title: Lipopolysaccharide exposure during the early postnatal period adversely affects the structure and function of the developing rat carotid body.
abstract: The carotid body (CB) substantially influences breathing in premature infants by affecting the frequency of apnea and periodic breathing. In adult animals, inflammation alters the structure and chemosensitivity of the CB, yet it is not known if this pertains to neonates. We hypothesized that early postnatal inflammation leads to morphological and functional changes in the developing rat CB, which persists for 1 wk after the initial provoking insult. To test our hypothesis, we exposed rat pups at postnatal day 2 (P2) to lipopolysaccharide (LPS; 100 μg/kg) or saline (SAL) intraperitoneally. At P9-10 (1 wk after treatment), LPS-exposed animals had significantly more spontaneous intermittent hypoxic (IH) events, attenuated ventilatory responses to changes in oxygen tension (measured by whole body plethysmography), and attenuated hypoxic chemosensitivity of the carotid sinus nerve (measured in vitro), compared with SAL-exposed controls. These functional changes were associated with the following: 1) increased inflammatory cytokine mRNA levels; 2) decreased volume of supportive type II cells; and 3) elevated dopamine levels (a major inhibitory neuromodulator) within the CB. These findings suggest that early postnatal inflammation in newborn rats adversely affects the structure and function of the CB and is associated with increased frequency of intermittent desaturations, similar to the phenomenon observed in premature infants. Furthermore, this is the first newborn model of spontaneous intermittent desaturations that may be used to understand the mechanisms contributing to IH events in newborns.
authors.affiliation: Department of Pediatrics, Division of Neonatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland;
authors.forename: Zankhana R
authors.initials: ZR
authors.lastname: Master
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy; and.
authors.forename: Andrea
authors.initials: A
authors.lastname: Porzionato
authors.affiliation: Department of Pediatrics, Division of Neonatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland;
authors.forename: Kalpashri
authors.initials: K
authors.lastname: Kesavan
authors.affiliation: Department of Pediatrics, Division of Neonatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland;
authors.forename: Ariel
authors.initials: A
authors.lastname: Mason
authors.affiliation: Department of Pediatrics, Division of Neonatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland;
authors.forename: Raul
authors.initials: R
authors.lastname: Chavez-Valdez
authors.affiliation: Department of Environmental Health Sciences, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Machiko
authors.initials: M
authors.lastname: Shirahata
authors.affiliation: Department of Pediatrics, Division of Neonatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; egauda@jhmi.edu.
authors.forename: Estelle B
authors.initials: EB
authors.lastname: Gauda
keywords: carotid body; intermittent hypoxia; lipopolysaccharide; mast cells; premature infants