Effects of Stimulus Pattern on Inspiratory Muscle Activation during High Frequency Spinal Cord Stimulation in an Animal Model

Abstract

Background: High Frequency Spinal Cord Stimulation (HF-SCS) is a unique method of inspiratory muscle activation and has the potential to restore breathing in ventilator dependent tetraplegic subjects. Objective: To evaluate the pattern of diaphragm (D), parasternal (PA) and external intercostal (EI) activation during rectangular vs ramp-shape HF-SCS, compared to spontaneous breathing. Methods: In 8 anesthetized dogs, a stimulating disc electrode was positioned on the ventral surface of the spinal cord at the T2 level. Stimulus train duration for ramp-shape and rectangular HF-SCS was set at 1.3s since this duration approximated that occurring during spontaneous breathing. Stimulus amplitude during HF-SCS was adjusted such that inspired volumes approximated that occurring during SB. The ramp-shape pattern of stimulation was linearly increased from zero to the desired stimulus amplitude. Single motor unit (SMU) EMG activity of the PA, EI and D muscles was assessed during SB and HF-SCS (following spinalization at the C2 level) with rectangular and ramp-shape stimulation patterns, in separate trials. Time of onset (To), b) time to peak discharge frequency (TTP) and c) peak firing frequency (PFF) were measured under each condition. To and TTP were determined relative to the onset of inspiratory flow and expressed as a percentage of inspiratory time (Ti). The patterns of the inspiratory muscle activation during HF-SCS were compared to that obtained during spontaneous breathing. Results: During SB, D was recruited first followed by PA and EI; mean ± SE To was 19.6±1.4, 32.1±2.4 and 40.4±2.3%Ti, respectively. During rectangular HF-SCS, To was 3.0±0.4, 5.8±1.2 and 4.3±0.9%Ti for D, PA and EI, respectively (p<0.05 for each compared to SB). During ramp-shape HF-SCS, To was 23.1±3.7, 33.6±4.5 and 39.9±4.6%Ti for D, PA and EI respectively (NS for each compared to SB). During SB, TTP was 65.2±2.2, 71.0±2.0 and 74.0±2.0%Ti for D, PA and EI. During rectangular HF-SCS, TTP was 30.4±3.7, 25.4±3.3 and 35.2±2.8%Ti, for D, PA and EI (p<0.05 for each compared to SB). During ramp-shape HF-SCS, TTP was 60.5±2.9, 58.2±2.7 and 62.6±6.0%Ti for Dia, PA and EI (p<0.05 for PA and EI compared to SB). During SB, PFF of SMUs of the D, PA and EI were 10.3±0.5, 12.8±0.4 and 12.2±0.7Hz, respectively. However, during rectangular HF-SCS, PFF were 14.0±0.6, 14.7±0.7 and 14.5±0.5Hz for D, PA and EI, respectively (p<0.05 for each compared to SB). During ramp-shape HF-SCS, PFF were 12.3±0.8, 13.8±0.9 and 12.6±1.2 for D, PA and EI, respectively (NS for each compared to SB). Conclusion: Activation of the inspiratory motoneuron pools via HF-SCS is receptive to different patterns of electrical stimulation.Ramp-shape HF-SCS compared to rectangular HF-SCS results in a more physiologic pattern of inspiratory muscle activation. National Institutes of Health grant no. R01 NS105785. Conflict of interest: Dr. A. DiMarco is a founder of and has a significant financial interest in Synapse BioMedical, a manufacturer of diaphragm pacing systems (nos. 5,678,535 and 5,911,218). Dr. A. DiMarco and Dr. K. Kowalski hold the U.S. patents for technology related to the content of this study, Respiratory Muscle Activation by Spinal Cord Stimulation (no. 8,352,036). This is the full abstract presented at the American Physiology Summit 2023 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.