Mark Wefers Bettink

Chapter 6 106 Abstract In vivo measurement of mitochondrial respiration and acute changes thereof is notoriously difficult. We measured changes in mitochondrial oxygen tension (mitoPO 2 ) and mitochondrial oxygen consumption (mitoVO 2 ) using the bedside COMET (Cellular Oxygen METabolism) system during endotoxin-induced systemic inflammation in humans in vivo . 48 healthy male subjects received 2 ng/kg lipopolysaccharide (LPS) intravenously, without (LPS-group, n = 12) or with a cold- and or respiration-induced intervention (Intervention-group, n = 36). Four subjects, receiving no LPS, served as controls group. MitoPO 2 and mitoVO 2 , were measured: just prior to LPS administration and 1.45 hours, 4 hours, and 7 hours thereafter, and at the corresponding timepoints in the control group. In the control group no significant changes over time in were found. COMET measurements were available in 10 of participants in the LPS group. MitoPO 2 decreased from 61[53-72] mmHg at baseline to 42[37-51] mmHg at 1.45 hours post- LPS (p < 0.01) and returned to baseline afterwards. MitoVO 2 showed an increasing trend, without significant changes in the post-hoc analysis. Our results indicate that the COMET monitor can detect changes in mitochondrial parameters in a relatively mild model of systemic inflammation. This study paves the way for bedside monitoring of alterations in mitochondrial oxygenation and respiration. Trial registration ClinicalTrials.gov, NCT03240497. toetsingonline.nl , NL65767.078.18 Key words: Mitochondria, Endotoxemia, Lipopolysaccharides, Healthy volunteers, 5-aminolevulinic acid,