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Suppression of breathing by Gram‐positive bacterial proteins in neonatal Sprague Dawley rat pups
Author(s) -
Dias Casacao Maria,
O'Connor Karen,
Dempsey Gene,
O'Halloran Ken,
McDonald Fiona
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02945
Subject(s) - ventilation (architecture) , medicine , respiratory system , bradycardia , hypoxia (environmental) , hyperoxia , corticosterone , anesthesia , endocrinology , physiology , immunology , lung , heart rate , oxygen , chemistry , blood pressure , hormone , mechanical engineering , organic chemistry , engineering
Preterm infants regularly present with immature and unstable respiratory control networks at birth leading to oxygen dysregulation in the newborn (Hofstetter et al., 2007). Sequentially, the requirement for prolonged medical support and hospital stays increases the risk of late‐onset infection. Hypoxic stress during early life can alter central networks that control the cardiorespiratory system with profound autonomic dysregulation. We hypothesised that chronic neonatal exposure to intermittent hypoxia and hyperoxia (cIHH) with subsequent Gram‐positive bacterial infection alters respiratory control. On postnatal day (PND) three, Sprague Dawley litters were exposed for 10 days to either cIHH or room air gas exposure. On PND13, pups were studied using whole body plethysmography at 30 ◦ C. After an initial acclimatisation period, a baseline normoxic measurement was taken. Following intraperitoneal administration of lipoteichoic acid and peptidoglycan (LTA+PGN) or pyro‐free saline (n=10 per group), animals were monitored for 3 hours under normoxic conditions. Oxygen dysregulation in early life in and of itself, did not alter breathing frequency (P=0.37) or minute ventilation (P=0.07). Administration of LTA+PGN suppressed breathing as shown by a decrease in frequency and minute ventilation (both P<0.05). Furthermore, administration of LTA+PGN on PND13 increased cytokine expression in both sexes as well as corticosterone concentration in male pups compared to relevant controls. Administration of LTA+PGN did not significantly alter rectal temperature compared to controls. Neonatal infection remains a significant challenge, with a paucity of studies investigating the response to Gram‐positive bacterial proteins despite its clinical relevance. We report that Gram‐positive bacterial proteins can quickly suppress breathing frequency and elicit both an inflammatory and stress response. Further studies are necessary to elucidate the mechanisms underlying aberrant respiratory control. References Hofstetter AO, Legnevall L & Ericherleniuskise EH (2007). Cardiorespiratory development in extremely preterm infants: vulnerability to infection and persistence of events beyond term‐equivalent age. 285–292.