Mark Wefers Bettink

Chapter 5 98 endotoxemic rats (Protti et al.). In addition, it shows the feasibility of the PpIX-TSLT as an in vivo monitoring tool to determine the therapeutic effect of mitochondrial targeted drugs. The administration of LPS leads to inhibition of complex I of the mitochondrial electron transport chain (Choumar et al., 2011), measured as a decrease of mitochondrial oxygen disappearance rate (Harms et al., 2015a). We did not replicate the detrimental effect of endotoxemia on ex vivo mitochondrial respiration experiments as shown by Protti et al. However, Protti et al used a different model (cegal ligation and puncture) to initiate an endotoxemia with no fluid resuscitation. Furthermore, their experiment lasted longer and they only used clinical severity grade as a marker for sepsis at 48 hours. This discrepancy with our results might imply that changes in ODR precede the changes measured with ex vivo mitochondrial function tests. In the measurement of mitoPO 2 directly on the muscle a marked increase of mitoPO 2 on T1 was found compared to T0 in the time control group but not in the LPS treated group. In 6 hours a wound starts with it first phases of the healing process, it is unclear if a higher or lower oxygen concentration is expected since both are mentioned (Gottrup et al., 1984; Niinikoski et al., 1972). Endotoxemia has a marked diminutive effect on the pathophysiology of wound healing, this may explain the relatively low mitoPO 2 found in the LPS group compared to the time control group (Kawaguchi et al., 1995). In our in vivo respirometry experiments, the administration of LPS resulted in decreased ODR. Fluid resuscitation in the LPS+- group prevented macro-hemodynamic deterioration, although a significant lower value of mitoPO 2 was found compared to time control, this may be in part explained by a relatively high mitoPO 2 found in the time control group at T1. A decrease in MAP and cardiac output often occurs after rapid and/ or long-term LPS infusion (Harms et al., 2015a). In all our endotoxemia groups, lactate was significantly higher compared to the control groups. Lactate is only a crude marker of disease, depicting the balance between aerobic and aerobic metabolism in the tissues at the one site and on the other site an indication of slowing of liver metabolism. An increase of mitoPO 2 in the time control group, although not significant, may overestimate the changes found compared to the other experimental groups. The mitoPO 2 of 74 ± 17 mmHg at T1 in the time control group may be explained by a relative liberal fluid regime (succinate infusion was replaced with extra saline infusion in the other groups) used in this experiment. A constant mitoPO2 in the succinate control group indicates unaltered and adequate tissue oxygenation. Despite maintained mitoPO2 values at T1, the ODR of