Ventilatory long-term facilitation at rest increases the feedforward contribution to subsequent exercise ventilatory responses

The respiratory control system exhibits neural plasticity, adjusting future ventilatory responses based on experience. We tested the hypothesis that ventilatory long-term facilitation induced by hypercapnic acute intermittent hypoxia (AIH) at rest enhances subsequent ventilatory responses to steady-state exercise. Fourteen healthy adults (age = 27 ± 5 yr; 7 males) participated in the study. On day 1, pulmonary function testing was performed. On days 2 and 3, in a pseudorandomized counterbalanced order, participants were exposed to AIH or Sham; AIH consisted of 15, 1-min hypoxic episodes with 1.5-min room air intervals. Mild hypercapnia (end-tidal Pco₂ clamped ∼3 mmHg above baseline) was sustained throughout AIH and Sham and for 40 min after. Approximately 20-30 min later, participants performed continuous mild to moderate constant-load cycle exercise in room air at 30, 60, and 90 W for 5 min each. Inspired minute ventilation (V̇i) increased by 3.6 ± 1.2 L·min^-1 after AIH versus baseline and was significantly greater than Sham (P = 0.013), signifying the onset of ventilatory long-term facilitation. Although V̇i during subsequent steady-state exercise was not significantly different between AIH and Sham (P = 0.511), the slope of the relationship between V̇i and CO₂ production rate (i.e., the system gain) and the calculated feedforward exercise gain were significantly increased (P = 0.021 and P < 0.001, respectively). Consequently, end-tidal Pco₂ was regulated ∼1 mmHg lower across all exercise workloads after AIH versus Sham (P = 0.006). Thus, ventilatory plasticity induced at rest alters future ventilatory responses to mild or moderate steady-state exercise.