Tanaka T, Morishima Y, Watanabe K, Shibutani T, Yasuoka M, Shibano T
Exploratory Research Laboratories II, Daiichi Pharmaceutical Co Ltd, Tokyo, Japan.
Cardiovasc Res. 1993 Jul;27(7):1374-9. doi: 10.1093/cvr/27.7.1374.
The aim was to study the combined effect of DV-7028, a selective 5-hydroxytryptamine2 receptor antagonist, and aspirin or heparin on cyclic flow reductions in the canine coronary artery.
Anaesthetised open chest beagle dogs under artificial respiration were used. Cyclic flow reductions were induced by partial occlusion of the left anterior descending coronary artery at the site of endothelial injury. After induction of cyclic flow reductions, test drugs were given to the animals intravenously.
DV-7028 (0.1 mg.kg-1) reduced the frequency of cyclic flow reductions by 77% and improved the nadir of coronary blood flow velocity that indicated the severity of cyclic flow reductions. Also, aspirin (1 or 3 mg.kg-1) or heparin (200 U.kg-1) attenuated the cyclic flow reductions. In experiments with drug combinations, DV-7028 was given to animals that had already received aspirin (1 mg.kg-1) or heparin (200 U.kg-1). DV-7028 (0.1 mg.kg-1) completely abolished the cyclic flow reductions remaining after aspirin treatment in three of four animals. Heparin inhibited the cyclic flow reductions in one of five animals and the addition of DV-7028 abolished the remaining cyclic flow reductions in the other four animals. After combined injection of DV-7028 with aspirin or heparin, the coronary blood flow with cyclical reductions returned to the baseline.
The 5-HT2 receptor antagonist DV-7028 can inhibit the cyclic flow reductions that are resistant to aspirin or heparin. The combined regimen of DV-7028 and aspirin or heparin in treatment of acute coronary stenosis is more effective than that of aspirin or heparin alone.
研究选择性5-羟色胺2受体拮抗剂DV-7028与阿司匹林或肝素联合应用对犬冠状动脉循环血流减少的影响。
采用人工呼吸下麻醉开胸的比格犬。通过在冠状动脉左前降支内皮损伤部位部分闭塞来诱导循环血流减少。诱导循环血流减少后，给动物静脉注射受试药物。
DV-7028（0.1毫克·千克-1）使循环血流减少的频率降低了77%，并改善了冠状动脉血流速度最低点，该最低点表明循环血流减少的严重程度。此外，阿司匹林（1或3毫克·千克-1）或肝素（200单位·千克-1）减轻了循环血流减少。在药物联合实验中，给已接受阿司匹林（1毫克·千克-1）或肝素（200单位·千克-1）的动物注射DV-7028。DV-7028（0.1毫克·千克-1）在四只动物中的三只中完全消除了阿司匹林治疗后剩余的循环血流减少。肝素在五只动物中的一只中抑制了循环血流减少，加入DV-7028后消除了其他四只动物中剩余的循环血流减少。DV-7028与阿司匹林或肝素联合注射后，伴有周期性减少的冠状动脉血流恢复到基线水平。
5-羟色胺2受体拮抗剂DV-7028可抑制对阿司匹林或肝素耐药的循环血流减少。DV-7028与阿司匹林或肝素联合治疗急性冠状动脉狭窄的方案比单独使用阿司匹林或肝素更有效。
