Compensatory Function of the Diaphragm after High Cervical Hemisection in the Rat

Unilateral high cervical spinal hemisection (i.e., C2Hx) interrupts the respiratory bulbospinal pathway and results in paralysis of the hemidiaphragm. The ipsilateral diaphragmatic activity can partially recover over weeks to months; however, its contribution to the tidal volume generation is less than 20%. Accordingly, we hypothesized that the contralateral diaphragm exerts a compensatory function to maintain the essential ventilation following C2Hx. The cardiorespiratory pattern and bilateral diaphragm electromyogram (EMG) signals were measured in urethane-anesthetized and spontaneously breathing adult rats at 1 day, and 2 or 8 weeks post-C2Hx or C2 laminectomy. The functional contribution of the diaphragm was assessed by measuring immediate changes of the tidal volume following phrenic nerve section. At 1 day post-injury, the tidal volume was significantly reduced after contralateral phrenicotomy in C2Hx animals (54 ± 3% decline) compared with uninjured controls (20 ± 2% decline). Moreover, the arterial carbon dioxide partial pressure was significantly elevated in C2Hx animals (from 76 ± 8 mmHg to 117 ± 5 mmHg) but not in uninjured animals (from 51 ± 4 mmHg to 55 ± 3 mmHg). By 2 and 8 weeks post-injury, contralateral phrenicotomy still caused a greater reduction in the tidal volume in C2Hx than in uninjured animals, and the percentage decline of the tidal volume was similar to the response at 1 day post-injury. These data suggested that unilateral cervical spinal cord injury induced a persistent compensatory plasticity in the contralateral diaphragm, which plays a critical role in maintenance of essential ventilation.