Keh D, Kürer I, Dudenhausen J W, Woltmann W, Falke K J, Gerlach H
Clinic of Anesthesiology and Intensive Care Medicine, Humboldt University of Berlin, Germany.
Intensive Care Med. 2001 Jan;27(1):283-6. doi: 10.1007/s001340000778.
Several studies have demonstrated altered platelet function during nitric oxide inhalation (iNO) in adults and neonates. In vitro NO inhibits activation of fibrinogen receptor glycoprotein (GP) IIb/IIIa in a dose-dependent manner. In neonates GPIIb/IIIa response to stimulation is physiologically attenuated during the first days after birth in comparison to adults; the effects of NO on GPIIb/IIIa in neonates, however, are less established. We investigated the response of platelets from neonates, their mothers, and nonpregnant controls to the NO donor SIN-1 in vitro.
Umbilical cord and venous (mother, controls) platelet-rich plasma was stimulated in vitro with 10 microM ADP or 0.05 U/ml thrombin in the presence or absence of 10 microM SIN-1. GPIIb/IIIa activation was determined by two-color flow cytometry.
Delivery department of an university hospital.
Ten healthy term neonates, their mothers and nonpregnant controls.
NO significantly reduced GPIIb/IIIa activation in thrombin- and ADP-stimulated platelets in all groups (p < 0.001). Neonatal platelets were significantly hyporeactive to stimulation (p < 0.05), but the relative response to SIN-1 was similar in all three groups (70 +/- 5 %).
The relative amount of NO-induced inhibition of GPIIb/ IIIa activation in neonates is thus similar to that of adults. However, due to the intrinsic hyporesponsiveness of neonatal platelets and NO-synergistic pharmacodynamic profiles of other drugs (e.g., prostacyclin), possible adverse effects of iNO must be considered.
多项研究表明，一氧化氮吸入（iNO）过程中成人和新生儿的血小板功能会发生改变。体外实验中，一氧化氮以剂量依赖方式抑制纤维蛋白原受体糖蛋白（GP）IIb/IIIa的激活。与成人相比，新生儿出生后的头几天内，GPIIb/IIIa对刺激的反应在生理上会减弱；然而，一氧化氮对新生儿GPIIb/IIIa的影响尚不明确。我们在体外研究了新生儿、其母亲及非孕对照者的血小板对一氧化氮供体SIN-1的反应。
在有或无10微摩尔SIN-1存在的情况下，用10微摩尔ADP或0.05单位/毫升凝血酶体外刺激脐血和静脉血（母亲、对照者）富含血小板的血浆。通过双色流式细胞术测定GPIIb/IIIa的激活情况。
一所大学医院的分娩科。
10名健康足月儿、他们的母亲及非孕对照者。
在所有组中，一氧化氮均显著降低了凝血酶和ADP刺激的血小板中GPIIb/IIIa的激活（p<0.001）。新生儿血小板对刺激的反应明显低下（p<0.05），但三组对SIN-1的相对反应相似（70±5%）。
因此，一氧化氮诱导的新生儿GPIIb/IIIa激活抑制的相对量与成人相似。然而，由于新生儿血小板固有的低反应性以及其他药物（如前列环素）的一氧化氮协同药效学特征，必须考虑iNO可能产生的不良反应。
