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Project

Intermittent Hypoxia, Respiratory and Motor Plasticity, and Sleep Apnea

Funder: Craig H Neilsen Foundation

Funding period
USD 300 K
Funding amount
Abstract
Recent animal and human studies suggest that exposure to acute intermittent hypoxia (AIH) enhances respiratory and motor function in individuals with chronic spinal cord injury (SCI). Important questions remain on effective dose and duration of AIH, long term effects of AIH including the threshold above which AIH is detrimental and identifying the SCI sub-population in whom AIH would be most beneficial. Obstructive sleep apnea (OSA) is characterized by periods of complete cessation of breathing (apnea) or marked reductions in airflow (hypopnea), sleep fragmentation, and frequent oxygen desaturations, leading to a state of chronic intermittent hypoxia (CIH). Many of the adverse cardiovascular, and cognitive consequences of OSA are likely related to CIH. In studies conducted by our team and others, the prevalence of OSA in SCI ranges from 56% to as high as 91% in those with complete lesions. It is unknown whether subjects with OSA and SCI have worse respiratory and motor function at baseline due to CIH, and whether OSA in this population attenuates the motor plasticity observed with AIH.The overall goal of this pilot project is to determine whether OSA and its associated CIH, plays a role in respiratory and motor plasticity, and function in chronic SCI. We hypothesize that subjects with moderate to severe OSA and chronic SCI will have no change in baseline pulmonary function (measured by FVC, MIP), and hand grip strength, when exposed to a 3-day AIH protocol. By contrast SCI subjects without OSA will show an improvement in all measured outcomes. Individuals with chronic SCI having residual hand function, age = 18, > 1-year post injury will be recruited to participate in the study. Home-based portable sleep studies will be performed to identify 15 individuals with moderate to severe OSA (defined as Apnea-hypopnea Index [AHI] = 15) and 15 individuals without OSA (AHI <5). During baseline visit, a medical history and physical exam will be completed for all 30 participants. Day 1, baseline measures for pulmonary function (FVC, MIP), hand grip strength, finger EMG activity, and serum BDNF and VEGF (shown to increase with repeated exposure to AIH in animal models) will be measured. Participants will then receive AIH (Hypoxico Altitude Training System, Hypoxico Inc, New York, NY) for 3 days entailing 15, 90-second hypoxic intervals (FIO2 = 0.09) with 60-second normoxic intervals (FIO2 = 0.21). Study outcomes will be measured at 30 minutes post completion of AIH on Days 1 and 3. and on Days 10 and 17 (no AIH exposure on later final days).Before AIH can be recommended as a treatment in the clinical setting, much more research is needed, including determining the subset of individuals with chronic SCI who would benefit the most from such a novel intervention. Given the exceptionally high prevalence of sleep apnea in the SCI population, the benefit of identifying OSA as a potential mediator of AIH plasticity is substantial. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    1102 Cardiorespiratory Medicine and Haematology

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Lung

  • RCDC

    Rehabilitation

  • RCDC

    Sleep Research

  • RCDC

    Spinal Cord Injury

  • RCDC

    Clinical Research

  • RCDC

    Neurodegenerative

  • HRCS HC

    Cardiovascular

  • HRCS HC

    Respiratory

  • Health Research Areas

    Clinical

  • Broad Research Areas

    Clinical Medicine and Science