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

Ventilatory long-term facilitation (vLTF) refers to respiratory neuroplasticity that manifests as increased minute ventilation ( V ̇ I ) 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 years; mean ± SD), measurements of tidal volume (VT ), breathing frequency (fB ), V ̇ I , and end-tidal gases ( P ET O 2 and P ETC O 2 ), were made at baseline, during IHH and 50 min of recovery. Totalling 40 min, IHH included 1 min intervals of 40 s hypercapnic hypoxia (target P ET O 2  = 50 mmHg and P ETC O 2  = +4 mmHg above baseline) and 20 s normoxia. During baseline and recovery, dynamic end-tidal forcing maintained resting P ET O 2 and P ETC O 2 and delivered 1 min of hyperoxia ( P ET O 2  = 355 ± 7 mmHg) every 5 min. The depression in V ̇ I during hyperoxia was considered an index of peripheral chemoreflex drive. Throughout recovery V ̇ I was increased 4.6 ± 3.7 l min-1 from baseline (P < 0.01). Hyperoxia depressed V ̇ I at baseline, and augmented depression was evident following IHH (Δ V ̇ I  = -0.8 ± 0.9 vs. -1.7 ± 1.3 l min-1 , respectively, P < 0.01). The vLTF was similar between sexes (P = 0.15), but males had larger increases in VT than females (sex-by-time interaction, P = 0.03), and females tended to increase fB (P = 0.09). During isocapnic-normoxic recovery following IHH: (1) vLTF is expressed in healthy humans; (2) vLTF expression is attenuated but not abolished with peripheral chemoreflex inhibition by hyperoxia, suggesting a contribution from central nervous pathways in vLTF expression; and (3) males and females develop similar vLTF through different ventilatory recruitment strategies.