Abstract 19150: Real Time Mitochondrial Monitoring Using Surface Raman Resonance Spectroscopy Detects Impending Cardiac Arrest
Aims: Global markers of perfusion (e.g. serum lactic acid) are unable to detect critical defects in myocardial (or other local) tissue oxygen delivery. As oxygen becomes limiting, electrons accumulate and proteins in the mitochondrial electron transport system become more reduced. We sought to continuously monitor mitochondrial redox status in order to rapidly detect impending organ dysfunction.
Methods and Results: We developed a Raman resonance spectroscopy system (RRS, A) to quantify the ratio of reduced versus oxidized mitochondrial proteins (reduced mitochondrial fraction, RMF).
We first generated oxidized (100% O2) and reduced (100% N2 and sodium dithionate) RRS spectra in isolated rat cardiac mitochondria; the RRS spectra of oxy- and deoxy- hemoglobin and myoglobin spectra were similarly defined (B). Using these spectra, we quantified RMF in an isolated Langendorff rat heart model (C, n=8) where coronary flow rate was decreased in graded fashion from 100% (baseline) to 0% (10 minutes at each flow rate). Increases in RMF (worsening critical oxygen deprivation) correlated inversely with tissue PO2 (Clark electrode) and contractility (dP/dTmax, LV pressure balloon). We then tested the ability of RMF to predict cardiac arrest (i.e. critical myocardial oxygen deprivation) in a model of arterial hypoxemia. Rodents (n=31) were ventilated with FiO2 0.08 to create severe arterial oxyhemoglobin desaturation (SaO2, 31±7%). RMF exceeded 40% in 23/31 animals, among whom 12 (52%) experienced cardiac arrest within 30 minutes of reaching/exceeding an RMF>40% (D). Hearts demonstrating RMF>40% had significantly lower tissue [ATP] and higher [NADH] (indicating impending energy failure) compared to those whose RMF remained <40% (E).
Conclusion: RRS may represent a new monitoring tool for postoperative (e.g. following cardiac surgery) care to detect critical limitations in local mitochondrial oxygenation and impending cardiac arrest.
Author Disclosures: D.A. Perry: None. J. Salvin: None. B. Polizzotti: None. L. Thomson: None. F.X. McGowan: None. P. Romfh: Employment; Significant; Director of Clinical Development, Pendar Technologies. D. Vakhshoori: Employment; Significant; CEO, Pendar Technologies. J.N. Kheir: None.
- © 2016 by American Heart Association, Inc.