Enhanced Na+/H+ exchange during ischemia and reperfusion impairs mitochondrial bioenergetics and myocardial function.
Enhanced Na+/H+ exchange during ischemia and reperfusion impairs mitochondrial bioenergetics and myocardial function.
复制标题
缺血期间增强的Na+/H+交换会损害线粒体生物能和心肌功能。
DOI：
10.1097/fjc.0b013e3181831337
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发表时间：
2008-09
影响因子：
3
通讯作者：
Camara AK
中科院分区：
文献类型：
--
作者：
Aldakkak M;Stowe DF;Heisner JS;Spence M;Camara AK
在缺血期间抑制Na+/H+交换（NHE）可减少由于反向模式Na+/Ca 2+交换减少而引起的心脏损伤。我们假设在缺血期间在pH 8的缓冲液中激活NHE-1会增加线粒体氧化、Ca 2+过载和活性氧（ROS）水平，并促进离体心脏的功能恢复，而NHE抑制会逆转这些作用。在缺血前和缺血35分钟后，用pH 7.4的缓冲液（对照）或pH 8 +/− NHE抑制剂eniporide灌注豚鼠心脏10分钟，然后单独用pH 7.4缓冲液灌注110分钟。荧光分光光度法测定线粒体NADH和FAD、[Ca 2 +]和超氧化物。pH 8与pH 7.4相比，在整个再灌注过程中，NADH和FAD更多氧化，心功能更差，再灌注10 min时Ca 2+超载更大，再灌注30 min时超氧化物生成更高。pH 7.4和eniporide组表现出相似的线粒体功能，并且在pH 7.4+eniporide后心脏性能得到最大改善。pH 8+依泊利后再灌注的心功能优于pH 8后。%梗死在pH 8后最大，在pH 7.4+依匹立得后最小。用pH 8缓冲液激活NHE以及随后的氧化还原状态的下降与更大的ROS和Ca 2+负荷是缺血和再灌注后功能恢复不良的基础。
Inhibition of Na+/H+ exchange (NHE) during ischemia reduces cardiac injury due to reduced reverse mode Na+/Ca2+ exchange. We hypothesized that activating NHE-1 at buffer pH 8 during ischemia increases mitochondrial oxidation, Ca2+ overload and reactive O2 species (ROS) levels, and worsens functional recovery in isolated hearts and that NHE inhibition reverses these effects. Guinea pig hearts were perfused with buffer at pH 7.4 (control) or pH 8 +/− NHE inhibitor eniporide for 10 min before and for 10 min after 35 min ischemia and then for 110 min with pH 7.4 buffer alone. Mitochondrial NADH and FAD, [Ca2+], and superoxide were measured by spectrophotofluorometry. NADH and FAD were more oxidized and cardiac function was worse throughout reperfusion after pH 8 vs. pH 7.4, Ca2+ overload was greater at 10 min reperfusion, and superoxide generation was higher at 30 min reperfusion. The pH 7.4 and eniporide groups exhibited similar mitochondrial function and cardiac performance was most improved after pH 7.4+eniporide. Cardiac function on reperfusion after pH 8+eniporide was better than after pH 8. % infarction was largest after pH 8 and smallest after pH 7.4+eniporide. Activation of NHE with pH 8 buffer and the subsequent decline in redox state with greater ROS and Ca2+ loading underlie the poor functional recovery after ischemia and reperfusion.