Aspirin as a Potlwial Antithrombotic Drug: An Experimental Approach for more Rational Clinical Use

Blood platelets and vascular walls generate prostaglandin (PG) derivatives with oppening effects. Since aspirin (ASA) inhibits synthesis of common precursors of these derivatives, the rationale for its clinical use in thrombosis prevention trials has been questioned. This is an experimental approach to this important therapeutic dilemma. Male CD rats (250-350g) were given a single i.p. dose of ASA (0.5-200mg/kg) and killed from 1 to 120 h thereafter. Platelet PG production was measured by a thiobarbiturate assay of malondialdehyde (MDA) under thrombin (25u/ml) stimulation. Vascular PG activity released from rings of abdominal aorta and inferior vena cava was determined as platelet aggregation inhibitory potency and characterized as PGI₂ by standard criteria. The inhibitory effect of ASA lasted longer in platelets (96-120 h) than in venous (24-48 h) or arterial tissues (<24 h). Platelets were more sensitive to ASA (ID₅₀=3.6mg/kg) than arterial tissues (ID₅₀=25mg/kg) but as sensitive as venous tissues (ID₅₀=2.3mg/kg) when PG synthesis was measured 1 h after treatment. The proposed unique sensitivity of platelet cyclo-oxygenase to ASA therefore needs reconsidering. ASA’s effect on various systems might be better dissociated based on the different duration of inhibition. We suggest that the lowest single dose of ASA totally inhibiting platelet PG synthesis should be given at the longest possible intervals.