Mark Wefers Bettink

Samenvatting, slotopmerkingen en toekomstperspectieven 10 185 measures a faster and more profound decline of mitoPO 2 compared to the arterial occlusion test used with the other monitors. With the new protoporphyrin IX-triplet state lifetime technique (PpIX-TSLT), the technique behind the COMET monitor, in vivo determination of cellular oxygenation and oxygen consumption can be measured. In chapter 5 the PpIX-TSLT technique to asses mitochondrial function is compared to the most commonly used ex vivo technique based on isolated mitochondria from muscle biopsies using a Clark-type oxygen electrode. In the endotoxemia model used in rat, which is based on infusion of lipopolysaccharide and thereby creating an sepsis like endotoxemia, we measured a decrease in mitochondrial function in vivo but not ex vivo. Earlier studies suggested the diminutive effect of endotoxemia on mitochondrial function is predominantly by inhibition of complex 1 of the electron transporter chain. The electron transporter chain is the functional unit of the mitochondria responsible for ATP production, one of the essential functions of mitochondria for cellular homeostasis. The dominant electron pathway for the electron transporter chain is via complex 1 and NADH. We showed the expected decrease in mitochondrial function was prohibited by administration of succinate, an electron donor for complex 2 of the electron transporter chain. Showing the possibility of the PpIX-TSLT to measure decline and preservation of mitochondrial function in this endotoxemia model. Using the same model of endotoxemia in human volunteers we used the COMET monitor to evaluate changes in mitoPO 2 and mitoVO 2 during the experiment as described in chapter 6 . Although the LPS-induced endotoxemiawas onlymild in the healthy volunteers we measured a decline of mitoPO 2 directly after LPS administration. Interestingly the mitoVO 2 increased compared to the baseline measurement, showing a different pattern in this endotoxemia model. Measurement of these changes at bedside paves the way for monitoring of mitochondrial function in patients. In chapter 7 we described the interim analysis of our first study on the ICU using the COMET monitor. We measured mitochondrial function in ICU patients with sepsis at bedside using the COMET monitor. Off-site mitochondrial function was measured ex vivo in platelets and mitochondrial damage was assessed by determining mitochondrial DNA in plasma. Another very dynamic and demanding environment for optical measurement is the operating theatre. In chapter 8 we showed the first measurements of mitoPO 2 over time