Mark Wefers Bettink

Chapter 6 118 Discussion In the present study, we were able to obtain mitoPO 2 and mitoVO 2 in 46 out of 48 subjects and the systemic inflammatory response induced by LPS administration results in decreased mitoPO 2 values and a trend towards increased mitoVO 2 levels. We demonstrate the feasibility of using the COMET measurement system to perform sequential mitochondrial respiration (mitoPO 2 and mitoVO 2 ) measurements in a dynamic setting during experimental human endotoxemia. Due to the set-up of the experiments (volunteers arrived at the hospital early in the morning), we choose to apply the ALA-plaster longer before the first measurement than in earlier studies. In 46 out of 48 subjects who complied with the instructions pertaining to the application of the ALA plaster, a reliable PpIX signal was nevertheless obtained. The 4 subjects who did not comply with the instruction applied the plaster a maximum of 3 hours before the first measurement, so a relevant rise in PpIX was not expected. The normal values measured by the COMET monitor determined in this study are higher compared to earlier work by our lab, however these previous measurements were performed using a preclinical monitor with a different probe[10]. Compared to COMET normal values reported in a previous exercise study performed by another group [11], mitoPO 2 values in the present work show a similar distribution. However, direct comparison of mitoVO 2 values between our study and theirs is difficult due to a different kind of mitoVO 2 analysis used, namely a mathematical approach [11] instead of our kinetic approach. A recently published verification of mitoPO 2 calibration in healthy volunteers showed accuracy of mitoPO 2 and thereby mitoVO 2 values[17]. To the best of our knowledge, we are the first to show changes in in vivo mitochondrial function during experimental human endotoxemia. LPS administration resulted in an early and significant decrease inmitoPO 2 and a nonsignificant and later-occurring increase in mitoVO 2 . No changes were observed in the control group, indicating that these effects can be attributed to the LPS-induced systemic inflammatory response and not to diurnal variation. Similar to the present work, our previous studies in rats showed stable values of mitoPO 2 and mitoVO 2 in the control groups over time, and a sharp decline in mitoPO 2 following LPS administration, an effect that was reversed by aggressive fluid resuscitation [13,18] However, LPS administration decreased mitoVO 2 by 30% in rats [13,14]. This discrepancy with the results of the current study may be explained by the use of a high dosage of LPS in rats, resulting in a more severe grade of systemic inflammation [13,18].