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Increased platelet sensitivity toward platelet inhibitors during physical exercise in patients with coronary artery
S Lindemann1, B Klingel, A Fisch
1Department of Medicine II, Johannes Gutenberg-University, Mainz, Germany.
Insights
Platelets in patients with coronary artery disease (CAD) show reduced activation during exercise-induced myocardial ischemia. These platelets are more sensitive to inhibitory agents like prostacyclin and nitric oxide.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Platelet Biology
Background:
- Coronary artery disease (CAD) is linked to endothelial dysfunction.
- Acute myocardial ischemia can trigger platelet activation.
- Activated platelets express GP IIb/IIIa receptors and CD 62p, markers of activation.
Purpose of the Study:
- To investigate ischemia-induced alterations in platelet activation markers.
- To assess changes in fibrinogen binding to GP IIb/IIIa receptors and CD 62p expression.
- To evaluate platelet sensitivity to thrombin and inhibitory agents before and after exercise in CAD patients.
Main Methods:
- Patients with proven CAD underwent bicycle exercise testing.
- Basal and thrombin-induced platelet activation (GP IIb/IIIa, CD 62p) were measured.
- Inhibition of platelet activation by iloprost and SIN-1 was examined.
Main Results:
- Patients with CAD exhibited reduced basal platelet activation and thrombin sensitivity.
- Exercise-induced myocardial ischemia led to diminished GP IIb/IIIa and CD 62p expression.
- CAD platelets showed increased sensitivity to iloprost and SIN-1 after exercise.
Conclusions:
- Platelet activation is significantly reduced during exercise-induced ischemia in CAD patients.
- Despite ischemia, platelets are not generally activated, suggesting counter-regulatory mechanisms.
- Enhanced sensitivity to prostacyclin and nitric oxide may result from increased endogenous inhibitory mediators.
Abstract:
Generalized atherosclerosis and coronary artery disease (CAD) are associated with endothelial dysfunction and during acute myocardial ischemia platelet activation has been reported. Activated platelets exert activated fibrinogen receptors (GP IIb/IIIa) and express CD 62p being regarded as reliable marker for platelet activation. Patients with angiographically proven CAD performed a bicycle exercise test until the onset of angina or ST-segment depression. We studied the ischemia-induced alterations in fibrinogen binding to activated platelet GP IIb/IIIa receptors and CD 62p expression. Therefore, the basal fibrinogen binding to GP IIb/IIIa and CD 62p expression and the thrombin-concentration for half-maximal platelet activation before and after exercise testing were determined. Additionally, inhibition of thrombin-induced platelet activation by increasing concentrations of the prostacyclin-analog iloprost and the NO-donor SIN-1 was examined. In patients with CAD, a significantly reduced basal activation and a highly significant reduction in sensitivity towards thrombin was measured. The thrombin-induced expression of GP IIb/IIIa and CD 62p was significantly diminished in patients with CAD after physical exercise and their platelets were significantly more sensitive towards the inhibitory effects of iloprost and SIN-1. These data demonstrate a significant reduction in platelet activation in response to physical exercise in patients with CAD and advanced atherosclerosis. Despite exercise induced myocardial ischemia as evidenced by angina and ECG-changes, the platelets are not generally activated, as it could be expected. Thus, patients with myocardial ischemia experienced a reduced platelet activity and enhanced sensitivity towards prostacyclin (PGI2) and nitric oxide, probably due to an augmented release of endogenous platelet inhibitory mediators.