Sensitivity of the human ventilatory response to muscle metaboreflex activation during concurrent mild hypercapnia

New Findings What is the central question of this study? What is the relationship between the level of systemic hypercapnia and the magnitude of the additional hyperpnoea produced in response to a standardized level of muscle metaboreflex activation? What is the main finding and its importance? When a standardized activation of the muscle metaboreflex was combined with exposure to increasing levels of hypercapnia, the hyperpnoea this caused increased linearly. The concept of a synergistic interaction between the muscle metaboreflex and the central chemoreflex in humans is supported by this finding. Abstract Ventilation increases during muscle metaboreflex activation when postexercise circulatory occlusion (PECO) traps metabolites in resting human muscle, but only in conditions of concurrent systemic hypercapnia. We hypothesize that a linear relationship exists between the level of hypercapnia and the magnitude of the additional hyperpnoea produced in response to a standardized level of muscle metaboreflex activation. Fifteen male subjects performed four trials, in which the end‐tidal partial pressure of carbon dioxide ( ) was elevated by 1, 3, 7 or 10 mmHg above resting values using a dynamic end‐tidal forcing system. In each trial, subjects were seated in an isometric dynamometer designed to measure ankle plantar flexor force. Rest for 2 min in room air was followed by 15 min of exposure to one of the four levels of hypercapnia, at which 5 min further rest was followed by 2 min of sustained isometric calf muscle contraction at 50% of predetermined maximal voluntary strength. Immediately before cessation of exercise, a cuff around the upper leg was inflated to a suprasystolic pressure to cause PECO for 3 min, before its deflation and a further 5 min of rest, concluding exposure to hypercapnia. The PECO consistently elevated mean arterial blood pressure by ∼10 mmHg in all trials, indicating similar levels of metaboreflex activation. Increased ventilation during PECO was related to as described by the following linear regression equation: Change in minute ventilation (l min −1 ) = 0.85 × (mmHg) + 0.80 (l min −1 ). This finding supports our hypothesis and furthers the idea of a synergistic interaction between muscle metaboreflex activation and central chemoreflex stimulation.