RAPID AND SELECTIVE-INHIBITION OF PLATELET-AGGREGATION AND THROMBOXANE FORMATION BY INTRAVENOUS LOW-DOSE ASPIRIN IN MAN

1. One of the major problems in the clinical use of low dose aspirin f or the prevention of vascular occlusion is that it takes about 3-5 day s to become effective, a time too long for patients with unstable angi na or coronary thrombolysis. Intravenous aspirin may be expected to ex ert a more rapid effect, but its influence on endothelial prostacyclin synthesis is uncertain. 2. In a single-blind, randomized, prospective study, we compared the effects of a single intravenous low dose (50 m g) or high dose (500 mg) of aspirin or placebo infused over a 60 min p eriod on platelet aggregation, platelet thromboxane A2 production and whole-body prostanoid synthesis in 10 healthy male subjects by gas chr omatography-tandem mass spectrometry. 3. Before the study, blood flow rates in the basilic and subclavian veins were determined by sonograph ic colour velocity imaging; the infusion rate for low dose aspirin was calculated to avoid biologically effective plasma levels of aspirin i n the systemic circulation. 4. Platelet aggregation induced by 1 mmol/ l arachidonic acid was similarly inhibited by >85% within 30 min after the start of the infusion of high dose or low dose aspirin, respectiv ely, and remained suppressed for 24 h. Platelet thromboxane A2 release declined gradually after low dose aspirin, reaching a minimum of 93% inhibition after 60 min. High dose aspirin suppressed platelet thrombo xane A2 release to below the detection limit after 10 min. 5. Urinary excretion of the major urinary metabolite of thromboxane A2 (2,3-dinor -thromboxane B2) WaS equally suppressed by both dosages of aspirin [no significant difference between high dose (-83.2%) and low dose (-67.4 %)]. The urinary excretion of the major urinary metabolite of prostacy clin (2,3-dinor-6-keto-prostaglandin F1alpha) and of prostaglandin E2 was also markedly decreased, by 79.2% and 63.5%, respectively, by high dose aspirin, whereas low dose aspirin suppressed 2,3-dinor-6-keto-pr ostaglandin F1alpha excretion significantly less (-30.3%; P<0.02), and had no inhibitory effect at all on prostaglandin E2 excretion, indica ting that after intravenous low dose aspirin no biologically active ac etylsalicylate was present in the systemic circulation. 6. These data show that intravenous low dose aspirin can inhibit platelet aggregatio n and thromboxane B2 synthesis within less than 2 h while sparing syst emic cyclo-oxygenase activity. Partial inhibition of prostacyclin form ation seems to be an unavoidable consequence of effective inhibition o f platelet cyclo-oxygenase by aspirin.