Metabolic determinants of electrical failure in ex-vivo canine model of cardiac arrest: evidence for the protective role of inorganic pyrophosphate.
Metabolic determinants of electrical failure in ex-vivo canine model of cardiac arrest: evidence for the protective role of inorganic pyrophosphate.
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DOI：
10.1371/journal.pone.0057821
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zaitsev AV
中科院分区：
文献类型：
--
作者：
Shibayama J;Taylor TG;Venable PW;Rhodes NL;Gil RB;Warren M;Wende AR;Abel ED;Cox J;Spitzer KW;Zaitsev AV
心室颤动 (VF) 恶化为心搏停止或严重心动过缓（电衰竭）预示着心脏骤停的致命后果。新陈代谢在电力故障发生时间中的作用仍不清楚。确定心脏骤停（室颤+全身缺血）离体犬模型中早期电衰竭的代谢因素。对室颤和全身缺血 0.3、2、5、10 和 20 分钟前后收集的左心室活检进行代谢组学筛查。通过插入针电极和伪心电图监测电活动。九颗心脏中的四颗在 10.1±0.9 分钟时出现电衰竭（早期 asys），而 5/9 颗心脏维持 VF 至少 19.7 分钟（晚期 asys）。与晚期 asys 相比，早期 asys 心脏在 VF/缺血期间的某些时间点具有更高的 ADP、更少的磷酸肌酸和更高水平的乳酸（所有比较 p<0.05）。来自晚期 asys 心脏的缺血前样本含有比早期 asys 心脏多约 25 倍的无机焦磷酸盐 (PPi)。然后，通过使用电位探针 TMRM 监测与 PPi 孵育的兔成体心室肌细胞与对照组相比的 20 分钟模拟需求缺血期间的线粒体膜电位 (ΔΨ)，测试 PPi 在心脏保护中的机制作用。未经处理的心肌细胞经历了 ΔΨ 的显着损失，而在经过 PPi 处理的心肌细胞中，与对照相比，在整个 20 分钟的模拟需求缺血期间，ΔΨ 相对保持不变（p<0.05）。高组织水平的 PPi 可以防止缺血应激早期的 ΔΨm 损失和电故障。这两种保护作用之间的联系可能涉及线粒体 ATP 水解和乳酸积累速率的降低。
Deterioration of ventricular fibrillation (VF) into asystole or severe bradycardia (electrical failure) heralds a fatal outcome of cardiac arrest. The role of metabolism in the timing of electrical failure remains unknown. To determine metabolic factors of early electrical failure in an Ex-vivo canine model of cardiac arrest (VF+global ischemia). Metabolomic screening was performed in left ventricular biopsies collected before and after 0.3, 2, 5, 10 and 20 min of VF and global ischemia. Electrical activity was monitored via plunge needle electrodes and pseudo-ECG. Four out of nine hearts exhibited electrical failure at 10.1±0.9 min (early-asys), while 5/9 hearts maintained VF for at least 19.7 min (late-asys). As compared to late-asys, early-asys hearts had more ADP, less phosphocreatine, and higher levels of lactate at some time points during VF/ischemia (all comparisons p<0.05). Pre-ischemic samples from late-asys hearts contained ∼25 times more inorganic pyrophosphate (PPi) than early-asys hearts. A mechanistic role of PPi in cardioprotection was then tested by monitoring mitochondrial membrane potential (ΔΨ) during 20 min of simulated-demand ischemia using potentiometric probe TMRM in rabbit adult ventricular myocytes incubated with PPi versus control group. Untreated myocytes experienced significant loss of ΔΨ while in the PPi-treated myocytes ΔΨ was relatively maintained throughout 20 min of simulated-demand ischemia as compared to control (p<0.05). High tissue level of PPi may prevent ΔΨm loss and electrical failure at the early phase of ischemic stress. The link between the two protective effects may involve decreased rates of mitochondrial ATP hydrolysis and lactate accumulation.
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影响因子：
4.8
作者：
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通讯作者：
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作者：
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通讯作者：
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影响因子：
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作者：
ROVETTO, MJ;LAMBERTON, WF;NEELY, JR
通讯作者：
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