Serotonin-induced coronary contraction increases after blood cardioplegia-reperfusion: role of COX-2 expression.
Serotonin-induced coronary contraction increases after blood cardioplegia-reperfusion: role of COX-2 expression.
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DOI：
10.1161/01.cir.100.suppl_2.ii-328
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发表时间：
1999-11
期刊：
影响因子：
37.8
通讯作者：
C. Métais;J. Li;M. Simons;F. Sellke
中科院分区：
文献类型：
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作者：
C. Métais;J. Li;M. Simons;F. Sellke
背景冠状动脉收缩与冠状动脉搭桥手术后心肌功能不佳有关。研究表明，在心脏停跳液中添加血液可以改善心脏停跳后的内皮功能。在本研究中，检查了心脏停跳液和短暂再灌注对冠状动脉疾病患者血管反应性以及参与血管舒缩调节的酶的表达（mRNA 和蛋白质）的影响。方法和结果 接受冠状动脉手术的患者的心耳在体外循环之前（对照，n=8）和非缺血组织心房段搭桥后暴露于冷、高钾血心脏停搏液（平均，60 分钟）和短暂的再灌注期（10 分钟）（CP-Rep，n=8）后采集。通过视频显微镜在体外研究心房小动脉的反应。使用逆转录酶聚合酶链反应和蛋白质印迹分别检测参与血管舒缩调节的酶的表达和蛋白质含量。血清素在基线条件下引起最小的扩张，但在 CP-Rep 引发有效的收缩反应后，这种反应在选择性诱导型环氧合酶 (COX-2) 抑制剂 NS398 的存在下被抑制。 P物质通过释放一氧化氮引起心房小动脉内皮依赖性舒张，ADP通过释放前列腺素引起舒张。 CP-Rep 后，对 P 物质的舒张受到损害，而对硝普钠的内皮依赖性舒张和对 ADP 的反应则没有变化。 CP-Rep 后 COX-2 的表达和蛋白水平显着增加。相反，诱导型（一氧化氮合酶-2）或组成型内皮（一氧化氮合酶-3）一氧化氮合酶、前列环素合酶和组成型环氧合酶（COX-1）的表达在CP-Rep后没有改变。结论 CP-Rep 增加了由 COX-2 产物释放和一氧化氮释放受损引起的血清素诱导的人体微血管收缩。这些发现对于改变冠状动脉微血管调节和心脏手术后冠状动脉痉挛的原因具有重要意义。
BACKGROUND Coronary contraction has been implicated in causing suboptimal myocardial function after coronary bypass surgery. Addition of blood to cardioplegic solutions has been shown to improve endothelial function after cardioplegia. In this study, the effects of blood cardioplegia and brief reperfusion on vascular reactivity in patients with coronary artery disease and the expression (mRNA and protein) of enzymes involved in vasomotor regulation were examined. METHODS AND RESULTS The atrial appendages of patients undergoing coronary artery surgery were harvested before cardiopulmonary bypass (control, n=8) and after bypass from a nonischemic tissue atrial segment exposed to cold, hyperkalemic blood cardioplegia (mean, 60 minutes) and a brief period (10 minutes) of reperfusion (CP-Rep, n=8). Responses of atrial arterioles were studied in vitro with video-microscopy. Reverse-transcriptase polymerase chain reaction and Western blotting were used to examine the expressions and protein content, respectively, of enzymes involved in vasomotor regulation. Serotonin caused a minimal dilation under baseline conditions but after CP-Rep elicited a potent contractile response that was inhibited in the presence of the selective inducible cyclooxygenase (COX-2) inhibitor NS398. Substance P caused an endothelium-dependent relaxation of atrial arterioles through release of nitric oxide, and ADP caused relaxation mediated through release of prostaglandins. After CP-Rep, relaxation to substance P was impaired, whereas endothelium-independent relaxation to nitroprusside and response to ADP were unchanged. Expression and protein level of COX-2 were significantly increased after CP-Rep. In contrast, expression of inducible (nitric oxide synthase-2) or constitutive endothelial (nitric oxide synthase-3) nitric oxide synthase, prostacyclin synthase, and constitutive cyclooxygenase (COX-1) were not altered after CP-Rep. CONCLUSIONS CP-Rep increases serotonin-induced contraction of human microvessels caused by the release of products of COX-2 and the impaired release of nitric oxide. These findings have implications regarding altered coronary microvascular regulation and the cause of coronary spasm after cardiac surgery.