Dietary fish oil accelerates the response to coronary thrombolysis with tissue-type plasminogen activator. Evidence for a modest platelet inhibitory effect in vivo.
To assess the platelet inhibitory effect of high doses of fish oils and relate it to alterations in eicosanoid synthesis, we used a canine model in which coronary thrombosis, the time to reperfusion induced by recombinant tissue-type plasminogen activator (rt-PA), and the rate of spontaneous reocclusion are sensitive to platelet inhibition. In the animals fed fish oil, the time to rt-PA induced thrombolysis was accelerated (mean, 63 vs. 27 minutes; p less than 0.003). The time to thrombotic occlusion and the rate of reocclusion were unaltered. The ratio of eicosapentaenoic acid (EPA) to arachidonic acid rose in platelet and endothelial cell membranes, whereas serum thromboxane (Tx) B levels fell a mean 86%, and basal excretion of 2,3-dinor-TxB2 (TxA2-M) declined. Basal prostaglandin (PG) I2 formation was unaltered, whereas biosynthesis of EPA-derived TxA3 and PGI3 increased. In control animals, TxA2 formation increased during thrombosis; there was a further, more marked rise during reperfusion. PGI2 formation also increased, probably as a response to platelet-vascular interactions. Stimulated production of both eicosanoids was strikingly suppressed in the animals fed fish oil. Fish oils significantly enhance the efficacy of rt-PA in vivo, albeit to a modest extent. Because the time to reperfusion is highly sensitive to Tx-dependent platelet activation, this effect is likely to reflect the demonstrated suppression of TxA2 biosynthesis by fish oils.
Braden
G A
GA
Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN 37232.
Knapp
H R
HR
Fitzgerald
D J
DJ
FitzGerald
G A
GA
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology*; D003328:Coronary Thrombosis / Q000378:metabolism / Q000503:physiopathology*; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D004285:Dogs; D011464:Epoprostenol / Q000096:biosynthesis; D005395:Fish Oils / Q000494:pharmacology*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000096:biosynthesis; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D004042:Dietary Fats, Unsaturated; D005395:Fish Oils; D008563:Membrane Lipids; D010743:Phospholipids; D010975:Platelet Aggregation Inhibitors; D013928:Thromboxane A2; D011464:Epoprostenol; D010959:Tissue Plasminogen Activator