The muscle reflex and chemoreflex interaction: ventilatory implications for the exercising human

Abstract

We examined the interactive influence of the muscle reflex (MR) and the chemoreflex (CR) on the ventilatory response to exercise. Eleven healthy subjects (5 women/6 men) completed three bouts of constant-load single-leg knee-extension exercise in a control trial and an identical trial conducted with lumbar intrathecal fentanyl to attenuate neural feedback from lower-limb group III/IV muscle afferents. The exercise during the two trials was performed while breathing ambient air ([Formula: see text] ~97%, [Formula: see text]~84 mmHg, [Formula: see text] ~32 mmHg, pH ~7.39), or under normocapnic hypoxia ([Formula: see text] ~79%, [Formula: see text] ~43 mmHg, [Formula: see text] ~33 mmHg, pH ~7.39) or normoxic hypercapnia ([Formula: see text] ~98%, [Formula: see text] ~105 mmHg, [Formula: see text] ~50 mmHg, pH ~7.26). During coactivation of the MR and the hypoxia-induced CR (O2-CR), minute ventilation (V̇e) and tidal volume (VT) were significantly greater compared with the sum of the responses to the activation of each reflex alone; there was no difference between the observed and summated responses in terms of breathing frequency (fB; P = 0.4). During coactivation of the MR and the hypercapnia-induced CR (CO2-CR), the observed ventilatory responses were similar to the summated responses of the reflexes (P ≥ 0.1). Therefore, the interaction between the MR and the O2-CR exerts a hyperadditive effect on V̇e and VT and an additive effect on fB, whereas the interaction between the MR and the CO2-CR is simply additive for all ventilatory parameters. These findings reveal that the MR:CR interaction further augments the ventilatory response to exercise in hypoxia.NEW & NOTEWORTHY Although the muscle reflex and the chemoreflex are recognized as independent feedback mechanisms regulating breathing during exercise, the ventilatory implications resulting from their interaction remain unclear. We quantified the individual and interactive effects of these reflexes during exercise and revealed differential modes of interaction. Importantly, the reflex interaction further amplifies the ventilatory response to exercise under hypoxemic conditions, highlighting a potential mechanism for optimizing arterial oxygenation in physically active humans at high altitude.

Keywords: control of breathing; exercise hyperpnea; group III and IV muscle afferents; hypercapnia; hypoxia.

Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the authors.

Figures

Fig. 1.

Schematic illustration of the individual and the concurrent activation of the muscle reflex (MR) and the chemoreflex (CR) during exercise. Each of the two experimental trials (control and fentanyl) included 3 conditions (normoxia, normocapnic hypoxia, and normoxic hypercapnia). This design resulted in 6 bouts of single-leg knee-extension exercise, performed at a constant workload. NormCtrl and NormFent, control and fentanyl trials conducted in ambient room air, i.e., normoxia; HypoCtrl and HypoFent, control and fentanyl trials conducted under normocapnic hypoxia conditions; HyperCtrl and HyperFent, control and fentanyl trials conducted under normoxic hypercapnia conditions. The straight arrows denote the comparisons used to estimate the ventilatory effects of activation of the MR (black arrow), activation of the CR (light gray arrow), and coactivation of the MR and CR (dark gray arrow).

Fig. 2.

Oxyhemoglobin saturation and gas exchange during exercise. Exercise was performed with intact (control) and blocked (fentanyl) leg muscle afferent feedback in nomoxia, normocapnic hypoxia, and normoxic hypercapnia conditions. SpO2, estimated oxyhemoglobin saturation; PETO2, end-tidal partial pressure of O2; PETCO2, end-tidal partial pressure of CO2.

Fig. 3.

Ventilatory responses during exercise. Exercise was performed with intact (control) and blocked (fentanyl) leg muscle afferent feedback in nomoxia, normocapnic hypoxia, and normoxic hypercapnia conditions. V̇e, minute ventilation; fB, breathing frequency; VT, tidal volume. *Significantly different from the fentanyl trial, P < 0.05.

Fig. 4.

Ventilatory changes during individual and concurrent activation of the muscle reflex (MR) and the hypoxia-induced chemoreflex (O2-CR). MR & O2-CR, observed changes during coactivation of the MR and O2-CR; MR + O2-CR, sum of the changes induced by each reflex alone; V̇e, minute ventilation; fB, breathing frequency; VT, tidal volume. Individual subject data are shown for females (○ and broken lines) and males (△ and solid lines). *Significantly different from zero, P < 0.05; †significantly different between MR & O2-CR and MR + O2-CR, P < 0.05.

Fig. 5.

Ventilatory changes during individual and concurrent activation of the muscle reflex (MR) and the hypercapnia-induced chemoreflex (CO2-CR). MR & CO2-CR, observed changes during coactivation of the MR and CO2-CR; MR + CO2-CR, sum of the changes induced by each reflex alone; V̇e, minute ventilation; fB, breathing frequency; VT, tidal volume. Individual subject data are shown for females (○ and broken lines) and males (△ and solid lines). *Significantly different from zero, P < 0.05. No differences between MR & CO2-CR and MR + CO2-CR.