Platelet thromboxane production during endotoxin shock

Abstract

Circulating thromboxane (TX) is elevated following endotoxin, and platelets become hyperaggregable. Thromboxane synthesis was therefore studied in platelets during endotoxemia. Rabbit blood and platelets were taken at 0, 60 and 120 min after start ofE. coli endotoxin infusion (1.10 μg/kg min, i.v.). Blood incubated with arachidonic acid (AA, 10⁻⁴ M) generated TXA₂, which was measured using a superfused rabbit aorta bioassay. Washed platelets were stimulated with 1-¹⁴C AA (0.1 μCi) to generate radiolabeled TXB₂, which was isolated by TLC and quantitated by scintillation spectrometry. Control (0 time) platelet count was 488×10³/mm³. In the test group, platelet counts fell to 65% of control at 60 min and to 52% at 120 min, while TXA₂ generation was 95% (60 min) and 94% (120 min) of control. In contrast a serial dilution of untreated platelets yielded a progressive decline in thromboxane generation. In endotoxemic platelets, the conversion of 1-¹⁴C AA to TXB₂ (percent/10⁹ platelets) was increased at 120 min (0 min, 34.7; 120 min, 40.0;P<0.05). Endotoxemic platelets generated greater amounts of thromboxane than did normal platelets, and this condition may account for platelet hyperaggregability in shock.