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Platelet activation in acute myocardial infarction and unstable angina is inhibited by nitric oxide donors
E J Langford1, R J Wainwright, J F Martin
1Cardiology Department, King's College Hospital, London, UK.
Insights
Platelet activation persists in acute myocardial infarction (AMI) and unstable angina (UA) despite aspirin. Nitric oxide donors, particularly S-nitrosoglutathione, effectively inhibit this activation and are well-tolerated in patients.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Pharmacology
Background:
- Platelet activation and thrombus formation are critical in acute myocardial infarction (AMI) and unstable angina (UA).
- Persistent platelet activation correlates with adverse prognosis in these conditions.
- Aspirin is a standard antiplatelet therapy, but its efficacy may be limited in some patients.
Purpose of the Study:
- To assess persistent platelet activation in patients with AMI and UA despite aspirin treatment.
- To evaluate the inhibitory effect of nitric oxide donors (glyceryl trinitrate and S-nitrosoglutathione) on platelet activation markers.
- To compare the tolerability of different nitric oxide donors in this patient population.
Main Methods:
- Flow cytometry was used to measure P-selectin and glycoprotein IIb/IIIa expression on platelets.
- Platelet activation was assessed in 20 patients with AMI and 20 with UA, all on aspirin therapy.
- Measurements were repeated after infusion of glyceryl trinitrate or S-nitrosoglutathione, monitoring for hemodynamic changes.
Main Results:
- Patients with AMI and UA showed significantly higher P-selectin and glycoprotein IIb/IIIa expression compared to controls (P < .001 and P < .01, respectively).
- Both glyceryl trinitrate and S-nitrosoglutathione significantly reduced P-selectin and glycoprotein IIb/IIIa expression in AMI and UA patients (P < .001 to P < .02).
- S-nitrosoglutathione was better tolerated than glyceryl trinitrate, with fewer adverse events like headache or hypotension.
Conclusions:
- Platelet activation remains significant in AMI and UA patients even with aspirin therapy.
- Nitric oxide donors, especially S-nitrosoglutathione, can effectively inhibit this persistent platelet activation.
- S-nitrosoglutathione presents a well-tolerated therapeutic option for managing platelet activation in these cardiovascular conditions.
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.