Anne M Fink1, Irina Topchiy2, Michael Ragozzino3, Dionisio A Amodeo3, Jonathan A Waxman4, Miodrag G Radulovacki5, David W Carley2. 1. Center for Narcolepsy, Sleep and Health Research, College of Nursing, University of Illinois at Chicago, Chicago, IL ; Department of Biobehavioral Health Science, College of Nursing, University of Illinois at Chicago, Chicago, IL. 2. Center for Narcolepsy, Sleep and Health Research, College of Nursing, University of Illinois at Chicago, Chicago, IL ; Department of Biobehavioral Health Science, College of Nursing, University of Illinois at Chicago, Chicago, IL ; Department of Medicine, University of Illinois at Chicago, Chicago, IL. 3. Department of Psychology, University of Illinois at Chicago, Chicago, IL. 4. Center for Narcolepsy, Sleep and Health Research, College of Nursing, University of Illinois at Chicago, Chicago, IL ; Department of Bioengineering, University of Illinois at Chicago, Chicago, IL. 5. Center for Narcolepsy, Sleep and Health Research, College of Nursing, University of Illinois at Chicago, Chicago, IL ; Department of Pharmacology, University of Illinois at Chicago, Chicago, IL.
Abstract
STUDY OBJECTIVES: Circadian rhythms influence many biological systems, but there is limited information about circadian and diurnal variation in sleep related breathing disorder. We examined circadian and diurnal patterns in sleep apnea and ventilatory patterns in two rat strains, one with high sleep apnea propensity (Brown Norway [BN]) and the other with low sleep apnea propensity (Zucker Lean [ZL]). DESIGN/ SETTING: Chronically instrumented rats were randomized to breathe room air (control) or 100% oxygen (hyperoxia), and we performed 20-h polysomnography beginning at Zeitgeber time 4 (ZT 4; ZT 0 = lights on, ZT12 = lights off). We examined the effect of strain and inspired gas (twoway analysis of variance) and analyzed circadian and diurnal variability. MEASUREMENTS AND RESULTS: Strain and inspired gas-dependent differences in apnea index (AI; apneas/h) were particularly prominent during the light phase. AI in BN rats (control, 16.9 ± 0.9; hyperoxia, 34.0 ± 5.8) was greater than in ZL rats (control, 8.5 ± 1.0; hyperoxia, 15.4 ± 1.1, [strain effect, P < 0.001; gas effect, P = 0.001]). Hyperoxia reduced respiratory frequency in both strains, and all respiratory pattern variables demonstrated circadian variability. BN rats exposed to hyperoxia demonstrated the largest circadian fluctuation in AI (amplitude = 17.9 ± 3.7 apneas/h [strain effect, P = 0.01; gas effect, P < 0.001; interaction, P = 0.02]; acrophase = 13.9 ± 0.7 h; r (2) = 0.8 ± 1.4). CONCLUSIONS: Inherited, environmental, and circadian factors all are important elements of underlying sleep related breathing disorder. Our method to examine sleep related breathing disorder phenotypes in rats may have implications for understanding vulnerability for sleep related breathing disorder in humans.
STUDY OBJECTIVES: Circadian rhythms influence many biological systems, but there is limited information about circadian and diurnal variation in sleep related breathing disorder. We examined circadian and diurnal patterns in sleep apnea and ventilatory patterns in two rat strains, one with high sleep apnea propensity (Brown Norway [BN]) and the other with low sleep apnea propensity (Zucker Lean [ZL]). DESIGN/ SETTING: Chronically instrumented rats were randomized to breathe room air (control) or 100% oxygen (hyperoxia), and we performed 20-h polysomnography beginning at Zeitgeber time 4 (ZT 4; ZT 0 = lights on, ZT12 = lights off). We examined the effect of strain and inspired gas (twoway analysis of variance) and analyzed circadian and diurnal variability. MEASUREMENTS AND RESULTS: Strain and inspired gas-dependent differences in apnea index (AI; apneas/h) were particularly prominent during the light phase. AI in BN rats (control, 16.9 ± 0.9; hyperoxia, 34.0 ± 5.8) was greater than in ZL rats (control, 8.5 ± 1.0; hyperoxia, 15.4 ± 1.1, [strain effect, P < 0.001; gas effect, P = 0.001]). Hyperoxia reduced respiratory frequency in both strains, and all respiratory pattern variables demonstrated circadian variability. BN rats exposed to hyperoxia demonstrated the largest circadian fluctuation in AI (amplitude = 17.9 ± 3.7 apneas/h [strain effect, P = 0.01; gas effect, P < 0.001; interaction, P = 0.02]; acrophase = 13.9 ± 0.7 h; r (2) = 0.8 ± 1.4). CONCLUSIONS: Inherited, environmental, and circadian factors all are important elements of underlying sleep related breathing disorder. Our method to examine sleep related breathing disorder phenotypes in rats may have implications for understanding vulnerability for sleep related breathing disorder in humans.
Entities:
Keywords:
Brown Norway rat; Zucker Lean rat; sleep apnea; sleep related breathing disorder