Hirakata H, Ushikubi F, Toda H, Nakamura K, Sai S, Urabe N, Hatano Y, Narumiya S, Mori K
Department of Anesthesia, Kitano Hospital, Iazuke Kofukai Foundation Medical Research Institute, Osaka, Japan.
Anesthesiology. 1996 Dec;85(6):1447-53. doi: 10.1097/00000542-199612000-00027.
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.
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).
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.
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.
氟烷可延长出血时间，并在体内和体外抑制血小板聚集。作者之前的一项研究表明，氟烷通过降低血栓素（TX）A2受体结合亲和力来抑制血小板聚集。然而，尚未有关于七氟醚对血小板聚集影响的研究发表。
研究了七氟醚、氟烷和异氟醚在0.13 - 1.4 mM剂量下的作用。通过二磷酸腺苷、肾上腺素、花生四烯酸、前列腺素G2和TX A2激动剂（[+]-9,11-环氧-11,12-甲撑-TX A2，STA2）诱导人血小板聚集，并采用凝集测定法进行测量。通过放射免疫测定法测量血小板TXB2水平，并使用[3H]标记的TX A2受体拮抗剂（5Z-7-(3-内-([环-4-[3H]苯基)磺酰氨基-[2.2.1.]双环庚-2-外-基)庚烯酸，[3H]S145）通过Scatchard分析检测TX A2受体的配体结合特性。
异氟醚（0.28 - 0.84 mM）对二磷酸腺苷和肾上腺素诱导的血小板聚集无显著影响。七氟醚（0.13 - 0.91 mM）和氟烷（0.49 - 1.25 mM）抑制二磷酸腺苷（1 - 10 microM）和肾上腺素（1 - 10 microM）诱导的继发性血小板聚集，而不改变原发性聚集。七氟醚（0.13 mM）也抑制花生四烯酸诱导的聚集，但不抑制前列腺素G2或STA2诱导的聚集，尽管氟烷（0.49 mM）抑制后者。七氟醚（3 mM）不影响[3H]S145与血小板的结合，而氟烷（3.3 mM）则强烈抑制。七氟醚（0.26 mM）和氟烷（0.98 mM）强烈抑制花生四烯酸刺激的血小板TXB2形成。
七氟醚抑制花生四烯酸的作用，但不抑制前列腺素G2和STA2的作用，这一发现强烈表明七氟醚通过抑制环氧化酶活性来抑制TX A2的形成。氟烷似乎既抑制TX A2的形成，又抑制其与受体的结合。七氟醚在亚麻醉浓度（大于0.13 mM；即约0.5 vol/%）时具有强大的抗聚集作用，而氟烷在稍高的麻醉浓度（0.49 mM；即约0.54 vol/%）时具有类似作用。临床浓度（0.84 mM；即约1.82 vol/%）的异氟醚对血小板聚集无显著影响。
