Effects of a selective thromboxane synthetase inhibitor, dazoxiben, and of acetylsalicylic acid on myocardial ischemia in patients with coronary artery disease.
Thromboxane A2 (TxA2) may aggravate myocardial ischemia by inducing vasoconstriction and platelet aggregation in small coronary vessels, whereas prostacyclin (PGI2) counteracts these effects. Acetylsalicylic acid (ASA) inhibits the formation of TxA2 as well as PGI2, whereas dazoxiben, a thromboxane synthetase inhibitor, reduces TxA2 formation selectively. In 25 patients with coronary artery disease, 2 identical atrial pacing stress tests were performed: before and after the administration of dazoxiben (200 mg) in 15 patients and before and after ASA (250 mg) in 10. The ischemic response, quantified by coronary sinus and aortic lactate levels and by ST depression, was significantly reduced after administration of dazoxiben (p less than 0.02) but not after ASA. Heart rate at rest, myocardial extraction of free fatty acids and the arteriovenous oxygen difference was unaffected by medication. Both drugs reduced TxB2 levels to the same extent, whereas collagen-induced aggregation was more reduced after ASA than after dazoxiben. The effect of dazoxiben on ischemia was probably a result of inhibited TxA2 and preserved PGI2 production, which increased blood flow to ischemic regions.
D001241:Aspirin / Q000627:therapeutic use*; D002304:Cardiac Pacing, Artificial; D003327:Coronary Disease / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D007773:Lactates / Q000097:blood; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D007773:Lactates; C029166:dazoxiben; D010088:Oxidoreductases; D013930:Thromboxane-A Synthase; D001241:Aspirin