The ventilatory response to muscle afferent activation during concurrent hypercapnia in humans: central and peripheral mechanisms

Abstract

New Findings r What is the central question of this study?During hypercapnia but not normocapnia, activation of muscle afferents by postexercise circulatory occlusion increases ventilation, possibly due to additional activation of metabolite-stimulated muscle afferents. Alternatively, chemoreflex activation caused by hypercapnia may have a synergistic interaction with muscle afferent feedback, so stimulating breathing. r What is the main finding and its importance?Muscle afferent activation during muscle hypercapnia with concurrent systemic normocapnia did not increase breathing. With systemic hypercapnia, there was a response that did not change with hyperoxic hypercapnia. A synergistic interaction between central chemoreception and muscle afferent feedback is therefore indicated.During hypercapnia, activation of thin-fibre muscle afferents using postexercise circulatory occlusion (PECO) provokes a ventilatory response not seen in normocapnia. We investigated the ventilatory responses to PECO when hypercapnia was restricted to the active muscle ('Local' trial) or during systemic hypercapnia ('Systemic' trial). In the Local trial, a hypercapnic gas mixture (5% CO 2 in air) was inhaled for 5 min when circulation to the active calf muscle was open, then rapidly closed by thigh-cuff inflation (200 mmHg), immediately before a return to breathing room air and performance of isometric exercise and PECO. In the Systemic trial, circulation through the muscle was closed throughout the exercise and PECO phases, performed during the hypercapnic gas inhalation. In a third trial, in Systemic conditions a hyperoxic hypercapnic gas mixture (95% O 2 and 5% CO 2 ) was breathed for 1 min during PECO ('Hyperoxia' trial). The increase in ventilation during calf muscle exercise was not different between trials. In the Local trial, ventilation fell to pre-exercise levels during PECO, but in the Systemic trial it remained at end-exercise levels (4.9 ± 0.8 l min

Ventilatory responses to muscle metaboreflex activation in chronic obstructive pulmonary disease

“…In additional experiments this and hyperventilation, during PECO, was shown to be unrelated to exposure of the active muscle to hypercapnia and it was not attenuated by acute exposure to hyperoxia, thereby reducing peripheral chemoreflex stimulation (Bruce & White, ). These observations have been argued to be evidence of a synergistic interaction between the central chemoreflex and muscle afferent input (Coote, ).…”

“…Additionally, we have shown that in healthy participants activation of muscle afferents using PECO, combined with mild hypercapnia, generates a ventilatory response and there is evidence of a synergistic interaction between central chemoreflex activation and muscle afferent feedback (Lykidis et al . ; Bruce & White, , ).…”

“…(Lykidis et al . ; Bruce & White, , ). We hypothesise that chronically hypercapnic patients will generate a larger ventilatory response during PECO in comparison to normocapnic patients.…”

Mechanisms of ventilatory control: who is really in charge?

“…The findings of Bruce & White (2015) reported in this issue of Experimental Physiology take us one step closer to a more clear understanding of these underlying mechanisms and require us to pause and re-evaluate how peripheral afferent pathways interact, not only with central command, but also with each other.…”

“…In this issue of Experimental Physiology, Bruce & White (2015) examine the interaction between feedback from the central chemoreflex and the metaboreflex in an attempt to unmask their interactive influence on ventilation in humans. Specifically, these investigators used a novel systemic versus local hypercapnia model, in which, during the 'systemic hypercapnia' trial, subjects were exposed to room air immediately prior to circulatory occlusion of the calf muscle, after which the participants were exposed to an elevated concentration of carbon dioxide in the inspirate.…”