0097 Cardiovascular Effects of Long-Term Sleep Fragmentation in Mice

Abstract Introduction Sleep Fragmentation (SF) is a prevalent phenomenon and also a pathognomonic feature of obstructive sleep apnea (OSA). SF is associated with OSA-related morbidities. However, it remains unclear whether prolonged SF exposures contribute to the development of specific cardiovascular morbidities in OSA. In this study, we postulate that chronic SF may induce structural and functional changes in the cardiac and vascular systems. Methods Male C57Bl/6J mice (n=8) were housed in custom-designed cages with a near-silent motorized mechanical sweeper crossing the cage in 2-min intervals or sleep control (SC, sweeper inactive) for 12 hours during the light period for 12 weeks. 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 and thoracic aorta were excised, mounted on wire myographs, and used to obtain endothelium-dependent relaxation dose-response curves to acetylcholine (ACh) Results MBP was significantly elevated in SF mice (107 ± 7 mmHg) after 12 weeks when compared to SC (89 ± 5 mmHg, p < 0.0001). Systolic and diastolic function, and CFVR were not affected by the 12 weeks of SF exposure. However, SF mice had higher PWV (4.3 ± 0.6 mm/msec) when compared to SC mice (3.1 ± 0.2 mm/msec). Coronary maximal ACh-induced vasodilation was impaired in SF mice (67 ± 9%) when compared to SC (86 ± 5%, p < 0.001). Aortic maximal ACh-induced vasodilation was not affected by 12 weeks of SF. Conclusion long-term SF, a hallmark characteristic of OSA, promotes cardiovascular perturbations including coronary artery dysfunction and arterial stiffness, thereby supporting a role for sleep fragmentation in the cardiovascular morbidity of OSA. Support (if any) Supported by NIH grant R01-HL166617