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

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% ( = 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.

Optical biopsy identification and grading of gliomas using label-free visible resonance Raman spectroscopy

“…In addition to tryptophan, we consider that the Raman mode of 1588 cm −1 may be contributed by mitochondria, hemeproteins, and DNA bases (Supplemental Table S1). [71][72][73] Based on our previous experimental data using VRR method and autofluorescence method (to be published) on human glioma tumors 23,26,42,43,74 and the experimental and theoretical studies reported in the literature, 47,[67][68][69][70]75 we propose tryptophan as the main contributor to the Raman mode of 1588 cm −1 . One possible form of the tryptophan contribution to 1588 cm −1 mode may be tryptophan radicals because of the microenvironment in the malignant tumor tissues.…”

Polymer Therapeutics: Biomarkers and New Approaches for Personalized Cancer Treatment

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Ex vivo detection of cadmium‐induced renal damage by using confocal Raman spectroscopy

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“…Raman spectrum combined with confocal microscopy, enables the estimate of the subcellular localization of biomolecules, and helps the determination of the correlation and differentiation between the cells or tissues . According to analysis of the characteristic molecular fingerprints, the components of the sample could be determined, such as nucleic acids, proteins, lipids, glycogen and collagen, which are the major biochemical compositions in cells .…”