SS7. Antioxidant Therapy Reverses Impaired Graft Healing in Hypercholesterolemic Rabbits

Article Outline

• Objective
• Methods
• Results
• Conclusions
• Copyright

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Objective 

Limited endothelial cell coverage and anastomotic intimal hyperplasia contribute to thrombosis and failure of prosthetic grafts. Lipid accumulation and lipid oxidation are associated with decreased endothelial cell migration and intimal hyperplasia. The goal of this study was to assess the ability of antioxidants to improve graft healing under hypercholesterolemic conditions.

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Methods 

Rabbits were placed on one of four diets: chow plus N-acetylcysteine, chow plus probucol, chow with 1% cholesterol plus N-acetylcysteine, or chow with 1% cholesterol plus probucol. After two weeks, 12 cm long, 4 mm internal diameter expanded polytetrafluoroethylene grafts were implanted in the abdominal aorta. Six weeks after implantation, the grafts were removed and analyzed for cholesterol content, endothelial cell coverage, anastomotic intimal thickness, and the cellular composition of the neointima. Plasma samples were obtained to assess systemic oxidative stress levels. The data was compared with previously reported data from animals on a chow and chow plus 1% cholesterol diet.

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Results 

Prosthetic grafts from rabbits on a 1% cholesterol diet had significantly greater anastomotic intimal thickening and lower endothelial cell coverage than grafts from rabbits on a chow diet. Antioxidant therapy decreased global oxidative stress in hypercholesterolemic rabbits. In rabbits on the 1% cholesterol diet, N-acetylcysteine decreased intimal hyperplasia atthe proximal anastomosis by 29% and significantly increased graft endothelial cell coverage from 46% to 71% (P = .03). Similarly, probucol decreased intimal hyperplasia by 43% and increased graft endothelial cell coverage to 53% in hypercholesterolemic rabbits.

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Conclusions 

Endothelialization of prosthetic grafts is significantly reduced and anastomotic intimal hyperplasia is significantly increased in rabbits on a high cholesterol diet. Treatment with antioxidants improves endothelial cell coverage and decreases intimal hyperplasia. Reducing oxidative stress may promote patency of prosthetic grafts.