A randomized animal study evaluating the efficacies of locally delivered heparin and urokinase for reducing in-stent restenosis

Ran Kornowski, Mun K. Hong, Fermin O. Tio, Suk K. Choi, Orville Bramwell, Martin B. Leon

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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. Methods and 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 (250,000 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 ≃ 1.3) to facilitate intramural drug impregnation. After local therapy, one Palmaz-Schatz stent (mean stent:artery diameter ratio ≃ 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.

Original languageEnglish (US)
Pages (from-to)293-298
Number of pages6
JournalCoronary Artery Disease
Volume8
Issue number5
DOIs
StatePublished - 1997
Externally publishedYes

Keywords

  • Heparin
  • Local delivery
  • Restenosis
  • Stents
  • Urokinase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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