Direct evidence for increased hydroxyl radicals originating from superoxide in the failing myocardium
Direct evidence for increased hydroxyl radicals originating from superoxide in the failing myocardium
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DOI：
10.1161/01.res.86.2.152
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发表时间：
2000-02-04
影响因子：
20.1
通讯作者：
Takeshita, A
中科院分区：
文献类型：
--
作者：
Ide, T;Tsutsui, H;Takeshita, A
实验和临床研究表明，在衰竭心肌中活性氧（ROS）的产生增加。本研究旨在获得增加的ROS的直接证据，并确定超氧阴离子（O-）的贡献。(2)-)、H_2O_2和羟基自由基（（OH）-O-.）在衰竭的心肌组织中成年杂种犬经240次/分快速心室起搏4周后，建立心衰模型。为了直接评估ROS的产生，将冷冻夹持的心肌组织匀浆与氮氧自由基4-羟基-2，2，6，6-四甲基哌啶-N-氧基反应，并通过电子自旋共振光谱检测其自旋信号。电子自旋共振信号衰减的速率，与（OH）-O-成正比。在心力衰竭中，水平显著增加，这通过向反应混合物中加入二甲基硫脲COH清除剂来抑制。增加（OH）-O-。在去铁胺（铁螯合剂）、过氧化氢酶（H2 O2清除剂）和4，5-二羟基-1，3-苯二磺酸（Tiron; LaMotte）（O-. (2)-清除剂），表明（OH）-O-。H_2O_2和O ~-。(2)-此外，O。(2)-在线粒体复合物III抑制剂抗霉素A存在下，正常心肌产生的H2 O2和（OH）-O-的增加可再现。在坏死的组织中心肌ROS水平与左室收缩功能障碍呈显著正相关。总之，在衰竭心肌中，（OH）-O-。作为O-的反应产物产生。(2)-H_2O_2可能在左心室衰竭中起重要作用。
Experimental and clinical studies have suggested an increased production of reactive oxygen species (ROS) in the failing myocardium. The present study aimed to obtain direct evidence for increased ROS and to determine the contribution of superoxide anion (O-.(2)-), H2O2, and hydroxy radical ((OH)-O-.) in failing myocardial tissue. Heart failure was produced in adult mongnl dogs by rapid ventricular pacing at 240 bpm for 4 weeks. To assess the production of ROS directly, freeze-clamped myocardial tissue homogenates were reacted with the nitroxide radical, 4-hydroxy-2,2,6,6,-tetramethyl-piperidine-N-oxyl, and its spin signals were detected by electron spin resonance spectroscopy. The rate of electron spin resonance signal decay, proportional to (OH)-O-. level, was significantly increased in heart failure, which was inhibited by the addition of dimethylthiourea COH scavenger) into the reaction mixture. Increased (OH)-O-. in the failing heart was abolished to the same extent in the presence of desferrioxamine (iron chelator), catalase (H2O2 scavenger), and 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron; LaMotte) (O-.(2)- scavenger), indicating that (OH)-O-. originated from H2O2 and O-.(2)- Further, O-.(2)- produced in normal myocardium in the presence of antimycin A (mitochondrial complex III inhibitor) could reproduce the increase of H2O2 and (OH)-O-. seen in the failing tissue. There was a significant positive relation between myocardial ROS level and left ventricular contractile dysfunction. In conclusion, in the failing myocardium, (OH)-O-. was produced as a reactive product of O-.(2)- and H2O2, which might play an important role in left ventricular failure.