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Effects of Intra-Amniotic Endotoxin on Lung Structure and Function Two Months After Term Birth in Sheep

School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, and Department of Physiology, Monash University, Clayton, Victoria, Australia; Lotteries Commission Perinatal Research Laboratories, School of Women's and Infants' Health, The University of Western Australia, 35 Stirling Highway, Crawley WA Australia 6009 tmoss{at}cyllene.uwa.edu.au

Marcus G. Davey, PhD

Richard Harding, DSc

John P. Newnham, MD

School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, and Department of Physiology, Monash University, Clayton, Victoria, Australia

Objective: Intra-amniotic endotoxin causes chorioamnionitis and results in improved lung function after preterm delivery in sheep. Our aim was to determine the effects on lung structure and function after term birth in lambs exposed to intra-amniotic or intra-allantoic endotoxin.

Methods: At 119 days' gestation, pregnant ewes bearing singleton fetuses received intra-amniotic or intra-allantoic injections of either saline (allantoic, n = 1; amniotic, n = 10) or Escherichia coli (055:B5) endoxin (allantoic, n = 5; amniotic, n = 7). Amniotic or allantoic fluid was aspirated for white blood cell counts 24 hours after the injections. Ewes (n = 20) were allowed to deliver spontaneously. At 8 weeks' postnatal age we measured ventilation, lung volumes, and compliance in the offsprig and collected their lungs for morphologic analysis.

Results: Higher amniotic or allantoic cell counts were confined to the fluid space into which endotoxin was injected. Saline injections did not increase amniotic or allantoic white blood cell counts. Gestation length, birth weight, and postnatal growth were unaffected by endotoxin treatments. Lung volumes and compliances at 8 weeks of age were not different between saline-treated and endotoxin-treated groups. Lung morphometry was not significantly altered by endotoxin, with one minor exception. interlobular septal volume was increased by intra-amniotic endotoxin, but this effect had no functional consequences.

Conclusions: Intra-amniotic or intra-allantoic endotoxin caused a localized inflammatory response but did not cause preterm delivery or intrauterine growth restriction. The functional improvements and corresponding structural alterations in the lungs of preterm lambs, reported previously in this model, were not associated with improved or impaired long function or marked alterations in lung structure 2 months after birth at term.

Key Words: Fetus • inflammation • bronchopulmonary dysplasia • lung development

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