Single-session effects of acute intermittent hypoxia on breathing function after human spinal cord injury

Abstract

After spinal cord injury (SCI) respiratory complications are a leading cause of morbidity and mortality. Acute intermittent hypoxia (AIH) triggers spinal respiratory motor plasticity in rodent models, and repetitive AIH may have the potential to restore breathing capacity in those with SCI. As an initial approach to provide proof of principle for such effects, we tested single-session AIH effects on breathing function in adults with chronic SCI. 17 adults (13 males; 34.1 ± 14.5 years old; 13 motor complete SCI; >6 months post injury) completed two randomly ordered sessions, AIH versus sham. AIH consisted of 15, 1-min episodes (hypoxia: 10.3% O2; sham: 21% O2) interspersed with room air breathing (1.5 min, 21% oxygen); no attempt was made to regulate arterial CO2 levels. Blood oxygen saturation (SpO2), maximal inspiratory and expiratory pressures (MIP; MEP), forced vital capacity (FVC), and mouth occlusion pressure within 0.1 s (P0.1) were assessed. Outcomes were compared using nonparametric Wilcoxon's tests, or a 2 × 2 ANOVA. Baseline SpO2 was 97.2 ± 1.3% and was unchanged during sham experiments. During hypoxic episodes, SpO2 decreased to 84.7 ± 0.9%, and returned to baseline levels during normoxic intervals. Outcomes were unchanged from baseline post-sham. Greater increases in MIP were evident post AIH vs. sham (median values; +10.8 cmH2O vs. -2.6 cmH2O respectively, 95% confidence interval (-18.7) - (-4.3), p = .006) with a moderate Cohen's effect size (0.68). P0.1, MEP and FVC did not change post-AIH. A single AIH session increased maximal inspiratory pressure generation, but not other breathing functions in adults with SCI. Reasons may include greater spared innervation to inspiratory versus expiratory muscles or differences in the capacity for AIH-induced plasticity in inspiratory motor neuron pools. Based on our findings, the therapeutic potential of AIH on breathing capacity in people with SCI warrants further investigation.

Keywords: Acute intermittent hypoxia; Human; Rehabilitation; Respiratory function; Respiratory plasticity; Spinal cord injury.

Conflict of interest statement

Disclosures

The authors have no competing financial interests.

Declarations of Interest: none

Copyright © 2021 Elsevier Inc. All rights reserved.

Figures

Figure 1.

Procedures and experimental timeline. After recruitment and consenting, participants were randomized to receive an acute intermittent hypoxia (AIH) or sham on Day 1. Outcomes were collected before and 30 minutes after AIH or sham. At least 7 days later, participants repeated the procedures (Day 2) but received the opposite intervention.

Figure 2.

Baseline maximal inspiratory and expiratory pressure generation (MIP, MEP; n=17). Group medians and distributions for sham (white boxes) and AIH (gray boxes) baseline outcomes are shown. cmH2O = centimeters of water.

Figure 3.

Changes in maximal inspiratory and expiratory pressures. Group medians and distributions for sham (white boxes) and AIH (gray boxes) changes from baseline pressures are shown. * = significant change (p<.01 cmh>2O = centimeters of water.

Figure 4.

Mouth occlusion pressure (P0.1) outcomes for participants 5, 6, and 8–17. Group medians and distributions for baseline (A) and changes from baseline (B) pressures for sham (white boxes) and AIH (gray boxes) are shown. cmH2O = centimeters of water.

Figure 5.

Forced vital capacity outcomes for participants 4–17. Bars representing means and error bars representing 95% confidence intervals are shown for pre and post sham (white bars) and AIH (gray bars).