Nobuyoshi M, Tanaka M, Fujii M, Asanuma A, Takimoto M
Department of Cardiology, Kokura Memorial Hospital, Fukuoka, Japan.
Thromb Res. 1989 Jun 15;54(6):561-72. doi: 10.1016/0049-3848(89)90122-9.
To estimate the effect of dilazep in preventing restenosis after a transluminal angioplasty, we have attempted an animal experiment in which the efficacy of drug was tested on an angioplastic injury superimposed on to atherosclerotic lesions. Using a modification of Block's method, atherosclerotic lesions first were made in the rabbit aorta by an initial ablation of the endothelium, followed by successive cholesterol feedings. Then, for our second step, an angioplastic injury was inflicted on the atherosclerotic lesions. The thirty two rabbits used were divided into 3 groups: those given dilazep (100 micrograms/kg i.v.), those given dipyridamole (100 micrograms/kg i.v.) and a control group that was given the same volume of 0.9% saline. The angioplastic area in which thrombi developed was semiquantitatively measured and compared among all three groups. The mean value of the thrombus area in the dilazep group was 60% smaller and the distribution pattern of the thrombus by size was found to be composed of smaller thrombi than those of the control group. Dipyridamole showed the same trend as did dilazep, but less effectively. Our animal model and semiquantitative evaluation method that we employed were found useful from the view point of an easy applicable and inexpensive methodology. Our results point towards the possible clinical use of dilazep in the future, so as to prevent thrombus formation, which seems to cause the restenosis phenomenon that often occurs in patients who have undergone a coronary angioplasty.
为评估地拉卓预防经皮腔内血管成形术后再狭窄的效果,我们进行了一项动物实验,在动脉粥样硬化病变基础上叠加血管成形损伤,以测试药物疗效。采用改良的布洛克方法,先通过初次剥脱兔主动脉内皮,随后连续喂食胆固醇制造动脉粥样硬化病变。接着,在动脉粥样硬化病变上造成血管成形损伤。所用的32只兔子分为3组:给予地拉卓(静脉注射100微克/千克)的组、给予双嘧达莫(静脉注射100微克/千克)的组和给予相同体积0.9%盐水的对照组。对所有三组中形成血栓的血管成形区域进行半定量测量并比较。地拉卓组血栓面积的平均值小60%,且发现血栓大小的分布模式是由比对照组更小的血栓组成。双嘧达莫显示出与地拉卓相同的趋势,但效果较差。从易于应用且成本低廉的方法学角度来看,我们所采用的动物模型和半定量评估方法是有用的。我们的结果表明地拉卓未来可能有临床应用价值,以预防血栓形成,而血栓形成似乎会导致接受冠状动脉血管成形术的患者中经常出现的再狭窄现象。