Nuclear magnetic resonance studies of cationic and energetic alterations with oxidant stress in the perfused heart. Modulation with pyruvate and lactate.
Nuclear magnetic resonance studies of cationic and energetic alterations with oxidant stress in the perfused heart. Modulation with pyruvate and lactate.
复制标题
灌注心脏中氧化应激引起的阳离子和能量变化的核磁共振研究。
DOI：
10.1161/01.res.77.4.773
复制
发表时间：
1995
影响因子：
20.1
通讯作者：
Pike,MM
中科院分区：
文献类型：
--
作者：
Yanagida,S;Luo,CS;Doyle,M;Pohost,GM;Pike,MM
缺血后氧自由基的产生可能通过影响肌膜离子转运而参与心肌再灌注损伤。最近的证据表明，暴露于活性氧中间体诱导心肌细胞内游离Ca 2+（Ca 2 +i）的快速增加。其机制尚未确定，但可能涉及Na+稳态紊乱。我们用23 Na和31 P核磁共振（NMR）测量了葡萄糖灌注的大鼠心脏暴露于H2 O2和Fe 3+产生的羟基自由基中的Na+和高能磷酸盐，从而验证了这一假设。在单独的实验中，K+ i和Ca 2 + i分别用39 K和19 F NMR测量。心脏迅速出现挛缩。Na+浓度增加3倍，K+浓度明显降低。糖酵解抑制表明快速糖磷酸盐积累和细胞能量消耗。然而，值得注意的是，在观察到大量Na+ i积累或K+ i耗尽之前，就发生了严重的功能和能量退化以及Ca 2 + i的大量升高。进一步的实验研究了丙酮酸盐抑制H2 O2和保护心肌免受氧化应激的能力。丙酮酸（1或2.5mmol/L）可显著减弱功能和能量的改变以及Na+ i和K+i的改变，而乙酸（2.5mmol/L）则无保护作用。与丙酮酸盐不同，乳酸盐（5 mmol/L）几乎没有或根本没有吸收H2 O2的能力，但具有类似的保护作用。总之，丙酮酸有效地保护H2 O2/Fe 3+，主要是通过直接清除H2 O2。乳酸盐保护可能涉及细胞内丙酮酸盐增加。在没有外源性丙酮酸盐或乳酸盐的情况下，氧化应激可能会通过细胞能量消耗而显着改变心肌Na+稳态。过量的Na+ i积累反过来可能加速代谢和功能的恶化，但不支持与功能或Ca 2 + i的初始改变的因果关系。
The postischemic generation of oxygen-derived free radicals may contribute to myocardial reperfusion injury by affecting sarcolemmal ion transport. Recent evidence indicates that exposure to reactive oxygen intermediates induces rapid increases in myocardial cytosolic free Ca2+(Ca2+i). The mechanism is undetermined but may involve disturbances in Na+homeostasis. We tested this hypothesis by interleaving23Na and31P nuclear magnetic resonance (NMR) measurements of Na+iand high-energy phosphates in glucose-perfused rat hearts exposed to hydroxyl radicals generated from H2O2and Fe3+. In separate experiments, K+iand Ca2+iwere measured with39K and19F NMR, respectively. The hearts rapidly exhibited contracture. Threefold Na+iincreases and substantial K+idepletion were observed. Glycolytic inhibition was indicated by rapid sugar phosphate accumulation and cellular energy depletion. Notably, however, severe functional and energetic deterioration and substantial elevation of Ca2+ioccurred before substantial Na+iaccumulation or K+idepletion was observed. Further experiments investigated the ability of pyruvate to scavenge H2O2and to protect the myocardium from oxidant stress. Pyruvate (1 or 2.5 mmol/L) dramatically attenuated functional and energetic alterations and alterations in Na+iand K+i, whereas acetate (2.5 mmol/L) offered no protection. Unlike pyruvate, lactate (5 mmol/L) has little or no capacity to scavenge H2O2but has similar protective effects. In conclusion, pyruvate effectively protects against H2O2/Fe3+, largely by direct H2O2scavenging. Protection with lactate may involve intracellular pyruvate augmentation. Without exogenous pyruvate or lactate, myocardial Na+homeostasis can be substantially altered by oxidant stress, possibly via cellular energy depletion. Excess Na+iaccumulation may, in turn, hasten metabolic and functional deterioration, but a causal link with the initial alterations in function or Ca2+iwas not supported.