Department of Cardiology, Boston Children's Hospital, Boston, MA 02115, USA.
Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Sci Transl Med. 2017 Sep 20;9(408). doi: 10.1126/scitranslmed.aan0117.
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 metric we 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 from baseline values of 18.1 ± 5.9 to 44.0 ± 16.9% ( = 0.0039) after inferior vena cava occlusion in rodents ( = 8). To demonstrate the diagnostic power of this measurement, 3RMR was continuously measured in rodents ( = 31) ventilated with 5 to 8% inspired oxygen for 30 min. 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.
评估组织氧输送的充分性至关重要，特别是在重症监护医学和外科领域。随着细胞的氧输送变得不足，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术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部分，我们将其命名为共振拉曼还原线粒体比（3RMR）。随着氧缺乏的恶化，电子传递链中的血红素部分变得越来越还原，导致 3RMR 增加。在啮齿动物下腔静脉闭塞后，心肌 3RMR 从基线值 18.1±5.9%增加到 44.0±16.9%（ = 0.0039）（ = 8）。为了证明该测量的诊断能力，在接受 5%至 8%吸入氧通气的啮齿动物（ = 31）中连续测量 3RMR 30 分钟。在 10 分钟时超过 40%的 3RMR 值预测随后的心脏骤停，具有 95%的敏感性和 100%的特异性[曲线下面积（AUC），0.98]，优于所有当前的测量方法，包括收缩性（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的指数相关。该技术可实时识别器官特异性氧输送的关键缺陷。
