PLATELET ACTIVATION IN ACUTE MYOCARDIAL-INFARCTION AND UNSTABLE ANGINA IS INHIBITED BY NITRIC-OXIDE DONORS

Platelet activation and thrombus formation within the coronary artery are major factors in acute myocardial infarction (AMI) and unstable an gina (UA), and continuing platelet activation is associated with an ad verse prognosis. We assessed platelet activation by using flow cytomet ry to measure platelet surface expression of P-selectin and glycoprote in IIb/IIIa in 20 patients with AMI and 20 with UA, all of whom were t reated with aspirin. Platelet studies were repeated after the infusion of a nitric oxide donor (glyceryl trinitrate or S-nitrosoglutathione) that produced a fall in mean arterial pressure of no more than 10 mm Hg. P-selectin was expressed on 2.5% (range, 1.4% to 6.3%) of platelet s from AMI and 2.3% (range, 1.6% to 3.3%) from UA subjects compared wi th 1.0% (range, 0.6% to 1.9%) of platelets from 20 control volunteers without angina (P<.001). Glycoprotein Ilb/IIIa expression was 101.6 +/ - 2.7 arbitrary units of relative fluorescence in AMI and 100.2 +/- 3. 3 in UA compared with 87.8 +/- 2.5 in control subjects (P<.01). In bot h AMI and UA, S-nitrosoglutathione reduced P-selectin (P<.001) and gly coprotein IIb/IIIa (P<.05) expression, as did glyceryl trinitrate (P<. 02 and P<.01, respectively). In 3 of 20 patients receiving glyceryl tr initrate the lowest dose was not tolerated due to headache or xhypoten sion. These findings show that platelet activation persists in AMI and UA despite aspirin treatment and that this can be inhibited by using glyceryl trinitrate or S-nitrosoglutathione. S-nitrosoglutathione is b etter tolerated at the doses required.