Cam Betul, Sagdilek Engin, Yildirim Nalan, Savci Vahide
*Department of Physiology, Faculty of Medicine, Uludag University, Bursa, Turkey; †Center for Surgical Research, University of Alabama at Birmingham, Birmingham, Alabama; ‡Department of Biophysics and §Department of Pharmacology, Faculty of Medicine, Uludag University, Bursa, Turkey; and ∥MVZ Radiologie und Nukleermedizin, Kompetenznetz Franken, Fuerth, Germany.
Shock. 2015 Apr;43(4):387-94. doi: 10.1097/SHK.0000000000000301.
Cytidine 5'-diphosphocholine (CDP-choline) has several physiological and pharmacological effects on various bodily functions, including hemostasis. This study determined the impact of CDP-choline on hemostasis in a trauma-hemorrhage (T-H) model in rats or under in vitro conditions or after chronic treatment via thromboelastography. Trauma-hemorrhage resuscitation was induced, and either saline (1 mL/kg) or CDP-choline (50 mg/kg) was injected intravenously just prior to resuscitation in the T-H group and at the same time point in the sham-control group. The effects of CDP-choline on thromboelastogram parameters, coagulation markers, and platelet aggregation were investigated under in vitro conditions (1.5 mM, 30- or 3-min incubation in blood or plasma) and after chronic use (50 mg/kg, i.p., 10 days). Acute CDP-choline treatment was shown to decrease the initial and maximum clot formation time, accelerate clotting rapidity, reduce the lysis percentage, and increase the coagulation index in the T-H resuscitation group, whereas the same treatment in the sham-control rats did not alter any of the thromboelastogram parameters. However, the incubation of whole blood with CDP-choline prolonged the initial and maximum clot formation time, and CDP-choline treatment significantly decreased the slopes of the disaggregation and aggregation curves when platelets were stimulated with ADP and collagen, respectively. Interestingly, the chronic use of this drug did not influence any of these hemostatic parameters. These data implicate that acute but not chronic CDP-choline administration may differentially alter the hemostatic parameters under diverse conditions. The drug may produce a hypercoagulable state in activated situations but cause opposite effects under normal in vitro conditions.
胞苷5'-二磷酸胆碱（CDP-胆碱）对包括止血在内的各种身体功能具有多种生理和药理作用。本研究通过血栓弹力图测定了CDP-胆碱对大鼠创伤性出血（T-H）模型、体外条件下或慢性治疗后的止血影响。诱导创伤性出血复苏，在T-H组复苏前静脉注射生理盐水（1 mL/kg）或CDP-胆碱（50 mg/kg），假手术对照组在同一时间点注射。在体外条件下（1.5 mM，在血液或血浆中孵育30分钟或3分钟）和慢性使用后（50 mg/kg，腹腔注射，10天），研究了CDP-胆碱对血栓弹力图参数、凝血标志物和血小板聚集的影响。急性CDP-胆碱治疗可缩短T-H复苏组的初始和最大凝血形成时间，加快凝血速度，降低溶解百分比，并提高凝血指数，而假手术对照组的相同治疗未改变任何血栓弹力图参数。然而，全血与CDP-胆碱孵育会延长初始和最大凝血形成时间，并且CDP-胆碱治疗分别在用ADP和胶原刺激血小板时显著降低了解聚和聚集曲线的斜率。有趣的是，该药物的慢性使用并未影响任何这些止血参数。这些数据表明，急性而非慢性给予CDP-胆碱可能会在不同条件下差异性地改变止血参数。该药物在激活状态下可能会产生高凝状态，但在正常体外条件下会产生相反的效果。
