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% (mean +/- SEM) of initial levels (P less than 0.01); mean platelet volume decreased from 6.90 +/- 0.25 micron3 to 6.05 +/- 0.33 micron3 (P less than 0.01); platelet dispersion increased from 1.73 +/- 0.02 to 2.14 +/- 0.09 (P less than 0.01) and platelets no longer aggregated in response to epinephrine or thrombin. In contrast, when blood was recirculated with either ZK (0.003 microM) or PGE1 (0.3 microM), platelet counts were significantly preserved when compared to blood recirculated without drug (82 +/- 5% and 89 +/- 7%, respectively; P less than 0.01); mean platelet volume did not change; and dispersion only increased from 1.74 +/- 0.02 to 1.85 +/- 0.04 (P less than 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 less than 0.05) or thrombin (37 vs 65%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)