Ischemia-induced norepinephrine release, but not norepinephrine-derived free radicals, contributes to myocardial ischemia-reperfusion injury.
Ischemia-induced norepinephrine release, but not norepinephrine-derived free radicals, contributes to myocardial ischemia-reperfusion injury.
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DOI：
10.1253/circj.69.590
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发表时间：
2005-04
期刊：
影响因子：
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通讯作者：
M. Nonomura;T. Nozawa;A. Matsuki;T. Nakadate;Norio Igarashi;Bun-ichi Kato;Nozomu Fujii;A. Igawa;H. Asanoi;T. Kondo;H. Inoue
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作者：
M. Nonomura;T. Nozawa;A. Matsuki;T. Nakadate;Norio Igarashi;Bun-ichi Kato;Nozomu Fujii;A. Igawa;H. Asanoi;T. Kondo;H. Inoue
背景去甲肾上腺素(NE)衍生的自由基可能参与了缺血再灌注后心肌细胞的损伤，因此本研究探讨了去交感神经对心肌缺血再灌注损伤的影响。方法与结果Wistar大鼠在缺血前1周用10%苯酚溶液造成心脏交感神经失神经损伤。冠脉阻断前10min静脉注射阿替洛尔(0.5 mg/kg)。结扎左冠状动脉30min后再灌流。以5，5-二甲基-1-吡咯啉-N-氧化物为自旋捕捉剂，用微透析器收集心脏间质液，用电子顺磁共振(EPR)自旋捕捉法测定透析液中的自由基。与对照组相比，酚组和阿替洛尔组心肌梗死面积与缺血危险面积的比值(I/R)均降低(28.5+/-11.3，31.8+/-10.7vs50.6+/-14.7%，p<；0.05)。冠脉结扎期间，对照组和阿替洛尔组心肌间质NE浓度显著升高，而酚组则无明显变化。EPR信号强度(相对于内标值)在再灌流后1h达到最大，酚组与对照组相似(0.32+/-0.15比0.45+/-0.19)。结论心脏去神经通过减少去甲肾上腺素的直接毒性，而不是通过减少去甲肾上腺素产生的自由基来保护心肌细胞免受缺血再灌注损伤。
BACKGROUND Norepinephrine (NE)-derived free radicals may contribute to myocyte injury after ischemia -reperfusion, so the influence of sympathetic denervation on myocardial ischemia - reperfusion injury was investigated in the present study. METHODS AND RESULTS Cardiac sympathetic denervation was produced in Wistar rats by a solution of 10% phenol 1 week before ischemia. Atenolol (0.5 mg/kg) was intravenously administered 10 min before the coronary occlusion. The left coronary artery was occluded for 30 min and thereafter reperfused. Cardiac interstitial fluid was collected by a microdialysis probe and free radicals in dialysate were determined by electron paramagnetic resonance (EPR) spin trapping, using 5,5-dimethyl-1-pyrroline-N-oxide as a spin trap. The ratio of infarct size to the ischemic area at risk (I/R) was decreased in both the phenol and atenolol groups compared with control (28.5+/-11.3, 31.8+/-10.7 vs 50.6+/-14.7%, p<0.05). During the coronary occlusion, concentrations of interstitial NE increased markedly in the control and atenolol groups, but was unchanged in the phenol group. EPR signal intensity (relative value to internal standard) was maximal at 1 h after reperfusion and was similar in the phenol and control groups (0.32+/-0.15 vs 0.45+/-0.19). CONCLUSIONS Cardiac denervation protected myocyte against ischemia-reperfusion injury through decreasing direct NE toxicity, but not through decreasing NE-derived free radicals.