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Ann Thorac Surg 1998;66:1948-1952
© 1998 The Society of Thoracic Surgeons

Original Articles

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

John D. Mannion, MDa, Michael L. Ormont, MDa, Michael G. Magno, PhDa, James E. O’Brien, MDa, Yi Shi, MD, PhDb, Andrew Zalewski, MDb

a Cardiovascular Research Center, Jefferson Medical College, Philadelphia, Pennsylvania, USA
b Departments of Surgery and Medicine, Jefferson Medical College, Philadelphia, Pennsylvania, USA

Address reprint requests to Dr. Mannion, Jefferson Medical College, 1025 Walnut Street, 607 College Building, Philadelphia, PA 19107
e-mail: (john.mannion{at}mail.tju.edu)

Presented at the Poster Session of the Thirty-fourth Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 26–28, 1998.

Background. Treatment of saphenous veins with c-myc antisense oligomers during preparation for grafting reduces medial cellular proliferation and macrophage infiltration, and preserves medial smooth muscle content at 3 days. Accordingly, the purpose of this study was to examine whether c-myc antisense 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 (control group) or 20-µmmol/L or 200-µmmol/L concentrations of c-myc antisense oligomers (treated groups) for 30 minutes intraoperatively. Three months after surgery, vein graft histology was assessed.

Results. Forty-five of 62 randomized animals survived the experiment; no differences in animal survival or graft patency among the groups were observed (p = NS, {chi}2). C-myc antisense oligomers significantly decreased neointimal and wall thickness, as well as increased lumenal index, in treated groups (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 antisense oligomers decreased neointimal formation at 3 months after grafting. In conjunction with our previous reports, these findings suggest that early inhibition of cellular proliferation and inflammatory infiltration results in a sustained reduction in neointimal formation and favorable graft remodeling.




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