Mild Intermittent Hypoxia Elicits Long-term Facilitation of Minute Ventilation and Improvements in Upper Airway Function in Participants with Motor Incomplete Spinal Cord Injury

Research Objectives: To investigate the impact of 8 days of mild intermittent hypoxia (MIH) on long-term facilitation (LTF) of minute ventilation (VE) and upper airway function during sleep in those with a motor incomplete spinal cord injury (SCI).

Design: 2-arm parallel design.

Setting: Research Laboratory.

Participants: Five individuals (3M, 2F) with a chronic motor incomplete SCI (C4, T1, C7/T5, C5, C4/C7) with signs of autonomic dysfunction. All participants scored as C or D (American Spinal Injury Association Impairment Score). Age 43.8 ± 2.0 with a body mass index of 23.4 ± 2.1.

Interventions: 8 days of MIH consisting of twelve two-minute bouts of hypoxia interspersed with two-minute of normoxic recovery. Slight hypercapnia (+2 mmHg) was maintained throughout.

Main Outcome Measures: Long-term facilitation (LTF) of VE (VE after MIH divided by hypercapnic baseline) on day 1 and day 8. Upper airway collapsibility was measured using a step-down positive airway pressure protocol. Sleep apnea severity, as measured by apnea hypopnea index (AHI), during polysomnography. Data are presented as fractional change relative to baseline and presented as mean ± standard error with Cohen’s d effect sizes presented for the sleep data.

Results: LTF of VE was present on both Day 1 (1.32 ± 0.11) and Day 8 (1.27 ± 0.10, p ≤ 0.049) with no difference between days (p > 0.73). No LTF of breathing frequency (1.09 ± 0.07 vs 1.15 ± 0.11, p > 0.23) or tidal volume (1.15 ± 0.09 vs 1.17 ± 0.09, p > 0.14) were observed on Day 1 and Day 8 with no difference between days (p ≥ 0.59). Upper airway collapsibility improved (n = 4, 0.45 ± 0.31, d = 0.7), and was present two weeks post-intervention (0.66 ± 0.46, d = 0.4). Apnea-hypopnea index (AHI) reduced following MIH (0.44 ± 0.20, d = 0.6) and two weeks after (0.63 ± 0.28, d = 0.2). A significant reduction in sleep fragmentation was also observed (0.64 ± 0.14, d = 0.95).

Conclusions: MIH elicited ventilatory plasticity following acute and repeated MIH, with no augmented effect on VE. However, following daily MIH, there was an improvement in upper airway function suggesting the ventilatory plasticity is likely present during sleep. These findings, along with the reduction in the number of arousals, suggest that the neural plasticity elicited by MIH may improve sleep quality in individuals with motor incomplete SCI, which may have positive effects on autonomic function and cognition.

Author(s) Disclosures: None