DEMONSTRATION OF FREE-RADICAL GENERATION IN THE STUNNED MYOCARDIUM IN THE CONSCIOUS DOG AND IDENTIFICATION OF MAJOR DIFFERENCES BETWEEN CONSCIOUS AND OPEN-CHEST DOGS
DEMONSTRATION OF FREE-RADICAL GENERATION IN THE STUNNED MYOCARDIUM IN THE CONSCIOUS DOG AND IDENTIFICATION OF MAJOR DIFFERENCES BETWEEN CONSCIOUS AND OPEN-CHEST DOGS
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DOI：
10.1172/jci116608
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发表时间：
1993-08-01
影响因子：
15.9
通讯作者：
BOLLI, R
中科院分区：
文献类型：
--
作者：
LI, XY;MCCAY, PB;BOLLI, R
清醒的狗进行了15分钟的冠状动脉闭塞，α-苯基N-叔丁基硝酮（PBN）和局部冠状静脉血浆进行了分析，通过电子顺磁共振光谱。观察到PBN自由基加合物的心肌释放延长，其在再灌注的最初几分钟（3分钟时达到峰值）表现出爆发，然后减弱，但在再灌注后持续1-3小时。计算机模拟显示存在至少两种PBN加合物（a（N）= 15.2 G和a（beta）H = 6.0 G; a（N）= 14.6 G和a（beta）H = 3.0 G），这两者与捕获二级碳中心自由基一致。当侧支血流超过非缺血性血流的30-40%时，没有观察到明显的PBN加合物产生，表明至少60%的血流减少是触发自由基反应所必需的。PBN加合物产生的幅度和收缩功能障碍的严重程度之间存在直接关系（r = 0.77），表明再灌注后产生的自由基在随后的顿抑中起因果作用。PBN加合物的总释放后3小时的再灌注15分钟的冠状动脉闭塞被认为是大约5倍以上，在开胸清醒的狗相比，在同一时间，恢复壁增厚明显较少开胸犬。本研究首次将自旋捕获技术应用于清醒的心肌缺血动物模型。结果表明：（a）在不存在与先前使用的模型相关的人工或异常条件的情况下，在顿抑心肌中产生自由基（离体心脏，开胸制备），和（B）在开胸犬中，缺血后功能障碍的严重性和伴随的自由基产生的幅度都被大大夸大，这意味着以前从这个模型得出的结论可能不适用于有意识的动物或人类。本研究还提供了一种方法来测量清醒动物的自由基。
Conscious dogs undergoing a 15-min coronary occlusion were given alpha-phenyl N-tert-butyl nitrone (PBN) and the local coronary venous plasma was analyzed by electron paramagnetic resonance spectroscopy. A prolonged myocardial release of PBN radical adducts was observed, which exhibited a burst in the initial minutes of reflow (peaking at 3 min) and then abated but continued for 1-3 h after reperfusion. Computer simulation revealed the presence of at least two PBN adducts (a(N) = 15.2 G and a(beta)H = 6.0 G; a(N) = 14.6 G and a(beta)H = 3.0 G), both consistent with the trapping of secondary carbon-centered radicals. No appreciable PBN adduct production was observed when collateral flow exceeded 30-40% of nonischemic flow, indicating that a flow reduction of at least 60% is necessary to trigger free radical reactions. There was a direct relationship between the magnitude of PBN adduct production and the severity of contractile dysfunction (r = 0.77), suggesting that the radicals generated upon reperfusion play a causal role in the subsequent stunning. The total release of PBN adducts after 3 h of reperfusion following a 15-min coronary occlusion was found to be approximately five times greater in open-chest compared with conscious dogs; at the same time, the recovery of wall thickening was markedly less in open-chest dogs. This study represents the first application of spin trapping to a conscious animal model of myocardial ischemia. The results demonstrate (a) that free radicals are generated in the stunned myocardium in the absence of the artificial or abnormal conditions associated with previously used models (isolated hearts, open-chest preparations), and (b) that both the severity of postischemic dysfunction and the magnitude of the attendant free radical production are greatly exaggerated in the open-chest dog, implying that previous conclusions derived from this model may not be applicable to conscious animals or to humans. This investigation also provides a method to measure free radicals in awake animals.