title: Initial responses to ventilation of premature lambs exposed to intra-amniotic endotoxin 4 days before delivery.
abstract: Preterm delivery is frequently preceded by chorioamnionitis, resulting in exposure of the fetal lung to inflammation. We hypothesized that ventilation of the antenatally inflamed lung would result in amplification of the lung injury. Therefore, we induced fetal lung inflammation with intra-amniotic endotoxin (10 mg of Escherichia coli 055:B5) 4 days before premature delivery at 130 days of gestation. Lung function and lung inflammation after surfactant treatment and 4 h of mechanical ventilation were evaluated. Inflammatory cell numbers in amniotic fluid were increased >10-fold by antenatal endotoxin exposure. Antenatal endotoxin exposure had minimal effects on blood pressure, heart rate, lung compliance, and blood gas values. The endotoxin-exposed lungs required higher ventilation pressures. Ventilation did not increase the number of inflammatory cells or the protein in bronchoalveolar lavage fluid of the endotoxin-exposed animals above that measured in endotoxin-exposed fetuses that were not ventilated. IL-1beta, IL-6, and IL-8 mRNA in cells from bronchoalveolar lavage fluid were increased by antenatal endotoxin exposure but not changed by ventilation. IL-1beta and IL-8 protein was increased in lung tissue by 4 h of ventilation. Very little inflammation was induced by ventilation in this premature lamb model of surfactant treatment and gentle ventilation. After lung inflammation was induced by intra-amniotic endotoxin injection, ventilation did not increase lung injury.
authors: Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA. machiko.Ikegami@cchmc.org
authors: Machiko
authors: M
authors: Ikegami
authors: Suhas G
authors: SG
authors: Kallapur
authors: Alan H
authors: AH
authors: Jobe
mesh_terms: D000818:Animals; D015415:Biomarkers; D001724:Birth Weight; D001997:Bronchopulmonary Dysplasia / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D002821:Chorioamnionitis / Q000276:immunology / Q000503:physiopathology*; D004731:Endotoxins / Q000494:pharmacology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007752:Obstetric Labor, Premature; D011014:Pneumonia / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D012121:Respiration, Artificial; D012756:Sheep
chemical_list: D015415:Biomarkers; D004731:Endotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger