Modulation of fibrinolytic response to venous occlusion in humans by a combination of low-dose aspirin and n-3 polyunsaturated fatty acids.
Aspirin at high but not at low doses reduces the fibrinolytic response to venous occlusion. Inhibition of vascular prostacyclin synthesis could be involved in this effect. Fish oil supplementation may redirect prostanoid metabolism toward an overall "antithrombotic" condition but with controversial effects on prostacyclin formation. In this study we investigated the effect of low-dose aspirin together with n-3 polyunsaturated fatty acid (PUFA) supplementation on the fibrinolytic response to venous occlusion. Following a double-blind, randomized, crossover design, six healthy volunteers (three men and three women, 24-37 years old) were given for 29 days 5.3 g eicosapentaenoic and docosahexaenoic acids or a corresponding dose of n-6 PUFAs as control; aspirin (40 mg/day) was then added for an additional 14 days. A 2-month washout period was allowed before the crossover. Blood was collected before and after venous stasis on days 0, 29, and 43 of each test period. A combination of aspirin with n-3 PUFAs reduced the fibrinolytic response to venous occlusion in all subjects, the mean value of fibrinolytic activity after stasis being 240 +/- 40 mm2, a value significantly lower than at baseline (366 +/- 51 mm2, mean +/- SEM, p < 0.05). Similarly, the tissue-type plasminogen activator (t-PA) antigen level was lower in the aspirin + PUFA-treated group. Plasminogen activator inhibitor activity before stasis was enhanced by n-3 PUFA supplementation (from 7.5 +/- 2 to 14.8 +/- 3 IU/ml, p < 0.05), an effect not affected by aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)
Iacoviello
L
L
Istituto di Ricerche Farmacologiche Mario Negri-Consorzio Mario Negri Sud Santa Maria Imbaro, Italy.
Amore
C
C
De Curtis
A
A
Tacconi
M T
MT
de Gaetano
G
G
Cerletti
C
C
Donati
M B
MB
D000328:Adult; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004311:Double-Blind Method; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D017293:Protein S / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000097:blood; D014689:Venous Insufficiency / Q000097:blood
D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D017395:Plasminogen Activator Inhibitor 1; D017293:Protein S; D005340:Fibrinogen; D010959:Tissue Plasminogen Activator; D001241:Aspirin