TESTS OF CHEMORECEPTOR SENSITIVITY

When lung function is normal, the sensitivity of the peripheral and central chemoreceptors to CO2 can be evaluated by measuring the ventilatory response to inspired CO2. In the conventional steady-state test, the inspired CO2 is increased in steps, and ventilation at each step is related to the change in PaCO2. Sensitivity to CO2 is determined from the slope of the line relating ventilation to CO2. Although the central chemoreceptors are readily accessible to CO2, the size of cerebral CO2 stores increases the time required for ventilation to reach a steady state when PCO2 changes. Usually, the inspired CO2 concentrations at each step must be maintained constant for 10 to 20 minutes to ensure equilibration. Relative rates of equilibration of PCO2 in arterial and brain venous blood (Fig. 9) indicate that PaCO2 reaches its steady-state level long before the venous PCO2. It is apparent from Fig. 9 that if ventilation, which closely tracks cerebral venous PCO2, is measured too soon, chemosensitivity will be underestimated.

FIG. 9. Changes of ventilation, PaCO2, and cerebral venous PaCO2 when inspired CO2 is changed.

When CO2 is rebreathed from a bag containing CO2 at the mixed venous level together with O2, arterial and venous blood equilibrate more rapidly. After a brief transition period, PCO2 at all sites in arterial, cerebral, and mixed venous blood and alveolar air rises at the same rate. Consequently, the rate of change of PCO2 in alveolar air can be used as an index of the rate of change in PCO2 in the central chemoreceptors. The exact length of the transition period depends on the size of the rebreathing bag. When the volume of the rebreathing bag is about the same as the vital capacity, chemosensitivity can be estimated by continuous recording of ventilation and PCO2 after 45 to 60 seconds of rebreathing. Measurements for wide variations in PCO2 can be obtained in a few minutes. Estimates obtained by this rebreathing method agree with those obtained by the more prolonged steady-state technique. However, the rebreathing tests measure CO2 sensitivity at much higher levels of PCO2 than are usually encountered. Moreover, differences have been noted between rebreathing and steady-state ventilatory response to CO2 when metabolic acidosis or alkalosis is present. With the steady-state technique, moderate alkalosis and acidosis produce larger changes in the position of the ventilatory response line but relatively small changes in its slopes, whereas the reverse is true in the rebreathing tests. The explanation for this difference is obscure, but it may be related to the different levels of PCO2 at which steady-state and rebreathing tests are performed.

The average ventilatory response to CO2 is about 2.5 L/min/mmHg in normal adult men. It is somewhat less in women than in men and tends to decline with advanced age. It varies greatly between individuals but is much more constant in repeated measurements from a single subject. Some of this variability is caused by differences in personality, genetic makeup, and body size, and it is reduced when the CO2 response is corrected for differences in vital capacity.

Cortical activity is known to affect the response to CO2. Ventilatory responses to CO2 measured with the subject's eyes open are greater than ventilatory responses to CO2 measured with the subject's eyes shut.