Mickelson J K, Simpson P J, Gallas M T, Lucchesi B R
Am Heart J. 1987 Jun;113(6):1345-52. doi: 10.1016/0002-8703(87)90646-6.
The focus of this investigation was to examine the potential beneficial effects of the selective thromboxane synthetase inhibitor CGS 13080 (imidazo [1,5-a] pyridine-5-hexanoic acid) on coronary blood flow after streptokinase-induced thrombolysis. Thrombotic occlusion of the circumflex coronary artery was produced by electrolytic (100 microA anodal current) injury to the intimal surface of the circumflex coronary artery at the site of a noncircumferential stenosis in dogs anesthetized with pentobarbital to have open-chest surgery. Intracoronary streptokinase, 6000 IU/kg in 3 ml saline solution, was infused at 0.05 ml/min for 1 hour, beginning 30 minutes after the formation of an occlusive thrombus. The animals were assigned randomly to two groups. In group I (n = 10) the intravenous infusion of vehicle was begun simultaneously with the intracoronary administration of streptokinase and continued for 2 hours after thrombolysis had been achieved. The animals in group II (n = 10) received intravenous CGS 13080 (1 mg/kg/hr) along with intracoronary streptokinase. Infarct size was assessed by a dual perfusion technique with Evans blue and triphenyltetrazolium stains to demarcate the normally perfused myocardium from the area at risk and the infarct zone within the risk region. The two groups did not differ with respect to baseline coronary blood flow, time to the development of coronary artery thrombotic occlusion, or time to achieve thrombolysis. Oscillations in coronary blood flow were more frequent in group I than in group II (group I, 9 +/- 2.2; group II, 4.4 +/- 0.8 oscillation/min X 100, p less than 0.05 [mean +/- SEM)].(ABSTRACT TRUNCATED AT 250 WORDS)
本研究的重点是检测选择性血栓素合成酶抑制剂CGS 13080(咪唑并[1,5-a]吡啶-5-己酸)对链激酶诱导溶栓后冠状动脉血流的潜在有益作用。在戊巴比妥麻醉下行开胸手术的犬中,通过对左旋冠状动脉非圆周狭窄部位内膜表面进行电解(100微安阳极电流)损伤,造成左旋冠状动脉血栓性闭塞。在闭塞性血栓形成30分钟后,以0.05毫升/分钟的速度在3毫升盐溶液中注入6000国际单位/千克的冠状动脉内链激酶,持续1小时。将动物随机分为两组。在第一组(n = 10)中,在冠状动脉内给予链激酶的同时开始静脉输注溶媒,并在溶栓成功后持续2小时。第二组(n = 10)的动物在冠状动脉内给予链激酶的同时接受静脉注射CGS 13080(1毫克/千克/小时)。通过伊文思蓝和三苯基四氮唑双重灌注技术评估梗死面积,以区分正常灌注心肌与危险区域以及危险区域内的梗死区。两组在基线冠状动脉血流、冠状动脉血栓性闭塞发生时间或溶栓时间方面无差异。第一组冠状动脉血流的振荡比第二组更频繁(第一组,9±2.2;第二组,4.4±0.8次振荡/分钟×100,p<0.05[平均值±标准误])。(摘要截短于250字)