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

被引:52
作者
Hirakata, H
Ushikubi, F
Toda, H
Nakamura, K
Sai, S
Urabe, N
Hatano, Y
Narumiya, S
Mori, K
机构
[1] KYOTO UNIV,KYOTO,JAPAN
[2] KITANO HOSP,DEPT ANESTHESIA,TAZUKE KOFUKAI FDN MED RES INST,KITA KU,OSAKA 530,JAPAN
[3] KYOTO UNIV,FAC MED,DEPT ANESTHESIA,KYOTO,JAPAN
[4] KYOTO UNIV,FAC MED,DEPT PHARMACOL,KYOTO,JAPAN
关键词
anesthetic; volatile; sevoflurane; halothane; isoflurane; eicosanoids; thromboxane A(2); prostaglandin G(2); arachidonic acid; blood; platelets; aggregation;
D O I
10.1097/00000542-199612000-00027
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
Background: Halothane increases bleeding time and suppresses platelet aggregation in vitro 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 mere 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 [H-3]-labeled TXA(2) receptor antagonist (5Z-7-(3-endo-([ring-4-[H-3] phenyl) sulphonylamino-[2.2.1.] bicyclohept-2-exo-yl) heptenoic acid, [H-3]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 mu M) and epinephrine (1-10 mu M) 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 [H-3]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.
引用
收藏
页码:1447 / 1453
页数:7
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