A Pilot Study on the Association of Mitochondrial Oxygen Metabolism and Gas Exchange During Cardiopulmonary Exercise Testing: Is There a Mitochondrial Threshold?

Figure 1. Metabolic phases and exemplary location of lactate (LT1, LT2) and ventilatory thresholds (VT1, VT2) during maximum cardiopulmonary exercise testing.

Figure 2. Experimental setup. (A) All measurements at baseline, during cardiopulmonary exercise testing (CPET) and in the recovery phase followed the same sequence. PpIX-TSLT measurements were performed every 10 s during the first and last 2 min of each phase to obtain mitochondrial oxygen tension (mitoPO2). Capillary blood samples for blood gas analysis (CBG) were taken after 180 s. Subjective ratings of exertion and dyspnea were assessed by the Borg Scale at the end of each phase. ECG and gas exchange parameters were monitored continuously. In addition, guideline-conform non-invasive blood pressure measurements were performed every 180 s. (B) After 2 min phase duration, dynamic PpIX-TSLT measurements were performed to assess mitochondrial oxygen consumption (mitoV.O2) and delivery (mitoD.O2). During the first 20 s, baseline mitoPO2 measurements were obtained. Thereafter, pressure was applied to the sensor in order to locally inhibit microcirculation. When mitoPO2 reached near to zero levels or showed no further decline, pressure was maintained for 10 s and then released. Based on the fitted parameters mitoV.O2 (F1: left part of the equation) and mitoD.O2 (F2: right part of the equation)…

Figure 3. Example of MT-identification (mitochondrial threshold, vertical black line). Raw mitoPO2 values of single measurements were smoothed (locally estimated scatterplot smoothing, LOESS) and the maximum of the fitted curve was set as MT.

Figure 4. Summary of (A–C) selected variables of CPET (end-tidal oxygen tension, PETO2; end-tidal carbon dioxide tension, PETCO2; heart rate), (D–F) main variables of PpIX-TSLT measurements (mitochondrial oxygen tension, mitoPO2; mitochondrial oxygen consumption, mitoV.O2; mitochondrial oxygen delivery, mitoD.O2), and (G–I) variables of the capillary blood gas analysis (partial pressure of oxygen, PcO2; partial pressure of carbon dioxide, PcCO2; lactate). The dots refer to individual values of the variables during aerobic (ae, < VT1), aerobic-anaerobic (ae/an, ≥VT1 and < VT2), and anaerobic phase (an, ≥VT2). In addition, model predicted means (squares), corresponding 95% confidence intervals (lines) and adjusted p-values of comparisons between phases are displayed. *p < 0.05, **p < 0.01, ***p < 0.001.

Figure 5. Boxplots of time differences in lactate (LT1, LT2), ventilatory (VT1, VT2), and mitochondrial (MT) thresholds. The circles refer to the individual differences. Negative values indicate a later occurrence of MT compared to the other thresholds.

Figure 6. Smoothed course (locally estimated scatterplot smoothing, LOESS) of mitochondrial oxygen tension (mitoPO2), end-tidal oxygen tension (PETO2), and end-tidal carbon dioxide tension (PETCO2) for all subjects (n = 14). Values of the x-axis (percent ergometry) were scaled individually to the minimum (first measurement during baseline) and maximum power output level of the CPET (e.g., last measurement at 250 W). The vertical lines indicate end of baseline (median), first and second ventilatory and lactate threshold (medians of VT1|2, LT1|2) and mitochondrial threshold (median, MT). In addition, the gray area marks the interquartile range of MT.

Figure 7. Results of the exploratory analyses on the associations between the variables of PpIX-TSLT measurements (A: mitoPO2, B: mitoV.O2, C: mitoD.O2), CPET-derived gas exchange and capillary blood gases (CBG). The first column lists the dependent variables, the second column displays the independent variables. The overall column indicates the standardized regression coefficients for the independent variable (one coefficient for all three phases, basic models). Asterisks indicate, if the models estimating separate regression coefficients for the phases show a better model fit compared to the basic models. The columns aerobic, aerobic-anaerobic and anaerobic display the corresponding standardized regression coefficients for each phase. The column n refers to the number (n) of data points, which were entered into the model. Regression coefficients with raw p-values ≥0.05 were set to zero (white). Framed cells indicate regression coefficients with Bonferroni-Holm adjusted p-values <0.05.