Neuromuscular electrical stimulation of the respiratory muscles based on breathing modelization in a mouse model of cervical spinal cord injury

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 ± 0.11 mL, 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.