The influence of dose, time of administration, body temperature and salicylate kinetics on the antithrombotic action of acetylsalicylic acid in male rats.

Acetylsalicylic acid (ASA), given i.v. to male rats 10 min before electrical injury to the carotid artery, was found to reduce rate and extent of thrombosis at 3.3 and 10.0 mg/kg but not at 1.7, 20 or 100 mg/kg, indicating a narrow, low-dose window for antithrombotic effect. ASA was more effective in rats in which body temperature was allowed to fall greater than 0.5 degrees C but protection was lost if injury was delayed 15 min or more after ASA administration. Serum salicylate studies did not support the view that loss of protection was due to competition between salicylate and ASA for cyclooxygenase-binding sites. ASA was also protective at 200 mg/kg i.v., possibly through non-specific toxic effects.