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.


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.
Bozzo
J
J
Hospital Clínic, Servei d'Hemoteràpia i Hemostàsia, Barcelona, Spain.
Hernández
M R
MR
Galán
A M
AM
Heras
M
M
Ordinas
A
A
Escolar
G
G
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
D010975:Platelet Aggregation Inhibitors; D000255:Adenosine Triphosphate; D001241:Aspirin