Effect of thromboxane and serotonin receptor antagonists on intracoronary platelet deposition in dogs with experimentally stenosed coronary arteries.
Effect of thromboxane and serotonin receptor antagonists on intracoronary platelet deposition in dogs with experimentally stenosed coronary arteries.
复制标题
血栓素和血清素受体拮抗剂对实验性冠状动脉狭窄狗冠状动脉内血小板沉积的影响。
DOI：
10.1161/01.cir.78.3.701
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发表时间：
1988
期刊：
影响因子：
37.8
通讯作者：
Willerson,JT
中科院分区：
文献类型：
--
作者：
Golino,P;Buja,LM;Ashton,JH;Kulkarni,P;Taylor,A;Willerson,JT
我们之前报道过血栓素A2 （TXA2）和5-羟色胺（5-HT， 5-羟色胺）是犬冠状动脉狭窄和内皮损伤模型中循环血流变化（CFVs）的重要介质。本研究验证了TXA2受体拮抗剂在减少内皮损伤和严重狭窄部位冠状动脉内血小板沉积方面比5-HT2受体拮抗剂更有效的假设。56只狗中的51只在左冠状动脉前降支（LAD）周围放置塑料收缩器后发生CFVs。48只动物注射了111In标记的自体血小板。10只对照犬（1A组）在冠状动脉血流最低点CFVs后观察1小时。5只犬（1B组）在置入收缩器后未发生cfv。两种不同的TXA2和PGH2受体拮抗剂SQ 28668 （2.75 +/- 0.36 mg/kg，组2）和SQ 29548 （0.45 +/- 0.1 mg/kg，组3）分别消除了10只狗中的8只和7只狗中的6只CFVs。在10只狗中有8只（第4组），用酮色林（0.66 +/- 0.12 mg/kg）（一种5-HT2受体拮抗剂）消除CFVs。在第2、3和4组狗中，分别给予相应的药物，以便给予消除CFVs所需的最小剂量。在6只狗中的6只（第5组）中，使用更高剂量的酮色林（即1.5 mg/kg）来消除cfv。死亡时，通过计算43只狗的LAD血小板积累比（LAD中的111In活性/旋冠状动脉中的111In活性）和22只狗的LAD显微镜检查来评估冠状动脉内血小板沉积。在1A组犬狭窄部位及其远端节段中发现明显的LAD血小板积累比率。与1A组相比，低剂量和高剂量酮色林均显著降低了LAD血小板积累比率（p < 0.001）。然而，与酮色林处理的动物相比，两种TXA2受体拮抗剂进一步降低了LAD血小板积累比率（p < 0.01）。显微镜检查证实了这些发现。我们得出结论，两种不同的TXA2受体拮抗剂SQ 28668和SQ 29548比5-HT2受体拮抗剂酮色林更有效地减少与CFVs相关的冠状动脉内残余血小板沉积。
We have reported previously that thromboxane A2 (TXA2) and serotonin (5-HT, 5-hydroxytryptamine) are important mediators of cyclic flow variations (CFVs) in a canine model of coronary artery stenosis and endothelial injury. The present study tested the hypothesis that a TXA2 receptor antagonist is more effective in reducing intracoronary platelet deposition at sites of endothelial injury and severe stenosis than a 5-HT2 receptor antagonist. CFVs developed after placing a plastic constrictor around the left anterior descending coronary artery (LAD) in 51 of 56 dogs. Autologous platelets labeled with 111In were injected in 48 animals. Ten control dogs (group 1A) were killed after CFVs were observed for 1 hour at the nadir of coronary blood flow. Five dogs (group 1B) did not develop CFVs after placement of the constrictor. CFVs were abolished with SQ 28668 (2.75 +/- 0.36 mg/kg, group 2) and SQ 29548 (0.45 +/- 0.1 mg/kg, group 3), two different TXA2 and PGH2 receptor antagonists, in eight of 10 and six of seven dogs, respectively. In eight of 10 dogs (group 4), CFVs were abolished with ketanserin (0.66 +/- 0.12 mg/kg), a 5-HT2 receptor antagonist. In group 2, 3, and 4 dogs, the respective drugs were given so that the minimal dose required to abolished CFVs was administered. In six of six dogs (group 5), a higher dose of ketanserin (i.e., 1.5 mg/kg) was used to abolish CFVs. At death, intracoronary platelet deposition was evaluated by calculating the LAD platelet accumulation ratio (111In activity in the LAD/111In activity in the circumflex coronary artery) in 43 dogs and, in 22 dogs, by microscopic examination of the LAD. A marked LAD platelet accumulation ratio was found in group 1A dogs at the stenotic site and in segments immediately distal to it. The LAD platelet accumulation ratio was significantly reduced by both the low and the high doses of ketanserin compared with group 1A dogs (p less than 0.001). However, the two TXA2 receptor antagonists further reduced the LAD platelet accumulation ratio compared with ketanserin-treated animals (p less than 0.01). Microscopic examination confirmed these findings. We conclude that SQ 28668 and SQ 29548, two different TXA2 receptor antagonists, reduce residual intracoronary platelet deposition associated with CFVs in this canine model more effectively than ketanserin, a 5-HT2 receptor antagonist.