Step changes in end-tidal CO2: methods and implications.

A dynamic end-tidal forcing technique for producing step changes in end-tidal CO2 with end-tidal O2 held constant independent of the ventilation response or the mixed venous return is introduced for characterizing the human ventilation response to end-tidal CO2 step changes for both normoxic (PAO2 = 125 Torr) and hypoxic (PAO2 = 60 Torr) conditions. The ventilation response approaches a steady state within 5 min. In normoxia, the on-transient is faster than the off-transient, presumably reflecting the action of cerebral blood flow. The hypoxic step response is faster than the normoxic response presumably reflecting the increased contribution from the carotid body. The delay in the ventilation response after the change in end-tidal CO2 is less in hypoxia than in normoxia and reflects the action of a transport delay and that of a virtual delay. These delays are interpreted with respect to the high-frequency phase shift data for the same subject, generated using sinusoidal end-tidal forcing. The methods of others for experiments utilizing step changes in inspired CO2 are considered with respect to our methods.