Aortocoronary vein bypass grafts occlude at the rate of approximately 37% within 12 years of surgery, with an additional one-half of patent grafts showing signs of atherosclerotic narrowing. Several million patients in the USA alone are therefore at risk of graft failure today. This has important medical and economic impact through loss of productivity, medication to treat symptoms, hospitalization, and procedures to correct the problem including angioplasty and redo vein bypass operations. The effect of platelet inhibitor therapy is to merely delay this process, not to prevent it. The proposed study is an interdisciplinary effort to test in a tightly controlled clinically relevant model whether dietary fish all alone or with additive pharmacological platelet inhibition can favorably modify the predisposition of vein grafts to undergo this degenerative atherosclerotic process that leads to graft failure. Our intent Is to elucidate fundamental information that is essential to determine whether such treatment is meritorious or harmful, to design future studies regarding the mechanism(s) for protection, and to construct meaningful clinical trials of risk factor modification. The treatment duration required to establish steady-state tissue levels of marine fatty acids will be delineated, along with the influence thereon of plasma lipid status and dose of fish oil. The correlation between tissue function and tissue levels of marine fatty acids will be determined. In a dose-response study, the effect of three different doses of fish oil on early graft lipid changes will be evaluated. other studies will include the influence of marine fatty acids on the physical properties of membranes, and their influence on the interaction of blood elements with the vein graft wall. The long-term effect of fish oil on graft composition and morphology will be evaluated alone and in combination with aspirin.
