Iloprost (ZK36374), a stable analogue of prostacyclin, preserves platelets during simulated extracorporeal circulation

Abstract

Contact between blood and synthetic surfaces of an extracorporeal circuit results in extensive alterations in platelet function. These platelet abnormalities have been reproduced in vitro by recirculating heparinized (5 units/ml) human blood at 37 degrees C in a silicone rubber circuit (0.1 m2) containing a spiral coil membrane oxygenator (0.9 m2). During control recirculation trials, platelet counts fell to 29% +/- 8% (mean +/- standard error of the mean) of initial levels within 30 minutes, and sensitivity to the soluble agonists, adenosine diphosphate and epinephrine, disappeared. Plasma levels of the platelet-specific protein platelet factor 4 rose to 2,600 +/- 200 ng/ml, indicating extensive platelet granule release. Similarly, plasma concentrations of thromboxane B2 rose from less than or equal to 100 pg/ml to 500 +/- 200 pg/ml at 120 minutes, and transmission electron microscopy demonstrated disruption of platelet subcellular architecture. In contrast, when ilioprost, a stable prostacyclin derivative (1 ng/ml), was added to the circuit prior to recirculation, the thrombocyte count remained at 85% +/- 4% of initial values. Platelets incubated or recirculated for 2 hours in the presence of iloprost responded normally to both adenosine diphosphate and epinephrine after separation from the drug by gel-filtration. Furthermore, plasma concentrations of platelet factor 4 remained below 300 ng/ml, plasma levels of thromboxane B2 failed to reach detectable levels, and platelet ultrastructure remained intact. Thus, iloprost effectively preserves the circulating platelet count, prevents platelet granule release, and preserves platelet functional and morphological integrity during simulated extracorporeal circulation.