Mild Acute Intermittent Hypoxia Improves Respiratory Function in Unanesthetized Rats With Midcervical Contusion

Abstract

Background: Mild intermittent hypoxia has been considered a potential approach to induce respiratory neuroplasticity.

Objective: The purpose of the present study was to investigate whether mild acute intermittent hypoxia can improve breathing function in a clinically relevant spinal cord injury animal model.

Methods: Adult male rats received laminectomy or unilateral contusion at the C3-C4 spinal cord using a MASCIS Impactor (height: 6.25 or 12.5 mm). At 4 weeks postinjury, the breathing patterns of unanesthetized rats were measured by whole body plethysmography before, during and after 10 episodes of 5 minutes of hypoxia (10% O₂, 4% CO₂, balance N₂) with 5 minutes of normoxia intervals.

Results: The results demonstrated that cervical contusion resulted in reduction in breathing capacity and number of phrenic motoneurons. Acute hypoxia induced significant increases in frequency and tidal volume in sham surgery and contused animals. In addition, there was a progressive decline in the magnitude of hypoxic ventilatory response during intermittent hypoxia. Further, the tidal volume was significantly enhanced in contused but not sham surgery rats at 15 and 30 minutes postintermittent hypoxia, suggesting intermittent hypoxia can bring about long-term facilitation of tidal volume following cervical spinal contusion.

Conclusions: These results suggest that mild acute intermittent hypoxia can elicit differential forms of respiratory plasticity in sham surgery versus contused animals, and may be a promising neurorehabilitation approach to improve respiratory function after cervical spinal cord injury.

Keywords: cervical spinal contusion; intermittent hypoxia; ventilation.