PLATELET-MEDIATED THROMBOSIS IN STENOSED CANINE CORONARY-ARTERIES - INHIBITION BY NICERGOLINE, A PLATELET-ACTIVE ALPHA-ADRENERGIC ANTAGONIST
PLATELET-MEDIATED THROMBOSIS IN STENOSED CANINE CORONARY-ARTERIES - INHIBITION BY NICERGOLINE, A PLATELET-ACTIVE ALPHA-ADRENERGIC ANTAGONIST
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DOI：
10.1016/s0735-1097(84)80280-6
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发表时间：
1984-01-01
影响因子：
24
通讯作者：
MACE, ML
中科院分区：
文献类型：
--
作者：
BOLLI, R;WARE, JA;MACE, ML
尼麦角林，一种阻断α-羟色胺的新药剂的作用肾上腺素能受体和抑制血小板磷脂酶，在血小板介导的冠状动脉血栓形成的犬模型中进行评价。在48只开胸犬上，用缝线折叠冠状动脉壁使其狭窄。在48只狗中，34只表现出狭窄血管中的血流周期性减少，随后突然恢复到对照水平。肝素给药（1000 U/kg/h）后，除2只犬外，所有犬的血流减少均未减弱，不受大剂量硝酸甘油和硝苯地平的影响，并与狭窄节段中的血小板聚集有关（通过组织学和电子显微镜检查证实）。血流量减少显然是由血小板聚集引起的，而不是由纤维蛋白沉积或血管痉挛引起的。在肝素给药后监测犬（20只）1小时，然后将其分配至对照组（n = 7）或尼麦角林给药组（n = 13; 1 mg/kg i. v.）组在对照犬中，血流周期性减少持续1小时不变，而在治疗组中，1只犬血流周期性减少明显减少，其他12只犬血流周期性减少完全消失。阿司匹林（30 mg/kg i. v.）抑制所有对照犬的血流减少，证实血小板聚集在该现象中的主要作用。本研究提供了一种改良的血小板介导的冠状动脉狭窄血栓形成模型。尼麦角林在体内可有效干扰血小板功能。尼麦角林表现出的强效抗血栓形成活性可能增强这种血管扩张剂的治疗作用。
The effects of nicergoline, a new agent that blocks .alpha.-adrenergic receptors and inhibits platelet phospholipase, were evaluated in a canine model of platelet-mediated coronary thrombosis. In 48 open chest dogs, the circumflex coronary artery was stenosed by plicating the artery wall with a suture. Of the 48 dogs, 34 exhibited cyclic reductions in flow in the stenotic vessel, followed by a sudden return to control levels. The reductions in flow were unabated in all but 2 dogs after heparin administration (1000 U/kg per h), unaffected by large doses of nitroglycerin and nifedipine and associated with platelet aggregates in the stenotic segment (demonstrated by histologic and electron microscopic examination). The flow reductions apparently were caused by platelet aggregation rather than by fibrin deposition or vasospasm. Dogs (20) were monitored for 1 h after heparin administration and then assigned to a control (n = 7) or nicergoline-treated (n = 13; 1 mg/kg i.v.) group. In control dogs, cyclic reductions in flow continued unchanged for another hour, whereas in the treated group they were markedly decreased in 1 dog and completely abolished in the other 12 dogs. Aspirin (30 mg/kg i.v.) suppressed flow reductions in all control dogs, confirming the primary role of platelet aggregation in the phenomenon. This study provides a modified model of platelet-mediated thrombosis in stenosed coronary arteries. Nicergoline evidently can effectively interfere with platelet function in vivo. The potent antithrombotic activity exhibited by nicergoline might enhance the therapeutic usefulness of this vasodilator.