Contribution of the carotid body chemoreceptors to eupneic ventilation in the intact, unanesthetized dog

Abstract

We used extracorporeal perfusion of the reversibly isolated carotid sinus region to determine the effects of specific carotid body (CB) chemoreceptor inhibition on eupneic ventilation (Vi) in the resting, awake, intact dog. Four female spayed dogs were studied during wakefulness when CB was perfused with 1) normoxic, normocapnic blood; and 2) hyperoxic (>500 mmHg), hypocapnic ( approximately 20 mmHg) blood to maximally inhibit the CB tonic activity. We found that CB perfusion per se (normoxic-normocapnic) had no effect on Vi. CB inhibition caused marked reductions in Vi (-60%, range 49-80%) and inspiratory flow rate (-58%, range 44-87%) 24-41 s following the onset of CB perfusion. Thereafter, a partial compensatory response was observed, and a steady state in Vi was reached after 50-76 s following the onset of CB perfusion. This steady-state tidal volume-mediated hypoventilation ( approximately 31%) coincided with a significant reduction in mean diaphragm electromyogram (-24%) and increase in mean arterial pressure (+12 mmHg), which persisted for 7-25 min until CB perfusion was stopped, despite a substantial increase in CO(2) retention (+9 Torr, arterial Pco(2)) and systemic respiratory acidosis. We interpret these data to mean that CB chemoreceptors contribute more than one-half to the total eupneic drive to breathe in the normoxic, intact, awake animal. We speculate that this CB contribution consists of both the normal tonic sensory input from the CB chemoreceptors to medullary respiratory controllers, as well as a strong modulatory effect on central chemoreceptor responsiveness to CO(2).

Breathing without CO2Chemosensitivity in ConditionalPhox2bMutants

“…This is suggested both by our results showing an immediate drop in VE after switching to 100% O 2 , which was stronger in the mutants (Fig. 6 E, F ), and by evidence from the literature obtained in rat pups after intermittent hypoxia or lung injury (Peng et al, 2004;Jacono et al, 2006), after CB resection in man (Dahan et al, 2007), or by extracorporeal CB perfusion in dogs (Blain et al, 2009). …”

“…Second, why are the CBs unable to compensate for the lack of central CO 2 sensitivity, despite the fact that they contribute a still debated, but probably substantial fraction to the overall CO 2 response (Forster et al, 2000;Blain et al, 2009)? One possibility is that in the newborn period, the CBs still respond poorly to CO 2 /pH while the response to hypoxia is already well developed, although in the rat, there is evidence for a well developed peripheral CO 2 chemosensitivity at birth (Saetta and Mortola, 1987).…”

Carbon Dioxide in Sleep Medicine: The Next Frontier for Measurement, Manipulation, and Research

“…Papers are published with scant new information every so often that largely focus on clinical descriptions of hypercapnic individuals, often obese. While there is intense basic science interest in CO 2 sensitive neurons in the brainstem, including the Phox2b/neurokinin-1 receptor (NK1R)-expressing neurons in the pre-Bötzinger complex (pre-BötzC), 1 and exposing the carotid bodies to hypocapnia induces periodic breathing, 2,3 the science and industry of sleepbreathing medicine has generally neglected CO 2 . Much of the information on chronic exposure to elevated but low levels of CO 2 comes from submarine research, targeting sustained ambient concentrations in the low single digits.…”

“…17 The paper by Wang et al is a timely reminder that we neglect CO 2 to our peril. 18 Though the study was not primarily designed to answer the specifi c question of CO 2 the data strongly suggest an adverse and partially reversible impact of hypercapnia on brain function in the context of sleep disordered breathing. Detailed neurocognitive assessments were not reported, and if done, perhaps will be in another publication.…”

Neural Control of Respiration by the Retrotrapezoid Nucleus.

“…The main supportive evidence for CB contribution to resting ventilation under normoxia is that carotid body denervation (CBD) produces a long-lasting (days to weeks) hypoventilation and elevates the steady-state level of arterial PCO 2 (PaCO 2 ) in all mammals, humans included Mouradian et al, 2012). Also, in unanesthetized dogs, resting ventilation is reduced and arterial PCO 2 rises when an isolated CB is perfused with hyperoxic blood (Blain et al, 2009.…”