Dissociation between hemodynamic and platelet antiaggregant effects of prostacyclin in dogs determined with a rapid platelet isolation technique.
Prostacyclin, a potent vasodilator and inhibitor of platelet aggregation, is being increasingly used in disease states in which platelets may play a pathophysiologic role. A literature review revealed a variable dissociation between the in vitro platelet antiaggregant activity of prostacyclin and both the in vivo hemodynamic and platelet antiaggregant activities. Because widely variable platelet isolation techniques may have contributed to this variability, we investigated the hemodynamic and platelet antiaggregant effects of prostacyclin infusion in the dog, using in vitro techniques limiting the time from blood sampling to aggregometry to 2 1/2 and 10 1/2 min. Using the short technique, we demonstrate complete inhibition of platelet aggregation at a prostacyclin infusion rate that caused only a mild decrease in arterial pressure. In contrast, the longer technique requires an eightfold higher prostacyclin infusion rate to achieve the same degree of antiaggregant activity. The prostacyclin activity apparent half-life was 3 min. Because interspecies differences exist in both the hemodynamic and antiaggregant effects of prostacyclin and in their relationship to each other, we suggest that a closer approximation of in vivo antiaggregant effects may be obtained with in vitro methods that are rapid, thus taking into account the lability of prostacyclin. We conclude that the variable in vitro platelet antiaggregant effects of prostacyclin reported in the literature are due to the variable and longer techniques.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D002469:Cell Separation / Q000379:methods*; D004285:Dogs; D011464:Epoprostenol / Q000008:administration & dosage / Q000494:pharmacology*; D007263:Infusions, Parenteral; D010974:Platelet Aggregation / Q000187:drug effects*; D011453:Prostaglandins / Q000494:pharmacology*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D011453:Prostaglandins; D011464:Epoprostenol