title: The Ovine Fetal and Placental Inflammatory Response to Umbilical Cord Occlusions With Worsening Acidosis.
abstract: 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.
authors: Department of Obstetrics and Gynaecology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Canada Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Canada.
authors: Alex
authors: A
authors: Xu
authors: Department of Obstetrics and Gynaecology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Canada.
authors: Brad
authors: B
authors: Matushewski
authors: Department of Obstetrics and Gynaecology and Neurosciences, CHU Ste-Justine Research Centre, University of Montreal, Montreal, Canada.
authors: Mingju
authors: M
authors: Cao
authors: Department of Pathology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Canada.
authors: Robert
authors: R
authors: Hammond
authors: Department of Obstetrics and Gynaecology and Neurosciences, CHU Ste-Justine Research Centre, University of Montreal, Montreal, Canada.
authors: Martin G
authors: MG
authors: Frasch
authors: Department of Obstetrics and Gynaecology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Canada Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Canada brichar1@uwo.ca.
authors: Bryan S
authors: BS
authors: Richardson
mesh_terms: D000138:Acidosis / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D001424:Bacterial Infections / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005311:Fetal Hypoxia / Q000150:complications* / Q000276:immunology / Q000503:physiopathology; D006340:Heart Rate, Fetal; D006863:Hydrogen-Ion Concentration; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; 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 / Q000503:physiopathology / Q000601:surgery*
chemical_list: D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; C482199:lipopolysaccharide, E coli O55-B5
keywords: LPS; fetal–placental hypoxia; interleukin 1β; interleukin 6; macrophages; neutrophils