Active oxygen species play a role in mediating platelet aggregation and cyclic flow variations in severely stenosed and endothelium-injured coronary arteries.
Active oxygen species play a role in mediating platelet aggregation and cyclic flow variations in severely stenosed and endothelium-injured coronary arteries.
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活性氧在介导严重狭窄和内皮损伤的冠状动脉中的血小板聚集和循环血流变化中发挥作用。
DOI：
10.1161/01.res.73.5.952
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发表时间：
1993
影响因子：
20.1
通讯作者：
Willerson,JT
中科院分区：
文献类型：
--
作者：
Yao,SK;Ober,JC;Gonenne,A;ClubbJr,FJ;Krishnaswami,A;Ferguson,JJ;Anderson,HV;Gorecki,M;Buja,LM;Willerson,JT
本文采用犬冠状动脉狭窄和内皮损伤的循环血流变化（CFVs）模型，研究了活性氧在血小板聚集中的作用。我们研究了90只麻醉犬，打开心包腔，暴露心脏。采用脉冲多普勒血流探头监测左冠状动脉前降支血流速度。在67只狗中，在内皮受到机械损伤的部位应用外部收缩剂进行lad狭窄。67只狗都出现了cfv。抗氧化剂重组人铜锌超氧化物歧化酶（r-h-CuZnSOD）、重组人锰超氧化物歧化酶（r-h-MnSOD）和过氧化氢酶分别在63%、62%和64%的动物中消除了血小板聚集相关的冠状动脉cfv。静脉输注肾上腺素可使大多数犬恢复cfv。Ketanserin是一种5-羟色胺受体拮抗剂，可以消除肾上腺素恢复的cfv，并消除未被自由基清除剂清除的cfv。在另外23只狗中，lad狭窄但没有机械损伤。作为对照研究，在5只狗的lad中注入生理盐水。采用黄嘌呤/黄嘌呤氧化酶灌胃8只犬，诱导4只犬发生CFVs。另外10只狗注射双氧水，9只诱导CFVs。冠状动脉的组织学分析显示，灌注后冠状动脉内膜明显受损。在离体血小板聚集研究中，体内用r-h-CuZnSOD、r-h-MnSOD和过氧化氢酶处理可显著抑制血小板活化因子诱导的血小板聚集。因此，活性氧在体内参与介导狭窄和内皮损伤犬冠状动脉的血小板聚集和循环血流变化。
A canine model with cyclic flow variations (CFVs) in stenosed and endothelium-injured coronary arteries was used to examine the role of active oxygen species in platelet aggregation in vivo. We studied 90 anesthetized dogs in which the pericardial cavity was opened and the heart was exposed. The velocity of blood flow in the left anterior descending coronary artery (LAD) was monitored by a pulsed Doppler flow probe. In 67 dogs, the LADs were stenosed by applying external constrictors at the site where the endothelium was mechanically injured. CFVs developed in all 67 dogs. Treatment with the antioxidants recombinant human copper-zinc superoxide dismutase (r-h-CuZnSOD), recombinant human manganese superoxide dismutase (r-h-MnSOD), and catalase eliminated platelet aggregation-associated coronary CFVs in 63%, 62%, and 64% of animals, respectively. Intravenous infusion of epinephrine restored CFVs in most dogs. Ketanserin, a serotonin (5-hydroxytryptamine2) receptor antagonist, abolished epinephrine-restored CFVs and eliminated CFVs in dogs in which CFVs had not been eliminated by free radical scavengers. In an additional 23 dogs, the LADs were stenosed but not mechanically injured. For control studies, saline was infused into the LADs of 5 dogs. Xanthine/xanthine oxidase was infused into the LADs of 8 dogs and induced CFVs in 4. Hydrogen peroxide was infused into the other 10 dogs and induced CFVs in 9. Histological analysis of the coronary artery revealed that the intima was significantly injured by the infusion. In ex vivo platelet aggregation studies, the in vivo treatment with r-h-CuZnSOD, r-h-MnSOD, and catalase significantly inhibited platelet aggregation induced by platelet-activating factor. Thus, active oxygen species are involved in mediating platelet aggregation and cyclic flow variations in stenosed and endothelium-injured canine coronary arteries in vivo.