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Am J Physiol Lung Cell Mol Physiol (November 14, 2003). doi:10.1152/ajplung.00211.2003
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Submitted on July 1, 2003
Accepted on November 11, 2003

Initial Responses to Ventilation of Premature Lambs Exposed to Intra-amniotic Endotoxin 4d before Delivery

Machiko Ikegami1*, Suhas G. Kallapur1, and Alan H. Jobe1

1 Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA

* To whom correspondence should be addressed. E-mail: machiko.ikegami{at}cchmc.org.

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. Escherichia coli 055:B5) given 4d prior to premature delivery at 130d gestation. Lung function and lung inflammation after surfactant treatment and 4h mechanical ventilation were evaluated. Inflammatory cell numbers in amniotic fluid were increased over 10 fold by antenatal endotoxin exposure. The antenatal endotoxin exposure had minimal effects on blood pressure, heart rates, lung compliance and blood gas values. The endotoxin exposed lungs required higher ventilation pressures. Ventilation did not increase the inflammatory cells or the protein in bronchoalveolar lavage fluid (BALF) of the endotoxin exposed animals above that measured in endotoxin-exposed fetuses that were not ventilated. IL-1{beta}, IL-6, IL-8 mRNA in cells from BALF were increased by antenatal endotoxin exposure but not changed by ventilation. IL-1{beta} and IL-8 protein were increased in lung tissue by 4h 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 in lungs that were inflamed as a result of exposure to intraamniotic endotoxin.




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