An interdependent model of central/peripheral chemoreception: evidence and implications for ventilatory control

Abstract

In this review we discuss the implications for ventilatory control of newer evidence suggesting that central and peripheral chemoreceptors are not functionally separate but rather that they are dependent upon one another such that the sensitivity of the medullary chemoreceptors is critically determined by input from the carotid body chemoreceptors and vice versa i.e., they are interdependent. We examine potential interactions of the interdependent central and carotid body (CB) chemoreceptors with other ventilatory-related inputs such as central hypoxia, lung stretch, and exercise. The limitations of current approaches addressing this question are discussed and future studies are suggested.

Figure 1

Schematic representation of the conventional (top) and interdependent (bottom) models of ventilatory control. Proposed new pathways of the interdependent model are indicated by the bold arrows. Note that in the interdependent model carotid body inputs via the NTS have the potential to change the gain of the CNS chemoreceptors/integrators. “Other Inputs”, such as from central hypoxia sensors, may also have this capability. Also note that communication between the CNS chemoreceptors/integrators and the NTS and Other Inputs could be bidirectional offering the potential for even more complex interactions.

Figure 2

Representative polygraph records showing the effect of progressive hypocapnia induced by pressure support ventilation (PSV; see Methods for details) during NREM sleep in a dog. The onset of PSV is indicated by the positive shift in airway pressure and increase in V_T. Numbers in each panel = the degree of hypocapnia relative to eupnea in Torr. When both sets of chemoreceptors sensed the hypocapnia (Central+peripheral) clear periodicity was present with as little as a 3.1 Torr decrease in PETCO₂ and persisted as hypocapnia became more severe. In contrast, when only central chemoreceptors sensed the hypocapnia (carotid bodies isolated and perfused with normal blood gases and pH), apneas were rare, short, delayed, and periodicity never occurred. We were unable to detect a true apneic threshold despite marked CNS hypocapnia indicating that peripheral hypocapnia is obligatory for the genesis of central apnea in sleep. (Data from (Smith et al. 2007) permission pending).

Figure 3

Minute-by-minute means of PETCO₂ & V̇_I response to PaO₂=52 mmHg (filled) and 38 mmHg (open) for CB+CNS (whole body) hypoxia and CNS (CBs isolated & held normal via perfusion) hypoxia alone. Note the graded ventilatory response to CNS hypoxia (proportional to stimulus) that is approximately 1/3 that of the response when both CBs and CNS can sense hypoxia. In CB+CNS hypoxia the hyperventilation was due to increases in both V_T and fb; in CNS hypoxia alone the hyperventilation was due almost entirely to increased fb. V_T/T_I increased in both conditions. Also note similar time courses of response. In both conditions onset of response was rapid (~20 sec.). (Data from (Curran et al. 2000) permission pending).

Figure 4

Time course of the ventilatory response to specific CB hypoxia vs. specific CB hypercapnia in the unanesthetized, CB perfused goat. Note the progressive increase in ventilation when CB hypoxia was imposed; when CB hypercapnia was imposed there was no further increase in ventilation over time after the initial increase. Also note that upon return to normoxic and normocapnic conditions CB hypoxia resulted in a persistent hyperventilation whereas CB hypercapnia did not. (Data from (Bisgard et al. 1986a) permission pending).