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

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 (O-CR), minute ventilation (V̇e) and tidal volume (V) 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 (f; = 0.4). During coactivation of the MR and the hypercapnia-induced CR (CO-CR), the observed ventilatory responses were similar to the summated responses of the reflexes ( ≥ 0.1). Therefore, the interaction between the MR and the O-CR exerts a hyperadditive effect on V̇e and V and an additive effect on f, whereas the interaction between the MR and the CO-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. 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.