Thromboxane synthesis and platelet secretion during cardiopulmonary bypass with bubble oxygenator

Abstract

Platelet secretion induced by certain soluble aggregating agents is associated with thromboxane formation. Whether synthetic surfaces activate similar biochemical pathways in the presence of an air interface is unknown. We therefore monitored platelet secretion and thromboxane formation during simulated extracorporeal circulation where contact between blood and artificial surfaces is extensive. When 500 ml of fresh, heparinized (5 U/ml) human blood was recirculated in a perfusion circuit constructed of silicone rubber tubing (0.1 m 2 ) and an infant bubble oxygenator (N = 6), platelet counts decreased progressively to 33% ± 4% SEM of initial levels within two hours. This platelet loss was associated with a progressive rise in plasma concentrations of thromboxane B 2 from <0.5 to 7 ± 1 pmole/ml and a concurrent rise in plasma levels of the platelet-specific protein, LA-PF 4 , from <0.5 to 13 ± 1 μg/ml, indicating significant thromboxane synthesis and pronounced release of platelet α granule contents. Aspirin, an inhibitor of cyclooxygenase and, hence, thromboxane synthesis abolished thromboxane formation but did not significantly alter platelet loss (42% ± 6% of initial levels at 2 hours) or platelet secretion (11 ± 2 μg of LA-PF 4 /ml at 2 hours). Clearly, thromboxane formation is temporally associated with platelet activation during extracorporeal circulation but is not necessary for surface-induced platelet secretion. Thromboxane B 2 formation, however, indicates prior release of thromboxane A 2 , which is a potent platelet activator and vasoconstrictor. Thromboxanes may thus compromise capillary perfusion and contribute to platelet microaggregate formation during cardiopulmonary bypass.