title: Poloxamer 188 facilitates the repair of alveolus resident cells in ventilator-injured lungs.
abstract: BACKGROUND
  Wounded alveolus resident cells are identified in human and experimental acute respiratory distress syndrome models. Poloxamer 188 (P188) is an amphiphilic macromolecule shown to have plasma membrane-sealing properties in various cell types.
  
  
  OBJECTIVE
  To investigate whether P188 (1) protects alveolus resident cells from necrosis and (2) is associated with reduced ventilator-induced lung injury in live rats, isolated perfused rat lungs, and scratch and stretch-wounded alveolar epithelial cells.
  
  
  METHODS
  Seventy-four live rats and 18 isolated perfused rat lungs were ventilated with injurious or protective strategies while infused with P188 or control solution. Alveolar epithelial cell monolayers were subjected to scratch or stretch wounding in the presence or absence of P188.
  
  
  RESULTS
  P188 was associated with fewer mortally wounded alveolar cells in live rats and isolated perfused lungs. In vitro, P188 reduced the number of injured and necrotic cells, suggesting that P188 promotes cell repair and renders plasma membranes more resilient to deforming stress. The enhanced cell survival was accompanied by improvement in conventional measures of lung injury (peak airway pressure, wet-to-dry weight ratio) only in the ex vivo-perfused lung preparation and not in the live animal model.
  
  
  CONCLUSIONS
  P188 facilitates plasma membrane repair in alveolus resident cells, but has no salutary effects on lung mechanics or vascular barrier properties in live animals. This discordance may have pathophysiological significance for the interdependence of different injury mechanisms and therapeutic implications regarding the benefits of prolonging the life of stress-activated cells.
authors.affiliation: Thoracic Diseases Research Unit, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Plataki
authors.forename: Yang D
authors.initials: YD
authors.lastname: Lee
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Rasmussen
authors.forename: Rolf D
authors.initials: RD
authors.lastname: Hubmayr
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002462:Cell Membrane / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007320:Inspiratory Capacity; D008168:Lung / Q000187:drug effects / Q000473:pathology; D018613:Microscopy, Confocal; D009336:Necrosis; D020442:Poloxamer / Q000494:pharmacology / Q000627:therapeutic use*; D011663:Pulmonary Surfactants / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D055397:Ventilator-Induced Lung Injury / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*
chemical_list: D011663:Pulmonary Surfactants; D020442:Poloxamer