Sevoflurane does not inhibit human platelet aggregation induced by thrombin

Background: Sevoflurane reportedly inhibits adenosine diphosphate-induced p latelet aggregation by suppressing thromboxane A(2) formation. The increase in intracellular calcium concentration that fosters platelet aggregation, however, is also induced by other cell signaling pathways, such as activati on of the production of inositol 1,4,5-triphosphate by thrombin. The curren t study aimed to clarify the net influence of sevoflurane on thrombin-induc ed platelet aggregation. Methods: Washed platelets were stimulated by thrombin after incubation with 0.5, 1.0, or 1.5 mM sevoflurane, halothane, or isoflurane. Aggregation cur ves were measured by an aggregometer. Intracellular calcium concentration w as measured fluorometrically using fura-2. Calcium mobilization via plasma membrane calcium channels and the dense tubular system was assessed differe ntially, Intracellular inositol 1,4,5-triphosphate was measured by radioimm unoassay, Results: Halothane significantly suppressed aggregation ratios at 5 min com pared with those in controls (89 +/- 7%) to 71 +/- 10% (1.0 mM) and GO +/- 11% (1.5 mM) and the increase in intracellular calcium concentration (contr ols, 821 +/- 95 nM vs. 440 +/- 124 nM [1.0 mM] or 410 +/- 74 nM [1.5 mM]). Halothane also significantly inhibited release of calcium from the dense tu bular system (controls, 220 +/- 48 nM vs 142 +/- 31 nM [1.0 mM]). Neither s evoflurane nor isoflurane produced a net change in aggregation ratios, intr acellular calcium concentration, or calcium mobilization, Halothane (1 mM) significantly suppressed inositol 1,4,5-triphosphate concentrations, wherea s neither 1 mM isoflurane nor 1 mM sevoflurane had any effect. Conclusions: Although sevoflurane has been reported to inhibit human platel et aggregation induced by weak agonists such as adenosine diphosphate, it d oes not inhibit human platelet aggregation induced by strong agonists such as thrombin.