title: Variability in preterm lamb lung mechanics after intra-amniotic endotoxin is associated with changes in surfactant pool size and morphometry.
abstract: Antenatal exposure to intra-amniotic (i.a.) endotoxin initiates a complex series of events, including an inflammatory cascade, increased surfactant production, and alterations to lung structure. Using the low frequency forced oscillation technique as a sensitive tool for measurement of respiratory impedance, we aimed to determine which factors contributed most to measured changes in lung mechanics. Respiratory impedance data obtained from sedated preterm lambs exposed to either i.a. injection with saline or 20 mg of endotoxin 1, 2, 4, and 15 days before delivery at 125 days gestation were studied, and association with indexes of standard lung morphometry, inflammatory response, and alveolar surfactant-saturated phosphatidylcholine (Sat PC) pool size was demonstrated. Reduction in tissue impedance with increasing interval between exposure and delivery was evident as early as 4 days after i.a. endotoxin injection, coinciding with resolution of inflammatory reaction, increased alveolar surfactant pools, and contribution of alveolar ducts to the parenchymal fraction, and a later decrease in the tissue component of the parenchymal fraction. Decreases in tissue damping (resistance) were more marked than decreases in tissue elastance. Log alveolar Sat PC accounted for most variability in tissue damping (88.9%) and tissue elastance (73.4%), whereas tissue fraction contributed 2 and 6.4%, respectively. The alveolar Sat PC pool size was the sole factor contributing to change in tissue hysteresivity. No changes were observed in airway resistance. Despite the complex cascade of events initiated by antenatal endotoxin exposure, variability in lung tissue mechanics is associated primarily with changes in alveolar Sat PC pool and lung morphology.
authors.affiliation: Centre for Child Health Research, The University of Western Australia, Perth, Australia. janep@ichr.uwa.edu.au
authors.forename: J Jane
authors.initials: JJ
authors.lastname: Pillow
authors.forename: Alan H
authors.initials: AH
authors.lastname: Jobe
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Collins
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Hantos
authors.forename: Machiko
authors.initials: M
authors.lastname: Ikegami
authors.forename: Timothy J M
authors.initials: TJ
authors.lastname: Moss
authors.forename: John P
authors.initials: JP
authors.lastname: Newnham
authors.forename: Karen E
authors.initials: KE
authors.lastname: Willet
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sly
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004731:Endotoxins / Q000494:pharmacology; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D016014:Linear Models; D008168:Lung / Q000473:pathology / Q000502:physiology*; D008170:Lung Compliance / Q000502:physiology; D011014:Pneumonia / Q000473:pathology / Q000503:physiopathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011663:Pulmonary Surfactants / Q000378:metabolism*; D015656:Respiratory Mechanics / Q000502:physiology*; D012756:Sheep
chemical_list: D004731:Endotoxins; D011663:Pulmonary Surfactants