Measuring mitochondrial oxygenation and respiration during systemic inflammation in humans in vivo

Disturbances in mitochondrial function are implicated in several chronic and acute diseases. Systemic inflammation has been described to affect mitochondrial respiration. Yet, in vivo measurement of mitochondrial respiration is notoriously difficult. We measured mitochondrial oxygen tension (mitoPO₂) and mitochondrial oxygen consumption (mitoVO₂) using the bedside COMET (Cellular Oxygen METabolism) system during systemic inflammation elicited by intravenous administration of 2 ng/kg lipopolysaccharide (LPS) in 42 healthy male volunteers. Four male subjects who did not receive LPS served as uninflamed controls. MitoPO₂ and mitoVO₂ were measured immediately prior to LPS administration, and at 1.45 h, 4 h, and 7 h, as well as at the corresponding timepoints in the control group. Compared to the control group, MitoPO₂ significantly decreased over time in the LPS group (p = 0.002), with the nadir observed at 1.45 h post-LPS administration (45.8 ± 1.8 vs. 75.2 ± 2.6 mmHg); while mitoVO₂ did not change. Concluding, the COMET monitor detects 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, which may represent a vital next step in early diagnosis of mitochondrial dysfunction and stratification of patients in the intensive care unit.Trial registration: ClinicalTrials.gov NCT03240497. (12/04/2016) toetsingonline.nl NL56686.091.16 (11/04/2016) and NL65767.078.18 (01/05/2018).