ROS scavenging before 27°C ischemia protects hearts and reduces mitochondrial ROS, Ca2+ overload, and changes in redox state
ROS scavenging before 27°C ischemia protects hearts and reduces mitochondrial ROS, Ca2+ overload, and changes in redox state
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DOI：
10.1152/ajpcell.00231.2006
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发表时间：
2007-06-01
影响因子：
5.5
通讯作者：
Stowe, David F.
中科院分区：
文献类型：
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作者：
Camara, Amadou K. S.;Aldakkak, Mohammed;Stowe, David F.
我们已经表明，心脏冷灌注产生活性氧和氮（ROS/RNS）。在这项研究中，我们确定了1）在全脑缺血前仅在冷灌注期间清除ROS是否改善线粒体和心肌功能，以及2）在缺血和再灌注（I/R）损伤期间哪种ROS导致心脏功能受损。用荧光分光光度法测定了氧化还原平衡（NADH和FAD）、O-2（.-）120只豚鼠离体心脏分为对照组（Con）、MnTBAP（一种超氧化物歧化酶2模拟物）、MnTBAP（M）+过氧化氢酶（C）+谷胱甘肽（G）（MCG）、C + G（CG）和NG-硝基-L-精氨酸甲酯（L-NAME;一种一氧化氮合酶抑制剂）组。在最初的一段时间的热灌注后，心脏在27 ℃之前和之后用药物处理。在27 ℃缺血2 h和37 ℃再灌注2 h前洗出药物。我们发现，在再灌注MnTBAP组有最差的功能恢复和最大的梗死与最高的m[Ca 2 +]，最氧化的氧化还原状态和增加的ROS水平。MCG组恢复最好，梗死最小，ROS水平最低，m[Ca 2 +]最低，氧化还原状态最还原。CG和L-NAME组的结果介于MnTBAP和MCG组之间。结果表明，低温诱导的O-2（.-）此外，在冷I/R期间和之后，通过保护线粒体功能，将物种转化为毒性较低的下游产品。由于MnTBAP治疗显示出最差的功能恢复沿着线粒体生物能量学的不良保存，因此在冷灌注期间H2 O2和/或羟基自由基的积累可能涉及随后的冷I/R损伤期间受损的功能。
We have shown that cold perfusion of hearts generates reactive oxygen and nitrogen species (ROS/RNS). In this study, we determined 1) whether ROS scavenging only during cold perfusion before global ischemia improves mitochondrial and myocardial function, and 2) which ROS leads to compromised cardiac function during ischemia and reperfusion (I/R) injury. Using fluorescence spectrophotometry, we monitored redox balance (NADH and FAD), O-2(.-) levels and mitochondrial Ca2+ (m[Ca2+]) at the left ventricular wall in 120 guinea pig isolated hearts divided into control (Con), MnTBAP (a superoxide dismutase 2 mimetic), MnTBAP (M) + catalase (C) + glutathione (G) (MCG), C + G (CG), and NG-nitro-L-arginine methyl ester (L-NAME; a nitric oxide synthase inhibitor) groups. After an initial period of warm perfusion, hearts were treated with drugs before and after at 27 C. Drugs were washed out before 2 h at 27 C ischemia and 2 h at 37 C reperfusion. We found that on reperfusion the MnTBAP group had the worst functional recovery and largest infarction with the highest m[Ca2+], most oxidized redox state and increased ROS levels. The MCG group had the best recovery, the smallest infarction, the lowest ROS level, the lowest m[Ca2+], and the most reduced redox state. CG and L-NAME groups gave results intermediate to those of the MnTBAP and MCG groups. Our results indicate that the scavenging of cold-induced O-2(.-) species to less toxic downstream products additionally protects during and after cold I/R by preserving mitochondrial function. Because MnTBAP treatment showed the worst functional return along with poor preservation of mitochondrial bioenergetics, accumulation of H2O2 and/or hydroxyl radicals during cold perfusion may be involved in compromised function during subsequent cold I/R injury.