Abstract
Saphenous vein grafting is associated with extensive medial remodeling, characterized by cellular proliferation, loss of smooth muscle cells, and an inflammatory response. In this study, we examined whether unfavorable responses to vein grafting could be modified by the intraoperative application of c-myc antisense oligomers. The intragraft cell proliferation, macrophage infiltration, and medial preservation were examined in a porcine model in the control and antisense-treated groups (n = 36). Saphenous veins showed transmural distribution of oligomers within 30 minutes of the ex vivo incubation. A concentration-dependent inhibition of cell proliferation in the media of saphenous grafts was noted 3 days later (0 to 200 mumol/L, p = 0.005). The growth inhibition was sequence-specific, because control oligomers produced only insignificant effects (20 mumol/L). Vascular effects of c-myc antisense were associated with a significant attenuation of macrophage infiltration in 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 of the arterialized venous conduits after c-myc antisense. Direct application of synthetic DNA to ...Continue Reading
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