Repeated Exposure to Mild Intermittent Hypoxia Mitigates the Severity of OSA, Reduces Blood Pressure and Improves Microvascular Function and Walking Endurance in Adults with OSA for 4 ‐ 8 Weeks Post Therapy
Authors: Puri Shipra , Kissane Dylan , Panza Gino , Lin Ho‐Sheng , Mateika Jason H. 
Published: May 2022

Objective

We previously reported that repeated exposure to mild intermittent hypoxia (MIH) improves autonomic function and lowers blood pressure (BP) in adults with hypertension and obstructive sleep apnea (OSA). We also showed that the reduction in BP was concurrent with an improvement in upper airway (UA) collapsibility that might lead to a reduction in the severity of OSA. However, whether mitigation of OSA severity occurs and whether decreases in BP and UA collapsibility are sustained for long periods of time is unknown. Moreover, whether improved microvascular (MV) function is coupled to reductions in BP following MIH is unknown in OSA. Improved MV function could lead to increased oxygen availability to skeletal muscles and improved exercise endurance. Thus, we investigated if MIH promotes long‐term positive effects on UA collapsibility, BP, MV function and walking endurance in adults with hypertension and OSA.

Methods

Two males (age: 46 ± 7 yrs; BMI: 32.5 ± 2.3 kg/m2; systolic BP: 158 ± 6 mmHg) with OSA [apnea hypopnea index (AHI): 55.7 ± 2.8 events/hr] were exposed to twelve 2‐min hypoxic episodes (PETO2 ≍ 50 mmHg) separated by 2‐min normoxic intervals with sustained PETCO2 maintained 2 mmHg above baseline for 15 days and were treated with in‐home continuous positive airway pressure on nightly basis throughout the study. The active critical closing pressure (Acrit), AHI, 24‐hr BP, BP variability, post‐occlusion reactive hyperemia (PORH), and fatigability (i.e. 10‐min walk test) were measured before and 1 day, 4 weeks and 8 weeks after exposure to MIH. Based on the small sample size, Cohen’s D effect sizes are reported. Data are expressed as Δ from baseline ± SE.

Results

Systolic BP was reduced 1 day after (17.2 ± 2.1 mmHg, d = 2.4), and 4 (12.8 ± 1.2 mmHg, d = 1.7) and 8 wks. (4.1 ± 0.7 mmHg, d = 0.5) after MIH. Likewise, improvements in autonomic function were evident at the three time points after MIH (HF norm: 23 ± 19, 8 ± 7 and 11 ± 5 n.u. LF norm: ‐26 ± 14, ‐10 ± 3 and ‐13 ± 3 n.u., d > 0.8 for all measures). Acrit decreased (‐2 ± 0 cmH2O) following MIH and the magnitude of this response was sustained for 4 and 8 wks. after MIH (d = 0.7 for all measures). Similarly, the AHI decreased at the three time points (‐10 ± 1.5 events/hr, d = 3.1, ‐20 ± 3 events/hr, d = 7.2, ‐24 ± 0.9 events/hr, d = 5.2) after MIH. In addition, the PORH response increased immediately after the MIH protocol (12.6 ± 2.2%, d = 5.9) and remained elevated at 4 wks. post MIH (3 ± 0.7%, d = 3.6) before returning to baseline values 8 wks. after MIH. The 10‐min walking distance increased (217 ± 48 m, d = 3.9) and fatigability reduced (‐17 ± 3.4% reduction in d = 4.9) 1 day following the MIH protocol. These modifications were sustained for 4 wks. (+151 ± 9 m, ‐11 ± 0.3% respectively, both d > 0.8) and 8 wks. (+86 ± 38 m, ‐6 ± 2% respectively, both d > 0.8) after MIH.

Conclusion

Our preliminary results suggest that exposure to MIH improves UA collapsibility and reduces the severity of OSA. Likewise, BP is reduced, and MV function is improved leading to increased walking endurance in adults with OSA. These modifications may be sustained for up to 8 weeks.