Long-term facilitation of ventilation in humans with chronic spinal cord injury.
BACKGROUND
Intermittent stimulation of the respiratory system with hypoxia causes persistent increases in respiratory motor output (i.e., long-term facilitation) in animals with spinal cord injury. This paradigm, therefore, has been touted as a potential respiratory rehabilitation strategy.


OBJECTIVE
To determine whether acute (daily) exposure to intermittent hypoxia can also evoke long-term facilitation of ventilation after chronic spinal cord injury in humans, and whether repeated daily exposure to intermittent hypoxia enhances the magnitude of this response.


METHODS
Eight individuals with incomplete spinal cord injury (>1 yr; cervical [n = 6], thoracic [n = 2]) were exposed to intermittent hypoxia (eight 2-min intervals of 8% oxygen) for 10 days. During all exposures, end-tidal carbon dioxide levels were maintained, on average, 2 mm Hg above resting values. Minute ventilation, tidal volume, and breathing frequency were measured before (baseline), during, and 30 minutes after intermittent hypoxia. Sham protocols consisted of exposure to room air and were administered to a subset of the participants (n = 4).


RESULTS
Minute ventilation increased significantly for 30 minutes after acute exposure to intermittent hypoxia (P < 0.001), but not after sham exposure. However, the magnitude of ventilatory long-term facilitation was not enhanced over 10 days of intermittent hypoxia exposures.


CONCLUSIONS
Ventilatory long-term facilitation can be evoked by brief periods of hypoxia in humans with chronic spinal cord injury. Thus, intermittent hypoxia may represent a strategy for inducing respiratory neuroplasticity after declines in respiratory function that are related to neurological impairment. Clinical trial registered with www.clinicaltrials.gov (NCT01272011).
1 Brain Rehabilitation Research Center, Malcom Randall Veterans Affairs Medical Center, Gainesville, Florida.
Nicole J
NJ
Tester
David D
DD
Fuller
Jason S
JS
Fromm
Martina R
MR
Spiess
Andrea L
AL
Behrman
Jason H
JH
Mateika
D000328:Adult; D000368:Aged; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D008134:Long-Term Care / Q000379:methods; D008297:Male; D008875:Middle Aged; D012123:Pulmonary Ventilation / Q000502:physiology; D015656:Respiratory Mechanics / Q000502:physiology; D012138:Respiratory Therapy / Q000379:methods*; D013119:Spinal Cord Injuries / Q000628:therapy*; D014797:Vital Capacity