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).

Fig. 1.

Polygraph record of a representative trial of carotid body (CB) inhibition (dog 2). Perfusion begins at time 0 (solid vertical line). V̇i, ventilation; EMG_di, moving-time-averaged electromyogram of the costal diaphragm; Vt, tidal volume; BP, blood pressure; Pet_CO2, end-tidal Pco₂; Pet_O2, end-tidal Po₂; au, arbitrary units. Interruption in the BP trace is due to blood sampling. Note that the immediate hypoventilation and Pet_CO2 increase with CB inhibition persists for the duration of the trial.

Fig. 2.

Pet_CO2 (left) and V̇i (right) responses from one representative trial of CB inhibition from each dog: dog 1 (A and B), dog 2 (C and D), dog 3 (E and F), and dog 4 (G and H). Data are breath by breath and normalized to control (endogenous CB perfusion; i.e., CB not inhibited). CB inhibition commenced at time 0 (vertical line). Numbers at arrow indicate arterial Pco₂ (Torr) and pH measured at that time. Note that the hypoventilation is maintained throughout CB inhibition, despite marked CO₂ retention and arterial acidosis. Δ, Change.

Fig. 3.

Bar graph of the time course of V̇i (top) and inspiratory flow rate [ratio of tidal volume to inspiratory time (Vt/Ti), bottom] during CB inhibition. Data are normalized to control (%control, where control is normal, endogenous CB perfusion; i.e., CB not inhibited) and presented as means ± SD. Control is arbitrarily set to zero to more clearly indicate the direction of change. For each dog, the first error bar (without associated bar) indicates the SD of the control values. >3 SD, the first V̇i response > 3 SDs below the control mean; Nadir, the mean of the lowest V̇i and its two surrounding breaths; Steady State, the mean values of the first 3 consecutive breaths within 1 SD of the mean V̇i from the last 30 s of the experiment (>7 min of perfusion); 5′, the mean ventilatory values of the last 30 s of the 5th min of CB inhibition; End, the mean ventilatory values from the last 30 s of each experiment, regardless of duration. Note that the nadir ventilatory response to CB inhibition averaged 60% below control, and the maintained steady-state response was 38% below control. Significant difference from *control values and †nadir values, P < 0.05.

Fig. 4.

Example of Pet_CO2 (A) and V̇i (B) responses to prolonged (25 min) CB inhibition in dog 2 (same dog shown in Fig. 1). Data are breath by breath and normalized to control (endogenous CB perfusion; i.e., CB not inhibited). Mean Pet_CO2 and V̇i during control were 43.1 Torr and 5.51 l/min, respectively. CB inhibition commenced at time 0 (first vertical line) and stopped after 25 min of CB inhibition (second vertical line). Note that the hypoventilation is maintained throughout CB inhibition, despite marked CO₂ retention, and, after a brief overshoot, it returned to control values within 30 s upon a return to endogenous CB perfusion.

Fig. 5.

Mean arterial pressure (MAP; left) and heart rate (HR; right) responses from one representative trial of CB inhibition from each dog: dog 1 (A and B), dog 2 (C and D), dog 3 (E and F), and dog 4 (G and H). Data are beat by beat and normalized to control (endogenous CB perfusion; i.e., CB not inhibited). CB inhibition commenced at time 0 (solid line). Discontinuities in the data are due to blood sampling, which interrupted pressure measurement. Note the persistent increase in MAP during CB inhibition. bpm, Beats per minute.