Mark Wefers Bettink

A monitor for Cellular Oxygen METabolism (COMET): monitoring tissue oxygenation at the mitochondrial level 3 45 1. Introduction Because of the importance of adequate tissue oxygen supply, many techniques have been developed for measuring oxygen in vivo over the last decades[1, 2]. The ultimate goal of measuring oxygen at the level of the mitochondria has recently become reality. We introduced the protoporphyrin IX-triplet state lifetime technique (PpIX-TSLT) for measuring mitochondrial oxygen tension (mitoPO 2 ) in 2006 [3]. In the mean time, the technique has been proven to be useful in isolated cells, isolated organs and in vivo in animal studies [4–7]. PpIX-TSLT is based on the principle of oxygen-dependent quenching of the excited triplet state of protoporphyrin IX (PpIX). Application of the porphyrin precursor 5-aminolevulinic acid (ALA) induces PpIX in the mitochondria where it acts as a mitochondrial located oxygen-sensitive dye. After photo-excitation with a pulse of green light PpIX emits delayed fluorescence of which the lifetime is inversely related to the amount of oxygen. The technique is non-invasive and can be safely used in humans [8]. The ability to measure optically intracellular oxygen is providing the possibility to assess oxygenation at the end of the oxygen cascade [3, 9]. Measurements in the intracellular compartment are complementary to for example hemoglobin-based oxygen measurements. Pulse-oximetry typically measures at the arteriolar side of the microcirculation [10] while near-infrared and visible light spectroscopy are biased toward the venous compartment [11, 12]. Interstitial oxygen measurements with e.g. oxygen electrodes measure close to the cellular compartment, but are cumbersome and tissue destructive [1]. Measuring at the end of the oxygen cascade is important since (pathologic) shunting in the microcirculation or the development of tissue edema can cause cellular hypoxia, which is otherwise not detectable [13]. Besides measuring mitoPO 2 PpIX-TSLT also provides the possibility to get insight in local tissue oxygen consumption at the mitochondrial level [14]. Mitochondrial oxygen consumption (mitoVO 2 ) can be estimated by measuring the oxygen disappearance rate (ODR) in the measuring volume [15]. Recently we have demonstrated that this enables bedside non-invasive monitoring of an important aspect of mitochondrial function in animal models of critical illness [16, 17]. A clinical device featuring PpIX-TSLT has now been developed and recently entered use in clinical trials in our institution. This monitor is called “COMET”, an acronym for Cellular Oxygen METabolism. The COMET measuring system enables physicians to measure