Mark Wefers Bettink

Monitoring mitochondrial respiration 5 99 the succinate control group, the LPS -- group and the LPS with fluid resuscitation group (LPS+-) showed a significant decrease compared to baseline measurements. Unclear is why succinate decreased ODR slightly compared to baseline, of interest is the decline of standard deviation compared to time control. Moreover, no intergroup differences were found on T1 in the ODR measurements. However, the greatest difference was observed between the LPS +- and the succinate and fluid resuscitated LPS-group (LPS++), in which ODR values did not decline from baseline values. Importantly, previous PpIX- TSLT measurements showed that mitochondrial respiration is independent of mitoPO 2 levels (Harms et al., 2013). Therefore, a distinction between problems related to oxygen supply or oxygen consumption on the cellular level in critical illness could be made using the PpIX-TSLT technique. Several mitochondrial respiration studies have shown that mitochondrial oxygen consumption recovers after administration of succinate (Protti et al., 2007; Silva and Oliveira, 2011). Protection of ODR by methyl-succinate administration can be explained by several effects. Methyl-succinate could increase mitochondrial membrane permeability, increase substrates in the citric acid cycle, or increase the activity of complex II. In our in vivo experiments, the infusion of methyl-succinate in the LPS-treated rats (LPS++) prevented a decline in ODR from baseline values. This demonstrates that in vivo ODR measurements are able to show changes in mitochondrial respiration which are subtler than changes in lactate. We reproduced the beneficial effect of methyl-succinate on mitochondrial oxygen consumption as previously found in isolated mitochondria (Protti et al.). We therefore think that our novel measurement method enables efficient monitoring of in vivo changes in mitochondrial respiration. In our study, methyl-succinate was already administered before the LPS mediated endotoxemia was induced, which is not comparable to the clinical situation. Therefore, our data mainly demonstrates the feasibility of our experimental technique to detect subtle changes in mitochondrial respiration. Further research is needed to determine whether the protective effect of methyl-succinate is still present when administered after endotoxemia has already developed. The clinical applicability of PpIX-TSLT (Harms et al., 2016; Mik, 2013) allows non-invasive real time monitoring of mitochondrial function. The absence of tissue damage and functional loss may overcome some of the current disadvantages experienced with biopsies (Jeger et al., 2013) and enables bedside monitoring. A limitation of the technique is the need to build up the PpIX signal following ALA application for at least 3 hours