Simulated hypoxia reduced respiratory rhythm from 2.82 Hz to 1.69 Hz and action potential frequency from 25.44 to 17.5 AP/s, indicating reduced efficiency in upper airway motor control in OSA.
Does simulated hypoxia alter the electrophysiological behavior of respiratory nerve centers controlling upper airway functionality?
In silico modeling demonstrates that hypoxia characteristic of OSA alters the firing frequency and amplitude of respiratory nerve centers, suggesting reduced efficiency in upper airway motor control.
Abstract Rationale Obstructive sleep apnea (OSA) is a chronic respiratory disorder characterized by upper airway (UA) obstruction during sleep. The functional inefficiency of the neuromuscular structures related to the UA during periods of hypoxia is a key manifestation of OSA. However its electrophysiological properties have been barely explored in these periods. The aim of this study is to analyze the effects of hypoxia on the electrophysiological behavior of the nerve centers that control UA functionality using in silico modeling. Methods The Pre-Bötzinger complex model by Butera et al. (1999) was employed to generate the respiratory rhythm, and the hypoglossal motoneuron model by Purvis and Butera (2005) was modified to simulate UA innervation. Both were implemented in MATLAB, incorporating a Na+/K+ pump model (Kueh et al., 2016) and potassium channel inhibition mechanisms, which allowed us to generate a computational model of the effects of hypoxia on the respiratory centers. Results The combination of the respiratory rhythm generation model with the UA innervation model allowed us to simulate the complete physiology of the respiratory centers. Under control conditions, the model showed a rhythm of 2.82 Hz, a pattern of 25.44 action potentials (AP)/s, with uniform bursts in terms of amplitude and duration of the first AP between the first and last burst (6.9 mV and 2.28 ms, respectively) and an average frequency of 0.115 s/burst, sufficient for effective nerve recruitment. Under hypoxia, the reduction of Na+/K+ pump activity decreased the rhythm to 1.69 Hz and 17.5 AP/s, showing differences between the first and last bursts of the simulation, with decreases in amplitude (5.3 vs. 2.19 mV), increases in duration (2.44 vs. 2.9 ms) of the first AP, and intraburst slowing (0.119 vs. 0.188 s/burst). Potassium channel inhibition produced a frequency of 2.9 Hz and 51.7 AP/s, with lower amplitude (6.31 vs. 1.66 mV), longer duration (2.71 vs. 3. 54 ms) of the first AP, and reduced intra-burst frequency (0.191 vs. 0.328 s/burst). Conclusions These results indicate that the characteristic hypoxia of OSA affects the quality of neural control of breathing. An altered firing frequency, a lower net amplitude of APs, and, especially, an increase in intra-burst firing frequency suggest a reduced capacity for posterior nerve recruitment and, therefore, reduced efficiency in the motor control of the upper airway muscles. This abstract is funded by: Preciosa PI24/00337, INNOCAM (SBPLY/24/180225/000091)
Puech et al. (Fri,) conducted a other in Obstructive Sleep Apnea. Simulated hypoxia vs. Control conditions was evaluated on Electrophysiological behavior of the nerve centers controlling upper airway functionality. Simulated hypoxia reduced respiratory rhythm from 2.82 Hz to 1.69 Hz and action potential frequency from 25.44 to 17.5 AP/s, indicating reduced efficiency in upper airway motor control in OSA.
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