title: Sevoflurane inhibits human platelet aggregation and thromboxane A2 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) A2 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 G2, and a TXA2 agonist ([+]-9, 11-epithia-11, 12-methano-TXA2, STA2) and measured by aggregometry. Platelet TXB2 levels were measured by radioimmunoassay, and the ligand-binding characteristics of the TXA2 receptors were examined by Scatchard analysis using a [3H]-labeled TXA2 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 microM) and epinephrine (1-10 microM) without altering primary aggregation. Sevoflurane (0.13 mM) also inhibited arachidonic acid-induced aggregation, but not that induced by prostaglandin G2 or STA2, 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 TXB2 formation by arachidonic acid-stimulated platelets.
  
  
  CONCLUSIONS
  The findings that sevoflurane suppressed the effects of arachidonic acid, but not those of prostaglandin G2 and STA2, suggest strongly that sevoflurane inhibited TXA2 formation by suppressing cyclooxygenase activity. Halothane appeared to suppress both TXA2 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.
authors.affiliation: Department of Anesthesia, Kitano Hospital, Iazuke Kofukai Foundation Medical Research Institute, Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hirakata
authors.forename: F
authors.initials: F
authors.lastname: Ushikubi
authors.forename: H
authors.initials: H
authors.lastname: Toda
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: S
authors.initials: S
authors.lastname: Sai
authors.forename: N
authors.initials: N
authors.lastname: Urabe
authors.forename: Y
authors.initials: Y
authors.lastname: Hatano
authors.forename: S
authors.initials: S
authors.lastname: Narumiya
authors.forename: K
authors.initials: K
authors.lastname: Mori
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000494:pharmacology; D001665:Binding Sites; D004347:Drug Interactions; D004837:Epinephrine / Q000378:metabolism / Q000494:pharmacology; D004987:Ethers / Q000378:metabolism / Q000494:pharmacology*; D006221:Halothane / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007530:Isoflurane / Q000378:metabolism / Q000494:pharmacology; D008738:Methyl Ethers; D010974:Platelet Aggregation / Q000187:drug effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011863:Radioimmunoassay; D000077149:Sevoflurane; D013928:Thromboxane A2 / Q000096:biosynthesis* / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; D004987:Ethers; D008738:Methyl Ethers; D016718:Arachidonic Acid; D000077149:Sevoflurane; D013929:Thromboxane B2; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D007530:Isoflurane; D011451:Prostaglandin-Endoperoxide Synthases; D006221:Halothane; D004837:Epinephrine