ANGIOPLASTY TRIGGERS INTRACORONARY LEUKOTRIENES AND LIPOXIN-A(4) - IMPACT OF ASPIRIN THERAPY
ANGIOPLASTY TRIGGERS INTRACORONARY LEUKOTRIENES AND LIPOXIN-A(4) - IMPACT OF ASPIRIN THERAPY
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DOI：
10.1161/01.cir.86.1.56
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发表时间：
1992-07-01
期刊：
影响因子：
37.8
通讯作者：
SERHAN, CN
中科院分区：
文献类型：
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作者：
BREZINSKI, DA;NESTO, RW;SERHAN, CN
背景。经皮腔内冠状动脉成形术（PTCA）是一种广泛应用且重要的冠状动脉再灌注方法。然而，它也与严重并发症相关，如急性再闭塞和加速再狭窄。PTCA相关并发症所涉及的因素及机制仍有待充分阐明。由于肽白三烯和脂氧素是强效的血管活性化合物，其形成在体外不受阿司匹林（ASA）治疗的抑制，所以这些类花生酸可能参与了PTCA相关的不良事件。为了验证这一点，我们测定了斑块破裂后冠状动脉内肽白三烯和脂氧素A4（LXA4）以及血栓素（TX）和5S,12S - 二羟基二十碳四烯酸（5S,12S - DiHETE；一种双加氧产物）的水平，并评估了ASA治疗的影响。
方法与结果。对12例冠状动脉疾病患者进行了PTCA，其中6例在PTCA前至少2周接受ASA治疗，6例未接受ASA治疗。通过一种允许在原位斑块部位采集冠状动脉内血液的技术，在斑块破裂开始前和开始后10秒采集样本。脂氧合酶（LO）衍生的产物，包括LXA4和5S,12S - DiHETE，以及一种环氧合酶活性的标志物，即TXB2，在提取和色谱分析后，使用氘标记的内标和电子捕获负离子化学电离质谱法进行定量。肽白三烯（LTC4和LTD4）在反相高效液相色谱与放射免疫分析联用后进行定量。PTCA前采集的冠状动脉内血液未检测到这些类花生酸的水平（检测下限在皮摩尔范围内）。相反，PTCA后检测到了每种LO产物。与未接受ASA的患者相比，接受ASA治疗的患者所检测的每种LO产物水平均升高。类花生酸水平为（平均值±标准误）：LTC4，7.10±1.22纳克/毫升（ASA）对0.48±0.10纳克/毫升；LTD4，4.92±0.56纳克/毫升（ASA）对1.17±0.48纳克/毫升；LXA4，24.98±4.11纳克/毫升（ASA）对15.83±2.43纳克/毫升；5S,12S - DiHETE，19.47±3.98纳克/毫升（ASA）对11.98±1.83纳克/毫升；TXB2，完全阻断（ASA）对31.04±7.38纳克/毫升（p<...此处似乎文本不完整）
Background. Percutaneous transluminal coronary angioplasty (PTCA) is a widely used and important method of reperfusing coronary arteries. However, it is also associated with serious complications such as acute reocclusion and accelerated restenosis. The factors as well as the mechanisms involved in PTCA-associated complications remain to be fully elucidated. Because peptidoleukotrienes and lipoxins are potent vasoactive compounds, the formation of which is not inhibited by aspirin (ASA) treatment in vitro, it is possible that these eicosanoids are involved in PTCA-associated untoward events. To test this, we determined the intracoronary levels of peptidoleukotrienes and lipoxin A4 (LXA4) as well as thromboxane (TX) and 5S,12S-dihydroxyeicosatetraenoic acid (5S,12S-DiHETE; a product of double dioxygenation) after plaque rupture and evaluated the impact of ASA therapy.Methods and Results. PTCA was performed on 12 patients with coronary artery disease, six undergoing ASA therapy and six without ASA therapy, for at least 2 weeks before PTCA. By means of a technique that permitted sampling of intracoronary blood at the plaque site in situ, samples were taken immediately before and 10 seconds after initiation of plaque rupture. Lipoxygenase (LO)-derived products, including LXA4 and 5S,12S-DiHETE, and a marker of cyclooxygenase activity, i.e., TXB2, were quantitated after extraction and chromatography using deuterium-labeled internal standards and electron capture negative ion chemical ionization mass spectrometry. Peptidoleukotrienes (LTC4 and LTD4) were quantitated after reverse-phase high-performance liquid chromatography coupled with radioimmunoassay. Intracoronary blood taken before PTCA showed no detectable levels of these eicosanoids (the minimum limits of detection were within the picomole range). In contrast, each of these LO products was detected after PTCA. Patients undergoing ASA treatment showed elevated levels of each LO product examined compared with those not receiving ASA. Eicosanoid levels were (mean+/-SEM): LTC4, 7.10+/-1.22 ng/ml (ASA) versus 0.48+/-0.10 ng/ml; LTD4, 4.92+/-0.56 ng/ml (ASA) versus 1.17+/-0.48 ng/ml; LXA4, 24.98+/-4.11 ng/ml (ASA) versus 15.83+/-2.43 ng/ml; 5S,12S-DiHETE, 19.47+/-3.98 ng/ml (ASA) versus 11.98+/-1.83 ng/ml; TXB2, complete blockage (ASA) versus 31.04+/-7.38 ng/ml (p