The Respiratory Response to Carbon Dioxide in Humans with Unilateral and Bilateral Resections of the Carotid Bodies

Abstract

The acute hypercapnic ventilatory response (AHCVR) arises from both peripheral and central chemoreflexes. In humans, one technique for identifying the separate contributions of these chemoreflexes to AHCVR has been to associate the rapid component of AHCVR with the peripheral chemoreflex and the slow component with the central chemoreflex. Our first aim was to validate this technique further by determining whether a single slow component was sufficient to describe AHCVR in patients with bilateral carotid body resections (BR) for glomus cell tumours. Our second aim was to determine whether the slow component of AHCVR was diminished following carotid body resection as has been suggested by studies in experimental animals. Seven BR subjects were studied together with seven subjects with unilateral resections (UR) and seven healthy controls. A multifrequency binary sequence in end‐tidal PCO2 was employed to stimulate ventilation dynamically under conditions of both euoxia and mild hypoxia. Both two‐ and one‐compartment models of AHCVR were fitted to the data. For BR subjects, the two‐compartment model fitted significantly better on 1 out of 13 occasions compared with 22 out of 28 occasions for the other subjects. Average values for the chemoreflex sensitivity of the slow component of AHCVR differed significantly (P < 0.05) between the groups and were 0.95, 1.38 and 1.50 l min−1 Torr−1 for BR, UR and control subjects, respectively. We conclude that, without the peripheral chemoreflex, AHCVR is adequately described by a single slow component and that BR subjects have sensitivities for the slow component that are lower than those of control subjects.

Carotid body denervation alters ventilatory responses to ibotenic acid injections or focal acidosis in the medullary raphe

“…Additionally, creating reversible dysfunction of the rostral ventrolateral medulla by thermode cooling reduces breathing more in awake CBD goats than in intact goats (20). Finally, Fatemian et al (4) found that the magnitude Fig. 4.…”

Non-linear dynamics of human periodic breathing and implications for sleep apnea therapy

“…Rate sensitivity of carotid chemoreceptors during the ''on'' transient of stimulation has not been conclusively demonstrated in humans. Human transient CO 2 responses reported on previously have found good fits to a first order dynamic model of the peripheral chemoreceptors with a single time constant, no rate sensitivity [1,5], and no apnea phase. Only with prolonged ventilatory stimulation has a lengthened ''off'' transient and apparent rate sensitivity appeared [21,24].…”

“…The original lungs-tissue model of Grodins et al [8] was used in combination with a controller model similar to that proposed by Belleville et al [1] and closest to that recently used by Fatemian et al [5]. One difference was the inclusion of a modified peripheral drive below the normal CO 2 level which could set the CO 2 reserve (P aCO 2 difference between eupnea and apnea) as defined by Dempsey [3].…”

“…Note that each unity step change will theoretically lead to an infinite value for the rate term but with unity integrated area (Dirac delta function). The chemoreceptor model corresponds to a ''leaky integrator'' so will have an output with instantaneous changes equal to the gain value at each step transition: positive at time zero of magnitude 1.5 and negative of magnitude 0.68 at 1 min justified by the measurements (mean 6.4 s) of Fatemian et al [5] in normal humans. The upper panels show the temporal responses of ventilation and the lower panels show phase plane plots of ventilation versus arterial CO 2 tension.…”

Neural Control of Respiration by the Retrotrapezoid Nucleus.

“…Consistent with this interpretation, breathing did not recover during ArchT photoactivation in intact rats exposed to 65% FiO 2 or in CBD rats under any oxygen condition. The slow time constant of the response of central chemoreceptors to changes in arterial PCO 2 likely explains why ventilation stayed constant throughout the period of RTN inhibition (Fatemian et al, 2003;Smith et al, 2006).…”