title: Saline infusion via local drug delivery catheters is associated with increased neointimal hyperplasia in a porcine coronary in-stent restenosis model.
abstract: BACKGROUND
  Catheter-based local drug delivery at the site of stent implantation has been proposed to reduce in-stent restenosis. We examined whether local delivery itself may cause additional vessel wall injury and negate the potential benefit of local drug delivery in a porcine coronary in-stent restenosis model.
  
  
  METHODS
  Pigs were randomly assigned to no local delivery (controls, n = 10) or local saline infusion (5 ml) using commercially available catheters (n = 39; Dispatch catheter, Microporous Infusion catheter, and InfusaSleeve) prior to oversized (stent:artery ratio 1.2) coronary stent implantation. The amount of in-stent neointima was evaluated 4 weeks later with angiography and histology.
  
  
  RESULTS
  There was no difference in vessel size or stent: artery ratio. However, at follow-up the local saline delivery group had significantly greater diameter stenosis (50 +/- 19% versus 25 +/- 17% in the controls, P < 0.01). Histology revealed similar injury scores but significantly greater neointimal area in the local saline group (3.61 +/- 1.11 mm2 versus 1.96 +/- 0.82 mm2 in the controls, P < 0.01). In a multivariate linear regression analysis, the use of the local delivery catheter was the only independent variable which was positively correlated with the amount of neointima (P = 0.0001).
  
  
  CONCLUSIONS
  In this in-stent restenosis model, catheter-based local saline delivery was associated with significantly increased neointimal hyperplasia. Thus, for local drug delivery to reduce in-stent restenosis, the antiproliferative agent should be potent enough to compensate for the additional neointimal hyperplasia from the infusion itself.
authors.affiliation: Department of Internal Medicine (Cardiology Division) of the Washington Hospital Center, Washington, DC, USA.
authors.forename: W H
authors.initials: WH
authors.lastname: Kim
authors.forename: M K
authors.initials: MK
authors.lastname: Hong
authors.forename: R
authors.initials: R
authors.lastname: Kornowski
authors.forename: F O
authors.initials: FO
authors.lastname: Tio
authors.forename: M B
authors.initials: MB
authors.lastname: Leon
mesh_terms: D000818:Animals; D002408:Catheters, Indwelling; D017023:Coronary Angiography; D003327:Coronary Disease / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000473:pathology; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000295:instrumentation*; D006965:Hyperplasia / Q000139:chemically induced / Q000473:pathology; D007261:Infusions, Intra-Arterial / Q000295:instrumentation; D011897:Random Allocation; D012008:Recurrence; D012965:Sodium Chloride / Q000008:administration & dosage / Q000009:adverse effects*; D015607:Stents; D013552:Swine; D017539:Tunica Intima / Q000473:pathology*
chemical_list: D012965:Sodium Chloride