Sustained reduction of neointima with c-myc antisense oligonucleotides in saphenous vein grafts

Background. Treatment of saphenous veins with c-myc antisense oligomers dur ing preparation for grafting reduces medial cellular proliferation and macr ophage infiltration, and preserves medial smooth muscle content at 3 days. Accordingly, the purpose of this study was to examine whether c-myc antisen se oligomers have an impact on late vein graft remodeling. Methods. Sixty-two pigs underwent unilateral saphenous vein-carotid artery interposition grafting. Harvested veins were incubated either in saline (co ntrol group) or 20-mu mmol/L or 200-mu mmol/L concentrations of c-myc antis ense oligomers (treated groups) for 30 minutes intraoperatively. Three mont hs after surgery, vein graft histology was assessed. Results. Forty-five of 62 randomized animals survived the experiment; no di fferences in animal survival or graft patency among the groups were observe d (p = NS, chi(2)). C-myc antisense oligomers significantly decreased neoin timal and wall thickness, as well as increased lumenal index, in treated gr oups (p < 0.04, p < 0.03, and p < 0.001, respectively, analysis of variance ). In contrast, there was no difference in medial thickness or perivascular wound healing. Conclusion. Intraoperative treatment of saphenous veins with c-myc antisens e oligomers decreased neointimal formation at 3 months after grafting. In c onjunction with our previous reports, these findings suggest that early inh ibition of cellular proliferation and inflammatory infiltration results in a sustained reduction in neointimal formation and favorable graft remodelin g. (C) 1998 by The Society of Thoracic Surgeons.