The antithrombotic effect of aspirin and dipyridamole in relation to prostaglandin synthesis.
The antithrombotic effect of aspirin (ASA) and dipyridamole (DIP) was evaluated in rabbits in which platelet thromboxane A2 (TXA2) and arterial prostacyclin (PGI2) were measured. An intracarotid cannula thrombosis model previously shown to be sensitive to antiplatelet agents was used. Prostaglandins were determined by radioimmunoassays for thromboxane B2 (TXB2) and 6-keto-prostaglandin PGF1 alpha, the stable metabolites of TXA2 and PGI2. In the aspirin-treated animals, reduction in thrombosis was seen only in rabbits which received a low-dose (1-2 mg/kg), and was related to a selective suppression of platelet TXA2. In contrast, higher doses of ASA (10 or 100 mg/kg), which suppressed both TXA2 and PGI2, were not associated with thrombus inhibition. DIP alone had a lesser antithrombotic effect which was augmented by low-dose ASA but not by high-dose ASA. It is concluded that 1) the antithrombotic effect of ASA in this animal model is dependent on selective TXA2 suppression; 2) ASA has no antithrombotic properties beyond its inhibition of prostaglandin synthesis by platelets; 3) selective suppression of TXA2 in vivo can be achieved in rabbits by a single dose of ASA but only over a narrow dose-range; 4) DIP may have an antithrombotic effect additive to that of low-dose ASA; 5) measurement of serum TXB2 may be used to determine the minimal ASA dose necessary to suppress TXA2 and therefore be most likely to spare PGI2.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001241:Aspirin / Q000627:therapeutic use*; D004176:Dipyridamole / Q000627:therapeutic use*; D011464:Epoprostenol / Q000096:biosynthesis*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis*; D011817:Rabbits; D013927:Thrombosis / Q000378:metabolism / Q000517:prevention & control*; D013931:Thromboxanes / Q000096:biosynthesis
D005343:Fibrinolytic Agents; D011453:Prostaglandins; D013931:Thromboxanes; D015121:6-Ketoprostaglandin F1 alpha; D004176:Dipyridamole; D011464:Epoprostenol; D001241:Aspirin