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Mild Intermittent Hypoxia: A Prophylactic for
Autonomic Dysfunction in
Individuals with Spinal Cord Injuries
Lexi Soltesz¹, Fei Zhao¹ ², Megan Hofman¹ ², and Gino Panza*¹ ²
Research and Development, John D. Dingell VA Medical Center, Detroit, MI ¹,
Department of Health Care Sciences, Program of Occupational Therapy ²
Abstract
A central health issue for those with a chronic spinal cord injury (SCI) above the sixth thoracic
vertebrae is autonomic dysfunction. Autonomic dysfunction results in significant increases and decreases
in blood pressure and negatively affects health-related quality of life. This uncontrolled blood pressure
also negatively impacts cognitive function and adherence to rehabilitation programs. Additionally, the
lesion itself impairs motor function thereby resulting in decreased physical activity and impaired
mitochondrial function. Moreover, autonomic dysfunction can lead to an increased risk of stroke, and
therefore increased mortality. Mild intermittent hypoxia (MIH), an experimental protocol in which
participants experience lower oxygen, in a controlled and repetitive sequence, has been shown to
improve blood pressure control in humans. Our study aims to investigate the impact of MIH on autonomic
dysfunction during in-lab provocation and during in-home testing. Likewise, we will also investigate the
impact of MIH on mitochondrial and microvascular function and motor function. Our preliminary data
shows that MIH may improve autonomic dysfunction which may be explained by improvements in
baroreceptor and/or mitochondrial and endothelial function. As evidenced by our preliminary data, MIH
is a promising potential protocol for improving health-related quality of life in those with SCI.
Introduction
• Autonomic Dysfunction
• Two primary measures of
autonomic dysfunction
• Autonomic Dysreflexia
• Sudden rises in BP
• Orthostatic Hypotension
• Sudden or sustained
drop in BP
• Potential Mechanisms
• Baroreceptor function
• Mitochondrial and
endothelial function
Spinal Cord
Injury
T6 and above
Impaired
motor
activation
Quality of
life &
disability
Deconditioning
Mitochondria &
endothelial
dysfunction
Autonomic
Dysfunction
Impaired
physical
function
Mild Intermittent
Hypoxia (MIH)
Methodology
• Pre/Post Design
• Autonomic Dysreflexia
• Occlusion pressure (300 mmHg)
• Orthostatic Intolerance
• Positional Change
• Blood Pressure Instability
• +/- 20/10 mmHg SBP/DBP in-home
• Mitochondrial Capacity
• Speed and Amplitude of muscle
deoxygenation during occlusion
• Endothelial Function
• Speed and amplitude of reoxygenation • Mild Intermittent Hypoxia
• Repeated for 8 Days
• Normoxic and hypercapnic baselines
10
min
10
min
2
min
20
min
50-55 mmHg
+2
mmHg
Hypotheses
Specific Aim 1: To determine the effect of MIH on autonomic cardiovascular
control in participants with SCI.
• We hypothesize that treatment with MIH will reduce the magnitude of AD and OH and
reduce the frequency of BP instability (frequency of OH and AD) during 24-hour in-home
BP monitoring.
Specific Aim 2: To determine the effect of MIH on mitochondrial and
endothelial function in individuals living with incomplete SCI.
• We hypothesize that 8 days of MIH will improve mitochondrial function and endothelial
function.
0 5 10 15 20 25 30 35
50
60
70
80
90
100
110
120
130
Results
Orthostatic Intolerance
Blood
Pressure
(mmHg)
+ 34%
+ 17%
Autonomic Dysreflexia
Blood
Pressure
(mmHg)
Time (seconds)
↓66.1%
↓71.2%
Positional
Change
Results
Results
Baroreceptor Function Mitochondrial and Endothelial
Function
Blood
Pressure
(mmHg)
Muscle
Oxygenation
(%
of
Baseline)
Time (seconds) Time (seconds)
Normalized to
Amplitude:
-28%
Intrathoracic Pressure
Conclusion
• 8 days of mild intermittent hypoxia may improve blood pressure
regulation both in the laboratory and in the community in individuals
with motor incomplete spinal cord injuries.
• 8 days of mild intermittent hypoxia may improve baroreceptor
function and mitochondrial and endothelial function.
• The improvements in autonomic function may be a result of
improvements in baroreceptor function and/or mitochondrial and
endothelial function.
Conclusion
Discussion
• Collaborators:
• Jason Mateika, PhD
• Safwan Badr, MD, MPH
• Luis Afonso, MD
• Jill Wecht, EdD
• Post-Doctoral Researchers:
• Fiona Zhao
• Graduate Researchers:
• Megan Hofman
Acknowledgements
• Undergraduate Researchers:
• Haya Javaid
• Jack Smith
• Douaa Yassine
• Nour Beydoun
• Lana Rihawi
• Funding source:
• Department of Veterans Affairs,
5Ik2RX003847-01A2 (GSP)
• GSP Start-up Funds
• Internal Post-doc Award

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Mild Intermittent Hypoxia: A Prophylactic for Autonomic Dysfunction in Individuals with Spinal Cord Injuries

