VASCULAR PROSTACYCLIN IS INCREASED IN PATIENTS INGESTING OMEGA-3 POLYUNSATURATED FATTY-ACIDS BEFORE CORONARY-ARTERY BYPASS GRAFT-SURGERY

Interest in the antithrombotic potential of diets enriched with fish oil-derived polyunsaturated fatty acids (ω-3 PUFAs) prompted us to examine how these fatty acids, when taken preoperativeiy, affect hemostasis, plasma lipid levels, and production of prostacyclin (PGI2) by vascular tissues in atherosclerotic patients undergoing coronary artery bypass graft surgery. Fifteen patients with angiographically proven coronary artery disease received 3 g/day eicosapentaenoic acid and 1.3 g/day docosahexaenoic acid as capsules of purified fish oil for 28 days before surgery. Platelet aggregation induced by low concentrations of ADP, collagen, and epinephrine decreased (p<0.05) and serum thromboxane B2 decreased 36% (p<0.01) from baseline values. Bleeding times increased 40% (p<0.01) from baseline. Serum triglycerides decreased 50% (p<0.05) without a change in total serum cholesterol. Spontaneous production of PGI2 measured as 6-ketoprostaglandin F1α (6-keto-PGF1α), its stable hydrolytic product, by saphenous vein and aortic and atrial tissues obtained at surgery was greater in tissues from patients receiving ù-3 PUFA supplements than in tissues from matched controls (13.8±2.2 versus 8.6, 21.0±3.1 versus 11.5±2.1, and 166±13 versus 102±15 ng/g, respectively, all p<0.05). Arachidonate-stimulated production of PGI2, as indicated by increased levels of 6-keto-PGF1a, was also increased. Despite changes in platelet function, bleeding time, and vascular PGI2, the perioperative blood loss was not increased in subjects receiving fish oil supplements. Thus, ω-3 PUFAs at moderate dosages may exert antithrombotic effects by increasing prostacyclin production by vessel walls as well as by direct inhibition of platelet activity.