Quantitation of platelet preservation with prostanoids during simulated bypass

Extensive blood-synthetic surface interactions during cardiopulmonary bypass produce adverse platelet alterations that can contribute to excessive blood loss following open cardiac surgery. These platelet alterations can be reduced by temporary inhibition of platelet function. In order to define further an optimal method of platelet inhibition during blood-synthetic surface contact, we quantitated platelet functional and structural alterations that occur during simulated extracorporeal circulation (SEC) despite platelet inhibition with Iloprost (ZK) or PGE1. Five-hundred milliliters of fresh heparinized human blood were recirculated for 2 hr in a circuit consisting of silicone rubber components and a spiral coil membrane oxygenator. When blood was recirculated for 2 hr without drug, platelet counts fell significantly to 46 ± 7% (x ± SEM) of initial levels (P < 0.01); mean platelet volume decreased from 6.90 ± 0.25 μm3 to 6.05 ± 0.33 μm3 (P < 0.01); platelet dispersion increased from 1.73 ± 0.02 to 2.14 ± 0.09 (P < 0.01) and platelets no longer aggregated in response to epinephrine or thrombin. In contrast, when blood was recirculated with either ZK (0.003 μM) or PGE1 (0.3 μM), platelet counts were significantly preserved when compared to blood recirculated without drug (82 ± 5% and 89 ± 7%, respectively; P < 0.01); mean platelet volume did not change; and dispersion only increased from 1.74 ± 0.02 to 1.85 ± 0.04 (P < 0.05). However, following gel filtration, platelets recirculated with PGE1 always responded less than platelets merely incubated with PGE1 when challenged with either epinephrine (50 vs 75%, P < 0.05) or thrombin (37 vs 65%, P < 0.05). Thus, although both ZK and PGE1 significantly reduced adverse platelet changes during blood-synthetic surface contact, this persistent diminution of functional response would indicate that there are subtle platelet alterations not prevented by either drug. Both drugs, however, permit significant quantitative and qualitative preservation of platelet function even after several hours of simulated extracorporeal circulation.