  • 1. Mild Intermittent Hypoxia: A Prophylactic for Autonomic Dysfunction in Individuals with Spinal Cord Injuries Lexi Soltesz¹, Fei Zhao¹ ², Megan Hofman¹ ², and Gino Panza*¹ ² Research and Development, John D. Dingell VA Medical Center, Detroit, MI ¹, Department of Health Care Sciences, Program of Occupational Therapy ²
  • 2. Abstract A central health issue for those with a chronic spinal cord injury (SCI) above the sixth thoracic vertebrae is autonomic dysfunction. Autonomic dysfunction results in significant increases and decreases in blood pressure and negatively affects health-related quality of life. This uncontrolled blood pressure also negatively impacts cognitive function and adherence to rehabilitation programs. Additionally, the lesion itself impairs motor function thereby resulting in decreased physical activity and impaired mitochondrial function. Moreover, autonomic dysfunction can lead to an increased risk of stroke, and therefore increased mortality. Mild intermittent hypoxia (MIH), an experimental protocol in which participants experience lower oxygen, in a controlled and repetitive sequence, has been shown to improve blood pressure control in humans. Our study aims to investigate the impact of MIH on autonomic dysfunction during in-lab provocation and during in-home testing. Likewise, we will also investigate the impact of MIH on mitochondrial and microvascular function and motor function. Our preliminary data shows that MIH may improve autonomic dysfunction which may be explained by improvements in baroreceptor and/or mitochondrial and endothelial function. As evidenced by our preliminary data, MIH is a promising potential protocol for improving health-related quality of life in those with SCI.
  • 3. Introduction • Autonomic Dysfunction • Two primary measures of autonomic dysfunction • Autonomic Dysreflexia • Sudden rises in BP • Orthostatic Hypotension • Sudden or sustained drop in BP • Potential Mechanisms • Baroreceptor function • Mitochondrial and endothelial function Spinal Cord Injury T6 and above Impaired motor activation Quality of life & disability Deconditioning Mitochondria & endothelial dysfunction Autonomic Dysfunction Impaired physical function Mild Intermittent Hypoxia (MIH)
  • 4. Methodology • Pre/Post Design • Autonomic Dysreflexia • Occlusion pressure (300 mmHg) • Orthostatic Intolerance • Positional Change • Blood Pressure Instability • +/- 20/10 mmHg SBP/DBP in-home • Mitochondrial Capacity • Speed and Amplitude of muscle deoxygenation during occlusion • Endothelial Function • Speed and amplitude of reoxygenation • Mild Intermittent Hypoxia • Repeated for 8 Days • Normoxic and hypercapnic baselines 10 min 10 min 2 min 20 min 50-55 mmHg +2 mmHg
  • 5. Hypotheses Specific Aim 1: To determine the effect of MIH on autonomic cardiovascular control in participants with SCI. • We hypothesize that treatment with MIH will reduce the magnitude of AD and OH and reduce the frequency of BP instability (frequency of OH and AD) during 24-hour in-home BP monitoring. Specific Aim 2: To determine the effect of MIH on mitochondrial and endothelial function in individuals living with incomplete SCI. • We hypothesize that 8 days of MIH will improve mitochondrial function and endothelial function.
  • 6. 0 5 10 15 20 25 30 35 50 60 70 80 90 100 110 120 130 Results Orthostatic Intolerance Blood Pressure (mmHg) + 34% + 17% Autonomic Dysreflexia Blood Pressure (mmHg) Time (seconds) ↓66.1% ↓71.2% Positional Change
  • 8. Results Baroreceptor Function Mitochondrial and Endothelial Function Blood Pressure (mmHg) Muscle Oxygenation (% of Baseline) Time (seconds) Time (seconds) Normalized to Amplitude: -28% Intrathoracic Pressure
  • 9. Conclusion • 8 days of mild intermittent hypoxia may improve blood pressure regulation both in the laboratory and in the community in individuals with motor incomplete spinal cord injuries. • 8 days of mild intermittent hypoxia may improve baroreceptor function and mitochondrial and endothelial function. • The improvements in autonomic function may be a result of improvements in baroreceptor function and/or mitochondrial and endothelial function. Conclusion
  • 10. Discussion • Collaborators: • Jason Mateika, PhD • Safwan Badr, MD, MPH • Luis Afonso, MD • Jill Wecht, EdD • Post-Doctoral Researchers: • Fiona Zhao • Graduate Researchers: • Megan Hofman Acknowledgements • Undergraduate Researchers: • Haya Javaid • Jack Smith • Douaa Yassine • Nour Beydoun • Lana Rihawi • Funding source: • Department of Veterans Affairs, 5Ik2RX003847-01A2 (GSP) • GSP Start-up Funds • Internal Post-doc Award

Editor's Notes

  1. Mild Intermittent Hypoxia Normoxic Baseline 10 Minutes of slight hypercapnia +2 mmHg PETCO2 12 2-minute bouts of hypoxia PETO2 = 55 mmHg FiO2 = 8% Slight hypercapnia is maintained throughout the protocol Repeated for 8 days