title: Fat embolism sensitizes rats to a "second hit" with lipopolysaccharide: An animal model of pulmonary fibrosis.
abstract: BACKGROUND
  Pulmonary fat embolism (FE) in patients after major bone fracture and other trauma may lead to acute respiratory distress, but few clinical evidence of lung injury remains, and there is a dearth of histopathologic information after the initial recovery. We recently reported histologic changes in the lungs of a patient who died after cesarian delivery, which were similar to a rat model of FE. In this model, we found that despite an apparent full recovery, modest fibrotic damage persisted up to 6 weeks. We tested whether at that time, an additional insult could exacerbate the effects.
  
  
  METHODS
  Triolein (0.2 mL intravenously administered) was given to 18 rats and saline to 18 controls. Six weeks later, each group received (intraperitoneal) lipopolysaccharide (LPS, 3 mg/kg; n = 9) or saline (n = 9). At necropsy 48 hours later, lungs and organs were harvested for study. Lung parenchymal, vascular, and bronchial damage was scored by two pathologists and by Image J analysis.
  
  
  RESULTS
  Animals given LPS after triolein showed reduced pulmonary arterial medial diameters compared with those that received LPS alone (p < 0.04). Lung small arterial patency (lumen) was reduced after triolein and even more after combined LPS and triolein (p = 0.018). Triolein increased fibrotic markers (trichrome and smooth muscle actin staining), and this was more severe after LPS. At 6 weeks, fat droplets remained in the lungs, localizing to the subpleural septa. These were smaller and more widespread after LPS.
  
  
  CONCLUSIONS
  This report describes an animal model to study exacerbation of lung histopathology induced by FE using a known pulmonary toxicant, LPS (a "second hit"). Vascular and fibrotic lung damage was more severe when LPS was given to rats 6 weeks after triolein compared with LPS alone. FE rendered the lungs extra sensitive to a second hit long after apparent clinical recovery. This experimental model of fat embolism provides useful informations for the treatment of patients suffering for similar conditions.
authors.affiliation: From the School of Medicine (A.P.), University of Kansas, Kansas City, Kansas; School of Medicine (B.H., A.L., S.K., K.L., A.M.), University of Missouri, Kansas City, Missouri; and University of California at San Francisco (A.A.H.), San Francisco, California.
authors.forename: Alan
authors.initials: A
authors.lastname: Poisner
authors.forename: Betty
authors.initials: B
authors.lastname: Herndon
authors.forename: Kamani
authors.initials: K
authors.lastname: Lankachandra
authors.forename: Alisa
authors.initials: A
authors.lastname: Likhitsup
authors.forename: Ahmad
authors.initials: A
authors.lastname: Al Hariri
authors.forename: Susamita
authors.initials: S
authors.lastname: Kesh
authors.forename: Agostino
authors.initials: A
authors.lastname: Molteni
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004620:Embolism, Fat / Q000150:complications*; D008070:Lipopolysaccharides; D008297:Male; D011658:Pulmonary Fibrosis / Q000209:etiology* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014304:Triolein; D014654:Vascular Patency / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides; D014304:Triolein