Diaphragm Pacing Elicits Ventilatory Plasticity in a Rodent Model of Spinal Cord Injury

Cervical spinal cord injury (cSCI) often results in respiratory impairments requiring the use of chronic mechanical ventilation (MV). Diaphragm pacing (DP) is an emerging clinical intervention designed to combat the deleterious effects of chronic MV by electrically stimulating the diaphragm muscle to maintain ventilation. Anecdotal clinical evidence suggests a rehabilitative benefit of DP; however, current clinical practice is limited by a lack of controlled investigations. Thus, the purpose of this ongoing study was to determine if daily DP could be used as a rehabilitative tool following cSCI. We hypothesized that following cSCI, DP would 1) induce a long-lasting increase in tidal volume 60 minutes after stimulation, and 2) result in sustained improvements in tidal volume after four days of daily DP in awake, behaving rats. To test these hypotheses, we implanted custom electromyography electrodes in the mid-costal region of the left and right hemidiaphragms of male Sprague-Dawley rats. One week later, all animals received a left C2 hemisection (C2Hx; n=14) and a subset also received a left C4-6 dorsal rhizotomy (n=3). One week after injury, rats received stimulation on the paralyzed hemidiaphragm (biphasic 30Hz, 0.8mA, 80 μs pulse width) in phase with breathing (Pacing n=5, Rhizotomy n=3), or served as controls (n=6). We delivered DP to animals within plethysmography chambers in an intermittent pattern (5 minutes on/5 minutes off) for 1 hour/day over 4 consecutive days. Using whole body plethysmography, we recorded ventilation before, during, and for 60 minutes after to examine the acute effects of DP. Additionally, we measured ventilation during normoxia (21% FiO 2 ) and respiratory challenge (10.5% FiO 2 , 7% FiCO 2 ) before and after C2Hx, and 24 hours after four days of DP to assess the rehabilitative potential of pacing. DP increased tidal volume (% change from pre-pacing) compared to control animals during stimulation (P =0.021). Animals receiving DP displayed an elevated tidal volume compared to controls for at least 60 minutes after DP (P=0.015). When compared to control animals 24 hours after the completion of the pacing protocol, DP animals displayed an increased tidal volume (mL/breath/100g) during both normoxia (P =0.006) and respiratory challenge (P =0.019). In contrast, animals pre-treated with rhizotomy showed a similar tidal volume (mL/breath/100g) compared to controls (normoxia: P=0.597; respiratory challenge: P=0.191), suggesting that DP-induced ventilatory plasticity requires phrenic afferents. Taken together, our data suggest that diaphragm pacing has rehabilitative potential and elicits functional respiratory improvements in rodents following C2Hx. Acknowledgements: This work was supported by funding from the National Institute of Health, grant numbers: R00 HL143207-01 (KAS), UL1TR001436 (TCH) and the APTA Acute Care Physical Therapy Seed Grant (TCH). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.