title: Vulnerability of neonatal respiratory neural control to sustained hypoxia during a uniquely sensitive window of development.
abstract: The first postnatal weeks represent a period of development in the rat during which the respiratory neural control system may be vulnerable to aberrant environmental stressors. In the present study, we investigated whether sustained hypoxia (SH; 11% O2) exposure starting at different postnatal ages differentially modifies the acute hypoxic (HVR) and hypercapnic ventilatory response (HCVR). Three different groups of rat pups were exposed to 5 days of SH, starting at either postnatal age 1 (SH1-5), 11 (SH11-15), or 21 (SH21-25) days. Whole body plethysmography was used to assess the HVR and HCVR the day after SH exposure ended. The primary results indicated that 1) the HVR and HCVR of SH11-15 rats were absent or attenuated (respectively) compared with age-matched rats raised in normoxia; 2) there was a profoundly high (∼84% of pups) incidence of unexplained mortality in the SH11-15 rats; and 3) these phenomena were unique to the SH11-15 group with no comparable effect of the SH exposure on the HVR, HCVR, or mortality in the younger (SH1-5) or older (SH21-25) rats. These results share several commonalities with the risk factors thought to underlie the etiology of sudden infant death syndrome, including 1) a vulnerable neonate; 2) a critical period of development; and 3) an environmental stressor.
authors.affiliation: Department of Pediatrics, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, Ohio.
authors.forename: C A
authors.initials: CA
authors.lastname: Mayer
authors.forename: J M
authors.initials: JM
authors.lastname: Di Fiore
authors.forename: R J
authors.initials: RJ
authors.lastname: Martin
authors.forename: P M
authors.initials: PM
authors.lastname: Macfarlane
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000401:mortality / Q000503:physiopathology*; D001835:Body Weight / Q000502:physiology; D002245:Carbon Dioxide / Q000378:metabolism; D006801:Humans; D006935:Hypercapnia / Q000503:physiopathology; D007223:Infant; D008297:Male; D008660:Metabolism / Q000502:physiology; D010101:Oxygen Consumption; D010991:Plethysmography; D051381:Rats; D011917:Rats, Inbred Lew; D015656:Respiratory Mechanics / Q000502:physiology*; D013398:Sudden Infant Death; D013990:Tidal Volume / Q000502:physiology
chemical_list: D002245:Carbon Dioxide
keywords: SIDS; development; hypoxia; respiratory control