Phrenic nerve stimulation increases genioglossal EMG output

Obstructive sleep apnea (OSA) is characterized by repeated episodes of partial or complete obstruction of the upper airway during sleep, leading to periodic cessation of breathing. Due to poor compliance with current management strategies such as continuous positive airway pressure, there remains a significant need for new strategies to alleviate upper airway collapse. Recent evidence indicates that phrenic nerve stimulation may relieve airway collapse during drug induced sleep endoscopy in individuals with OSA. However, the mechanisms by which phrenic nerve stimulation may impact the upper airway are unknown. Here we used anesthetized and spontaneously breathing male (n=8) and female (n=5) rats to assess the hypothesis that phrenic nerve stimulation increases genioglossus electromyography (EMG) amplitude. We also evaluated whether delivering stimulation at three separate times within the respiratory cycle: 1) during inspiration, 2) immediately before inspiration (pre-inspiration), and 3) immediately after inspiration (expiration) differentially impacts genioglossus EMG amplitude. To assess our hypotheses, we recorded left and right genioglossus EMG output and delivered stimulation to the left phrenic nerve for 1 breath at increasing currents (15, 160, and 300 mA) during inspiration, pre-inspiration, and expiration. We then repeated this to deliver stimulation for 5 consecutive breaths. We found a significant impact of stimulation on ipsilateral genioglossal EMG output (1 breath: (F (3,99) = 35.48, p < 0.0001), Two-Way ANOVA; 5 breaths: (F (3,98) = 25.00, p < 0.0001), Mixed-effects ANOVA). When stimulation at 160 mA and 300 mA is delivered for 1 breath during inspiration and pre-inspiration, ipsilateral EMG amplitude is significantly greater than baseline (inspiration stim vs BL: 160 mA: p = 0.0004, 300 mA: p < 0.0001; pre-inspiration stim vs BL – 160 mA: p = 0.0007, 300 mA: p < 0.0001; Tukey’s post-hoc). We also found that this response is significantly greater than the response when stimulation is delivered during expiration (inspiration stim vs expiration stim – 160 mA: p = 0.0261, 300 mA: p = 0.0019; pre-inspiration stim vs expiration stim – 160 mA: p = 0.0365, 300 mA: p < 0.0001; Tukey’s post-hoc). When delivered for 5 breaths, a similar significant increase from baseline and from expiration stim is observed when stimulation is delivered during inspiration (160 mA vs BL: p < 0.0001, 300 mA vs BL: p < 0.0001, 160 mA vs expiration stim: p = 0.0006, 300 mA vs expiration stim: p < 0.0001; Tukey’s post-hoc) whereas when delivered pre-inspiration only 300 mA is significantly increased compared to baseline (p < 0.0001; Tukey’s post-hoc) and expiration stim (p < 0.0001; Tukey’s post-hoc). These data suggest that phrenic nerve stimulation during both the pre-inspiratory and inspiratory phase can increase ipsilateral genioglossus EMG amplitude. While phrenic nerve stimulation is currently used in several patient populations to contract the diaphragm muscle and sustain breathing, these data suggest phrenic nerve stimulation may have a new therapeutic use of maintaining upper airway patency during OSA. Funding: This work was supported by funding from Lunair Medical Inc. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.