Related Experiment Videos
Platelet activation in unstable coronary disease
Insights
Platelet activation occurs during unstable angina and myocardial infarction, indicated by increased thromboxane and prostacyclin. This suggests targeted therapies for unstable angina, but not chronic stable angina.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Biochemistry
Background:
- Platelets are implicated in unstable angina and myocardial infarction pathogenesis.
- The link between platelet activation and episodic ischemia in unstable angina remains unclear.
Purpose of the Study:
- To investigate the relationship between platelet activation and episodic ischemia in patients with stable and unstable coronary disease.
- To assess thromboxane and prostacyclin biosynthesis as markers of platelet activation.
Main Methods:
- Physicochemical analysis of thromboxane and prostacyclin metabolites in plasma and urine.
- Correlating metabolite levels with clinical events like chest pain and creatine kinase levels.
Main Results:
- Prostacyclin biosynthesis was significantly elevated in acute myocardial infarction patients.
- Unstable angina patients showed the largest increase in thromboxane synthesis.
- Episodes of chest pain in unstable angina were often associated with increased thromboxane and prostacyclin metabolite excretion, sometimes occurring without chest pain (silent ischemia).
Conclusions:
- Platelet activation is a key event during spontaneous ischemia in unstable angina.
- Increased prostacyclin may be a compensatory endothelial response to limit platelet activation.
- Targeted inhibition of thromboxane A2 may benefit unstable angina treatment, while thromboxane inhibitors are unlikely to be effective for chronic stable angina.
Abstract:
Pathological and clinical studies have suggested that platelets have a role in the pathogenesis of unstable angina and myocardial infarction. However, the relation of platelet activation to episodic ischemia in patients with unstable angina is unknown. We assessed the biosynthesis of thromboxane and prostacyclin as indexes of platelet activation in patients with stable and unstable coronary disease by physicochemical analysis of metabolites in plasma and urine. Prostacyclin biosynthesis was markedly elevated in patients with acute myocardial infarction and correlated with plasma creatine kinase (r = 0.795; P less than 0.001). The largest rise in thromboxane synthesis was observed in patients with unstable angina, in whom 84 percent of the episodes of chest pain were associated with phasic increases in the excretion of thromboxane and prostacyclin metabolites. However, 50 percent of such increases were not associated with chest pain, possibly reflecting silent myocardial ischemia. These data indicate that platelet activation occurs during spontaneous ischemia in patients with unstable angina. The increment in prostacyclin biosynthesis during such episodes may be a compensatory response of vascular endothelium that limits the degree or effects of platelet activation. If so, biochemically selective inhibition of the synthesis or action of thromboxane A2 would be desirable in the treatment of unstable angina. In contrast, thromboxane inhibitors or antagonists would not be expected to be effective in patients with chronic stable angina, in whom there was no increase in the formation of thromboxane A2.