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

NEW FINDINGS: 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. 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% CO2 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% O2 and 5% CO2 ) 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(-1) ) and was equally well maintained throughout the Hyperoxia trial (4.3 ± 1 l min(-1) ). Cardiovascular responses during PECO were not different in the three trials, indicating similar activation of muscle afferents. Sustained elevation of ventilation during PECO in the Systemic but not the Local trial suggests that ventilation is stimulated via an interaction between muscle afferent feedback and hypercapnia-induced chemoreceptor activation. The similar ventilatory responses in Systemic and Hyperoxia conditions further suggest that in this respect, central rather than peripheral chemoreceptors play the major role.