Thiopental enhances human platelet aggregation by increasing arachidonic acid release

Abstract

Conflicting results have been reported regarding the effect of thiopental on aggregation and cytosolic calcium levels in platelets. The present study attempted to clarify these phenomena. Using platelet-rich plasma or washed suspensions, platelet aggregation, thromboxane (TX) B2formation, arachidonic acid (AA) release, and cytosolic free calcium concentrations ([Ca2+]i) were measured in the presence or absence of thiopental (30–300 µM). Platelet activation was induced by adenosine diphosphate (ADP, 0.5–15 µM), epinephrine (0.1–20 µM) arachidonic acid (0.5–1.5 mM), or (+)-9,11-epithia-11,12-methano-TXA2(STA2, 30–500 nM). Measurements of primary aggregation were performed in the presence of indomethacin (10 µM). Low concentrations of ADP and epinephrine, which did not induce secondary aggregation in a control study, induced strong secondary aggregation in the presence of thiopental ([Formula: see text]100 µM). Thiopental ([Formula: see text]100 µM) also increased the TXB2formation induced by ADP and epinephrine. Thiopental (300 µM) increased ADP- and epinephrine-induced3H-AA release. Thiopental (300 µM) also augmented the ADP- and epinephrine-induced increases in [Ca2+]iin the presence of indomethacin. Thiopental appears to enhance ADP- and epinephrine-induced secondary platelet aggregation by increasing AA release during primary aggregation, possibly by the activation of phospholipase A2.Key words: barbiturates, anesthetics, eicosanoids, phospholipase.