Repeated daily exposure to mild intermittent hypoxia leads to a 8 week reduction in blood pressure and improvement in microvascular function in OSA patients with hypertension
Authors: Kissane Dylan , Emmela David , Barok Rebecca , Lin Ho-Sheng , Mateika Jason 
Published: May 2024

Objective: We previously showed that blood pressure is reduced in individuals with obstructive sleep apnea (OSA) after 3 weeks of repeated daily exposure to mild intermittent hypoxia (MIH). However, we did not determine if these reductions are sustained over time. Likewise, the underlying mediator of these improvements is yet to be elucidated. Enhancement of microvascular function could lead to improved vasodilation and increased oxygen delivery to end organs and muscle. Furthermore, improvements in oxygen utilization could be indicative of heightened mitochondrial function. Therefore, in the present investigation we aimed to determine if reductions in blood pressure following treatment with MIH are sustained up to 8 weeks. We also explored if these changes were accompanied by modifications in microvascular function and oxygen utilization. Methods: Nineteen participants with OSA and hypertension have been enrolled in the study to date. Nine participants (8M, 1F) were randomized to a group treated with MIH while 10 participants were randomized to a group treated with sham MIH (8M, 2F). 5 participants in each group were also randomly assigned to use nightly continuous positive airway pressure (CPAP) for the duration of the study. Participants randomized to the MIH protocol were exposed to 12 — 2 minute episodes of 8% oxygen (PETO2 maintained at 50 mmHg) interspersed with room air. Following a ten-minute normoxic baseline, PETCO2 was maintained approximately 2 mmHg above baseline for the remainder of the protocol. Participants were exposed to this protocol for 15 days over a 3 week time period. Twenty-four hour blood pressure was measured using a Holter monitor programmed to measure blood pressure every 20 minutes starting at 6 AM. Microvascular function was assessed using a near infrared spectroscopy (NIRS) optode worn on the lateral gastrocnemius during a vascular occlusion test. These physiological measurements were obtained before and after 15 days of treatment, as well as, 4 and 8 weeks following treatment. Results: Age (45.22 ± 8.66 vs. 47.10 ± 9.48 years), BMI (31.59 ± 5.49 vs. 34.79 ± 4.57 kg/m2) and mean arterial pressure (105.00 ± 6.32 vs. 102.39 ± 6.52 mmHg) were similar at baseline prior to the start of the study. Similar to our previous findings, systolic (146.63 ± 8.00 mmHg vs. 132.67 ± 6.44 mmHg; p < 0.01) and diastolic (86.79 ± 6.83 mmHg vs. 80.98 ± 5.64 mmHg; p < 0.05) blood pressure was reduced immediately following treatment with MIH. This reduction was sustained for 4 and 8 weeks after treatment (p < 0.01 and p < 0.05 for all systolic and diastolic measurements respectively compared to baseline). This was not the case in the group treated with sham MIH. The maximal hyperemic response of oxygenated hemoglobin (HbO2) was significantly greater after treatment with MIH (127.06 ± 38.85% vs. 153.69 ± 31.51%; p < 0.01). Likewise, a reduction in blood pressure from pre-MIH to post-MIH was correlated with a reduction in time to maximal response of HbO2 standardized to hyperemic amplitude (p < 0.01; R2 = 0.754). Conclusions: Our results confirm that exposure to daily repeated MIH reduces blood pressure. In addition, we have shown that this reduction is sustained for up to 8 weeks. Likewise, our results suggest that improvements in microvascular function might contribute to the reduction in blood pressure along with improvement of mitochondrial utilization of oxygen. I01CX000125, IK6CX002287, R01HL142757, R56HL142757. This is the full abstract presented at the American Physiology Summit 2024 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.