Paced breathing and phrenic nerve responses evoked by epidural stimulation following complete high cervical spinal cord injury in rats
Abstract
Spinal cord injury (SCI) at the level of cervical segments often results in life-threatening respiratory complications and requires long-term mechanical ventilator assistance. Thus restoring diaphragm activity and regaining voluntary control of breathing are the primary clinical goals for patients with respiratory dysfunction following cervical SCI. Epidural stimulation (EDS) is a promising strategy that has been explored extensively for nonrespiratory functions and to a limited extent within the respiratory system. The goal of the present study is to assess the potential for EDS at the location of the phrenic nucleus (C3–C5) innervating the diaphragm: the main inspiratory muscle following complete C1cervical transection. To avoid the suppressive effect of anesthesia, all experiments were performed in decerebrate, C1cervical transection, unanesthetized, nonparalyzed ( n = 13) and paralyzed ( n = 7) animals. Our results show that C4segment was the most responsive to EDS and required the lowest threshold of current intensity, affecting tracheal pressure and phrenic nerve responses. High-frequency (200–300 Hz) EDS applied over C4segment (C4-EDS) was able to maintain breathing with normal end-tidal CO2level and raise blood pressure. In addition, 100–300 Hz of C4-EDS showed time- and frequency-dependent changes (short-term facilitation) of evoked phrenic nerve responses that may serve as a target mechanism for pacing of phrenic motor circuits. The present work provides the first report of successful EDS at the level of phrenic nucleus in a complete SCI animal model and offers insight into the potential therapeutic application in patients with high cervical SCI.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 01, 2018
- Source ID
- 10.1152/japplphysiol.00895.2017
Entities
People
- Michael A Lane
- Tatiana Bezdudnaya
- Vitaliy Marchenko
Organizations
- Congressionally Directed Medical Research Programs
- Craig H Neilsen Foundation
- Drexel University