Background: When poly(organo)phosphazene coated metallic stents are implanted into normal coronary arteries of pigs a severe histolymphocytic and fibromuscular reaction is induced. Corticosteroids possess potent anti-inflammatory and immunosuppressive effects, they have been shown to decrease migration and functional capability of the cells of inflammation and they may stabilize lysosomal cell membranes. This study aims to evaluates the feasibility and efficacy of local corticosteroid delivery by implantation of methylprednisolone loaded coronary stents into coronary arteries of pigs.
Methods: Tantalum balloon expandable coronary stents were coated with poly(organo)phosphazene impregnated with 5 wt% methylprednisolone. Methylprednisolone release was calculated in vitro and then randomly either a methylprednisolone loaded stent or a plain polymercoated stent was implanted into the right coronary artery of 20 pigs. Quantitative coronary artery analysis was done before, immediately after and 6 weeks after stent implantation. The pigs were then killed and the stented arteries processed for histopathological and morphometric evaluation.
Results: In-vitro testing revealed that the methylprednisolone loaded stents, when incubated in physiological saline, released 96% of the drug within 24 h. Quantitative angiography of the implanted stents showed similar angiographic parameters in both treatment groups immediately after implantation, but, after 6 weeks of follow-up study the minimal luminal diameter of the stented arterial segment was considerably larger in the methylprednisolone-treated pigs than it was in the control pigs (2.74 +/- 0.34 versus 1.36 +/- 0.72 mm, P < 0.005) This angiographic finding was confirmed at post-mortem morphometry where the respective values for neointimal thickness were 0.99 +/- 0.28 and 1.74 +/- 0.84 mm (P < 0.02).
Conclusions: Polymer coated stents can be loaded with methylprednisolone which inhibits the severe foreign-body reaction induced by the combination of overstretch injury and the poly(organo)phosphazene polymer coating of metallic stents.