Mark Wefers Bettink

Chapter 1 12 In chapter 2 we give an overview of the physiology of mitochondrial function and adaptation. We describe possible causes of mitochondrial dysfunction, the concept of cytopathic hypoxia, the loss of hemodynamic coherence and ways to assess aspects of mitochondrial function in patients. Part one In part one we answer the research questions: (i) are we able to measure changes in mitochondrial oxygenation in the human skin with the new COMET monitor, and (ii) how do the measurements of the COMET monitor relate to traditional methods of measuring cellular oxygenation? In chapter 3 we give a description of the COMET monitor. We discuss the output of the monitor and the first human data of perioperative use of the monitor during neurosurgery. In the case described, the COMET monitor was able to measure a decline in mitochondrial oxygenation, whereas the O2C monitor (a monitor for observing tissue oxygenation and measuring microcirculation) was not able to detect a change in tissue oxygenation. This is the first indication of the potential accuracy of the COMET monitor in specifically detecting subtle changes in mitochondrial oxygenation. In chapter 4 we describe calibrating the COMET monitor in human skin. In the same experiment, we directly compare different methods to measure oxygen metabolism. Although the technique of the COMET monitor has extensively been calibrated in cell cultures, organs, a rat model and healthy volunteers, the final monitor had not yet been calibrated in human use. Furthermore, we compare how the different methods and measurement sites react to stop flow conditions and respond to the dynamic measurement of mitoVO 2 by the COMET monitor. Part two In part two we answer the questions: (i) are we able to measure changes of mitochondrial function in a rat model of sepsis and how do these changes translate to an identical model in human volunteers, and (ii) are we able to measure these changes in mitochondrial function in ICU patients with sepsis? In chapter 5 we compare the non-invasive COMET technique to asses mitochondrial function with the most commonly used ex vivo technique based on isolated mitochondria frommuscle biopsies using a Clark-type oxygen electrode. A secondary goal is to stop the