Mark Wefers Bettink

Monitoring mitochondrial respiration 5 85 Introduction Acute changes in mitochondrial function may play a role in the pathophysiology of sepsis (Fink, 2002). However, the options for monitoring mitochondrial function in patients are limited since only ex vivo techniques are available. The most common ex vivo technique measures oxygen consumption using oxygen electrodes (Estabrook, 1967), such as high-resolution respirometry (Gnaiger et al., 1995). Respirometry measures oxygen consumption in suspensions of isolated cells, isolated mitochondria or homogenates of small tissue biopsies and, therefore, might not adequately reflect the in vivo situation in acute changes of mitochondrial function (Jeger et al., 2013). A new non-invasive method to measure mitochondrial function could therefore improve the diagnosis of sepsis, and maybe even open the door to new therapies for which there is an urgent need (Jeger et al., 2013). Techniques to study mitochondrial function in vivo are the Nuclear Magnetic Resonance (NMR)-technique and NADH fluorometry (Fosslien, 2001). NMR and NADH fluoroscopy both show determinants of metabolic state. The current inability of bedside monitoring and its costs make NMR less suitable for clinical use. Changes of mitochondrial metabolic states measured by NADH fluoroscopy have been shown in a research setting. Despite these results, standard clinical monitoring of mitochondrial function by NADH fluoroscopy is not yet an option due to its sensitivity to artifacts and difficult interpretation. An innovative method to monitor mitochondrial function in vivo has been developed and evaluated in our laboratory (Harms et al., 2013). The protoporphyrin IX-triplet state lifetime technique (PpIX-TSLT) enables measurement of mitochondrial oxygen tension (mitoPO 2 ) in living cells and tissues (Mik et al., 2008; 2006). Further development of this technique allowed the detection of mitoPO 2 and mitochondrial oxygen disappearance rate (ODR) in the skin in vivo (Harms et al., 2013; 2012; 2011). Recently, the COMET monitor (Photonics Healthcare B.V., Utrecht, The Netherlands) has become commercially available. This device allows measurements of mitoPO 2 and ODR non-invasively in healthy volunteers and patients at the bedside based on PpIX-TSLT (Baumbach et al., 2018; Ubbink et al., 2016). In two previous studies with the PpIX-TSLT we have measured a decreased ODR in the skin of LPS-induced rats (Harms et al., 2015a; 2015b). The effect of LPS administration