title: Hypoxia-hyperoxia paradigms in the development of oxygen-induced retinopathy in a rat pup model.
abstract: BACKGROUND
  Retinopathy of prematurity [ROP] continues to be a significant clinical problem in preterm infants. There is a need for animal models to better understand the roles of hypoxia/hyperoxia in the pathogenesis and management of ROP.
  
  
  OBJECTIVE
  To test the hypothesis that multiple daily cycles of intermittent hypoxia, followed by brief hyperoxia, would provide a clinically relevant protocol for generation of ROP in a rat pup.
  
  
  METHODS
  Rat pups were exposed for the first 14 days to one of three protocols: room air [RA], sustained cycles of hyperoxia/hypoxia [SHH] as previously employed to produce ROP in rat pups, and intermittent hypoxia/hyperoxia [IHH] in order to more closely simulate clinical conditions in preterm infants. Retinae were obtained at 18 days and imaged for both avascularization and neovascularization.
  
  
  RESULTS
  As expected, the SHH group demonstrated significantly increased avascularity [40.9 ± 7.9% of retina] which was minimal in both RA and IHH groups. All SHH exposed pups exhibited neovascularization which occurred in 5/7 IHH exposed retinae versus 0 in the RA group [p = 0.02]. However, mean number of clock hours of neovascularization after IHH was 1.9 ± 2.1 which did not differ from the RA group, and was less than in the SHH group [8.3 ± 1.9, p < 0.001].
  
  
  CONCLUSIONS
  A more clinically relevant intermittent hypoxia/hyperoxia [IHH] protocol does not produce the same degree of ROP as the traditional sustained hypoxia/hyperoxia [SHH] paradigm. Nonetheless, further refinement of our model may provide a suitable model for understanding the lesser degrees of ROP which predominate in preterm infants.
authors.affiliation: All Children's Hospital, St. Petersburg, FL, USA.
authors.forename: O G
authors.initials: OG
authors.lastname: Winners-Mendizabal
authors.affiliation: Rainbow Babies & Children's Hospital, Cleveland, OH, USA Case Western Reserve University, Cleveland, OH, USA.
authors.forename: F H
authors.initials: FH
authors.lastname: Orge
authors.affiliation: Case Western Reserve University, Cleveland, OH, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Di Fiore
authors.affiliation: Rainbow Babies & Children's Hospital, Cleveland, OH, USA Case Western Reserve University, Cleveland, OH, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Martin
authors.affiliation: Case Western Reserve University, Cleveland, OH, USA.
authors.forename: P
authors.initials: P
authors.lastname: Kc
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D019084:Fluorescent Antibody Technique, Indirect; D018496:Hyperoxia / Q000473:pathology*; D000860:Hypoxia / Q000473:pathology*; D009389:Neovascularization, Pathologic; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000473:pathology*; D012178:Retinopathy of Prematurity / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A
chemical_list: D042461:Vascular Endothelial Growth Factor A; D010100:Oxygen
keywords: Intermittent hypoxia-hyperoxia; retinopathy of prematurity; rodent model