Beneficial effects of ibuprofen in pacing-induced myocardial ischemia

Lysosomal membrane instability and platelet activation are both associated with acute myocardial ischemia. The effect of ibuprofen on cathepsin D as a marker of lysosomal membrane "leakiness" and thromboxane B2 as a marker of platelet activation was evaluated in 44 patients with angina pectoris. Samples of blood analyzed for cathepsin D, thromboxane B2, and lactate were withdrawn from the coronary sinus and brachial artery before and after pacing to 140 beats/min for 4 minutes. Myocardial ischemia was assessed by determination of transmyocardial lactate extraction or production. Ibuprofen (800 mg) or placebo was administered orally 2 hours before cardiac catheterization. Patients were classified into 4 groups on the basis of administration of placebo or ibuprofen and the presence or absence of myocardial ischemia as determined by demonstration of lactate extraction or production after atrial pacing. In patients with lactate extraction, no significant efflux of cathepsin D or thromboxane B2 occurred after pacing. In patients with lactate production given placebo, a 64 +/- 25% increase in the thromboxane B2 level and a 113 +/- 37% increase in cathepsin D activities occurred in the coronary sinus effluent sampled after pacing. In contrast, in patients with comparable coronary artery disease and comparable lactate production who were given ibuprofen, no release of thromboxane B2 (p = 0.05 compared with patients given placebo) or cathepsin D (p less than 0.01 compared with patients given placebo) occurred after pacing-induced ischemia. These findings suggest that ibuprofen stabilizes membranes and prevents platelet-activated release of thromboxane A2 in pacing-induced myocardial ischemia.