Peripheral chemoreflex contribution to ventilatory long‐term facilitation induced by acute intermittent hypercapnic hypoxia in males and females

Key points Ventilatory long-term facilitation (vLTF) refers to respiratory neuroplasticity that develops following intermittent hypoxia in both healthy and clinical populations. A sustained hypercapnic background is argued to be required for full vLTF expression in humans. We determined whether acute intermittent hypercapnic hypoxia elicits vLTF during isocapnic-normoxic recovery in healthy males and females. We further assessed whether tonic peripheral chemoreflex drive is necessary and contributes to the expression of vLTF. Following 40-minutes of intermittent hypercapnic hypoxia, minute ventilation was increased throughout 50-minutes of isocapnic-normoxic recovery. Inhibition of peripheral chemoreflex drive with hyperoxia attenuated the magnitude of vLTF. Males and females achieve vLTF through different respiratory recruitment patterns. Abstract Ventilatory long-term facilitation (vLTF) refers to respiratory neuroplasticity that manifests as increased minute ventilation (VI ) following intermittent hypoxia. In humans, hypercapnia sustained throughout intermittent hypoxia and recovery is considered necessary for vLTF expression. We examined whether acute intermittent hypercapnic hypoxia (IHH) induces vLTF, and if peripheral chemoreflex drive contributes to vLTF throughout isocapnic-normoxic recovery. In 19 individuals (9 females, age: 22±3, mean±SD), measurements of tidal volume (VT ), breathing frequency (fB ), VI , and end-tidal gases (PET O2 and PET CO2 ), were made at baseline, during IHH and 50-minutes of recovery. Totalling 40-minutes, IHH included 1-minute intervals of 40-s hypercapnic hypoxia (target PET O2 = 50 mmHg and PET CO2 = +4 mmHg above baseline) and 20-s normoxia. During baseline and recovery, dynamic end-tidal forcing maintained resting PET O2 and PET CO2 and delivered 1-minute of hyperoxia (PET O2 : 355±7 mmHg) every 5-minutes. The depression in VI during hyperoxia was considered an index of peripheral chemoreflex drive. Throughout recovery VI was increased 4.6±3.7 l/min from baseline (P