title: Impaired antiplatelet effects of aspirin associated with hypoxia and ATP release from erythrocytes. Studies in a system with flowing human blood.
abstract: BACKGROUND
  We have explored how hypoxic conditions may affect the antiplatelet effects of aspirin.
  
  
  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.
  
  
  CONCLUSIONS
  Our results suggest that, under hypoxic conditions, the presence of aspirin would not help to inhibit further platelet activation.
authors.affiliation: Hospital Clínic, Servei d'Hemoteràpia i Hemostàsia, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Bozzo
authors.forename: M R
authors.initials: MR
authors.lastname: Hernández
authors.forename: A M
authors.initials: AM
authors.lastname: Galán
authors.forename: M
authors.initials: M
authors.lastname: Heras
authors.forename: A
authors.initials: A
authors.lastname: Ordinas
authors.forename: G
authors.initials: G
authors.lastname: Escolar
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology*; D001784:Blood Gas Analysis; D015687:Cell Hypoxia; D004907:Erythrocyte Deformability / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D010477:Perfusion; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D010975:Platelet Aggregation Inhibitors; D000255:Adenosine Triphosphate; D001241:Aspirin