CO 2 chemoreflex contributions to ventilatory long‐term facilitation

Ventilatory long‐term facilitation (LTF) is a persistent increase in minute ventilation () elicited by acute intermittent hypoxia (AIH) that outlasts the stimulus duration. In humans, AIH‐induced ventilatory LTF is dependent upon a sustained background of mild hypercapnia. It is not known whether changes in CO 2 chemoreflex sensitivity contribute to ventilatory LTF. We hypothesised that hypercapnic AIH increases the sensitivity of peripheral, but not central, chemoreflex responses to CO 2 . Twenty healthy adults (age = 25 ± 4 years) completed the study. On days 1 and 2, pulmonary function testing and three hyperoxic modified CO 2 rebreathing tests were performed to determine baseline central CO 2 chemoreflex sensitivity. On days 3 and 4, participants were randomly assigned to hypercapnic AIH or mild hypercapnia alone. On day 5, 16 participants returned to the laboratory to complete a time‐matched control (CTRL). Two CO 2 rebreathing tests were performed approximately 45 and 75 min post‐trial. Transient CO 2 tests were used to quantify peripheral CO 2 chemoreflex sensitivity pre‐ and post‐trial. Twenty minutes after hypercapnic AIH, was increased 32 ± 22% versus baseline, which was significantly greater than CTRL ( P < 0.001), demonstrating the presence of ventilatory LTF. Central CO 2 chemoreflex sensitivity ( P = 0.880) and the ventilatory recruitment threshold ( P = 0.425) were unchanged after all trials. Peripheral CO 2 chemoreflex sensitivity was increased 41 ± 46% after hypercapnic AIH, which was significantly greater than CTRL ( P < 0.001). We conclude that enhanced peripheral CO 2 chemoreflex sensitivity contributes to ventilatory LTF induced by hypercapnic AIH in awake humans. image Key points In awake humans, induction of ventilatory long‐term facilitation (LTF) by acute intermittent hypoxia (AIH) requires a continuous background of mild hypercapnia; thus, ventilatory LTF may arise from increases in central and/or peripheral CO 2 chemoreflex sensitivities. Central and peripheral CO 2 chemoreflex sensitivity were assessed by modified hyperoxic CO 2 rebreathing and transient CO 2 tests, respectively, before and after hypercapnic AIH, sustained hypercapnia, and a time‐matched control on separate days in 20 healthy young adults. Peripheral CO 2 chemoreflex sensitivity was increased 41 ± 46% after hypercapnic AIH but no statistically significant changes were found in central CO 2 chemoreflex sensitivity. These data indicate plasticity in the peripheral CO 2 chemoreflex after exposure to hypercapnic AIH that contributes to ventilatory LTF in a background of mild hypercapnia.