Myocardial response in preterm fetal sheep exposed to systemic endotoxinaemia.

Exposure of the fetus to antenatal inflammation can occur from chorioamnionitis, which may progress to a fetal inflam- matory 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 re- spond to inflammation by changes in hypoxia-inducible factor- (HIF-1), 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 endotoxi- naemia, 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 dysfunc- tion within these 72 h. Cardiac mRNA and protein levels of HIF-1 and TLR2 and TLR4 mRNA increased, whereas STAT3 phosphor- ylation decreased significantly. IL-6 and iNOS mRNA remained unchanged. Fetal systemic endotoxinaemia induced myocardial in- flammation by activating TLR2 and 4. The following cardiac dys- function seems not to be mediated via cardiac iNOS. (Pediatr Res 70: 242-246, 2011)