LOCAL-EFFECTS OF NITRIC-OXIDE SUPPLEMENTATION AND SUPPRESSION IN THE DEVELOPMENT OF INTIMAL HYPERPLASIA IN EXPERIMENTAL VEIN GRAFTS

Objectives: The universal response of vein grafts after insertion into the arterial circulation is the development of intimal hyperplasia; s mooth muscle cell proliferation and connective tissue deposition, whic h may be modulated in part by dysfunctional endothelial nitric oxide ( NO) metabolism. This study examines the effects of single dose, local application by pluronic gel of a NO donor, S-nitroso-N-acetylpenicilla mine (SNAP) and an NO synthase inhibitor nitro-L-arginine methyl ester (L-NAME) on the formation of intimal hyperplasia. Materials: Forty Ne w Zealand white rabbits underwent jugular vein interposition grafting of the common carotid artery. Design: Ten animals were controls, 10 an imals had the outer surface of the vein graft coated with 30% pluronic gel (2.5 ml), and 10 each were immersed for 15 min prior to insertion in Ringer lactate containing 10(-3)M of SNAP or L-NAME and then had t heir vein grafts coated with 2.5 ml of gel containing either SNAP (10( -3)M) or L-NAME (10(-3)M), which allows for sustained delivery for up to 6 h. On the 28th post operative day, the animals were sacrificed an d vein grafts were harvested for morphology by electron microscopy (SE M and TEM) and dimensional analysis by videomorphometry. Results: All vein grafts developed intimal hyperplasia. On SEM the vein grafts had a confluent layer of endothelial cells with multiple layers of smooth muscle cells representing intimal hyperplasia in TEM. There were no de monstrable morphological differences between the four groups. Local tr eatment with SNAP produced a significant 36% decrease in mean intimal thickness (72+/-4 mu m vs. 45+/-4 mu m; mean +/-S.E.M; p<0.01) without a change in medial thickness compared to gel-only treated groups (58/-6 mu m vs. 61+/-7 mu m; p=ns). Inhibition of NO synthase by L-NAME h ad no effect on the development of intimal hyperplasia (72+/-4 mu m vs 79+/-10 mu m; p=ns); medial thickness was also unchanged. Conclusion: These data confirm the protective effect of NO in vascular injury and suggest that NO synthase activity is either absent or reduced to such a level that further inhibition in this short time course is not rele vant to the pathophysiology of vein graft intimal hyperplasia.