Articles |
From the Cardiology Department (E.J.L., R.J.W.), King's College Hospital, and the Department of Medicine (E.J.L., J.F.M.), King's College School of Medicine, London, England.
Correspondence to Prof J.F. Martin, Professor of Cardiovascular Science, Department of Medicine, King's College School of Medicine, Bessemer Rd, London SE5 9PJ, UK.
Abstract Platelet activation and thrombus formation within the coronary artery are major factors in acute myocardial infarction (AMI) and unstable angina (UA), and continuing platelet activation is associated with an adverse prognosis. We assessed platelet activation by using flow cytometry to measure platelet surface expression of P-selectin and glycoprotein IIb/IIIa in 20 patients with AMI and 20 with UA, all of whom were treated 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 platelets from AMI and 2.3% (range, 1.6% to 3.3%) from UA subjects compared with 1.0% (range, 0.6% to 1.9%) of platelets from 20 control volunteers without angina (P<.001). Glycoprotein IIb/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 both AMI and UA, S-nitrosoglutathione reduced P-selectin (P<.001) and glycoprotein IIb/IIIa (P<.05) expression, as did glyceryl trinitrate (P<.02 and P<.01, respectively). In 3 of 20 patients receiving glyceryl trinitrate the lowest dose was not tolerated due to headache or hypotension. 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 better tolerated at the doses required.
Key Words: myocardial infarction unstable angina platelets nitric oxide
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