In vivo inhibition of platelet aggregation and occlusive coronary thrombus formation by a new calcium antagonist (R023-6152).
In vivo inhibition of platelet aggregation and occlusive coronary thrombus formation by a new calcium antagonist (R023-6152).
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新型钙拮抗剂 (R023-6152) 体内抑制血小板聚集和闭塞性冠状动脉血栓形成。
DOI：
10.1097/00005344-199110000-00005
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发表时间：
1991
影响因子：
3
通讯作者：
Benedict,CR
中科院分区：
文献类型：
--
作者：
Sordahl,LA;Rex,KA;Benedict,CR
有报道表明，所有三种主要类型的钙拮抗剂都能在体外抑制血小板聚集。在这项研究中，我们比较了R 023 -6152，一种硫氮卓酮类钙拮抗剂，与地尔硫卓在犬自发性冠状动脉血栓形成的体内模型中的血小板抗聚集作用。在冠状窦中测量的血浆5-羟色胺（5-HT）水平被用作体内血小板聚集和通过多普勒血流探针测量的冠状动脉血流的指标。未治疗的对照组在用于引发血栓形成的电流中断后62× 18分钟内发生完全冠状动脉闭塞。对照组5-HT水平在闭塞前达到峰值213× 63 ng/ml。电流中断后立即静脉（iv）给予R 023 -6152（200 μg/kg）或地尔硫卓（50 μg/kg）的犬在接下来的3小时内未显示出5-HT值显著升高（R 023 -6152和地尔硫卓分别为12.3× 1.4和1.84× 0.42 ng/ml）或冠状动脉闭塞。在两种药物输注期间，动脉压（8-10 mm Hg）和收缩力发生了短暂的小幅下降。血栓重量的重量测定显示，与对照组相比，给药组动物的血栓显著较小。结果表明，R 023 -6152和地尔硫卓均能有效抑制与闭塞性冠状动脉血栓形成相关的体内血小板聚集。
Reports have shown that all three major classes of calcium antagonists can inhibit platelet aggregation in vitro. In this study, we compared the platelet antiaggregatory effects of R023–6152, a thiazepinone-type calcium antagonist, with diltiazem in an in vivo canine model of spontaneous coronary thrombosis. Plasma serotonin (5-HT) levels measured in the coronary sinus were used as an index of in vivo platelet aggregation and coronary flow measured by a Doppler flow probe. Untreated controls developed total coronary occlusion in 62× 18 min after the current used to initiate thrombus formation was discontinued. Control 5-HT levels peaked at 213× 63 ng/ml just before occlusion. Dogs receiving intravenous (iv) R023–6152 (200 μg/kg) or diltiazem (50 μg/kg) immediately after the current was discontinued exhibited no significant elevations in 5-HT values (12.3× 1.4 and 1.84× 0.42 ng/ml for R023–6152 and diltiazem, respectively) or development of coronary occlusions in the next 3 h. Small, transient decreases in arterial pressure (8–10 mm Hg) and changes in contractility occurred during infusion of both drugs. Gravimetric determinations of thrombus weights showed significantly smaller thrombi in the drug-treated animals as compared with controls. The results indicate that both R023–6152 and diltiazem are effective in suppressing in vivo platelet aggregation associated with occlusive coronary thrombus formation.