The Ovine Fetal and Placental Inflammatory Response to Umbilical Cord Occlusions With Worsening Acidosis.
We hypothesized that repetitive umbilical cord occlusions (UCOs) leading to severe acidemia will stimulate a placental and thereby fetal inflammatory response which will be exacerbated by chronic hypoxemia and low-grade bacterial infection. Chronically instrumented fetal sheep served as controls or underwent repetitive UCOs for up to 4 hours or until fetal arterial pH was <7.00. Normoxic-UCO and hypoxic-UCO fetuses had arterial O2 saturation pre-UCOs of >55% and <55%, respectively, while lipopolysaccharide (LPS)-UCO fetuses received LPS intra-amniotic (2 mg/h) starting 1 hour pre-UCOs. Fetal plasma and amniotic fluid were sampled for interleukin (IL) 6 and IL-1β. Animals were euthanized at 48 hours of recovery with placental cotyledons processed for measurement of macrophage, neutrophil, and mast cell counts. Repetitive UCOs resulted in severe fetal acidemia with pH approaching 7.00 for all 3 UCO groups. Neutrophils, while unchanged within the cotyledon fetal and intermediate zones, were ∼2-fold higher within the zona intima for all 3 UCO groups. However, no differences were observed in macrophage counts among the treatment groups and no cotyledon mast cells were seen. Fetal plasma and amniotic fluid cytokines remained little changed post-UCOs and/or at 1 and 48 hours of recovery in the normoxic-UCO and hypoxic-UCO groups but increased several fold in the LPS-UCO group with IL-6 plasma values at 1 hour recovery highly correlated with the nadir pH attained (r = -.97). As such, repetitive UCOs with severe acidemia can induce a placental inflammatory response and more so with simulated low-grade infection and likely contributing to cytokine release in the umbilical circulation.
['Xu|Alex|A|', 'Matushewski|Brad|B|', 'Cao|Mingju|M|', 'Hammond|Robert|R|', 'Frasch|Martin G|MG|', 'Richardson|Bryan S|BS|']
D000138:Acidosis D000653:Amniotic Fluid D000818:Animals D001424:Bacterial Infections D004195:Disease Models, Animal D005260:Female D005312:Fetal Blood D005311:Fetal Hypoxia D006340:Heart Rate, Fetal D006863:Hydrogen-Ion Concentration D018836:Inflammation Mediators D053583:Interleukin-1beta D015850:Interleukin-6 D008026:Ligation D008070:Lipopolysaccharides D020556:Neutrophil Infiltration D021041:Placental Circulation D011247:Pregnancy D012720:Severity of Illness Index D012756:Sheep D013997:Time Factors D014470:Umbilical Cord
LPS macrophages neutrophils fetal–placental hypoxia interleukin 1β interleukin 6