title: Mitigating effects of captopril and losartan on lung histopathology in a rat model of fat embolism.
abstract: BACKGROUND
  Fat embolization (FE) is an often overlooked and poorly understood complication of skeletal trauma and some orthopedic procedures. Fat embolism can lead to major pulmonary damage associated with fat embolism syndrome (FES).
  
  
  METHODS
  A model of FE in unanesthetized rats, using intravenous injection of the neutral fat triolein, was used to study the potential therapeutic effect on lung histopathology of altering the production of, or response to, endogenous angiotensin (Ang) II. Either captopril, an Ang I converting enzyme inhibitor, or losartan, an Ang II type 1 receptor blocker, was injected 1 hour after FE by triolein injection. After euthanasia at 48 hours, histopathologic evaluation was used to compare the drug-treated animals with control animals that received only triolein.
  
  
  RESULTS
  Histology of the lungs of rats treated only with triolein revealed severe, diffuse pathology. Alveolar septa showed severe, diffuse inflammation. Bronchial lumina showed severe mucosal epithelial loss. The media of the pulmonary small arteries and arterioles was thicker, and the lumen patency was reduced 60% to 70%. Trichrome staining confirmed the abundant presence of collagen in the media and adventitia, as well as collagen infiltrating the bronchial musculature. Both captopril and losartan treatments reduced the inflammatory, vasoconstrictor, and profibrotic effects present at 48 hours (p<0.001). With treatment, the vascular lumen remained patent, and the fat droplets were reduced in size and number. There was a reduction in the number of infiltrating leukocytes, macrophages, myofibroblasts, and eosinophils, along with a significant decrease in hemorrhage and collagen deposition (p<0.001). Pathologic changes in bronchial epithelium were also diminished.
  
  
  CONCLUSIONS
  The results suggest that the use of drugs that act on the renin-Ang system might provide an effective and targeted therapy for fat embolism syndrome.
authors.affiliation: Department of Orthopedic Surgery, University of Kansas Medical Center, Kansas City, Kansas 66160, USA. tmciff@kumc.edu
authors.forename: Terence E
authors.initials: TE
authors.lastname: McIff
authors.forename: Alan M
authors.initials: AM
authors.lastname: Poisner
authors.forename: Betty
authors.initials: B
authors.lastname: Herndon
authors.forename: Kamani
authors.initials: K
authors.lastname: Lankachandra
authors.forename: Agostino
authors.initials: A
authors.lastname: Molteni
authors.forename: Federico
authors.initials: F
authors.lastname: Adler
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004620:Embolism, Fat / Q000188:drug therapy* / Q000473:pathology; D019808:Losartan / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D019808:Losartan