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J Appl Physiol (1985). 2016 Sep 01;121(3):816-827. doi: 10.1152/japplphysiol.01094.2015. Epub 2016 Jul 14.

Lipopolysaccharide exposure during the early postnatal period adversely affects the structure and function of the developing rat carotid body.

Journal of applied physiology (Bethesda, Md. : 1985)

Zankhana R Master, Andrea Porzionato, Kalpashri Kesavan, Ariel Mason, Raul Chavez-Valdez, Machiko Shirahata, Estelle B Gauda

Affiliations

  1. Department of Pediatrics, Division of Neonatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland;
  2. Department of Molecular Medicine, University of Padova, Padova, Italy; and.
  3. Department of Environmental Health Sciences, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
  4. Department of Pediatrics, Division of Neonatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; [email protected].

PMID: 27418689 DOI: 10.1152/japplphysiol.01094.2015

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.

Copyright © 2016 the American Physiological Society.

Keywords: carotid body; intermittent hypoxia; lipopolysaccharide; mast cells; premature infants

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