Shea M J, Driscoll E M, Romson J L, Pitt B, Lucchesi B R
Eur J Pharmacol. 1984 Oct 15;105(3-4):285-91. doi: 10.1016/0014-2999(84)90620-4.
OKY-1581, a new thromboxane synthetase inhibitor, was studied in a conscious canine model of coronary thrombosis. After thoracotomy with placement of a left circumflex coronary artery flow probe and implantation of an electrode into the circumflex artery, animals were assigned randomly to the following groups: 0.9% NaCl vehicle control or OKY-1581 1 mg/kg every 4 intravenously for 24 h. During the drug treatment period, a 50 microA anodal current was passed through the circumflex electrode, and venous blood was obtained for platelet aggregation studies. As compared to control animals, the OKY-1581 treated animals developed a greater mean coronary flow at the end of the treatment period, smaller thrombi by wet weight, smaller infarcts, and fewer ventricular arrhythmias. Ex vivo platelet aggregation studies revealed significant inhibition of aggregation to standard aggregating agents for the drug treated group only. OKY-1581 is an effective antithrombotic agent which maintains coronary flow after a thrombogenic stimulus, presumably via blockade of the synthesis of thromboxane by blood platelets.
新型血栓素合成酶抑制剂OKY - 1581在清醒犬冠状动脉血栓形成模型中进行了研究。在开胸并放置左旋冠状动脉血流探头以及将电极植入左旋动脉后，动物被随机分为以下几组：0.9%氯化钠载体对照组或OKY - 1581，静脉注射，剂量为1毫克/千克，每4小时一次，共24小时。在药物治疗期间，50微安的阳极电流通过左旋电极，采集静脉血进行血小板聚集研究。与对照动物相比，接受OKY - 1581治疗的动物在治疗期结束时平均冠状动脉血流更大，血栓湿重更小，梗死面积更小，室性心律失常更少。体外血小板聚集研究显示，仅药物治疗组对标准聚集剂的聚集有显著抑制作用。OKY - 1581是一种有效的抗血栓形成药物，在血栓形成刺激后可维持冠状动脉血流，推测是通过阻断血小板血栓素的合成来实现的。
