Mark Wefers Bettink

Chapter 6 114 BL 1.45 4 7 35 36 37 38 39 40 Temp (C) *** ** Control: P = 0.053 LPS: P<0.0001 BL 1.45 4 7 60 80 100 120 140 MAP (mmHg) ** ** Control: P = 0.46 LPS: P<0.0001 A B C D BL 1.45 4 7 0 50 100 150 HR (BPM) Control (n=4) LPS (n=12) *** ** Control: P = 0.43 LPS: P<0.0001 BL 1.45 4 7 0 5 10 15 20 TSS (0-25) ** ** Control: P > 0.999 LPS: P<0.0001 Fig 3. Measurement of vital parameters and symptom score over time. A. Mean arterial pressure (MAP, mmHg) B. Heart rate (HR, BPM) C. Temperature (Temp, C), Total symptom score (TSS, 0-25). Individual data and median values are shown. P-values in panels were calculated using Friedman tests. * P<0.05 compared to baseline, ** P<0.01 compared to baseline, calculated using Dunn’s post- hoc multiple comparison tests. Mitochondrial function parameters At the debriefing, no side effects of the ALAplaster were observedor reported. Fig. 4 shows a representative example of the mitoVO 2 tracing for a single time point, analyzed using an adapted Michaelis-Menten fit procedure [16]. Analysis of the tracing with Michaelis- Menten kinetics yield an mitoVO 2 of -8 mmHg*s -1 , value for oxygen concentration change per second, and a baseline mitoPO 2 of 73 mmHg. In 46 out of the total of 52 subjects in whom baseline measurements were performed, a sufficient PpIX signal was obtained (4 subjects did not follow instructions and applied the ALA-plaster later than told, 2 subjects showed an insufficient signal despite the fact that the plaster was timely applied). MitoPO 2 followed a normal distribution (D’Agostino & Pearson p-value of 0.41) with a mean and standard deviation of 61.8 ± 11.3 mmHg (Fig 5A). MitoVO 2 also followed a normal distribution (D’Agostino & Pearson p-value of 0.51) with a mean and standard deviation of -8.4 ± 1.7 mmHg*s -1 (Fig 5B).