SEVOFLURANE INHIBITS HUMAN PLATELET-AGGREGATION AND THROMBOXANE A(2) FORMATION, POSSIBLY BY SUPPRESSION OF CYCLOOXYGENASE ACTIVITY

Background: Halothane increases bleeding time and suppresses platelet aggregation in vitro and in vitro. A previous study by the authors sug gests that halothane inhibits platelet aggregation by reducing thrombo xane (TX) A(2) receptor-binding affinity. However, no studies of the e ffects of sevoflurane on platelet aggregation have been published. Met hods: The effects of sevoflurane, halothane, and isoflurane mere exami ned 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 TX A(2) receptors were examined by Scatchard analysis using a [H-3]-label ed TXA(2) receptor antagonist (5Z-7-(3-endo-([ring-4-[H-3] phenyl) sul phonylamino-[2.2.1.] bicyclohept-2-exo-yl) heptenoic acid, [H-3]S145). Results: Isoflurane (0.28-0.84 mM) did not significantly affect plate let aggregation induced by adenosine diphosphate and epinephrine. Sevo flurane (0.13-0.91 mM) and halothane (0.49-1.25 mM) inhibited secondar y platelet aggregation induced by adenosine diphosphate (1-10 mu M) an d epinephrine (1-10 mu M) without altering primary aggregation. Sevofl urane (0.13 mM) also inhibited arachidonic acid-induced aggregation, b ut not that induced by prostaglandin G(2) or STA(2), although halothan e (0.49 mM) inhibited the latter. Sevoflurane (3 mM) did not affect th e binding of [H-3]S145 to platelets, whereas halothane (3.3 mM) suppre ssed it strongly. Sevoflurane (0.26 mM) and halothane (0.98 mM) strong ly suppressed TXB(2) formation by arachidonic acid-stimulated platelet s. Conclusions: The findings that sevoflurane suppressed the effects o f arachidonic acid, but not those of prostaglandin G(2) and STA(2), su ggest strongly that sevoflurane inhibited TXA(2) formation by suppress ing cyclooxygenase activity. Halothane appeared to suppress both TXA(2 ) formation and binding to its receptors. Sevoflurane has strong antia ggregatory effects at subanesthetic concentrations (greater than 0.13 mM; i.e., approximately 0.5 vol%), whereas halothane has similar effec ts at somewhat greater anesthetic concentrations (0.49 mM; i.e., appro ximately 0.54 vol%). Isoflurane at clinical concentration (0.84 mM; i. e., approximately 1.82 vol%) does not affect platelet aggregation sign ificantly.