Minami M, Driscoll E M, Lucchesi B R
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Higashi-Nippon-Gakuen University, Hokkaido, Japan.
Jpn Circ J. 1993 Oct;57(10):979-92. doi: 10.1253/jcj.57.979.
BMY21190, an inhibitor of cyclic AMP phosphodiesterase, has a coronary vasodilating effect. BMY21190 was evaluated for its ability to modify the development of experimental thrombosis resulting from anodal current injury (100 microA for 6 h) of the intimal surface of the left circumflex coronary artery (LCX) in anesthetized dogs. Two groups of dogs were studied. One group received BMY21190 (1 mg/kg) and the other group received an equal volume of vehicle infused into the left jugular vein. After a 30 min administration of BMY21190, heart rate and mean coronary blood flow were increased significantly and mean arterial pressure was decreased. However, the myocardial tension of the left anterior descending coronary artery (LAD) and LCX areas did not increase significantly after BMY21190 infusion. During LCX stimulation, the first LCX occlusion and hyperemic reaction of the control group both occurred significantly earlier than those of the BMY21190 group. BMY21190 treatment reduced the development of the LCX thrombus mass, as compared to that in the controls. In ex vivo studies, platelet aggregation in response to arachidonic acid, ADP or collagen was inhibited by BMY21190. These results suggest that BMY21190 possesses anti-thrombotic and coronary vasodilating effects which may be mediated through the inhibition of cyclic AMP phosphodiesterase.
环磷腺苷磷酸二酯酶抑制剂BMY21190具有冠状动脉扩张作用。对BMY21190在麻醉犬体内改变左旋冠状动脉（LCX）内膜表面阳极电流损伤（100微安，持续6小时）所致实验性血栓形成发展的能力进行了评估。研究了两组犬。一组给予BMY21190（1毫克/千克），另一组经左颈静脉注入等体积的赋形剂。给予BMY21190 30分钟后，心率和平均冠状动脉血流量显著增加，平均动脉压降低。然而，注入BMY21190后，左前降支冠状动脉（LAD）和LCX区域的心肌张力没有显著增加。在刺激LCX期间，对照组的首次LCX闭塞和充血反应均显著早于BMY21190组。与对照组相比，BMY21190治疗减少了LCX血栓块的形成。在体外研究中，BMY21190抑制了花生四烯酸、ADP或胶原诱导的血小板聚集。这些结果表明，BMY21190具有抗血栓和冠状动脉扩张作用，可能是通过抑制环磷腺苷磷酸二酯酶介导的。
