Evaluating the Importance of the Carotid Chemoreceptors in Controlling Breathing during Exercise in Man

Abstract

Only the carotid chemoreceptors stimulate breathing during hypoxia in Man. They are also ideally located to warn if the brain's oxygen supply falls, or if hypercapnia occurs. Since their discovery ~80 years ago stimulation, ablation, and recording experiments still leave 3 substantial difficulties in establishing how important the carotid chemoreceptors are in controlling breathing during exercise in Man: (i) they are in the wrong location to measure metabolic rate (but are ideally located to measure any mismatch), (ii) they receive no known signal during exercise linking them with metabolic rate and no overt mismatch signals occur and (iii) their denervation in Man fails to prevent breathing matching metabolic rate in exercise. New research is needed to enable recording from carotid chemoreceptors in Man to establish whether there is any factor that rises with metabolic rate and greatly increases carotid chemoreceptor activity during exercise. Available evidence so far in Man indicates that carotid chemoreceptors are either one of two mechanisms that explain breathing matching metabolic rate or have no importance. We still lack key experimental evidence to distinguish between these two possibilities.

Reappraisal of systemic venous chemoreceptors: might they explain the matching of breathing to metabolic rate in humans?

“…; Kumar & Prabhakar, ; Parkes, ; Paterson, ). There are difficulties too in the proposal that matching is explained only by combining more than one mechanism, in either an additive or a multiplicative manner (Comroe, ; Cunningham, ; Parkes, ; Paterson, ). After nearly 100 years of research, either a completely new discovery awaits us or there may be better interpretations of published data.…”

“…; Forster, ). (i)Figures and show that the arterial chemoreceptors are in the wrong location to measure metabolic rate, as they receive no known blood‐borne signal related to metabolic rate ( fails to rise and fails to fall during exercise). (ii)Their severest stimulation by hypoxia, to levels that can cause unconsciousness, fails to increase breathing to anywhere near the levels seen at maximal exercise (Dripps & Comroe, ; Parkes, ). (iii)Bilateral denervation of carotid chemoreceptors has remarkably little effect on breathing in humans at rest or during exercise (Lugliani et al . ; Wasserman et al .…”

“…; Dejours et al . ; Forster & Pan, ; Parkes, ). Neither is there evidence in humans that aortic or central chemoreceptors could be the metabolic rate sensor, because they too receive no blood‐borne (or other) signal linked to metabolic rate.…”

“…The classical scientific approaches to search for venous chemoreceptors are recording, ablation and stimulation (Walshe, ; Cohen & Wang, ; Stein & Stoodley, ; Parkes, ).…”

“…Some of the basic principles for evaluating experimental evidence (Parkes, ) also need reiteration here, in particular the need for independent verification of the key experiments (at least two citations for each), for validation of negative results and to put stimulation experiments in the context of maximal metabolic rate being at ∼5.6 l O 2 min −1 (∼1.9 kW) in exercise (∼400 W of external work), with maximal breathing at ∼100–150 l min − 1 . Here, the useful terminology for quantifying breathing is as minute ventilation (; in litres per minute), for exercise and for metabolic rate is as litres of O 2 per minute or in watts, with external work as watts of external work (W ew ) and for variance in the data as ±SEM.…”