DEMONSTRATION OF FREE-RADICAL GENERATION IN STUNNED MYOCARDIUM OF INTACT DOGS WITH THE USE OF THE SPIN TRAP ALPHA-PHENYL N-TERT-BUTYL NITRONE
DEMONSTRATION OF FREE-RADICAL GENERATION IN STUNNED MYOCARDIUM OF INTACT DOGS WITH THE USE OF THE SPIN TRAP ALPHA-PHENYL N-TERT-BUTYL NITRONE
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DOI：
10.1172/jci113621
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发表时间：
1988-08-01
影响因子：
15.9
通讯作者：
MCCAY, PB
中科院分区：
文献类型：
--
作者：
BOLLI, R;PATEL, BS;MCCAY, PB
最近的研究表明，氧自由基可能介导缺血后心肌功能障碍（"休克"），但所有的证据都是间接的。因此，我们使用电子顺磁共振（EPR）光谱和自旋陷阱，苯-N-叔丁基硝酮（PBN）直接观察30只开胸犬冠状动脉阻断15分钟后再灌注是否产生自由基。冠状动脉内灌注PBN后，在从缺血/再灌注血管床引流的静脉血中检测到氧和碳中心自由基加合物的EPR信号特征。PBN加合物的心肌释放开始于冠状动脉闭塞期间，但在再灌注后的最初几分钟内急剧增加。在此初始突发后，自由基的产生减弱，但没有停止，持续到回流后3小时。EPR谱（a β H = 2.67 - 2.79 G，aN = 14.75 - 15.00 G）与二级氧中心和碳中心自由基如烷氧基和烷基自由基的PBN一致，所述二级氧中心和碳中心自由基可通过初级氧自由基与膜脂质反应形成。PBN加合物产生的幅度与缺血性血流减少的程度之间存在线性、直接关系。再灌注后收缩功能的恢复（以收缩期室壁增厚测量），给予PBN的狗比对照组更大（P <0.05）。这项研究表明，可逆的区域心肌缺血在完整的动物与长期的自由基生成，这种生成的强度与缺血的严重程度。结果提供了直接的证据，以支持这一假设，即活性氧代谢产物有助于观察短暂缺血后的持续收缩功能障碍（心肌顿抑）在体内。
Recent studies suggest that oxygen free radicals may mediate postischemic myocardialy dysfunction ("stunning"), but all the evidence for this hypothesis is indirect. Thus, we used electron paramagentic resonance (EPR) spectroscopy and the spin trap, .alpha.-phenyl N-tert-butyl nitrone (PBN), to directly investigate whether whether free radicals are produced after a 15-min coronary artery occlusion and subsequent reperfusion in 30 open-chest dogs. After intracoronary infusion of PBN, EPR signals characteristic of oxygen- and carbon-centered radical adducts were detected in the venous blood draining from the ischemic/reperfused vascular bed. The myocardial release of PBN adducts began during coronary occlusion but increased dramatically in the first few miniutes after reperfusion. After this inital burst, the production of radicals abated but did not cease, persisting up to 3 h after reflow. The EPR spectra (a.beta.H = 2.67-2.79 G, aN = 14.75-15.00 G) were consistent by PBN of secondary oxygen- and carbon-centered radicals, such as alkoxy and alkyl radicals, which could be formed by reaction of primary oxygen radicals with membrane lipids. There was a linear, direct relationship between the magnitude of PBN adduct production and the degree of ischemic flow reduction. Recovery of contractile function (measured as systolic wall thickening) after reperfusion was greater (P < 0.05) in dogs given PBN than in controls. This study demonstrates that reversible regional myocardial ischemia in the intact animal is associated with prolonged free radical generation, and that the intensity of such generation is related to the severity of ischemia. The results provide direct evidence to support the hypothesis that reactive oxygen metabolites contributes to the persistent contractile dysfunction (myocardial stunning) observed after brief ischemia in vivo.