Responsive monitoring of mitochondrial redox states in heart muscle predicts impending cardiac arrest
Responsive monitoring of mitochondrial redox states in heart muscle predicts impending cardiac arrest
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DOI：
10.1126/scitranslmed.aan0117
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发表时间：
2017-09-20
影响因子：
17.1
通讯作者：
Kheir, John N.
中科院分区：
文献类型：
--
作者：
Perry, Dorothy A.;Salvin, Joshua W.;Kheir, John N.
评估氧气输送到组织的充分性是至关重要的，特别是在重症监护医学和外科领域。当向细胞的氧输送变得不足时，线粒体氧化还原状态的变化先于细胞功能的变化。我们描述了一种使用共振拉曼光谱连续监测心外膜表面线粒体氧化还原状态的技术。我们量化了特定电子传递链细胞色素的还原分数，一种称为共振拉曼还原线粒体比率（3RMR）的度量。随着缺氧的加剧，电子传递链中的血红素部分逐渐减少，导致3RMR增加。在啮齿动物（n = 8）中，下腔静脉闭塞后，心肌3RMR从基线值18.1 ± 5.9增加到44.0 ± 16.9%（P = 0.0039）。为了证明该测量的诊断能力，在啮齿动物（n = 31）中连续测量3RMR，所述啮齿动物用5%至8%的吸入氧气通气30分钟。10分钟时3RMR值超过40%预测随后的心脏骤停，灵敏度为95%，特异性为100%[曲线下面积（AUC），0.98]，优于所有当前测量，包括收缩力（AUC，0.51）和射血分数（AUC，0.39）。3RMR与细胞内氧化还原状态和能量产生指标相关。这种技术可以允许真实的实时识别器官特异性氧气输送中的关键缺陷。
Assessing the adequacy of oxygen delivery to tissues is vital, particularly in the fields of intensive care medicine and surgery. As oxygen delivery to a cell becomes deficient, changes in mitochondrial redox state precede changes in cellular function. We describe a technique for the continuous monitoring of the mitochondrial redox state on the epicardial surface using resonance Raman spectroscopy. We quantify the reduced fraction of specific electron transport chain cytochromes, a metricwe name the resonance Raman reduced mitochondrial ratio (3RMR). As oxygen deficiency worsens, heme moieties within the electron transport chain become progressively more reduced, leading to an increase in 3RMR. Myocardial 3RMR increased frombaseline values of 18.1 +/- 5.9 to 44.0 +/- 16.9% (P = 0.0039) after inferior vena cava occlusion in rodents (n = 8). To demonstrate the diagnostic power of this measurement, 3RMR was continuously measured in rodents (n = 31) ventilated with 5 to 8% inspired oxygen for 30min. A 3RMR value exceeding 40% at 10 min predicted subsequent cardiac arrest with 95% sensitivity and 100% specificity [area under the curve (AUC), 0.98], outperforming all current measures, including contractility (AUC, 0.51) and ejection fraction (AUC, 0.39). 3RMR correlated with indices of intracellular redox state and energy production. This technique may permit the real- time identification of critical defects in organ- specific oxygen delivery.