LOCAL METHYLPREDNISOLONE INHIBITION OF FOREIGN-BODY RESPONSE TO COATED INTRACORONARY STENTS

Background When poly(organo)phosphazene coated metallic stents are imp lanted 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 infla mmation and they may stabilize lysosomal cell membranes. This study ai ms to evaluates the feasibility and efficacy of local corticosteroid d elivery by implantation of methylprednisolone loaded coronary stents i nto coronary arteries of pigs. Methods Tantalum balloon expandable cor onary stents were coated with poly(organo)phosphazene impregnated with 5 wt% methylprednisolone. Methylprednisolone release was calculated i n vitro and then randomly either a methylprednisolone loaded stent or a plain polymer-coated stent was implanted into the right coronary art ery 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 th e methylprednisolone loaded stents, when incubated in physiological sa line, released 96% of the drug within 24 h. Quantitative angiography o f 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 m m, P < 0.005) This angiographic finding was confirmed at post-mortem m orphometry where the respective values for neointimal thickness were 0 .99 +/- 0.28 and 1.74 +/- 0.84 mm (P < 0.02). Conclusions Polymer coat ed stents can be loaded with methylprednisolone which inhibits the sev ere foreign-body reaction induced by the combination of overstretch in jury and the poly(organo) phosphazene polymer coating of metallic sten ts.