Impaired antiplatelet effects of aspirin associated with hypoxia and ATP release from erythrocytes. Studies in a system with flowing human blood

BACKGROUND: We have explored how hypoxic conditions may affect the antiplatelet effects of aspirin. MATERIALS AND METHODS: For this purpose, a perfusion system containing a damaged vessel segment was modified in order to induce hypoxia (low Po2) in flowing blood. Blood samples were incubated with 50 mumol L-1 aspirin and divided into two aliquots, one being perfused under standard conditions (normoxic) and the other under hypoxic conditions. The interaction of platelets with the subendothelium was morphometrically evaluated. RESULTS: In studies with untreated blood under normoxic conditions, platelet interaction with the subendothelium was 0.3 +/- 0.1% of contact, 5.3 +/- 1.6% of adhesion, 24.3 +/- 3.3% of thrombus and 29.9 +/- 2.7% of total covered surface. Aspirin-treated blood perfused under normoxic conditions showed a marked decrease in thrombus with a concomitant increase in both platelet adhesion and covered surface percentages. However, when aspirin-treated blood was perfused under hypoxic conditions, platelet interaction was not significantly different from that observed in untreated blood. Hypoxia induced a 10-fold increase in ATP release from erythrocytes in the perfusates. If apyrase was added to the perfusates, ATP release was prevented and aspirin effects were evident again. CONCLUSION: Our results suggest that, under hypoxic conditions, the presence of aspirin would not help to inhibit further platelet activation.