Sevoflurane inhibits human platelet aggregation and thromboxane A 2 formation, possibly by suppression of cyclooxygenase activity

Abstract

Background. Halothane increases bleeding time and suppresses platelet aggregation in vivo and in vitro. A previous study by the authors suggests that halothane inhibits platelet aggregation by reducing thromboxane (TX) A 2 receptor-binding affinity. However, no studies of the effects of sevoflurane on platelet aggregation have been published. Methods: The effects of sevoflurane, halothane, and isoflurane were examined at doses of 0.13-1.4 mM. Human platelet aggregation was induced by adenosine diphosphate, epinephrine, arachidonic acid, prostaglandin G 2, and a TXA 2 agonist ([+]-9,11-epithia- 11,12-methano-TXA 2, STA 2) and measured by aggregometry. Platelet TXB 2 levels were measured by radioimmunoassay, and the ligand-binding characteristics of the TXA 2 receptors were examined by Scatchard analysis using a [ 3H]labeled TXA 2 receptor antagonist (5Z-7-(3-endo-([ring-4- [ 3H]phenyl) sulphonylamino-[2.2.1.] bicyclohept-2-exo-yl) heptenoic acid, [ 3H]S145). Results: Isoflurane (0.28-0.84 mM) did not significantly affect platelet aggregation induced by adenosine diphosphate and epinephrine. Sevoflurane (0.13-0.91 mM) and halothane (0.49-1.25 mM) inhibited secondary platelet aggregation induced by adenosine diphosphate (1-10 μM) and epinephrine (1-10 μM) without altering primary aggregation. Sevoflurane (0.13 mM) also inhibited arachidonic acid-induced aggregation, but not that induced by prostaglandin G 2 or STA 2, although halothane (0.49 mM) inhibited the latter. Sevoflurane (3 mM) did not affect the binding of [ 3H]S145 to platelets, whereas halothane (3.3 mM) suppressed it strongly. Sevoflurane (0.26 mM) and halothane (0.98 mM) strongly suppressed TXB 2 formation by arachidonic acid-stimulated platelets. Conclusions: The findings that sevoflurane suppressed the effects of arachidonic acid, but not those of prostaglandin G 2 and STA 2, suggest strongly that sevoflurane inhibited TXA 2 formation by suppressing cyclooxygenase activity. Halothane appeared to suppress both TXA 2 formation and binding to its receptors. Sevoflurane has strong antiaggregatory effects at subanesthetic concentrations (greater than 0.13 mM; i.e., approximately 0.5 vol/%), whereas halothane has similar effects at somewhat greater anesthetic concentrations (0.49 mM; i.e., approximately 0.54 vol/%). Isoflurane at clinical concentration (0.84 mM; i.e., approximately 1.82 vol/%) does not affect platelet aggregation significantly.