The effects of moderate hypoxia on circadian rhythm: implications in disease and treatment options (710.1)

Abstract

Impairments in O2 delivery are a common feature of many chronic diseases (e.g., COPD, diabetes, and anemia). It reduces quality of life and increases morbidity, mortality and hospitalizations in patients. Circadian rhythms in mammals, including humans, are essential to health whereas disruptions exacerbate disease pathogenesis. While severe hypoxia can abolish circadian rhythm, moderate hypoxia is more clinically relevant but its effects on circadian rhythm are unknown. Our objective was to investigate the effects of moderate hypoxia on circadian rhythm. Methods: Mice were implanted with telemetry devices to measure heart rate (HR) and body temperature (Tb). Baseline measurements were obtained and animals subjected to 24 hours of moderate hypoxia (O2 = 15%) followed by 24 hours of normoxic recovery. Results: Moderate hypoxia disrupted, but did not abolish, the circadian rhythm of HR and Tb. Amplitude of circadian rhythm for HR was altered during both sleep and active states whereas Tb amplitude was altered only during sleep. Importantly, these disruptions persisted following 24 hours of normoxic recovery. Conclusions: A single 24 hour exposure of moderate hypoxia is sufficient to alter HR and Tb circadian rhythm, which does not recover within 24 hours of reoxygenation. This suggests that moderate hypoxia may have a critical role in disease pathogenesis. Grant Funding Source: Supported by Canadian Institute of Health Research