Use of nitric-oxide-eluting polymer-coated coronary stents for prevention of restenosis in pigs

Background. Restenosis after angioplasty remains an unresolved problem despite an increase in use of coronary stents. It has been theorized that nitric oxide (NO) exerts several actions that can prevent restenosis. These include inhibition of proliferation of smooth muscle cells, prevention of arterial spasms, and decreasing aggregation of platelets in response to exposure to collagen. Objective. To determine whether NO coated stents decrease restenosis in a pig balloon injury model. Methods. We used coronary stents impregnated with a slow-release precursor of NO in the porcine model of restenosis. Tantalum coil coronary stents (Cordis) were coated with a polymer impregnated with a slow-release precursor of NO. Polymer-coated stents without active precursors were used as controls. Oversized stents were mounted on a delivery balloon and subsequently deployed in the right coronary and left anterior descending arteries of each animal. Results. Repeated recording of angiograms demonstrated that changes in minimum lumen diameter on going from immediately after stenting to 28-day follow-up for the control and NO-eluting-stent groups were similar, namely decreases of 1.89 ± 0.33 and 2.08 ± 0.28 mm, respectively. The morphometric results, showing that severe luminal narrowing occurred for both groups, were similar. The percentage area stenoses were 85 ± 5% for the control group and 84 ± 6% for the NO-eluting group. Histology demonstrated that profuse formation of neointima and an inflammatory cell infiltrate occurred. Conclusions. Severe diameter stenosis occurred both for control and for treatment groups. The degree of angiographic stenosis was markedly worse than that previously reported for this model. Sustained release of a precursor of NO did not prevent restenosis in this model. This might have been due to a lack of efficacy of nitric oxide or to a profuse and overwhelming stimulatory effect of the polymer in the coated stents. (C) 2000 Lippincott Williams and Wilkins.