Research ArticleCARDIAC IMAGING

Responsive monitoring of mitochondrial redox states in heart muscle predicts impending cardiac arrest

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Science Translational Medicine  20 Sep 2017:
Vol. 9, Issue 408, eaan0117
DOI: 10.1126/scitranslmed.aan0117

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Monitoring mitochondria to predict cardiac dysfunction

Mitochondria adapt to changing environmental conditions to try to meet the energy needs of a cell. Perry et al. used resonance Raman spectroscopy to monitor the mitochondrial redox state in the heart. Under low oxygen conditions, electron transport chain cytochromes within the mitochondria become progressively more reduced, which is detected on the basis of the spectral signal. The authors identified a threshold value that predicted the onset of cardiac arrest in rats under hypoxemic conditions and showed that they could monitor mitochondrial redox state during myocardial ischemia-reperfusion in pigs. Although the analysis was restricted to the heart, this approach could be useful for monitoring perfusion and viability of other tissues.

Abstract

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% (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 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.

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