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Continuous tissue perfusion monitoring by NADH redox state

Smart, Christopher; (2022) Continuous tissue perfusion monitoring by NADH redox state. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

This body of work concerns the development of a new clinical monitor which simultaneously reports tissue microvascular haemoglobin saturation (StO2) and the mitochondrial redox state (via NADH fluorescence). This monitor uses a fine fibreoptic probe (no wider than an 18 G cannula) inserted into skeletal muscle and is intended ultimately for use in an intensive care setting. Mitochondrial redox state monitoring allows a direct assessment of the adequacy of a given oxygen tension to support respiration, which is a question unanswerable by traditional haemodynamic monitoring. Nicotinamide dinucleotide hydride (NADH) is the reduced moiety of NAD and the principal electron carrier from the Krebs cycle to the electron transport chain (ETC). Under conditions of progressive mitochondrial hypoxia the NADH rises in a hyperbolic fashion, mirroring the rapidly stalling oxidative phosphorylation rate NADH is fluorescent under excitation by ultraviolet light whereas its oxidised counterpart (NAD+) is not. This autofluorescence provides a natural window through which mitochondrial oxygen supply sufficiency can be interrogated in real time. Combining NADH and tissue haemoglobin saturation (StO2) monitoring in one device allows direct assessment of the relationship between tissue oxygenation and oxygen sufficiency, which is vital to selecting physiological resuscitation targets. This work describes the development of this device and describes experiments designed to test its capabilities. The device responds to haemorrhagic shock at least as quickly as conventional measures (arterial lactate, blood pressure), and is able to produce detailed breakdown of the kinetics of tissue oxygen consumption under controlled conditions.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Continuous tissue perfusion monitoring by NADH redox state
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10144695
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