Mark Wefers Bettink

Preface and outline 13 1 diminutive effect of our endotoxemia model on mitochondrial function by administration of succinate. Aerobic metabolism, a primary function of the mitochondria, is enabled by the electron transport chain. The electron transport chain has two possible electron donors of which NADH via complex 1 is the dominant pathway. Our endotoxemia model is known to create dysfunction of complex 1. Therefore, administration of succinate, the electron donor for complex 2, might be a possible therapy for the altered mitochondrial function in our endotoxemia model. In chapter 6 we assess whether the measured changes in mitoPO 2 and mitoVO 2 during an endotoxemia model in rat translates to a human volunteer endotoxemia model. In the Radboud University experimental Intensive Care Department, human endotoxemia models are based on the same method described in chapter 5. In a collaboration between our laboratory and the experimental ICU of the Radboud UMC, we performed the first ever endotoxemia experiment, monitoring mitochondrial function on the bedside with our COMET technique. In chapter 7 we measure changes in mitochondrial function in ICU patients with sepsis. Bedside measurements were obtained by assessing mitochondrial function parameters (COMET) and microcirculatory parameters (O2C). Off-site mitochondrial function was measured ex vivo in platelets and mitochondrial damage was assessed by determining mitochondrial DNA in plasma. Part three In part three we answer the questions: (i) are we able to measure stable values of mitoPO 2 in adults during neurosurgery in stable operating conditions, and (ii) are we able to measure alterations in mitoPO 2 during high risk neonatal surgery? Measurement of mitochondrial oxygenation is possible with the COMET monitor. Perioperative dynamics of mitochondrial oxygenation is a promising tool for anesthesiologists to monitor oxygen delivery and intervene when required. The first feasibility of the COMET monitor during anesthesia and brain surgery is described in chapter 8. The first use of the COMET monitor in high risk neonatal surgery is described in chapter 9.