L -arginine polymers inhibit the development of vein graft neointimal hyperplasia

AbstractObjective: We sought to determine whether L -arginine polymer treatment of vein grafts enhances vascular production of nitric oxide and inhibits the development of neointimal hyperplasia. Methods: External jugular veins of New Zealand White rabbits (n = 42) were harvested; treated intraluminally for 15 minutes with phosphate-buffered saline solution or L -arginine polymer 5, 7, or 9 at either 10 or 100 μmol/L; and then grafted into the contralateral carotid artery. Rabbits were killed after 28 days, and 5-μm sections of vessels were stained with hematoxylin and scored for intima/media ratio by using computerized morphometric analysis. Separate veins were treated in a similar fashion with biotinylated polymers and phosphate-buffered saline solution to assess for translocation efficiencies. Finally, vein segments pretreated with either phosphate-buffered saline solution or L -arginine polymers were cultured in Dulbecco's modified Eagle's medium containing lipopolysaccharide (100 μg/mL) and interferon γ (200 U/mL) for 48 hours before measuring nitric oxide levels by means of the Griess reaction. Results: Biotinylated L -arginine polymers demonstrated a dose- and length-dependent uptake into intimal and medial cells of treated vessels. Nitric oxide levels were significantly higher in vein segments treated with 100 μmol/L of L -arginine polymer 9 compared with control segments. Finally, the intima/media ratio also reflected both length- and concentration-dependent inhibition of neointimal hyperplasia.intima/media ratioPBSR5R7R910 μmol/L0.909 ± 0.0720.920 ± 0.0730.861 ± 0.1380.710 ± 0.122100 μmol/L0.924 ± 0.0610.581 ± 0.089*0.529 ± 0.093**P <.001 versus phosphate-buffered saline solution and L -arginine polymer 5 controls (Bonferronicorrected value).PBS, Phosphate-buffered saline solution; R, L -arginine polymer.Conclusions: Arginine polymers of sufficient length and concentration were effective in increasing nitric oxide levels and reducing neointimal hyperplasia in this vein graft model. (J Thorac Cardiovasc Surg 2001;121:971-80