Martorana P A, Kettenbach B, Göbel H, Nitz R E
Basic Res Cardiol. 1984 Sep-Oct;79(5):503-12. doi: 10.1007/BF01910479.
Platelet activation and aggregation in the coronary circulation may be important in the pathogenesis of myocardial ischemia. Molsidomine (M), isosorbide dinitrate (ISDN) and nitroglycerin (NTG) have been found to inhibit platelet aggregation in vitro. In the present study, the activity of these compounds was investigated in a model of coronary artery thrombosis in vivo. Dogs were anesthetized, thoracotomized, and their heart was exposed. An electrode was inserted into the left circumflex coronary artery and set to rest on the intima. Electrical stimulation (9 V, 150 microA) lasted for 6 h. Compounds (each in 2 dose levels) were given as an i.v. infusion starting 30 min after the beginning of the stimulation and lasting for the duration of the experiment. All control (saline-treated) animals underwent thrombotic occlusion of the coronary artery as assessed by flow measurement. On the other hand, 2/8 dogs treated with the lower M dose and 4/8 dogs treated with the higher M dose did not have a coronary occlusion. Neither ISDN nor NTG, at both doses, prevented the coronary occlusion. In control animals thrombus wet weight was 74.43 +/- 11.25 mg. M reduced the thrombus weight in a dose-related manner, while ISDN (marginally) and NTG (significantly at the higher dose) increased this parameter. Following the coronary thrombosis, all control animals developed myocardial infarcts as assessed by the tetrazolium technique. Similarly all animals treated with ISDN and with NTG (at both doses) showed infarcts. However, 3/8 M-dogs did not have a myocardial infarction in the lower as well as in the higher dose groups. The hemodynamic changes induced by the 3 compounds were similar in magnitude. Thus M but not ISDN or NTG showed in this in-vivo study antithrombotic and consequently antiischemic activity.
冠状动脉循环中的血小板激活和聚集在心肌缺血的发病机制中可能起重要作用。已发现吗多明（M）、二硝酸异山梨酯（ISDN）和硝酸甘油（NTG）在体外可抑制血小板聚集。在本研究中，在体内冠状动脉血栓形成模型中研究了这些化合物的活性。将狗麻醉、开胸并暴露心脏。将电极插入左旋冠状动脉并置于内膜上。电刺激（9V，150微安）持续6小时。化合物（各有2个剂量水平）在刺激开始后30分钟开始静脉输注，并持续整个实验过程。通过流量测量评估，所有对照（盐水处理）动物均发生冠状动脉血栓闭塞。另一方面，接受较低剂量M治疗的2/8只狗和接受较高剂量M治疗的4/8只狗未发生冠状动脉闭塞。两种剂量的ISDN和NTG均未预防冠状动脉闭塞。对照动物的血栓湿重为74.43±11.25毫克。M以剂量相关的方式降低血栓重量，而ISDN（略有）和NTG（较高剂量时显著）增加该参数。冠状动脉血栓形成后，通过四氮唑技术评估，所有对照动物均发生心肌梗死。同样，所有接受ISDN和NTG（两种剂量）治疗的动物均出现梗死。然而，在较低和较高剂量组中，3/8只接受M治疗的狗未发生心肌梗死。这3种化合物引起的血流动力学变化幅度相似。因此，在这项体内研究中，M而非ISDN或NTG显示出抗血栓形成以及因此的抗缺血活性。
