Brief low-workload myocardial ischaemia induces protection against exercise-related increase of platelet reactivity in patients with coronary artery disease

OBJECTIVE: In patients with acute myocardial infarction, pre-infarction angina is associated with smaller infarct size, probably mainly through myocardial protection induced by ischaemic preconditioning. However, in models of recurrent thrombosis myocardial ischaemia also improves arterial patency. This study investigated whether myocardial ischaemia has any effect on platelet function in patients with coronary artery disease. PATIENTS AND DESIGN: Twenty patients with low-workload myocardial ischaemia underwent, in a randomised crossover study, two treadmill exercise stress tests (EST) on two separate days: a single maximal EST (EST-1) and a maximal EST (EST-2) performed 45 minutes after a low-workload EST stopped at 1-mm ST depression (p-EST). Platelet reactivity was evaluated by measuring the closure time in response to ADP/collagen by the PFA-100 method, and monocyte-platelet aggregate (MPA) formation and CD41 platelet expression, with and without ADP stimulation, by flow cytometry. RESULTS: Compared to resting values, closure time decreased at peak EST-1 (p<0.001) but not at peak EST-2. MPA after ADP stimulation increased more significantly at peak EST-1 compared with peak EST-2 (p<0.001). Repetition in seven patients of the pEST/EST-2 protocol after intravenous administration of the adenosine antagonist theophylline showed prevention of the effects of p-EST on exercise-induced platelet reactivity. CONCLUSIONS: A short episode of myocardial ischaemia induces protection against an exercise-induced increase of platelet reactivity. These data also suggest a role for adenosine in this phenomenon.