Age and estrogen-associated reductions in hypoxic ventilatory response and chemosensitivity in female rats

Figures

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  FIGURE 1. Representative data example and baseline comparisons of ventilation and respiration (mean, SEM). FIO2 = 0.21. (A) Representative raw data segments from plethysmography pressure sensor data across baseline and stepwise hypoxia collections. In this example, the depth and frequency of the pressure changes show the increased volume and frequency of breathing for this animal. Data presented in Panels (B–I) were gathered during the room air portion of the above example. Figure 2 contains data gathered during stepwise hypoxia. (B) Breathing frequency in breaths/minute. (C) Tidal volume (VT). (D) Minute ventilation (VE). (E) Inspiratory time in milliseconds. (F) VCO2 expressed in mL/minute. Significant between-group differences were found in baseline VCO2 (p > 0.001), and the aged group had reduced CO2 production as compared to the other two groups. (G) Minute ventilation controlling for metabolism (VE/VCO2) expressed in mL/minute. The aged group demonstrated higher basal ventilation than both other groups. (H) Neural drive expressed as tidal volume (VT) divided by inspiratory time (Ti). (I) Neural drive controlling for metabolism (VT/Ti/VCO2). When metabolism was controlled, the aged…

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  FIGURE 2. Responses to stepwise hypoxia (mean, SEM). (A) Breathing frequency across baseline (BL) and stepwise hypoxia. All groups showed a significant increase in breathing frequency (p < 0.0001). At FIO2 0.09 the OVX group has a significantly higher frequency than the aged group. (B) Inspiratory time (Ti) at BL and during exposure to stepwise hypoxia. All three groups significantly decreased in response to hypoxia Ti (p < 0.0001). No between group differences were found. (C) Tidal volume (VT), across BL and stepwise hypoxia. All groups had significant declines in VT at FIO2 0.15 and 0.12 before rebounding during maximal hypoxia. There were no significant differences between groups. (D) Minute ventilation (VE) across BL and stepwise hypoxia. All groups increased VE in response to hypoxia (p < 0.0001). Young and OVX groups demonstrated larger VE relative to the aged group during baseline and maximal hypoxia. The OVX group also had a significantly higher VE than aged at FIO2 0.12. (E) Carbon dioxide production (VCO2) during exposure to stepwise hypoxia. The young and OVX groups decreased VCO2 output in response to stepwise hypoxia, but the aged group did not change significantly. The aged…

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  FIGURE 3. Illustrations of the difference between rate of change and magnitude of change. These illustrations are based on slope and magnitude patterns seen during data analysis. (A) Illustration shows differing rates of change in response to stepwise hypoxia but similar magnitudes of response. The red (upper) line signifies data where there was a quick response to increasing hypoxia (high sensitivity) whereas the blue (lower) data set was slower to respond (low sensitivity). Rate of change is condensed into a single number, slope, which is signified by the dotted lines. However, both data sets begin and end at the same points, indicating similar magnitude of change despite very different slopes. (B) Illustration shows how small (non-significant) differences in rate of change can result in differing magnitudes of change. Both lines signify data where there were similarly fast responses to changes in oxygen concentration, but the red (top) line shows a larger amount of change from baseline (large magnitude of change) compared to the blue (bottom) line (small magnitude of change). Again, magnitude of change would be condensed into single values based on the dotted lines.

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  FIGURE 4. Hypoxic ventilatory response (HVR), neural drive, and chemosensitivity expressed as the rate of change (slope) in response to hypoxia (mean, SEM). (A) HVR calculated as the absolute rate of change (i.e., slope) in minute ventilation (VE; mL/min/100 g) across stepwise hypoxias. None of the differences in slope were significantly different. (B) Neural drive response to hypoxia calculated as the absolute change in neural drive while controlling for metabolism (VT/Ti/VCO2) over the course of stepwise hypoxias. All three groups showed a similar speed in the neural drive response to stepwise hypoxia. (C) Chemosensitivity as measured by the absolute change in VE/VCO2 across stepwise hypoxias. There were no significant differences in sensitivity between groups. *p < 0.05.

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  FIGURE 5. Magnitude of hypoxic responses expressed as percent change from baseline (mean, SEM). (A) Frequency (breaths/minute). (B) Tidal volume (VT). (C) Minute ventilation (VE). All groups increased their frequency, VT, and VE in similar magnitudes. (D) Magnitude of VCO2 change. As seen in Figure 2F, the aged group had a non-significant, though slightly positive, increase in VCO2 whereas the young and OVX groups had (mostly non-significant) decreases in VCO2. The result is a large difference in the magnitude of change in response to hypoxia between the aged group and both the young (p = 0.008) and OVX (p = 0.007) groups. (E) Magnitude of VE/VCO2 change. Although the groups showed similar sensitivity in their rates of change (Figure 4C), the aged group had a smaller magnitude of change compared to both the young (p = 0.05) and OVX (p = 0.018) groups because the aged rats started from a higher of VE/VCO2 at baseline (Figures 2G, 3C). (F) Magnitude of neural drive, controlling for metabolism (VT/Ti/VCO2). Figure 4B showed similar rates of neural drive response to hypoxia. Here the aged group demonstrated a smaller magnitude of VT/Ti/VCO2 output in response to stepwise hypoxia. In Figures…