Neuromuscular electrical stimulation of the respiratory muscles based on breathing modelization in a mouse model of cervical spinal cord injury - 09/03/22

High cervical spinal cord injuries (cSCI) induce profound denervation in respiratory muscles leading to hypoventilation that compromises quality of life and increases mortality rate. Neuromuscular electrical stimulation of extra-diaphragmatic respiratory muscles (rNMES) could be a non-invasive approach to improve ventilatory capacity in cSCI. We developed a model of rNMES synchronized with breathing (to avoid breathing pattern alteration) in a murine model of cSCI.

A theorical breathing signal was built based on an ordinary differential equation and compared to actual breathing signals during spontaneous breathing at rest obtained by plethysmography in 13 mice (OF1, 8 weeks old) after a C3 hemi-contusion (C3HC) or a laminectomy (LM). The signal was dilated to represent breathing during rNMES under anesthesia. Then, nine mice (6 C3HC and 3 LM) were trained using rNMES or sham-rNMES.

The modelized signal matched actual ventilation with a mean squared error of the residuals of 0.016 and a mean r² of 83%. rNMES algorithms allowed for intercostal NMES during inspiratory phases only while producing a thoracic expansion and abdominal NMES during expiratory phases only with a duty cycle of 25%. Although C3HC mice decreased tidal volume (Vt) by 17% (0.53±0.11 vs. 0.64±0.11mL, P=0.03, n=6), 10 sessions of rNMES tended to allow for ventilation recovery via an improved Vt in the stimulated C3HC mice (n=3) while there was no change in sham-rNMES mice (n=3) (Fig. 1).

This new model of rNMES could be of great interest to investigate the mechanisms of recovery after NMES in cSCI but also in various other models of respiratory failure.