Local delivery of a low molecular weight heparin following stent implantation in the pig coronary artery

Abstract

Background: The low molecular weight heparin Reviparin reduces smooth muscle cell proliferation in cell culture experiments. Clinical studies with systemic application of the substance did not show a reduction of the incidence of restenosis following balloon angioplasty. Local delivery, by achieving higher local concentrations of the drug, may have the potential to decrease smooth muscle cell proliferation in the treated arterial segment. Objectives: The aim of this study was to investigate the effects of local delivery of reviparin following stent implantation in the pig coronary artery. Methods: A coronary stent was implanted in the LAD of 34 pigs. In the treatment group 5 ml reviparin was injected with the Infusasleeve catheter at a proximal pressure of 80 psi. After 28 days the animals were sacrificed. Quantitative morphometric analysis comprised the intimal area, medial area and the lumen. The extent of vessel injury and the intimal thickness were assessed separately for each stent strut region. The correlation of injury and neointimal thickness was analysed using linear regression. Results: There was no relevant difference in the extent of vessel injury (1.9 ± 0.7 vs. 1.6 ± 0.6), the neointimal areas (2.4 ± 0.9 vs. 2.4 ± 1.0 mm²) and the resulting stenosis (46 ± 18 vs. 47 ± 17%). The medial area was larger in the animals treated with local delivery (2.2 ± 0.4 vs. 1.6 ± 0.4 mm²; p < 0,01). The correlation of injury and neointimal thickness was comparable in both groups. In two animals the passage of the stent area with the delivery system resulted in stent dislocation and fatal subacute thrombosis. Conclusion: In this animal model, local delivery of reviparin with the Infusasleeve catheter did not result in a reduction of neointimal proliferation following stent implantation. Local delivery after stent implantation carries the risk of stent dislocation as a result of the passage with the delivery system.