Objective: Intrauterine infection is associated with increased lipopolysaccharide (LPS) and proinflammatory cytokines in amniotic fluid. We hypothesized that intra-amniotic LPS launches a fetal inflammatory response leading to cardiac dysfunction. Methods: A mouse model was established. At 15-16 days of gestation, 52 fetuses of nine dams received LPS and 46 fetuses of nine dams vehicle intra-amniotically. Five dams underwent a sham operation. Echocardiography was performed before and 6 h after the injection to obtain inflow and outflow blood velocity waveforms. Outflow mean velocity (V mean) and the proportions of isovolumetric relaxation (IRT%) and contraction (ICT%) times of the cardiac cycle were calculated. Pulsatility indices (PI) were calculated from the umbilical and intracranial arteries and the descending aorta. Pulsatility indices for veins (PIV) were obtained from ductus venosus. Toll-like receptor-4 (TLR4) and several other inflammatory mediators were determined using ELISA, immunohistochemistry, or ribonuclease protection assay. Results: In the LPS group, outflow Vmean was significantly lower, and ICT% and IRT% longer than in the other groups. LPS increased PIs, except in the intracranial arteries, which showed a decrease in PIs. In ductus venosus, PIVs were increased after LPS. LPS increased interleukin (IL)-6 in amniotic fluid and induced the expression of proinflammatory cytokines in placenta and fetal membranes, but not in lung. In fetal myocardium, TLR4 was constitutional. LPS induced the expression of IL-1β and tumor necrosis factor (TNF)-α mRNA in myocardium, whereas inducible nitric oxide synthase (NOS2) protein and nitrotyrosine remained undetectable. Conclusions: As a response to endotoxin in amniotic fluid, fetal myocardium acutely generates cytokines and severe fetal cardiovascular compromise develops. These two may be linked through a mechanism that does not include NO.
- Contractile function
- Infection/ inflammation
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)