Hyperadditive ventilatory response arising from interaction between the carotid chemoreflex and the muscle mechanoreflex in healthy humans

Abstract

Physical exercise potentiates the carotid chemoreflex control of ventilation (VE). Hyperadditive neural interactions may partially mediate the potentiation. However, some neural interactions remain incompletely explored. As the potentiation occurs even during low-intensity exercise, we tested the hypothesis that the carotid chemoreflex and the muscle mechanoreflex could interact in a hyperadditive fashion. Fourteen young healthy subjects inhaled randomly, in separate visits, 12% O2 to stimulate the carotid chemoreflex and 21% O2 as control. A rebreathing circuit maintained isocapnia. During gases administration, subjects either remained at rest (i.e., normoxic and hypoxic rest) or the muscle mechanoreflex was stimulated via passive knee movement (i.e., normoxic and hypoxic movement). Surface muscle electrical activity did not increase during the passive movement, confirming the absence of active contractions. Hypoxic rest and normoxic movement similarly increased VE [change (mean ± SE) = 1.24 ± 0.72 vs. 0.73 ± 0.43 l/min, respectively; P = 0.46], but hypoxic rest only increased tidal volume (Vt), and normoxic movement only increased breathing frequency (BF). Hypoxic movement induced greater VE and mean inspiratory flow (Vt/Ti) increase than the sum of hypoxic rest and normoxic movement isolated responses (VE change: hypoxic movement = 3.72 ± 0.81 l/min vs. sum = 1.96 ± 0.83 l/min, P = 0.01; Vt/Ti change: hypoxic movement = 0.13 ± 0.03 l/s vs. sum = 0.06 ± 0.03 l/s, P = 0.02). Moreover, hypoxic movement increased both Vt and BF. Collectively, the results indicate that the carotid chemoreflex and the muscle mechanoreflex interacted, mediating a hyperadditive ventilatory response in healthy humans. NEW & NOTEWORTHY The main finding of this study was that concomitant carotid chemoreflex and muscle mechanoreflex stimulation provoked greater ventilation increase than the sum of ventilation increase induced by stimulation of each reflex in isolation, which, consequently, supports that the carotid chemoreflex and the muscle mechanoreflex interacted, mediating a hyperadditive ventilatory response in healthy humans.