Inhibition of indium-111 platelet accretion onto venous thrombi in dogs by prostacyclin.

The known platelet anti-aggregant effects of prostacyclin (epoprostenol) suggest that it may have therapeutic potential in conditions in which the platelet plays a pathophysiological role. The growth of venous thrombi is one such condition. We have attempted to determine, in a canine model of fresh venous thrombosis, whether prostacyclin infusion inhibits platelet accretion in vivo and how this in vivo event related to hemodynamic and in vitro platelet anti-aggregant effects. Gamma camera imaging over thrombi for accretion of indium-111-labeled platelets disclosed that prostacyclin, at an infusion rate of 50 ng/kg per min, inhibited platelet accretion in vivo and resulted in a 95 +/- 4% decrease in in vitro adenosine diphosphate-induced platelet aggregation, and a decrease in mean arterial pressure to 86 +/- 4% of pre-infusion values. Step-wise decrements of prostacyclin infusion demonstrated that platelet accretion occurred in vivo at infusion rates of approximately 10-20 ng/kg per min and correlated with an in vitro adenosine diphosphate-induced aggregation of 54 +/- 13% of control values. Thus, prostacyclin, in a dose that causes only a mild decrease in systemic pressure, can completely inhibit platelet uptake onto fresh venous thrombi in the dog, and this inhibition correlates closely with in vitro adenosine diphosphate-induced platelet aggregation. The potential therapeutic implications of these findings are discussed.