«RATE OF CHANGE OF ALVEOLAR CARBON DIOXIDE AND THE CONTROL OF VENTILATION DURING EXERCISE BY CHRISTOPHER J. ALLEN AND NORMAN L. JONES From the Ambrose ...»
Further support for APA, co./Ate as a factor in the control of ventilation at the onset of exercise is its close relationship to mean inspiratory flow rate (VT/TI). As an index of inspiratory drive (Milic-Emili, 1982), VT/TI correlates with both mouth occlusion pressure and ventilation during exercise (Siafakas, Morris & Prime, 1979). During the breath following an increase in exercise load, VT/TI increased in parallel with the increase in APA, Co2/Ate, but there was no change in VT' PA C02 or Rc02 Nor was the increase in APA, co,/Ate itself due to an increase in flow rate or to a change in the pattern of breathing. Systematic studies of these variables (Allen et al. 1984) have shown that the relationship between APA, C02/Ate and TC02o VT, and frequency of breathing (r.r.) during exercise can be described by a single multiple linear regression equation: APA, C02/Ate = 3-52 + 5-23 VCO2 - 2-23 VT-0-05 r.r. This relationship demonstrates that increases in VT or r.r. will decrease rather than increase APA, Co2/Ate during exercise, an effect predicted in a theoretical model by DuBois, Fowler, Soffer & Fenn (1952).
The mechanism by which APA co./Ate is linked to respiratory centre output (VT/TI) is too rapid to be accounted for by a feed-back mechanism: Saunders (1980) proposed a feed-forward mechanism in which APA, C02/Ate drives ventilation. In a model with the controller equation PE = 6-15 APA, C02/Ate110 acting solely in the feed-forward 8 C. J. ALLEN AND N. L. JONES mode, a simulated increase in PC02 was followed by a small initial increase in ventilation, followed after 30 S by a second rise to a new steady-state ventilation; during this second phase there was a transient rise in arterial PCo, (Saunders, 1980). From the data of the present study we derived the equation: VE = 6-76 APA, C02/Ate - 356 (95 % confidence limits for slope 4-7-8-9, and for intercept - 10-31 to + 3 20), which is remarkably similar to Saunders' (1980) theoretical controller equation and which supports the concept of a feed-forward model. During the second phase (from 30 to 60 s) there was an increase in mean alveolar PCO2 (Fig. 2). This suggests that there may be an additional error signal so that the increase in ventilation may reflect both the rate of rise of Pco2 and an increase in mean Pco2 Understanding of the physiological basis of this model continues to evolve; Band, Cameron & Semple (1969) showed that there are oscillations in arterial blood pH in cats which occur in phase with respiratory oscillations in alveolar Pco,. Infusing CO2 increased not only the amplitude of the oscillation but also the rate of rise of alveolar PCo2* Band et al. (1980) have demonstrated that an immediate increase in both the rate of change of alveolar PCO2 and arterial pH occur following the onset of exercise in man, a finding consistent with our observations. The carotid chemoreceptor is able to respond to oscillations of arterial PCo2, and carotid body stimulation increases inspiratory drive (Band et al. 1970), suggesting that the carotid body may be an important link between APA, C0O2/Ate and VT/TI. It appears that it is not an essential one; Lugliani, Whipp, Seard & Wasserman (1971) were able to demonstrate an increase in ventilation with exercise in carotid body denervated patients. However, the rate of rise in ventilation was considerably slower than it was in patients whose carotid bodies were intact.
The findings of the present study are consistent with the hypothesis that ventilation during exercise is related to CO2 output by a feed-forward control system responding to APA co2/Ate. The mechanisms and pathways mediating this response remain to be elucidated.
C. J. Allen is a Research Fellow of the Medical Research Council of Canada, which also supported this project (grant number MA 4243). The authors thank Geoff Lewis and George Obminski for development of the computer programs and Marilyn Craven, M.D. Ph.D. for her expert critical appraisal of the manuscript.
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