title: Alveolar formation is dysregulated by restricted nutrition but not excess sedation in preterm lambs managed by noninvasive support.
abstract: Preterm birth and respiratory support with invasive mechanical ventilation frequently leads to bronchopulmonary dysplasia (BPD). A hallmark feature of BPD is alveolar simplification. For our preterm lamb model of BPD, invasive mechanical ventilation is associated with postnatal feeding intolerance (reduced nutrition) and sedation. In contrast, preterm lambs managed by noninvasive support (NIS) have normal alveolar formation, appropriate postnatal nutrition, and require little sedation. We used the latter, positive-outcome group to discriminate the contribution of reduced nutrition vs. sedation on alveolar simplification. We hypothesized that, restricted nutrition, but not sedation with pentobarbital, contributes to impaired indices of alveolar formation in preterm lambs managed by NIS.
  
  
  
  Preterm lambs managed by NIS for 21d were randomized into three groups: NIS control, NIS plus restricted nutrition, and NIS plus excess sedation with pentobarbital. We quantified morphological and biochemical indices of alveolar formation, as well as mesenchymal cell apoptosis and proliferation.
  
  
  
  Restricted nutrition impaired morphological and biochemical indices of alveolar formation, and reduced mesenchymal cell apoptosis and proliferation. Excess sedation with pentobarbital did not alter these indices, although mesenchymal cell apoptosis was less.
  
  
  
  Our results demonstrate that restricted nutrition, but not excess sedation, contributes to impaired alveolar formation during the evolution of BPD in chronically ventilated preterm lambs.
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah.|Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Joss-Moore
authors.affiliation: Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah.
authors.forename: Synneva J
authors.initials: SJ
authors.lastname: Hagen-Lillevik
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Calan
authors.initials: C
authors.lastname: Yost
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jewell
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Wilkinson
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Sydney
authors.initials: S
authors.lastname: Bowen
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Mar Janna
authors.initials: MJ
authors.lastname: Dahl
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Li
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah.|Department of Internal Medicine, University of Utah, Salt Lake City, Utah.
authors.forename: Angela P
authors.initials: AP
authors.lastname: Presson
authors.affiliation: Department of Internal Medicine, University of Utah, Salt Lake City, Utah.
authors.forename: Chong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah.|Current address: Division of Neonatology, Department of Pediatrics, University of California at Davis, Sacramento, California.
authors.forename: Donald M
authors.initials: DM
authors.lastname: Null
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Yoder
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Kurt H
authors.initials: KH
authors.lastname: Albertine
mesh_terms: D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001997:Bronchopulmonary Dysplasia / Q000473:pathology*; D031204:Caloric Restriction; D049109:Cell Proliferation; D004032:Diet; D005260:Female; D005865:Gestational Age; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects; D008168:Lung / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D009752:Nutritional Status; D010424:Pentobarbital / Q000008:administration & dosage* / Q000009:adverse effects; D011650:Pulmonary Alveoli / Q000473:pathology*; D011897:Random Allocation; D012121:Respiration, Artificial / Q000009:adverse effects; D012756:Sheep; D034561:Sheep, Domestic; D013997:Time Factors
chemical_list: D006993:Hypnotics and Sedatives; D010424:Pentobarbital