Gir S, Reavis R, Turitto V T, Gollamudi R
Department of Mechanical Engineering, University of Memphis, TN 38152, USA.
Biotechnol Appl Biochem. 1996 Feb;23(1):63-6.
The purpose of the present study was to examine the role of antithrombotic agents in the activation of Factor X in the presence of the Tissue Factor-Factor VIIa (TF-VIIa) complex in a continuous-flow reactor. Tissue Factor immobilized in a phospholipid bilayer on the inner surface of a capillary tube (internal diameter = 0.27 mm) was exposed to a perfusate containing Factors VIIa and X flowing at a flow rate of 12.7 microliters/min, corresponding to a wall shear rate of 100 s-1. Factor Xa (the activated form of Factor X) in the effluent was determined by a chromogenic assay. The effectiveness of two platelet aggregation inhibitors, alpha,alpha'-bis-[3-(N,N-diethylcarbamoyl)piperidino-p-xylene dihydrobromide (A-1) and alpha,alpha'-bis-[3-N-benzyl-N-methylcarbamoyl)piperidino]-p-xylen e dihydrobromide (A-4) in inhibiting Factor X activation is reported here. The results suggest that the Tissue Factor pathway, mediated through TF-VIIa complex, produces significantly lower levels of Factor Xa in the presence of compounds A-1 and A-4. On the basis of these findings, it appears that the anticoagulation action of these compounds reinforces their platelet aggregation-inhibitory properties. These carbamoylpiperidines (nipecotamides) therefore appear to be useful antithrombotic agents.
本研究的目的是在连续流动反应器中，研究抗血栓形成剂在组织因子-因子VIIa（TF-VIIa）复合物存在的情况下对因子X激活的作用。固定在毛细管（内径 = 0.27 mm）内表面磷脂双层中的组织因子，暴露于含有因子VIIa和X的灌注液中，灌注液以12.7微升/分钟的流速流动，对应于100 s-1的壁剪切率。流出物中的因子Xa（因子X的活化形式）通过显色测定法测定。本文报道了两种血小板聚集抑制剂α,α'-双-[3-(N,N-二乙基氨基甲酰基)哌啶基对二甲苯二氢溴化物（A-1）和α,α'-双-[3-N-苄基-N-甲基氨基甲酰基)哌啶基]-对二甲苯二氢溴化物（A-4）抑制因子X激活的有效性。结果表明，在化合物A-1和A-4存在的情况下，通过TF-VIIa复合物介导的组织因子途径产生的因子Xa水平显著降低。基于这些发现，这些化合物的抗凝作用似乎增强了它们的血小板聚集抑制特性。因此，这些氨基甲酰哌啶（哌啶甲酰胺）似乎是有用的抗血栓形成剂。
