Effect of prostacyclin (epoprostenol) on the aggregation of human platelets in whole blood in vitro.
Prostacyclin (PGI2) is a potent endogenous inhibitor of platelet aggregation. The effect of PGI2 on platelet aggregation and disaggregation in whole human blood was studied at 37 degrees C in vitro. Aggregation or disaggregation was quantified by counting single platelets using the recently developed Ultra Flo 100 Whole Blood Platelet Counter. Aggregation of platelets in whole blood was induced by arachidonic acid (AA, 400 microM), adenosine 5'-diphosphate (ADP, 10 microM), thrombin (0.1 U/ml) and collagen (1 microgram/ml). At peak aggregation, each aggregating agent induced about a 90% fall in the number of single platelets counted. When whole blood was pre-incubated with PGI2 (0.5-8 nM), it dose dependently inhibited aggregation of platelets induced by all four aggregating agents. Platelet aggregates induced by ADP or thrombin could rapidly be disaggregated by PGI2 added to blood at peak aggregation. Disaggregation of collagen-induced platelet aggregation by PGI2 was slow and minimal and it was completely ineffective in disaggregating AA-induced platelet aggregates. Unlike platelet-rich plasma, which is routinely used to study platelet aggregation, the present whole-blood method allows red and white blood cells to exert their influences on platelet function, and is an important step towards a physiological state for evaluating the effects of pharmacological agents on platelets in whole blood in vitro and ex vivo.
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects; D003094:Collagen / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count / Q000295:instrumentation; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013997:Time Factors
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D003094:Collagen; D011464:Epoprostenol; D013917:Thrombin