Non-invasive measurement of changes in cerebral mitochondrial oxygenation in human volunteers.

oxygenation in human volunteers Tisdall MM, Tachtsidis I, Leung TS, Elwell CE, Smith M. Department of Neuroanaesthesia and Neurocritical Care, The National Hospital for Neurology and Neurosurgery, Queen Square, University College London Hospitals, London, UK; and Department of Medical Physics and Bioengineering, University College London, London, UK. Introduction: Near infrared spectroscopy (NIRS) is a non-invasive technique which can measure changes in the concentration of oxyhemoglobin (D[HbO2]), deoxy-hemoglobin (D[HHb]), and oxidised cytochrome c oxidase (D[oxCCO]). Assuming the total concentration of cytochrome c oxidase (CCO) remains constant during the measurement period then D[oxCCO] represents changes in the CCO redox state and the near infrared CCO signal therefore has potential as a clinical marker of changes in mitochondrial oxygen utilization. Methods: Following ethics committee approval, we induced a reduction in arterial oxygen saturation (SaO2) from baseline to 80% in eight healthy adult volunteers. We measured cerebral D[oxCCO], D[HbO2] and D[HHb] using broadband NIRS, and estimated change in cerebral oxygen delivery (DecDO2) using pulse oximetry and transcranial Doppler ultrasonography. Results: Results are presented as median (interquartile range). At the nadir of hypoxemia estimated cerebral oxygen delivery decreased by 9.2(5.4-12.1) % (p<0.0001). D[oxCCO] decreased by 0.24(0.06-0.28) micromoles/L (p<0.01), total hemoglobin concentration increased by 2.83(2.27-4.46) micromoles/L (p<0.0001) and change in haemoglobin difference concentration (D[Hbdiff]=D[HbO2] D[HHb]) decreased by 12.72(11.32-16.84) micromoles/L (p<0.0001). The time course of these changes for an individual subject and summary data for the whole group are shown in Figures 1 and 2 respectively. DecDO2 correlated with D[oxCCO] (r=0.78, p<0.001), but not with either change in total hemoglobin concentration (D[HbT]=D[HbO2]+D[HHb]), or D[Hbdiff]. The relationship between D[oxCCO], and D[HbO2] and D[HHb] differed between the hypoxemic and recovery phases of the study (p=0.01) suggesting that the D[oxCCO] signal is not merely a crosstalk artefact resulting from the large changes in D[HbO2] and D[HHb]. Conclusions: In the healthy human brain, change in concentration of oxidised cytochrome c oxidase occurs during moderate hypoxemia and is