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J Thorac Cardiovasc Surg 1998;115:152-161
© 1998 Mosby, Inc.

SURGERY FOR CONGENITAL HEART DISEASE

Saphenous vein graft protection: Effects of c-myc antisense

From the Cardiovascular Research Center, Departments of Medicine (Cardiology)^a and Surgery (Cardiothoracic Surgery),^b Thomas JeffersonUniversity, Philadelphia, Pa., and Clinica Olivos, Buenos Aires, Argentina.^c Supported by Lynx Therapeutics, Hayward, Calif

Received for publication June 24, 1997. Accepted for publication August 29, 1997. Revisions requested August 12, 1997; revisions received August 27,1997. Address for reprints: Andrew Zalewski, MD, Thomas Jefferson University,Cardiovascular Research Center, Division of Cardiology, Suite 410N, 1025 WalnutSt., Philadelphia, PA 19107.

Objective:Saphenousvein grafting is associated with extensive medial remodeling, characterizedby cellular proliferation, loss of smooth muscle cells, and an inflammatoryresponse. In this study, we examined whether unfavorable responses to veingrafting could be modified by the intraoperative application of c-myc antisense oligomers.
Methods: The intragraft cell proliferation,macrophage infiltration, and medial preservation were examined in a porcinemodel in the control and antisense-treated groups (n = 36).
Results: Saphenous veins showed transmuraldistribution of oligomers within 30 minutes of the ex vivo incubation. A concentration-dependentinhibition of cell proliferation in the media of saphenous grafts was noted3 days later (0 to 200 µmol/L,p = 0.005). The growth inhibition was sequence-specific, becausecontrol oligomers produced only insignificant effects (20 µmol/L). Vasculareffects of c-myc antisense were associated with a significant attenuation of macrophage infiltrationin saphenous grafts. A concentration-dependent decrease in tissue edema (p = 0.0005)and the attenuated loss of smooth muscle cells (p = 0.002) were noted in the media ofthe arterialized venous conduits after c-myc antisense.
Conclusions: Direct application of syntheticDNA to harvested saphenous veins resulted in a rapid transmural distribution.The inhibition of the intragraft cell proliferation in vivo after c-myc antisense was sequence dependent.Decrease in vein graft injury resulted in an attenuated inflammatory responseand better medial preservation. These findings provide a rationale for assessmentof the long-term effects of vein graft protection with c-myc antisense.

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