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首页> 外文期刊>American Journal of Physiology >Coronary and myocardial effects of acetaminophen: protection during ischemia-reperfusion.
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Coronary and myocardial effects of acetaminophen: protection during ischemia-reperfusion.

机译:对乙酰氨基酚对冠状动脉和心肌的影响:缺血再灌注时的保护作用。

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摘要

Acetaminophen is a phenol with antioxidant properties, but little is known about its actions on the mammalian myocardium and coronary circulation. We studied isolated, perfused guinea pig hearts, and tested the hypothesis that acetaminophen-treated hearts would be protected during ischemia-reperfusion. Acetaminophen concentrations in the range of 0.3-0.6 mmol/l caused modest but significant (P < 0.05) coronary vasoconstriction and positive inotropy. The effects were more brisk during constant pressure perfusion than during constant flow. During 20 min of low-flow, global myocardial ischemia and 40 min of reperfusion, hearts treated with acetaminophen retained or recovered a greater percentage of left ventricular function than hearts treated with vehicle. Myofibrillar ultrastructure appeared to be preserved in the reperfused myocardium with acetaminophen. By using chemiluminescence and spin-trap methodologies, we investigated acetaminophen-mediated antioxidant mechanisms to help explain the cardioprotection. The burst of hydroxyl radicals seen between 0 and 10 min of reperfusion was significantly attenuated (P < 0.05) by acetaminophen but not by vehicle. The 3-morpholinosydnominine (SIN-1) generation of peroxynitrite and its oxidative interaction with luminol to produce blue light during ischemia-reperfusion was also blocked by acetaminophen. Our results show that acetaminophen provides significant functional and structural protection to the ischemic-reperfused myocardium, and the mechanism of cardioprotection seems to involve attenuation of the production of both hydroxyl radicals and peroxynitrite.
机译:对乙酰氨基酚是一种具有抗氧化性能的酚,但对它对哺乳动物心肌和冠状动脉循环的作用知之甚少。我们研究了离体的灌注豚鼠心脏,并测试了对乙酰氨基酚治疗的心脏在缺血再灌注过程中会受到保护的假设。对乙酰氨基酚浓度在0.3-0.6 mmol / l范围内可引起适度但显着(P <0.05)的冠状动脉血管收缩和正性肌力。在恒定压力灌注下的效果比在恒定流量下的效果更明显。在20分钟的低流量,整体性心肌缺血和40分钟的再灌注期间,对乙酰氨基酚治疗的心脏保留或恢复的左心室功能百分比高于溶媒治疗的心脏。肌原纤维的超微结构似乎与对乙酰氨基酚一起保留在再灌注的心肌中。通过使用化学发光和自旋阱方法,我们研究了对乙酰氨基酚介导的抗氧化剂机制,以帮助解释心脏保护作用。对乙酰氨基酚可显着减弱再灌注0至10分钟之间出现的羟基自由基爆发(P <0.05),而不会被溶媒抑制。对乙酰氨基酚也阻断了过氧亚硝酸盐的3-morpholinosydminminine(SIN-1)生成及其与鲁米诺的氧化相互作用以产生蓝光。我们的结果表明,对乙酰氨基酚为缺血再灌注的心肌提供了重要的功能和结构保护,并且心脏保护的机制似乎涉及减少羟基自由基和过氧亚硝酸盐的产生。

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