Vasoconstrictor Potential of Coronary Aspirate From Patients Undergoing Stenting of Saphenous Vein Aortocoronary Bypass Grafts and Its Pharmacological Attenuation
Vasoconstrictor Potential of Coronary Aspirate From Patients Undergoing Stenting of Saphenous Vein Aortocoronary Bypass Grafts and Its Pharmacological Attenuation
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DOI：
10.1161/circresaha.110.235713
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发表时间：
2011-02-04
影响因子：
20.1
通讯作者：
Heusch, Gerd
中科院分区：
文献类型：
--
作者：
Kleinbongard, Petra;Boese, Dirk;Heusch, Gerd
原理：支架植入动脉粥样硬化斑块时，除了颗粒碎片外，还会释放可溶性物质，导致微血管灌注受损。目的：量化血管收缩剂的释放，并确定冠状动脉扩张剂减弱其作用的功效。方法和结果：使用远端保护/抽吸装置，在 22 名严重隐静脉主动脉冠状动脉搭桥术患者的支架置入术前和支架置入术期间回收冠状动脉血狭窄。测量了儿茶酚胺、内皮素、血清素、血栓素 B-2 和肿瘤坏死因子 (TNF)α 的释放。具有完整 (+E) 和剥脱 (-E) 内皮的大鼠肠系膜动脉对吸出血浆的反应被标准化为 KCl 的反应。确定了选择性受体阻断、腺苷、硝普钠和维拉帕米对抽吸引起的收缩的反应。支架植入前抽取的冠状动脉血浆诱导了 21 +/- 5% 的最大 KCl 诱导的血管收缩，支架植入后抽吸的血浆诱导了 95 +/- 8% 的最大 KCl 诱导的血管收缩。支架植入期间，释放到抽吸血浆中的血清素、血栓素 B-2 和 TNF α 分别增加了 1.9 +/- 0.2 μmol/L、25.6 +/- 3.1 pg/mL 和 19.7 +/- 6.1 pg/mL。抽吸物引起的血管收缩在很大程度上被选择性血清素受体阻断所拮抗，而额外的血栓素受体阻断几乎没有进一步拮抗作用。 TNF α本身并不诱导收缩，但通过动脉+E中的血清素和血栓素类似物U-46619增强收缩。硝普钠（+E，3.3 x 10(-8)；-E，1.9 x 10(-8) mol/L）和维拉帕米（+E，8.3 x 10(-8)；-E，7.8 x 10(-8) mol/L）诱导半最大血管舒张的浓度相当，最终消除血管收缩。腺苷的血管舒张反应依赖于功能性内皮细胞，且较弱。结论：支架置入后，5-羟色胺是主要的冠状血管收缩剂，血栓素和TNF-α在一定程度上增强5-羟色胺反应。硝普钠和维拉帕米比腺苷更有效地减弱吸入血浆引起的血管收缩，并且它们不依赖于功能性内皮。 （Circ Res. 2011；108:344-352。）
Rationale: Stent implantation into atherosclerotic plaques releases, apart from particulate debris, soluble substances that contribute to impaired microvascular perfusion.Objective: To quantify the release of vasoconstrictors and to determine the efficacy of coronary dilators to attenuate their action.Methods and Results: Using a distal protection/aspiration device, coronary arterial blood was retrieved before and during stenting in 22 patients with severe saphenous vein aorto-coronary bypass stenoses. The release of catecholamines, endothelin, serotonin, thromboxane B-2, and tumor necrosis factor (TNF)alpha was measured. The response of rat mesenteric arteries with intact (+E) and denuded (-E) endothelium to aspirate plasma was normalized to that by KCl. Responses to selective receptor blockade, adenosine, nitroprusside, and verapamil against the aspirate-induced constriction were determined. The coronary arterial plasma withdrawn before stenting induced 21 +/- 5% and the aspirate plasma after stenting induced 95 +/- 8% of maximum KCl-induced vasoconstriction. Serotonin, thromboxane B-2, and TNF alpha release into aspirate plasma increased by 1.9 +/- 0.2 mu mol/L, 25.6 +/- 3.1 pg/mL, and 19.7 +/- 6.1 pg/mL, respectively, during stenting. The aspirate-induced vasoconstriction was largely antagonized by selective serotonin receptor blockade, with little further antagonism by additional thromboxane receptor blockade. TNF alpha did not induce constriction per se but potentiated the constriction with serotonin and the thromboxane-analog U-46619 in arteries +E. The concentrations to induce half-maximal vasodilation were comparable for nitroprusside (+E, 3.3 x 10(-8); -E, 1.9 x 10(-8) mol/L) and verapamil (+E, 8.3 x 10(-8); -E, 7.8 x 10(-8) mol/L), and the vasoconstriction was eventually eliminated. The vasodilator response to adenosine was dependent on functional endothelium and weaker.Conclusion: Serotonin is the main coronary vasoconstrictor after stenting, and thromboxane and TNF alpha somewhat potentiate the serotonin response. Nitroprusside and verapamil are more potent than adenosine to attenuate the aspirate plasma-induced vasoconstriction, and they are not dependent on functional endothelium. (Circ Res. 2011;108:344-352.)