White B P, Sullivan A T, Lumley P
Department of Cardiovascular and Respiratory Pharmacology, Glaxo Group Research Ltd, Ware, Hertfordshire, UK.
Thromb Haemost. 1994 Mar;71(3):366-74.
Vapiprost (GR32191, a TxA2 antagonist), r-hirudin, aspirin, ticlopidine and aspirin plus ticlopidine were examined for their ability to prevent electrically-induced thrombosis in an artificially stenosed coronary artery in the anaesthetised dog. Drugs or vehicle were administered prior to a 2 h period of electrical damage which was followed by a further 2 h observation period. In all vehicle-treated animals, blood flow markedly declined with onset of the damaging current; 80% completely occluded. All treatments reduced the incidence of complete occlusion to a similar extent. Vapiprost and r-hirudin also largely prevented the decline in blood flow both during and following the damage period whilst aspirin and ticlopidine, either alone or in combination were much less effective. With r-hirudin treatment, marked cyclic changes in flow occurred throughout the experiment; these were abolished by administration of vapiprost. In this dog model, TxA2 and thrombin appear to work in concert to produce coronary thrombosis, ADP being of minor importance. The superior effect of vapiprost over aspirin suggests a beneficial role for endogenous prostacyclin.
对前列环醇（GR32191，一种血栓素A2拮抗剂）、重组水蛭素、阿司匹林、噻氯匹定以及阿司匹林加噻氯匹定进行了研究，观察它们在麻醉犬人工狭窄冠状动脉中预防电诱导血栓形成的能力。在进行2小时电损伤之前给予药物或赋形剂，随后再进行2小时观察期。在所有接受赋形剂治疗的动物中，随着损伤电流的开始，血流量显著下降；80%完全闭塞。所有治疗方法都将完全闭塞的发生率降低到了相似的程度。前列环醇和重组水蛭素在损伤期间及损伤后也在很大程度上防止了血流量的下降，而阿司匹林和噻氯匹定单独使用或联合使用时效果要差得多。使用重组水蛭素治疗时，整个实验过程中血流量出现明显的周期性变化；给予前列环醇后这些变化消失。在这个犬模型中，血栓素A2和凝血酶似乎协同作用导致冠状动脉血栓形成，二磷酸腺苷的作用较小。前列环醇比阿司匹林效果更好，这表明内源性前列环素具有有益作用。
