Mark Wefers Bettink

Chapter 6 120 interpreted as mitochondrial dysfunction per se. An increase of mitoVO 2 can be caused by an increase of ATP production, but may also be a sign of mitochondrial uncoupling during which mitochondrial oxygen usage is not coupled to ATP production. The observed trend towards a relatively late increase several hours following induction of systemic inflammation warrants a study in which daily measurements are made in patients admitted to the ICU with sepsis. In this respect, the COMET monitor could represent an important tool, offering frequent mitochondrial function monitoring during the day. The translation of these findings to clinical sepsis are restricted for several reasons. We studied healthy volunteers between 20-35 years of age, while most sepsis patients are much older, with a recent sepsis study reporting nearly a quarter of the study population being above 75 years of age[24]. Moreover, the inflammatory stimulus in the model we used is relatively mild and only short-lived, as opposed to an ongoing and often severe infection in patients. Nevertheless, experimental human endotoxemia is a highly controlled and reproducible model used to investigate the inflammatory response and possible therapeutics in sepsis[25–27]. For instance, the human efficacy of biologics as anakinra and infiliximab, were first established in the experimental human endotoxemia model[28,29]. Conclusion We show feasibility of measuring kinetics of mitochondrial oxygen tension and cellular oxygen usage in a model of systemic inflammation in humans in vivo , using a method that was previously established in rats[9,13,18]. We demonstrate a significant decrease in mitoPO 2 and a nonsignificant increase in mitoVO 2 following LPS administration. These findings show technical feasibility of more than once daily measurements of mitochondrial function parameters with the new COMET monitor, paving the way for clinical implementation of in vivo bedside monitoring of mitochondrial respiration.