Delanty N, Reilly M P, Pratico D, Lawson J A, McCarthy J F, Wood A E, Ohnishi S T, Fitzgerald D J, FitzGerald G A
Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia 19104, USA.
Circulation. 1997 Jun 3;95(11):2492-9. doi: 10.1161/01.cir.95.11.2492.
Myocardial reperfusion is believed to be associated with free radical injury. However, indexes of oxidative stress in vivo have been limited by their poor specificity and sensitivity. Isoprostanes are stable products of arachidonic acid formed in a nonenzymatic, free radical-catalyzed manner. We have developed a sensitive and specific assay for one of these compounds, 8-epi prostaglandin (PG) F2 alpha.
To address its utility as an index of oxidative stress during coronary reperfusion, we measured urinary levels by gas chromatography/mass spectrometry in a canine model of coronary thrombolysis, in patients with acute myocardial infarction treated with thrombolytic therapy, and in patients after elective coronary artery bypass surgery. Urinary 8-epi PGF2 alpha was unchanged after circumflex artery occlusion in a canine model of coronary thrombolysis (n = 13; 437.2 +/- 56.4 versus 432.7 +/- 55.2 pmol/mmol creatinine) but increased significantly (P < .05) immediately after reperfusion (553.8 +/- 64.7 pmol/mmol). Urinary levels were increased (P < .001) in patients (n = 12) with acute myocardial infarction given lytic therapy (265.8 +/- 40.8 pmol/mmol) compared with age-matched control subjects (n = 20; 91.5 +/- 11.8 pmol/mmol) and patients with stable coronary disease (n = 20; 95.7 +/- 6.3 pmol/mmol). Preoperative levels rose from 113.2 +/- 11.8 to 248.2 +/- 86.3 pmol/mmol at 30 minutes into revascularization to 332.2 +/- 82.6 pmol/mmol by 15 minutes after global myocardial reperfusion (P < .05) and dropped to 181.2 +/- 50.4 pmol/mmol at 30 minutes and 120.2 +/- 9.9 pmol/mmol at 24 hours after bypass surgery (n = 5). Corresponding changes in spin adduct formation, found with electron paramagnetic resonance, were noted in 2 patients.
These data support the hypothesis that free radical generation occurs during myocardial reperfusion. Measurement of isoprostane production may serve as a noninvasive index of oxidative stress.
心肌再灌注被认为与自由基损伤有关。然而，体内氧化应激指标因其特异性和敏感性较差而受到限制。异前列腺素是花生四烯酸以非酶促、自由基催化方式形成的稳定产物。我们已开发出一种针对其中一种化合物8-表前列腺素（PG）F2α的灵敏且特异的检测方法。
为探讨其作为冠状动脉再灌注期间氧化应激指标的效用，我们通过气相色谱/质谱法测量了犬冠状动脉溶栓模型、接受溶栓治疗的急性心肌梗死患者以及择期冠状动脉搭桥手术后患者的尿中水平。在犬冠状动脉溶栓模型中（n = 13），左旋支动脉闭塞后尿中8-表PGF2α无变化（437.2 ± 56.4对432.7 ± 55.2 pmol/mmol肌酐），但再灌注后立即显著升高（P <.05）（553.8 ± 64.7 pmol/mmol）。与年龄匹配的对照受试者（n = 20；91.5 ± 11.8 pmol/mmol）和稳定型冠心病患者（n = 20；95.7 ± 6.3 pmol/mmol）相比，接受溶栓治疗的急性心肌梗死患者（n = 12）尿中水平升高（P <.001）（265.8 ± 40.8 pmol/mmol）。术前水平在血管重建30分钟时从113.2 ± 11.8升至248.2 ± 86.3 pmol/mmol，在全心肌再灌注后15分钟时升至332.2 ± 82.6 pmol/mmol（P <.05），在搭桥手术后30分钟降至181.2 ± 50.4 pmol/mmol，24小时时降至120.2 ± 9.9 pmol/mmol（n = 5）。在2例患者中观察到了电子顺磁共振检测到的自旋加合物形成的相应变化。
这些数据支持心肌再灌注期间会产生自由基这一假说。异前列腺素生成的测量可作为氧化应激的无创指标。
