Increased platelet sensitivity toward platelet inhibitors during physical exercise in patients with coronary artery disease

Generalized atherosclerosis and coronary artery disease (CAD) are associate d with endothelial dysfunction and during acute myocardial ischemia platele t activation has been reported. Activated platelets exert activated fibrino gen receptors (GP IIb/IIIa) and express CD 62p being regarded as reliable m arker for platelet activation. Patients with angiographically proven CAD pe rformed a bicycle exercise test until the onset of angina or ST-segment dep ression. We studied the ischemia-induced alterations in fibrinogen binding to activated platelet GP IIb/IIIa receptors and CD 62p expression. Therefor e, the basal fibrinogen binding to GP IIb/IIIa and CD 62p expression and th e thrombin-concentration for half-maximal platelet activation before and af ter exercise testing were determined. Additionally, inhibition of thrombin- induced platelet activation by increasing concentrations of the prostacycli n-analog iloprost and the NO-donor SIN-1 was examined. In patients with CAD , a significantly reduced basal activation and a highly significant reducti on in sensitivity towards thrombin was measured. The thrombin-induced expre ssion of GP IIb/IIIa and CD 62p was significantly diminished in patients wi th 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 p hysical exercise in patients with CAD and advanced atherosclerosis. Despite exercise induced myocardial ischemia as evidenced by angina and EGG-change s, 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 (PGI(2)) and nitric oxide, p robably due to an augmented release of endogenous platelet inhibitory media tors. (C) 1999 Elsevier Science Ltd. All rights reserved.