title: A randomized animal study evaluating the efficacies of locally delivered heparin and urokinase for reducing in-stent restenosis.
abstract: BACKGROUND
  In-stent restenosis is primarily due to neointimal hyperplasia. Results from recent nonrandomized studies suggest that local delivery of heparin or urokinase to the site of angioplasty or stenting results in a lower rate of restenosis.
  
  
  OBJECTIVE
  To determine whether local delivery of heparin or urokinase reduces in-stent restenosis.
  
  
  RESULTS
  Thirty-three pigs were assigned randomly to one of three groups: controls (n = 9) administered local saline infusion, the heparin group (n = 15) administered local heparin (6000 u/10 min), and the urokinase group (n = 9) administered local urokinase (250000 u/10 min), via a local delivery catheter (Dispatch) at the site of subsequent stent implantation. Prior to local delivery, all of the animals were subjected to balloon injury (balloon:artery diameter ratio approximately or = 1.3) to facilitate intramural drug impregnation. After local therapy, one Palmaz-Schatz stent (mean stent: artery diameter ratio approximately or = 1.25) was implanted within the left anterior descending coronary artery. The degree of neointimal hyperplasia was evaluated 4 weeks later by angiography (as the maximal percentage diameter stenosis) and histology (as the maximal neointimal area stenosis). We found no difference in percentage diameter stenosis (46 +/- 18% control, 42 +/- 27% heparin group, and 37 +/- 20% urokinase group, P = 0.7) and corrected neointimal area (1.06 +/- 0.42 mm2 control, 0.94 +/- 0.29 mm2 heparin, and 0.88 +/- 0.26 mm2 urokinase group, P = 0.7) among groups at follow-up. The activated clotting time rose slightly for heparin-treated animals, suggesting that systemic delivery had occurred, whereas fibrinogen levels did not change in urokinase-treated animals.
  
  
  CONCLUSIONS
  Local deliveries of heparin and urokinase via the Dispatch catheter, at the chosen dosages, do not reduce in-stent neointimal hyperplasia in this porcine model.
authors.affiliation: Department of Internal Medicine (Cardiology Division) of the Washington Hospital Center, District of Columbia, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kornowski
authors.forename: M K
authors.initials: MK
authors.lastname: Hong
authors.forename: F O
authors.initials: FO
authors.lastname: Tio
authors.forename: S K
authors.initials: SK
authors.lastname: Choi
authors.forename: O
authors.initials: O
authors.lastname: Bramwell
authors.forename: M B
authors.initials: MB
authors.lastname: Leon
mesh_terms: D000818:Animals; D003251:Constriction, Pathologic; D003327:Coronary Disease / Q000517:prevention & control*; D003331:Coronary Vessels / Q000473:pathology*; D005069:Evaluation Studies as Topic; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006493:Heparin / Q000008:administration & dosage*; D006965:Hyperplasia / Q000517:prevention & control; D007262:Infusions, Intravenous; D010960:Plasminogen Activators / Q000008:administration & dosage*; D011897:Random Allocation; D012008:Recurrence; D015607:Stents; D013552:Swine; D017539:Tunica Intima / Q000473:pathology; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage*
chemical_list: D005343:Fibrinolytic Agents; D006493:Heparin; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator