EICOSANOID BIOSYNTHESIS IN PATIENTS WITH STABLE ANGINA - BENEFICIAL-EFFECTS OF VERY-LOW DOSE ASPIRIN

Objectives. We assessed the production of eicosanoids and the effects of very low dose aspirin in patients with stable angina under basal co nditions and during rapid atrial pacing. Background. Platelet activati on occurs in acute ischemic syn dromes but is still controversial in s table angina. Very low dose aspirin is known to be platelet selective and can be used to test the hypothesis of the platelet origin of incre ased thromboxane production in stable angina. Methods. Urinary excreti on of eicosanoids was measured in 42 patients, including 24 patients w ith and 18 patients without coronary artery disease. The effects of 50 mg/day of aspirin were measured at rest and during pacing induced isc hemia in 10 patients with stable angina and were compared with a simil ar group of patients not treated by aspirin. Results. Excretion of 11- dehydro-thromboxane B-2 was 2.6 times higher in patients with stable a ngina than in healthy subjects (mean [+/-SEM] 74.8 +/- 13.0 [24 patien ts] vs. 29.0 +/- 5.4 [18 patients] ng/mmol of creatinine, p < 0.01). U rinary prostacyclin metabolite levels did not differ between the two g roups. Treatment for 8 days with 50 mg/day of aspirin inhibited platel et cyclooxygenase, as reflected by the 97% reduction of in vitro serum thromboxane production. This aspirin regimen normalized the level of urinary thromboxane metabolites in patients with angina (17.3 +/- 3.4 ng/mmol of creatinine [10 patients], p < 0.001 from baseline level bef ore treatment) and did not change prostacyclin metabolite levels. Atri al pacing in patients with angina not treated with aspirin caused lact ate and thromboxane release into the coronary sinus. In patients with very low dose aspirin therapy, pacing did not cause thromboxane releas e despite inducing myocardial ischemia. However, fractional lactate ex traction decreased less sharply in patients with than without aspirin therapy. Conclusions. Thromboxane production is greatly increased in p atients with stable angina. Very low dose aspirin administered to thes e patients reduces thromboxane synthesis to normal levels, preserves p rostacyclin biosynthesis and prevents acute thromboxane release into t he coronary circulation during pacing induced ischemia. Our data sugge st that platelets (not monocytes/ macrophages) are activated in stable angina to produce thromboxane.