# Sleep-Disordered Breathing in patients with C-SCI: Mechanisms and Therapy

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2020 · $299,530

## Abstract

This proposal aims to investigate the mechanisms of sleep-disordered breathing (SDB) and to explore
therapeutic approaches for SDB in patients with chronic cervical spine (C-SCI) injury. We have discovered that
patients with C-SCI demonstrate a central sleep-disordered breathing (SDB), manifesting as central sleep
apnea (CSA) or periodic breathing pattern, associated with narrow CO2 reserve (≤1mmHg and modestly
elevated upper airway Pcrit (≤ 2cmH2O, independent of respiratory mechanics or daytime arterial blood gases.
Our preliminary data in patients with C-SCI demonstrated enhanced ventilatory LTF; thus, promoting breathing
stability. Therefore, we will examine v-LTF during sleep in C-SCI patients before and after treatment of SDB to
determine if increased v-LTF is a reversible phenomenon, due to pre-conditioning with chronic intermittent
hypoxia OR an immutable phenomenon, due to the injury per se. Our preliminary data also reveal increased
peripheral chemoreflex activity in patients with C-SCI. Therefore, we will determine the effect of dampening
peripheral chemoresponsiveness with supplemental oxygen and the effect of alleviating CIH with O2 on
breathing instability during sleep. Finally, our preliminary data showed decreased arousal threshold in C-SCI
patients. Therefore , we will test the effect of decreasing the frequency of arousals with Zolpidem on central
apnea in these patients. Our proposed protocols will address the following Specific Aims. Specific Aim 1 is to
test the hypothesis that treatment of SDB in patients with C-SCI will attenuate vLTF and peripheral
chemoreceptor activity. This aim will be accomplished by measuring the effect of acute episodic hypoxia on
post-hypoxic ventilation and upper airway mechanics before and after treatment of SDB in patients with C-SCI
and SDB. Specific Aim 2 is to test the hypothesis that dampening chemoreceptor sensitivity in patients with
C-SCI and central SDB with supplemental O2 will reduce central respiratory events and decrease respiratory
variability during sleep. This aim will be accomplished by providing supplemental O2 to patients with C-SCI and
central SDB. Specific Aim 3 is to test the hypothesis that administration of zolpidem, in patients with cervical
spinal cord injury and central SDB will decrease respiratory-related arousals and the central apneas index
compared to placebo. To accomplish this aim, Zolpidem, a short-acting hypnotic will be administered to C-SCI
patients with central SDB. This aim may also indicate an effective therapeutic intervention that will improve the
care of patients suffering with C-SCI and central SBD. The proposed experiments will identify potentially
generalizable pathophysiologic pathways for the treatment of central SDB in patients with neuromuscular
disease and across the continuum of SDB. We anticipate that it will yield significant new knowledge that
improves the health and quality of life of these patients.

## Key facts

- **NIH application ID:** 9984507
- **Project number:** 5R01HL130552-05
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** M.Safwan Badr
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $299,530
- **Award type:** 5
- **Project period:** 2016-08-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984507

## Citation

> US National Institutes of Health, RePORTER application 9984507, Sleep-Disordered Breathing in patients with C-SCI: Mechanisms and Therapy (5R01HL130552-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984507. Licensed CC0.

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