Peripheral chemoreceptors determine the respiratory sensitivity of central chemoreceptors to CO₂: role of carotid body CO₂

Abstract

Key Pointsr The influence of specific carotid body (CB) normoxic hypocapnia, hypercapnia and normocapnia on the ventilatory sensitivity of central chemoreceptors to systemic hypercapnia was assessed in seven awake dogs with extracorporeal perfusion of the vascularly isolated CB.r Chemosensitivity in this preparation was similar to that in the intact animal. r Separation of CB circulation from that of the brain was confirmed. r When the isolated CB was hypercapnic vs. hypocapnic and when the isolated CB was normocapnic vs. hypocapnic, the group mean central CO 2 response slopes of minute ventilation (V I ) (P ࣘ 0.01) and mean inspiratory flow rate (V T /T I ) (P ࣘ 0.05) increased significantly. Tidal volume (V T ), breathing frequency (f b )and rate of rise of diaphragm EMG were increased in 6 of 7 dogs but did not achieve statistical significance.r We propose that hyperaddition is the dominant form of chemoreceptor interaction under conditions of quiet wakefulness in intact animals and over a wide range of CB P CO 2 and P O 2 .Abstract We asked if the type of carotid body (CB) chemoreceptor stimulus influenced the ventilatory gain of the central chemoreceptors to CO 2 . The effect of CB normoxic hypocapnia, normocapnia and hypercapnia (carotid body P CO 2 22, 41 and 68 mmHg, respectively) on the ventilatory CO 2 sensitivity of central chemoreceptors was studied in seven awake dogs with vascularly-isolated and extracorporeally-perfused CBs. Chemosensitivity with one CB was similar to that in intact dogs. In four CB-denervated dogs, absence of hyper-/hypoventilatory responses to CB perfusion with P CO 2 of 19-75 mmHg confirmed separation of the perfused CB circulation from the brain. The group mean central CO 2 response slopes were increased 303% for minute ventilation (V I )(P ࣘ 0.01) and 251% for mean inspiratory flow rate (V T /T I ) (P ࣘ 0.05) when the CB was hypercapnic vs. hypocapnic; central CO 2 response slopes for tidal volume (V T ), breathing frequency (f b ) and rate of rise of the diaphragm EMG increased in 6 of 7 animals but the group mean changes did not reach statistical significance. Group mean central CO 2 response slopes were also increased 237% forV I (P ࣘ 0.01) and 249% for V T /T I (P ࣘ 0.05) when the CB was normocapnic vs. hypocapnic, but no significant differences in any of the central ventilatory response indices were found between CB normocapnia and hypercapnia. These hyperadditive effects of CB hyper-/hypocapnia agree with previous findings using CB hyper-/hypoxia.We propose that hyperaddition is the dominant form of chemoreceptor interaction in quiet wakefulness when the chemosensory control system is intact, response gains physiological, and carotid body chemoreceptors are driven by a wide range of O 2 and/or CO 2 .

Comparing and characterizing transient and steady‐state tests of the peripheral chemoreflex in humans

“…Not only does this isolate the peripheral chemoreceptors more accurately, but it may also avoid potential confounders of complex interactions between the central and peripheral chemoreceptors (e.g. Blain et al 2010;Cui et al 2012;Tin et al 2012;Duffin & Mateika, 2013;Teppema & Smith, 2013;Wilson & Day, 2013;Smith et al 2015).…”

“…hypoxic ventilatory decline; Powell et al 1998;Steinback & Poulin, 2007); (iii) concomitant cardiovascular and cerebrovascular responses (e.g. Poulin & Robbins, 1998;Steinback & Poulin, 2008;Ainslie & Duffin, 2009;Willie et al 2012;Hoiland et al 2015a); and (iv) the complex interactions between the central and peripheral chemoreceptors (Blain et al 2010;Cui et al 2012;Tin et al 2012;Duffin & Mateika, 2013;Teppema & Smith, 2013;Wilson & Day, 2013;Smith et al 2015).…”

Interdependent feedback regulation of breathing by the carotid bodies and the retrotrapezoid nucleus

“…Centrally, carotid body afferent activity and central chemoreceptors have additive or supra‐additive effects on breathing in intact and unanaesthetized mammals whereas hypo‐additive effects are observed in an arterially perfused rat preparation (Duffin & Mateika, ; Teppema & Smith, ; Wilson & Day, ; Smith et al . ).…”

“…In such situations the feedback exerted by carotid bodies and RTN is additive or even potentiative (Smith et al . ); its obvious function is to minimize arterial fluctuations.…”

Ventilatory and chemoreceptor responses to hypercapnia in neonatal rats chronically exposed to moderate hyperoxia

“…According to this model, central CO 2 sensitivity, and thus the HCVR, depends on the level of activation of carotid bodies. In awake dogs, for example, carotid body stimulation increases the slope of the ventilatory response to CNS hypercapnia while carotid body inhibition depresses it (Blain et al, 2010; Smith et al, 2015). However, the generality of this interaction across species and physiological states remains a matter of debate (e.g., Duffin and Mateika, 2013; Teppema and Smith, 2013; Wilson and Day, 2013; Cummings, 2014).…”