Biologic response to polymer-coated stents: in vitro analysis and results in an iliac artery sheep model.

PURPOSE: To evaluate biologic response to poly(hydroxymethyl-p-xylylene-co-p-xylylene) (PHPX)-coated stents in vitro and in vivo in sheep. MATERIALS AND METHODS: Physical stability, hemocompatibility, and cytotoxicity of the coating were first assessed in vitro. Thirty-six self-expanding nitinol (Memotherm), 24 stainless steel balloon-mounted (Palmaz), and 12 self-expanding nitinol (ZA) stents were coated with PHPX by using chemical vapor deposition polymerization. Seventy-two coated and 72 uncoated stents were placed into iliac arteries of 36 sheep. Sheep were classified into three groups of 12 animals each. In each group, six sheep were killed after 1 month; six, after 6 months. In each sheep, two uncoated stents were placed into one limb; two coated stents of the same type, into the opposite limb. In groups 1 and 2, Palmaz and Memotherm stents were used; in group 3, Memotherm and ZA stents were used. In groups 1 and 3, arteries were healthy. In group 2, arteries were pretreated with a Fogarty maneuver. Stent patency was measured with intravascular ultrasonography (US) and histologic analysis. Cellular response to coated and uncoated stents was assessed. Measurements were compared (Wilcoxon test). RESULTS: In vitro, PHPX coating was stable; hemocompatibility and cytotoxicity were similar to those of stainless steel. In vivo, patency of coated and uncoated Palmaz and ZA stents was not different (P >.05). Patency of coated and uncoated Memotherm stents did not differ in four of six follow-up subgroups, but it was significantly reduced in group 2 after 6 months (intravascular US, P =.03; histologic analysis, P =.01) and in group 3 after 1 month (histologic analysis, P =.01). Histologically, the cellular response to coated and uncoated stents was not different (P >.05). CONCLUSION: PHPX coating had good physical stability and biocompatibility in vitro and in vivo. Performance of coated and uncoated Palmaz and ZA stents was similar. Patency of Memotherm stents was similar in four of six follow-up subgroups. Materials effects did not result in severely enhanced neointimal hyperplasia.

Inhibition of neointimal proliferation with 188Re-labeled self-expanding nitinol stent in a sheep model.

PURPOSE: To evaluate a self-expanding rhenium 188 (188Re) radiochemically labeled radioactive stent in sheep. MATERIALS AND METHODS: A self-expanding nitinol stent (30 mm in length, 8 mm in diameter) coated with a functionalized polymer layer was radiolabeled with 188Re. Fifty prostheses, 25 of which were radioactive (mean radioactivity, 20 MBq +/- 3.8 [SD]) and 25 of which were nonradioactive, were implanted into the external iliac arteries of 25 sheep. Stent patency was assessed with angiography. Neointimal formation was assessed with intravascular ultrasonography and histologic examination 1 month (in all sheep) and 3 months (in 12 sheep) after implantation. The results were analyzed by using repeated-measures analysis of variance with two repeated factors and paired t tests for comparison at each measuring point. RESULTS: All stents were placed successfully. Data in one animal had to be excluded from the study. After 3 months, a mean neointimal area reduction of 70 mm2 +/- 55 (SD) was observed inside the radioactive stents, and a mean lumen reduction of 126 mm2 +/- 39 was observed inside the nonradioactive control stents (P =.022). An edge effect was observed in the radioactive stents in that they showed an amount of neointimal formation at the edges that was similar to that seen in control stents. This neointimal formation accounted for the maximum lumen loss in the vascular segment with the stent. CONCLUSION: As compared with a nonradioactive stent, a beta particle-emitting stent, through endovascular irradiation, significantly inhibits neointimal formation inside the stent but not at the stent edges.