Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCB037

Poster Communications

Testing the interaction between central and peripheral chemoreceptors in humans using a transient hypoxic chemoreflex test

K. Milloy1, M. G. White1, J. Chicilo1, T. Day1

1. Mount Royal University, Calgary, Alberta, Canada.


Arterial blood gas levels are maintained through respiratory chemoreflexes mediated by central (CCR; brainstem) and peripheral (PCR; carotid body) chemoreceptors. The CCRs are stimulated slowly (25-30 sec) by accumulating brainstem hypercapnia (central chemoreflex). The PCRs are stimulated quickly (10-15 sec) by rapid changes in arterial hypercapnia and hypoxia in a synergistic fashion (peripheral chemoreflex). There is currently controversy regarding the potential interaction between central and peripheral chemoreceptors, and few studies have investigated this interaction in humans. Experimental data using reduced animal models suggest one of three possibilities: (a) simple addition (i.e., no interaction), (b) hypo-additive (one reflex is inhibited with stimulation of the other) or (c) hyper-additive (one reflex is augmented with stimulation of the other). We aimed to investigate the interaction between the CCRs and PCRs in informed human volunteers using a transient hypoxic test of the PCR. Sixteen healthy human participants (23.3±2.9 yrs; BMI 24.3.8±4.0 kg/m2; 9 females) underwent a series of transient hypoxia tests (TT-N2; three consecutive breaths of 100% N2), which exploits the temporal and stimulus specificity of the PCRs. These TT-N2 were superimposed upon three background levels of steady-state inspired normoxic CO2 (FICO2; 0, 2 and 4%; randomized). Respiratory variables and end-tidal gases were assessed via a pneumotachometer and dual O2-CO2 gas analyzer. Following an eight-minute baseline, participants were exposed to three consecutive TT-N2 with a minimum two-minute recovery period between each test. Respiratory responses were averaged from all three TT-N2trials to represent an individual's response at each FICO2 level. Using 1F RM ANOVAs, we assessed the hypoxic frequency response (HFR), hypoxic tidal volume response (HVTIR) and the hypoxic ventilatory response (HVR) at each FICO2 to elucidate the interaction between PCRs and CCRs on various components of ventilation. The HFR (Δmin-1/Δ%ScO2) was not different between FICO2 levels (P=0.07), whereas the HVTIR (ΔL/Δ%ScO2) significantly decreased with increasing FICO2 levels (P<0.05). However, the overall HVR (ΔL/min/Δ%ScO2) was not different between FICO2 levels (P=0.50). Although HVTIR significantly decreased with incrementally larger FICO2, the HFR and HVR were not different across FICO2 levels. Thus, respiratory chemoreceptors in humans interact via simple addition between the CCRs and PCRs, mediated through additive and hypo-additive regulation of frequency and tidal volume, respectively.

Where applicable, experiments conform with Society ethical requirements