(Research Hub Theater) Therapeutic Electrical Stimulation Promotes Diaphragm Muscle Reinnervation After Spinal Accessory to Phrenic Nerve Transfer, but Not Phrenic Direct Repair in a Rat Model

Background and/or Objectives: Diaphragm paralysis is a serious complication of both high spinal cord injury and phrenic nerve injury. We hypothesized we could restore diaphragm muscle function by spinal accessory nerve to phrenic nerve transfer. Furthermore, we hypothesized that diaphragm muscle reinnervation and functional recovery would be accelerated by therapeutic electrical stimulation.

Design: Randomized, controlled study.

Setting: Laboratory

Participants: Rats with unilateral phrenic nerve transection were randomly separated into four treatment groups: phrenic-to-phrenic surgical repair with electrical stimulation, phrenic-to-phrenic repair only (sham), spinal-accessory-to-phrenic transfer with electrical stimulation, spinal-accessory-to-phrenic transfer only (sham).

Interventions: Our therapeutic electrical stimulation protocol consisted of 1-hour of 20 Hz electrical stimulation at 2-4 mA of current delivered immediately after nerve repair surgery.

Main Outcome Measures: Our primary outcome measurement was M-Mode ultrasound imaging for diaphragmatic excursion. Other outcome measurements include phrenic motor conduction studies, concentric needle electromyography, and whole cervical spinal cord fluorescent imaging for retrogradely labeled motoneurons.

Results: Phrenic nerve transection and direct repair (no stimulation) took 10 weeks to recover normal diaphragmatic excursion. Therapeutic electrical stimulation did not improve phrenic nerve regeneration. However, therapeutic electrical stimulation after spinal accessory nerve transfer significantly improved diaphragm muscle recovery rate compared to non-stimulation groups (phrenic-to-phrenic, and spinal-accessory-to-phrenic) by approximately 50% (5 weeks vs 10 weeks). In addition, electrical stimulation improved synchronicity of diaphragm needle electromyography (right vs. left side) and compound muscle action potential amplitude compared to non-stimulation group (17.4% vs 9.3%).

Conclusions: Spinal accessory nerve transfer is a promising option to re-innervate diaphragm and restore spontaneous synchronized respiratory movement. Brief therapeutic electrical stimulation selectively improves regeneration of spinal accessory axons, but not phrenic axons, for functional restoration of the paralyzed diaphragm.