Prosdocimi M, Finesso M, Tessari F, Gorio A, Languino L R, de Gaetano G, Dejana E
Thromb Res. 1985 Aug 15;39(4):399-409. doi: 10.1016/0049-3848(85)90163-x.
The action of AD6 as an anti-thrombotic agent was studied in a model of coronary artery thrombosis and on platelet aggregation in the dog. AD6 (10-100 microM) in vitro inhibited aggregation induced by ADP, epinephrine, collagen and PAF (platelet aggregating factor) used at their threshold concentration for maximal aggregation. Arterial thrombosis was induced in a coronary vessel by critically reducing (about 70%) the vessel lumen. Thrombus formation was estimated by measuring coronary flow in the stenosed vessel. Using this procedure on the left descending coronary artery (LAD), we obtained reproducible blood flow changes in 18 dogs. AD6 was given i.v. at three different doses. At 0.25 mg/kg two out of four dogs showed decreased thrombus formation at the stenosis site. Seven out of eleven dogs treated with 0.5 mg/kg and two out of three treated with 1.5 mg/kg showed decreased thrombus formation. Major decreases in coronary resistance, evaluated by measuring blood flow in the unstenosed left circumflex artery (LCX), were evident only after the highest dose. We conclude that AD6 has an inhibitory action on dog platelet aggregation and reduces thrombus formation in a stenosed coronary vessel.
在犬冠状动脉血栓形成模型和血小板聚集模型中研究了AD6作为抗血栓形成剂的作用。体外实验中，AD6（10 - 100微摩尔）能抑制由ADP、肾上腺素、胶原蛋白和PAF（血小板聚集因子）在其最大聚集阈值浓度下诱导的血小板聚集。通过严重减少（约70%）血管腔内径在冠状动脉中诱导动脉血栓形成。通过测量狭窄血管中的冠状动脉血流来估计血栓形成情况。在左冠状动脉前降支（LAD）上采用此方法，我们在18只犬身上获得了可重复的血流变化。AD6通过静脉注射给予三种不同剂量。在0.25毫克/千克剂量时，四只犬中有两只在狭窄部位的血栓形成减少。在接受0.5毫克/千克治疗的11只犬中有7只，接受1.5毫克/千克治疗的3只犬中有2只血栓形成减少。仅在最高剂量后，通过测量未狭窄的左旋支冠状动脉（LCX）中的血流评估的冠状动脉阻力才有明显下降。我们得出结论，AD6对犬血小板聚集有抑制作用，并能减少狭窄冠状动脉中的血栓形成。
