Mark Wefers Bettink

Measuring mitochondrial oxygenation and respiration in vivo in a human endotoxemia model 6 119 In any case, the findings of this study signify that the COMET measurement system is also able to detect changes in a relatively mild model of systemic inflammation. MitoPO 2 represents a measure of the balance between oxygen demand and supply in tissue. A decrease in mitoPO 2 may indicate a decrease in oxygen supply to the measurement site or an increase of oxygen usage while oxygen supply is maintained. Combined with the relatively minor change in mitoVO 2 , the increased mitoVO 2 observed after LPS administration in the present study is more likely indicative of decreased oxygen supply and thus blood supply to the skin, marking the first step of centralization of blood supply during endotoxemia. Although lactate is frequently used as a marker of organ hypoperfusion in clinical practice, this study shows that mitoPO 2 may represent a more sensitive measure, as lactate did not change following LPS administration. A more pronounced change in mitoPO 2 compared to lactate shows promise for the skin as a primary target for measuring changes in oxygen supply on a cellular level as an early marker of circulatory impairment. Mismatchof local tissue perfusion andmacrocirculation may cause an increase of lactate, but aggressive fluid loading did not change lactate concentrations[19]. As such, lactate may be associated with tissue hypoperfusion, but a direct correlation is questionable. A parameter that truly reflects local tissue perfusion and function might benefit the patient in guiding goal directed therapy. The detrimental effect of sepsis on mitochondrial function were already shown in thrombocytes obtained from adult and pediatric patients [3,20], showing an association between early mitochondrial function changes and development of multi-organ failure. Noninvasive measurement of mitochondrial function in vivo might be the step necessary for early diagnosis of mitochondrial dysfunction and stratification of patients in the intensive care unit[4]. Mitochondrial dysfunction is suggested to play a major role in the development of organ failure in sepsis[21]. Although the presences of pathophysiological changes in mitochondrial function in sepsis are well-described[22], the role of mitochondrial dysfunction in sepsis remains controversial[21]. Changes in mitochondrial function in blood cells, platelets and peripheral mononuclear blood cells, appear to be predictors of mortality and morbidity in adult and pediatric sepsis patients[3,23]. An in vivo bedside monitor could be of value for monitoring of mitochondrial dysfunction. Although we observed a trend towards increasedmitoVO 2 several hours following LPS administration, it is important to stress that clinically relevant mitochondrial dysfunction was not to be expected in this relatively mild model of systemic inflammation. Furthermore, mitoVO 2 is a parameter of mitochondrial respiration; as such, a change in mitoVO 2 cannot be