Apitz-Castro R, Badimon J J, Badimon L
Lab. Trombosis Exptl, IVIC, Caracas, Venezuela.
Thromb Res. 1994 Aug 1;75(3):243-9. doi: 10.1016/0049-3848(94)90235-6.
Ajoene, (E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide, is a potent antiplatelet compound isolated from alcoholic extracts of garlic. In vitro, ajoene reversibly inhibits platelet aggregation as well as the release reaction induced by all known agonists. We used a well characterized perfusion chamber to study the in vivo effects of ajoene on platelet deposition onto a highly thrombogenic, severely damaged arterial wall, obtained by stripping off the intimal layer and exposing tunica media. Platelet-vessel wall interaction and the effect of ajoene was studied under flow conditions of high and low local shear rate that mimics laminar blood flow in small and medium size arteries (1690 sec-1 and 212 sec-1). Our results indicate that administration of ajoene to heparinized animals, significantly prevents thrombus formation at local low blood shear rate. Ajoene does not inhibit binding of vWF to GPIb, therefore, it does not affect platelet adhesion. In fact, although ajoene impairs fibrinogen and vWF (less efficient) binding to GPlIb/IIIa, it does not totally inhibits platelet deposition to the substrates at any of the shear rates used in this study. Our present results, under in vivo flow conditions and in the presence of physiological calcium levels, suggest that ajoene may be potentially useful for the acute prevention of thrombus formation induced by severe vascular damage, mainly in arterial sites with local low shear rates.
阿霍烯，即（E，Z）-4,5,9-三硫杂十二碳-1,6,11-三烯9-氧化物，是一种从大蒜酒精提取物中分离出的强效抗血小板化合物。在体外，阿霍烯可可逆地抑制血小板聚集以及所有已知激动剂诱导的释放反应。我们使用一个特性明确的灌注室来研究阿霍烯对血小板沉积到高度致血栓形成、严重受损动脉壁上的体内作用，该动脉壁是通过剥去内膜层并暴露中膜获得的。在模拟中小动脉层流血液的高、低局部剪切率流动条件下（分别为1690秒⁻¹和212秒⁻¹）研究了血小板与血管壁的相互作用以及阿霍烯的作用。我们的结果表明，给肝素化动物施用阿霍烯可显著防止在局部低血流剪切率下形成血栓。阿霍烯不抑制血管性血友病因子（vWF）与糖蛋白Ib（GPIb）的结合，因此，它不影响血小板黏附。实际上，尽管阿霍烯会损害纤维蛋白原和vWF（效果较差）与糖蛋白IIb/IIIa（GPlIb/IIIa）的结合，但在本研究使用的任何剪切率下，它都不会完全抑制血小板在底物上的沉积。我们目前在体内流动条件和生理钙水平存在的情况下所得到的结果表明，阿霍烯可能对急性预防严重血管损伤诱导的血栓形成具有潜在作用，主要是在局部低剪切率的动脉部位。
