# Intermittent hypoxia initiated plasticity in humans: A multi-pronged therapeutic approach to treat sleep apnea and overlapping co-morbidities.

> **NIH VA I01** · JOHN D DINGELL VA MEDICAL CENTER · 2020 · —

## Abstract

Abstract
 The prevalence of obstructive sleep apnea (OSA) is high in the Veteran population and the prevalence
is increased further in Veterans with spinal cord injury. If not treated promptly, OSA may result in the
development of numerous cardiovascular, neurocognitive and metabolic abnormalities. Thus, OSA is a major
health concern in the Veteran population. However, treatment of OSA in many cases does not lead to
significant improvements in outcome measures. This inadequacy may be a consequence of reduced treatment
compliance with CPAP and/or because factors other than those directly linked to sleep apnea contribute to the
presence of coincident co-morbidities. Consequently, innovative therapies that increase CPAP compliance
and/or directly impact those co-morbidities typically associated with OSA independent of CPAP treatment
could improve outcomes strongly linked to sleep apnea.
 My laboratory has established that 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 CPAP required to treat 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 intermittent hypoxia has many
direct beneficial cardiovascular, neurocognitive and metabolic effects. Thus, mild intermittent hypoxia could
serve as 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) w...

## Key facts

- **NIH application ID:** 9856932
- **Project number:** 5I01CX000125-11
- **Recipient organization:** JOHN D DINGELL VA MEDICAL CENTER
- **Principal Investigator:** Jason H. Mateika
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2009-04-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856932

## Citation

> US National Institutes of Health, RePORTER application 9856932, Intermittent hypoxia initiated plasticity in humans: A multi-pronged therapeutic approach to treat sleep apnea and overlapping co-morbidities. (5I01CX000125-11). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9856932. Licensed CC0.

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