Mark Wefers Bettink

Mind the mitochondria! 2 33 underwent cytoreductive surgery of peritoneal metastases of a primary intestinal tumor and during the same operation, patients received hyperthermic intraperitoneal chemotherapy (HIPEC). The chemotherapeutic agent was Mitomycin C and was perfused at 42 °C. During surgery and directly post-operative macrohemodynamic support is given by a generous fluid regime and noradrenaline perfusion. An example of the change in ODR during intraperitoneal chemotherapy is shown in Figure 2A. As shown in Figure 2B, in 3 out of 4 patients COMET measured a reduced ODR independently of mitoPO2 after HIPEC perfusion. 0 5 10 15 20 0 10 20 30 40 Time (s) mitoPO 2 (mmHg) ODR = 5.8 mmHg/s ODR = 2.2 mmHg/s 0 50 100 150 Patient ODR (%) Baseline After HIPEC 1 2 3 4 A B Figure 2 MitoPO2 and ODR during cytoreductive surgery. (A) Typical examples of mitochondrial oxygen tension (mitoPO2) and Oxygen Disappearance Rate (ODR) measurements at start of surgery and after HIPEC perfusion. (B) Normalized ODR of 4 patients. After HIPEC perfusion ODR is shown as percentage compared to baseline, baseline is set to 100% for each individual patient. Oxygen balance Mitochondrial oxygen concentration depends on the concentration of hemoglobin and its saturation, the hemoglobin-oxygen disassociation characteristics in microcirculation and microvascular flow. In essence, the oxygen supply needs to meet the demand to prevent hypoxia and cellular adaptation (93). If oxygen supply exceeds demand it will lead to hyperoxia and oxidative stress induces a cellular response (94). Especially in newborn care, negative effects of hyperoxia on lung development have led to a strategy of permissive hypoxia (95,96). Current clinical practice is safeguarding macrohemodynamics and saturation without knowing the exact cellular oxygen concentration (97). Mitochondria are the oxygen consumers, thus maintaining a sufficient oxygen concentration in the