Mild Intermittent Hypoxia with Sustained Hypercapnia Improves Airflow, Reduces Therapeutic CPAP and Blood Pressure in Participants with Obstructive Sleep Apnea
Authors: El‐Chami Mohamad , Sudan Sukhesh , McCready Trevor , Lin Ho‐Sheng , Mateika Jason H. 
Published: November 2023

Intermittent hypoxia (IH) elicits long term facilitation of ventilation and upper airway muscle activity. The latter form of plasticity could contribute to stabilizing the upper airway. Based on this possibility, we examined if administration of mild IH accompanied by sustained hypercapnia reduces the continuous positive airway pressure (CPAP) required to treat obstructive sleep apnea (OSA). In addition, we investigated if daily exposure to mild IH would elicit changes in the autonomic nervous system, leading to a decrease in blood pressure in individuals with OSA.MethodsTen male participants with OSA initially visited the laboratory to confirm the presence of sleep apnea, while a second visit was used to determine the therapeutic CPAP (TP). On a third visit, the participants completed a sham protocol (i.e. normoxic and normocapnic conditions), which mimicked the timeframe of the IH protocol that would be introduced in a subsequent visit, while being treated with TP. During the sham recovery period, the CPAP was reduced in a step‐wise fashion to measure the change in flow and upper airway resistance. On a fourth visit participants were treated with TP. PETCO2 levels were increased and sustained 3 mmHg above baseline. Subsequently, twelve 2‐minute episodes of hypoxia (PETO2 ≈ 50 mmHg) separated by 2‐minute intervals of normoxia were administered. During recovery, the CPAP was reduced in a step‐wise fashion until flow limitation was evident. In a separate set of experiments two subjects with OSA underwent daily exposure to IH on 15 occasions over 3 weeks.ResultsFollowing exposure to intermittent hypoxia minute ventilation (P < 0.001) and tidal volume (P < 0.001) during end‐recovery and the step‐downs in positive pressure were greater compared to B2 (P < 0.001). Inspiratory flow and resistance remained at baseline levels following exposure to intermittent hypoxia after TP was reduced by 5 cmH2O. In contrast, after completion of the sham protocol inspiratory flow was reduced (P < 0.001) and resistance was increased (P < 0.01) in response to the 5 cmH2O reduction in positive airway pressure. Preliminary data in two participants showed that daily exposure to IH over a 3 week period led to a decrease in systolic (144 ± 1 vs. 128 ± 5 mmHg) blood pressure and an increase in baroreceptor sensitivity (6.5 ± 0.06 vs. 17.9 ± 1.7 ms/mmHg). CPAP compliance data was retrieved from one individual. CPAP use increased from 2 h 52 minutes in the 1st week to 5 h 52 minutes in the 3rd week.ConclusionThe administration of mild IH and sustained hypercapnia decreases the CPAP required to eliminate apneic events. Additionally, increases in resistance and decreases in flow following CPAP step‐downs were significantly mitigated following IH with sustained hypercapnia. Preliminary data from 2 individuals showed that mild IH could effectively treat cardiovascular co‐morbidities directly and indirectly by increasing CPAP compliance via reductions in TP.Support or Funding InformationVA Merit Award ‐ Department of Veterans Affairs