Document Detail

Intra-amniotic lipopolysaccharide leads to fetal cardiac dysfunction. A mouse model for fetal inflammatory response.
MedLine Citation:
PMID:  14522418     Owner:  NLM     Status:  MEDLINE    
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 V(mean) 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-1beta and tumor necrosis factor (TNF)-alpha 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.
Samuli Rounioja; Juha Räsänen; Virpi Glumoff; Marja Ojaniemi; Kaarin Mäkikallio; Mikko Hallman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cardiovascular research     Volume:  60     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-10-02     Completed Date:  2003-12-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  156-64     Citation Subset:  IM    
Department of Pediatrics and Biocenter Oulu, University of Oulu, P.O. Box 5000, FIN-90014, Oulu, Finland.
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MeSH Terms
Amniotic Fluid / immunology*
Blood Flow Velocity
Dose-Response Relationship, Drug
Echocardiography, Doppler
Extraembryonic Membranes / immunology
Fetal Diseases / immunology*
Interleukin-6 / analysis
Lipopolysaccharides / pharmacology
Membrane Glycoproteins / analysis
Mice, Inbred DBA
Models, Animal
Myocardial Contraction*
Placenta / immunology
Receptors, Cell Surface / analysis
Systemic Inflammatory Response Syndrome / embryology*,  immunology*
Toll-Like Receptor 4
Toll-Like Receptors
Tumor Necrosis Factor-alpha / analysis
Ultrasonography, Prenatal
Reg. No./Substance:
0/Interleukin-6; 0/Lipopolysaccharides; 0/Membrane Glycoproteins; 0/Receptors, Cell Surface; 0/Toll-Like Receptor 4; 0/Toll-Like Receptors; 0/Tumor Necrosis Factor-alpha

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