0281 Mortality and Cardiovascular Changes in a Murine Model of OSA: Aging and 22 Months of Intermittent Hypoxia

Abstract Introduction Obstructive sleep apnea (OSA) is a prevalent condition marked by intermittent hypoxia (IH), which significantly elevates the risk of cardiovascular disease (CVD) and overall mortality. Furthermore, aging is a widely acknowledged risk factor for the onset and progression of CVD. In this pioneering study, we aim to elucidate the interplay between 22 months of IH exposures and age-related factors by delineating their combined influence on a spectrum of cardiovascular parameters. Methods Male C57Bl/6J mice (n=19-23) were exposed to IH (cycles of FiO2 21% 90 s-6% 90s or room air (RA; 21%) for 12 hours/day during the light period) for 22 months. Mean arterial blood pressure (MBP) was assessed using tail-cuff method, while aortic peak velocity (indicator of systolic function), E/A ratio (indicator of diastolic function), coronary flow velocity reserve (CFVR), and pulse wave velocity (PWV) were assessed using Doppler Flow Velocity System. Then, left anterior descending coronary arteries were excised, mounted on wire myographs, and used to obtain vascular relaxation dose-response curves to acetylcholine (ACh). Results The mortality rate in IH-exposed mice was 26% versus 0% in RA-exposed mice. Compared to young (8 weeks old) RA mice, MBP was elevated in old RA mice (p 0.05) and further elevated in surviving IH mice (p 0.0001). Similarly, diastolic function was impaired in old RA mice (p 0.001) and further compromised in old IH mice (p 0.0001). Moreover, systolic function was preserved in old RA mice but impaired in old IH mice vs. old and young RA (p 0.0001). Similarly, CFVR was only impaired in old IH mice (p 0.0001). Interestingly, PWV was higher in old RA vs. young RA (p 0.001), but significantly lower in old IH mice vs. young and old RA (p 0.001). Coronary maximal ACh-induced vasodilation was significantly impaired in both old RA (52 ± 9%) and IH-exposed mice (47 ± 9%) when compared to young RA mice (86 ± 4%, p 0.0001). Conclusion Prolonged exposure to IH simulating OSA results in elevated mortality rates and imposes substantial cardiovascular disturbances in surviving mice when contrasted with normal aging. Support (if any) NIH grant R01-HL166617