# Mild intermittent hypoxia and CPAP: A multi-pronged approach to treat sleep apnea in intact and spinal cord injured humans

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2021 · $385,000

## Abstract

Mild intermittent hypoxia (IH) initiates sustained increases in chest wall and upper airway muscle
activity in humans. This sustained increase is a form of respiratory plasticity known as long-term facilitation
(LTF). Repeated daily exposure to mild IH that leads to the initiation of LTF of upper airway muscle activity
could lead to increased stability of the upper airway. In line with my laboratory’s mandate to develop
innovative therapies to treat sleep apnea, this increased stability could ultimately reduce the continuous
positive airway pressure (CPAP) required to treat obstructive sleep apnea (OSA) and improve compliance
with this gold standard treatment. Improved compliance could ultimately serve to mitigate those co-
morbidities linked to sleep apnea. Moreover, in addition to improving CPAP compliance numerous studies
indicate that mild IH has many direct beneficial cardiovascular, neurocognitive and metabolic effects. Thus,
mild IH could serve as a multipronged therapeutic approach to treat sleep apnea. In accordance with this
postulation, Aim 1 of our proposal will determine if repeated daily exposure to mild IH serves as an adjunct
therapy coupled with CPAP to mitigate associated co-morbidities via its direct effects on a variety of
cardiovascular, metabolic and neurocognitive measures and indirectly by improving CPAP compliance.
Modifications in autonomic (i.e. sympathetic nervous system activity) and cardiovascular (i.e. blood pressure)
function will be the primary outcome measures coupled to secondary measures of metabolic and
neurocognitive outcomes.
 Sleep is typically associated with a reduction in respiratory motoneuron excitability. This response is
exacerbated and coupled to obstructive apneic events as a consequence of spinal cord injury induced
morphological and neurological impairment of bulbospinal synaptic inputs to respiratory motoneurons, and
adaptations in brainstem respiratory and upper airway motor function. These modifications are coupled to an
incidence of sleep-disordered breathing (i.e. both central and obstructive sleep apnea) which is approximately
15 times higher in individuals with spinal cord injury than in the general population of the United States.
Thus, exposure to this stimulus could improve CPAP compliance and enhanced outcome measures as outlined
above. Additionally, repeated daily exposure to intermittent hypoxia promotes the recovery of respiratory and
motor limb function in animals and humans. Thus, daily repeated exposure to IH could have significant
therapeutic effects on respiratory and limb motor function in individuals with spinal cord injury accompanied
by sleep apnea. Thus, Aim 2 of our proposal will serve to determine if IH can serve to mitigate co-morbidities
linked to sleep apnea and promote the recovery of respiratory motor function during wakefulness and sleep,
and motor limb function during wakefulness.

## Key facts

- **NIH application ID:** 10251847
- **Project number:** 5R01HL142757-03
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Jason H. Mateika
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $385,000
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10251847

## Citation

> US National Institutes of Health, RePORTER application 10251847, Mild intermittent hypoxia and CPAP: A multi-pronged approach to treat sleep apnea in intact and spinal cord injured humans (5R01HL142757-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10251847. Licensed CC0.

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