title: Simulating obstructive sleep apnea patients' oxygenation characteristics into a mouse model of cyclical intermittent hypoxia.
abstract: Mouse models of cyclical intermittent hypoxia (CIH) are used to study the consequences of both hypoxia and oxidative stress in obstructive sleep apnea (OSA). Whether or not a mouse model of CIH that simulates OSA patients' oxygenation characteristics would translate into improved patient care remains unanswered. First we identified oxygenation characteristics using the desaturation and resaturation time in 47 OSA subjects from the Molecular Signatures of Obstructive Sleep Apnea Cohort (MSOSA). We observe that a cycle of intermittent hypoxia is not sinusoidal; specifically, desaturation time increases in an almost linear relationship to the degree of hypoxia (nadir), whereas resaturation time is somewhat constant (∼15 s), irrespective of the nadir. Second, we modified the Hycon mouse model of CIH to accommodate a 15-s resaturation time. Using this modified CIH model, we explored whether a short resaturation schedule (15 s), which includes the characteristics of OSA patients, had a different effect on levels of oxidative stress (i.e., urinary 8,12-iso-iPF2α-VI levels) compared with sham and a long resaturation schedule (90 s), a schedule that is not uncommon in rodent models of CIH. Results suggest that shorter resaturation time may result in a higher level of 8,12-iso-iPF2α-VI compared with long resaturation or sham conditions. Therefore, simulating the rodent model of CIH to reflect this and other OSA patients' oxygenation characteristics may be worthy of consideration to better understand the effects of hypoxia, oxidative stress, and their interactions.
authors.affiliation: Division of Sleep Medicine, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, Pennsylvania; limdiane@mail.med.upenn.edu.
authors.forename: Diane C
authors.identifier: http://orcid.org/0000-0001-5748-629X
authors.initials: DC
authors.lastname: Lim
authors.affiliation: Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, Pennsylvania;
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Brady
authors.affiliation: Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, Pennsylvania;
authors.forename: Pengse
authors.initials: P
authors.lastname: Po
authors.affiliation: Department of Thoracic Medicine and Department of Sleep Center, Chang Gung Memorial Hospital, Taipei, Taiwan and Graduate Institute of Clinical Medical Sciences, Chang Gung University, Tauyan, Taiwan; and.
authors.forename: Li Pang
authors.initials: LP
authors.lastname: Chuang
authors.affiliation: Superior School of Health Sciences, Brasilia, Brazil.
authors.forename: Laise
authors.initials: L
authors.lastname: Marcondes
authors.affiliation: Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, Pennsylvania;
authors.forename: Emily Y
authors.initials: EY
authors.lastname: Kim
authors.affiliation: Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, Pennsylvania;
authors.forename: Brendan T
authors.initials: BT
authors.lastname: Keenan
authors.affiliation: Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, Pennsylvania;
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Guo
authors.affiliation: Division of Sleep Medicine, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, Pennsylvania;
authors.forename: Greg
authors.initials: G
authors.lastname: Maislin
authors.affiliation: Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, Pennsylvania;
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Galante
authors.affiliation: Division of Sleep Medicine, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, Pennsylvania;
authors.forename: Allan I
authors.initials: AI
authors.lastname: Pack
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D012119:Respiration; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology*
keywords: 8,12-iso-iPF2α-VI; cyclical intermittent hypoxia; obstructive sleep apnea; oxidative stress