Myocardial Response in Preterm Fetal Sheep Exposed to Systemic Endotoxinaemia

Matthias Seehase, Markus Gantert, Andreas Ladenburger, Yves Garnier, Steffen Kunzmann, Wolfgang Thomas, Johannes Wirbelauer, Christian P. Speer, Boris W. Kramer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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-a (HIF-1 alpha), 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 iv. 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-1 alpha 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. (Pediatr Res 70: 242-246, 2011)
Original languageEnglish
Pages (from-to)242-246
JournalPediatric Research
Issue number3
Publication statusPublished - Sept 2011

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