title: Myocardial response in preterm fetal sheep exposed to systemic endotoxinaemia.
abstract: Exposure of the fetus to antenatal inflammation can occur from chorioamnionitis, which may progress to a fetal inflammatory response syndrome (FIRS) and to fetal sepsis. We tested whether the fetal myocardium responded to systemic Gram-negative endotoxinaemia. We hypothesized that the myocardium would respond to inflammation by changes in hypoxia-inducible factor-α (HIF-1α), inducible NO-synthase (iNOS), Toll-like receptors 2 and 4 (TLR2 and TLR4), IL-6, and phosphorylated signal transducer and activator of transcription-3 (pSTAT3). To model systemic endotoxinaemia, fetal sheep were exposed to Gram-negative endotoxin or saline i.v. 3 d before preterm delivery at 113 d of gestation (term = 147 d). All endotoxin-exposed animals developed cardiac dysfunction within these 72 h. Cardiac mRNA and protein levels of HIF-1α and TLR2 and TLR4 mRNA increased, whereas STAT3 phosphorylation decreased significantly. IL-6 and iNOS mRNA remained unchanged. Fetal systemic endotoxinaemia induced myocardial inflammation by activating TLR2 and 4. The following cardiac dysfunction seems not to be mediated via cardiac iNOS.
authors.affiliation: Department of Paediatrics, Maastricht University Medical Center, Maastricht NL-6202, The Netherlands.
authors.forename: Matthias
authors.initials: M
authors.lastname: Seehase
authors.forename: Markus
authors.initials: M
authors.lastname: Gantert
authors.forename: Andreas
authors.initials: A
authors.lastname: Ladenburger
authors.forename: Yves
authors.initials: Y
authors.lastname: Garnier
authors.forename: Steffen
authors.initials: S
authors.lastname: Kunzmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Thomas
authors.forename: Johannes
authors.initials: J
authors.lastname: Wirbelauer
authors.forename: Christian P
authors.initials: CP
authors.lastname: Speer
authors.forename: Boris W
authors.initials: BW
authors.lastname: Kramer
mesh_terms: D000818:Animals; D004731:Endotoxins / Q000097:blood* / Q000276:immunology* / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000033:anatomy & histology / Q000187:drug effects* / Q000276:immunology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D012756:Sheep; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology
chemical_list: D004731:Endotoxins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015850:Interleukin-6; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D052247:Nitric Oxide Synthase Type II