Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah, United States of America.
PLoS One. 2013;8(3):e57821. doi: 10.1371/journal.pone.0057821. Epub 2013 Mar 8.
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.
心室颤动（VF）恶化成心脏停搏时的无脉性电活动或严重心动过缓（电衰竭）预示着心脏骤停的致命结局。代谢在电衰竭时间中的作用仍不清楚。
在心脏骤停（VF+全脑缺血）的犬离体模型中，确定早期电衰竭的代谢因素。
在 VF 和全脑缺血前和后 0.3、2、5、10 和 20 分钟采集左心室活检标本，进行代谢组学筛选。通过 plunge 针电极和伪 ECG 监测电活动。在 9 个心脏中有 4 个在 10.1±0.9 分钟时出现电衰竭（早期无脉性电活动），而 5/9 个心脏至少维持 19.7 分钟的 VF（晚期无脉性电活动）。与晚期无脉性电活动相比，早期无脉性电活动的心脏在 VF/缺血期间的某些时间点具有更多的 ADP、更少的磷酸肌酸和更高的乳酸水平（所有比较 p<0.05）。晚期无脉性电活动心脏的缺血前样本含有约 25 倍于早期无脉性电活动心脏的无机焦磷酸（PPi）。然后通过监测用 TMRM 作为电化学探针在含有 PPi 的兔成年心室肌细胞中模拟需求缺血 20 分钟期间的线粒体膜电位（ΔΨ）来测试 PPi 在心脏保护中的机制作用，与对照组相比，未经处理的心肌细胞经历显著的 ΔΨ损失，而在 PPi 处理的心肌细胞中，ΔΨ在模拟需求缺血的 20 分钟内相对保持（p<0.05）。
高组织水平的 PPi 可能防止缺血应激早期的 ΔΨm 损失和电衰竭。这两种保护作用之间的联系可能涉及到线粒体 ATP 水解和乳酸积累的速率降低。
