SAPHENOUS-VEIN GRAFT PROTECTION - EFFECTS OF C-MYC ANTISENSE

Objective: Saphenous vein grafting is associated with extensive medial remodeling, characterized by cellular proliferation, loss of smooth m uscle cells, and an inflammatory response, In this study,we examined w hether unfavorable responses to vein grafting could be modified by the intraoperative application of c-myc antisense oligomers, Methods: The intragraft cell proliferation, macrophage infiltration, and medial pr eservation were examined in a porcine model in the control and antisen se treated groups (n = 36), Results: Saphenous veins showed transmural distribution of oligomers within 30 minutes of the ex vivo incubation , A concentration-dependent inhibition of cell proliferation in the me dia of saphenous grafts was noted 3 days later (0 to 200 mu mol/L, p = 0.005). The growth inhibition was sequence-specific, because control oligomers produced only insignificant effects (20 mu mol/L). Vascular effects of c-myc antisense were associated with a significant attenuat ion of macrophage infiltration in saphenous grafts. A concentration-de pendent 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 arte rialized venous conduits after c-myc antisense. Conclusions: Direct ap plication of synthetic DNA to harvested saphenous veins resulted in a rapid transmural distribution, The inhibition of the intragraft cell p roliferation in vivo after c-myc antisense was sequence dependent, Dec rease in vein graft injury resulted in an attenuated inflammatory resp onse and better medial preservation, These findings provide a rational e for assessment of the long-term effects of vein graft protection wit h c-myc antisense.