Perivascular nitric oxide delivery to saphenous vein grafts prevents graft stenosis after coronary artery bypass grafting: a novel sheep model.

OBJECTIVES: Graft stenosis is a major complication of coronary artery bypass grafting with autologous saphenous vein grafts. Nitric oxide (NO) is believed to prevent this phenomenon. We studied the effect of perivascular application of an NO donor on the degree of stenosis of such grafts in an ovine model. METHODS: Twenty white Iranian ewes were randomized to coronary artery bypass grafting using autologous saphenous vein grafts with application of an elastomer gel containing diethylenetriamine NO adduct in 0.9% sodium chloride solution around the grafted vessel (intervention group) or with the gel containing the saline solution alone (controls). Graft vessels were studied after 1 year using spot angiography and histological examination. RESULTS: The mean degree of stenosis was significantly lower in the intervention group than in the controls as found by histology (92.3 ± 5.5 vs. 80.9 ± 8.3%; p = 0.004). Although the difference in the angiographic score was not significant, the mean score was still lower in the intervention group (9.5 ± 11.3 vs. 12.0 ± 11.8). CONCLUSIONS: Perivascular application of an NO donor was, at least histologically, effective in reducing graft stenosis in our ovine model. This can be a step toward the development of drug-eluting coronary artery bypass grafts.

Atherosclerosis and vascular injury: the effect of a perivascular nitric oxide donor in a cholesterol-fed rabbit model.

Nitric oxide (NO) has been shown to prevent neointimal hyperplasia and decrease atherosclerosis in several animal models. It is a major modulator of vascular homeostasis and has vasoprotective effects against atherosclerosis. However, NO-based therapies with such purposes have not been used in the clinical arena. Our objective was to combine a medical grade elastomer and an NO donor, diethylenetriamine NO adduct (DETA/NO), to determine whether its perivascular administration can attenuate atherosclerosis and vascular injury. Aortic intimal injury was produced using paediatric pulmonary valvoplasty catheter in 22 healthy male New Zealand White rabbits, which were fed a high-cholesterol diet for 4 weeks beforehand. A mixture of the elastomer Silastic and DETA/NO was applied locally to cover the aortas in the experiment group. After 6 additional weeks on the high-cholesterol diet, the aortas and blood samples were harvested for pathologic analysis and comparison with the control group. Mean atherosclerosis and vascular injury surface area was 6.68 x 10(5) microm2 in the experiment group, compared with 3.44 x 10(5) microm2 in the controls. However, there was no statistically significant difference in atherosclerotic surface area between the two groups. Perivascular application of the NO donor DETA/NO, in the concentration we used, did not prevent atherosclerosis in high cholesterol-fed rabbits. This finding prompts more careful assessment before possible clinical uses.