Mark Wefers Bettink

Chapter 2 32 COMET (CellularOxygenMETabolism) In search for bedside in vivo real-time monitoring of mitochondrial function the Cellular Oxygen METabolism (COMET) monitor was developed (86). The COMET (Photonics Healthcare B.V., Utrecht, The Netherlands) measures mitochondrial oxygen tension (mitoPO 2 ) with delayed fluorescence of mitochondrial protoporphyrin IX (PpIX) (87). Stopping microcirculatory blood flow by pressing the measuring probe on the skin allows the measurement of the mitochondrial oxygen consumption (mitoVO 2 ), here expressed as oxygen disappearance rate (ODR) (88).The ODR measurement is a non-invasive technique to assess mitochondrial respiration in vivo . A first feasibility study with the COMET was performed by our group and mitoPO 2 and ODR were measured in healthy volunteers (89). Recently Baumbach et al. showed COMET measurements of mitoPO 2 , mitoVO 2 and mitoDO 2 during exercise in healthy volunteers (90). They introduced mitoDO 2 , a measure for mitochondrial oxygen delivery, as a parameter derived from the dynamics of mitoPO 2 during the microvascular reperfusion phase after the release of pressure used for measuring mitoVO 2 . MitoPO2 and ODR The principle of the technique and its development have been described elsewhere (17,87). In short, the COMET monitor uses oxygen-dependent quenching of the delayed fluorescence lifetime of an endogenously synthesized porphyrin, PpIX. Delayed fluorescence of mitochondrial PpIX is a method to measure mitoPO 2 in living cells and tissues, non-invasively and feasible in humans. PpIX is the final precursor of heme in the heme biosynthetic pathway. PpIX is synthesized in the mitochondria and administration of 5-aminolevulinc acid (ALA) substantially enhances the PpIX concentration. Photoexcitation of PpIX populates the first excited triplet state, and causes the emission of red delayed fluorescence. The delayed fluorescence lifetime is inversely related to the mitoPO 2 according to the Stern–Volmer equation. The background of the delayed fluorescence lifetime technique is extensively described elsewhere (87,91,92). Clinical example During a small clinical pilot, part of a larger observational study (IRB approved, CCMO number NL51937.078.15), we measured an example of change in mitochondrial oxygen consumption due to several “hits” on mitochondria. COMET measurements were intraoperatively performed in four patients in the presternal skin region. The patients