title: Perinatal hyperoxic exposure reconfigures the central respiratory network contributing to intolerance to anoxia in newborn rat pups.
abstract: Perinatal exposure to hyperoxia (30-60% O2) alters the respiratory control system via modulation of peripheral arterial chemoreceptor development and function. Furthermore, hyperoxic exposure during the first two postnatal weeks of life can alternatively modulate the different phases of the hypoxic ventilatory response. Given the effects of perinatal hyperoxia, the aims of our study were 1) to determine the effect on survival time in response to lethal anoxic stimuli in rat pups and 2) to characterize the output of the isolated central respiratory network in response to acute hypoxic stimuli. We hypothesized that perinatal hyperoxic exposure would modify the neonatal rat ventilatory response to anoxia by affecting a central component of the respiratory network in addition to the maturation of the carotid body chemoreceptors. We found that animals continuously exposed to 60% oxygen up to age 5 days after parturition (P5) have reduced breathing frequency at baseline and within the first 10 min of a fatal anoxic challenge. Hyperoxic rat pups also have a shortened time to last gasp in response to anoxia that is not associated with lung injury or inflammation. This study is the first to demonstrate that these in vivo findings correlate with reduced phrenic burst frequency from the isolated brainstem ex vivo. Thus hyperoxic exposure reduced the phrenic burst frequency at baseline and in response to ex vivo anoxia. Importantly, our data suggest that perinatal hyperoxia alters ventilation and the response to anoxia at P5 in part by altering the frequency of phrenic bursts generated by the central respiratory network.
authors.affiliation: Department of Pediatrics, Neonatology Research Laboratories, Johns Hopkins Medical Institutions, Baltimore, Maryland;
authors.forename: Alexis M
authors.initials: AM
authors.lastname: Bierman
authors.forename: Clarke G
authors.initials: CG
authors.lastname: Tankersley
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Wilson
authors.forename: Raul
authors.initials: R
authors.lastname: Chavez-Valdez
authors.forename: Estelle B
authors.initials: EB
authors.lastname: Gauda
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002344:Carotid Body / Q000378:metabolism / Q000503:physiopathology; D002490:Central Nervous System / Q000378:metabolism / Q000503:physiopathology*; D002628:Chemoreceptor Cells / Q000378:metabolism / Q000502:physiology; D004558:Electric Stimulation; D018496:Hyperoxia / Q000378:metabolism / Q000503:physiopathology*; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D010100:Oxygen / Q000378:metabolism; D010791:Phrenic Nerve / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration; D012137:Respiratory System / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D010100:Oxygen
keywords: anoxic exposure; brainstem-spinal cord preparation; chemoafferent input; hypoxic ventilatory response; perinatal hyperoxia