known to inhibit neointimal hyperplasia. However, delivery of NO to the vasculature is challenging. Our study aims to evaluate the efficacy of delivering NO to the site of injury using a permeable balloon catheter. Our hypothesis is that ultra-short duration NO delivery using a permeable balloon catheter will inhibit neointimal hyperplasia.
  
  
  METHODS
  Ten-week-old male Sprague-Dawley rats underwent carotid artery balloon injury. Groups included: (1) control, (2) injury, (3) injury + periadventitial NO, and (4) injury + endoluminal NO via permeable balloon catheter. The catheter was inflated to 5 atm pressure for 5 min. Arteries were harvested 2 wk following injury. Morphometric assessment for neointimal hyperplasia and immunohistochemical staining for inflammatory markers were performed.
  
  
  RESULTS
  Injury increased neointimal hyperplasia compared with control (intima/media area [I/M] ratio 1.07 versus 0.11, respectively, P < 0.001). Periadventitial delivery of NO reduced the I/M area ratio compared with injury alone (55% decrease, P < 0.001). Endoluminal delivery of NO also reduced the I/M area ratio compared with injury alone (65% decrease; P < 0.001). Both endoluminal and periadventitial NO affected the I/M ratio by reducing the intimal area (64% and 46%, respectively, P < 0.001) whereas neither affected the medial area. Periadventitial NO delivery increased lumen area (P < 0.05), whereas endoluminal NO delivery increased circumference (P < 0.05). Periadventitial NO delivery inhibited macrophage intimal infiltration compared with injury alone (P < 0.05).
  
  
  CONCLUSIONS
  These data demonstrate that short-duration endoluminal NO delivery via permeable balloon catheters inhibits neointimal hyperplasia following arterial interventions. Endoluminal delivery of NO could become a focus for future clinical interventions.
authors.affiliation: Division of Vascular Surgery, Northwestern University, Chicago, Illinois, USA.
authors.forename: George E
authors.initials: GE
authors.lastname: Havelka
authors.forename: Edward S
authors.initials: ES
authors.lastname: Moreira
authors.forename: Monica P
authors.initials: MP
authors.lastname: Rodriguez
authors.forename: Nick D
authors.initials: ND
authors.lastname: Tsihlis
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Janet
authors.initials: J
authors.lastname: Martínez
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Hrabie
authors.forename: Larry K
authors.initials: LK
authors.lastname: Kiefer
authors.forename: Melina R
authors.initials: MR
authors.lastname: Kibbe
mesh_terms: D000800:Angioplasty, Balloon; D000818:Animals; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000473:pathology; D006965:Hyperplasia; D008297:Male; D058426:Neointima / Q000473:pathology*; D009569:Nitric Oxide / Q000008:administration & dosage*; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009569:Nitric Oxide