Heesen M, Dietrich G V, Detsch O, Drevermann J, Boldt J, Hempelmann G
Abteilung Anaesthesiologie und Operative Intensivmedizin, Justus-Liebig-Universität Giessen.
Anaesthesist. 1996 Mar;45(3):255-8. doi: 10.1007/s001010050261.
alpha 2-Agonists are being used increasingly in anaesthesia and intensive care medicine because of their antihypertensive, analgesic and sedative properties. Platelets bear alpha 2-receptors on the cell surface. Stimulation of these receptors by agonists induces platelet aggregation. The present study examined whether in vitro incubation of blood with the alpha 2-agonists clonidine and dexmedetomidine decreases alpha 2-receptor density and hereby influences platelet aggregation.
Whole blood of 20 healthy volunteers was incubated over 24 h at 37 degrees C with 1 ng/ml clonidine or 1 or 10 ng/ml dexmedetomidine. Induced platelet aggregation was determined by means of turbidometry. Epinephrine (22 mumol/l) or collagen (20 mg/l) served as inductors. The density of alpha 2-receptors was measured in radioligand assays with 3H-Yohimbine. Phentolamine was used to assess unspecific binding. The data were analyzed with an analysis of variance.
Neither 1 ng/ml clonidine nor 1 ng/ml dexmedetomidine altered platelet aggregation or alpha 2-receptor density in comparison with the control sample. As a major result we found that 10 ng/ml dexmedetomidine caused a significant (P < 0.05) reduction in epinephrine-induced platelet aggregation (16.0 +/- 5.4%, n = 20, mean +/- SEM) compared with the control (46.0 +/- 1.3%, n = 20). alpha 2-Receptor density was not any different from the control.
This in vitro study showed that clinically relevant concentrations of 1 ng/ml clonidine or dexmedetomidine did not alter platelet aggregation or alpha 2-receptor density, even after 24 h exposure. However, 10 ng/ml dexmedetomidine was found to diminish significantly epinephrine-induced platelet aggregation, but did not change alpha 2-receptor density. This result showed that desensitization of platelet aggregation can occur without quantitative changes in alpha 2-receptors.
由于其具有抗高血压、镇痛和镇静特性，α2激动剂在麻醉和重症监护医学中的应用越来越广泛。血小板在细胞表面带有α2受体。激动剂对这些受体的刺激会诱导血小板聚集。本研究检测了血液与α2激动剂可乐定和右美托咪定在体外孵育是否会降低α2受体密度，从而影响血小板聚集。
将20名健康志愿者的全血在37℃下与1 ng/ml可乐定或1或10 ng/ml右美托咪定孵育24小时。通过比浊法测定诱导的血小板聚集。肾上腺素（22 μmol/l）或胶原蛋白（20 mg/l）用作诱导剂。用3H-育亨宾在放射性配体测定中测量α2受体的密度。酚妥拉明用于评估非特异性结合。数据采用方差分析进行分析。
与对照样本相比，1 ng/ml可乐定和1 ng/ml右美托咪定均未改变血小板聚集或α2受体密度。作为主要结果，我们发现与对照（46.0±1.3%，n = 20）相比，10 ng/ml右美托咪定使肾上腺素诱导的血小板聚集显著降低（P < 0.05）（16.0±5.4%，n = 20）。α2受体密度与对照无差异。
这项体外研究表明，即使在暴露24小时后，临床相关浓度的1 ng/ml可乐定或右美托咪定也不会改变血小板聚集或α2受体密度。然而，发现10 ng/ml右美托咪定可显著降低肾上腺素诱导的血小板聚集，但不改变α2受体密度。该结果表明血小板聚集脱敏可在α2受体无定量变化的情况下发生。
