Interaction of chemoreceptor effects and its dependence on the intensity of stimuli

We have studied the way in which carotid and medullary chemoreceptor effects combine to control respiration in pentobarbital anesthetized dogs. The carotid sinuses were autoperfused from a membrane oxygenator system to produce either normoxic or hypoxic-hypercapnic blood without producing brain stem hypoxia. The dogs breathed CO2 in O2, N2 mixtures regulated to produce isocapnic levels of arterial partial pressure of CO2 (PaCO2) of 36, 54, and 68 Torr at PaO2 = 87. Tidal volume (VT) increased (P less than 0.05) from a control value of 317 ml to 545 at PaCO2 = 54 but did not increase further at PaCO2 = 68. Carotid chemoreceptor stimulation increased VT to 432 ml at PaCO2 = 36 (P less than 0.05) but did not increase VT at the higher levels of PaCO2. Thus, VT has reached a maximum at PaCO2 = 54 Torr and was not increased further by either chemoreceptor drive. Breathing frequency (f) increased (P less than 0.05) from an eupnic value of 20.2 breaths/min to 35.5 and 41.3 at PaCO2 = 54 and 68, respectively. Carotid chemoreceptor stimulation increased (P less than 0.05) f by 7.7, 5.2, and 5.0 breaths/min at each of the levels of PaCO2. Tidal volume exhibited a less-than-additive (P less than 0.05) combination of chemoreceptor effects but f was not significantly different from additive. We conclude that, in pentobarbital-anesthetized dogs, f continues to increase at chemoreceptor drives beyond those at which VT reaches a maximum. This VT nonlinearity may be responsible for the different interactions found in these experiments.