title: Heterotopic tracheal transplantation animal model of bronchiolitis obliterans: a reproducible model.
abstract: BACKGROUND
  Chronic rejection or bronchiolitis obliterans (BO) is the main cause of morbidity and mortality 1 year after lung transplantation. The objective of this study was to develop a reproducible animal model that mimics the typical histological findings in human BO after lung transplantation.
  
  
  METHODS
  We used 2 rat strains - Lewis (L) and Wistar (W) - and transplanted a segment of donor trachea into each recipient. The animals were divided into 2 groups: 1) donor and recipient of the same strain (W-W), and 2) donor and recipient of different strains (L-W). From each group, we created 4 subgroups examined at different time-points after transplantation (7, 14, 21, and 28 days). Variables were: degree of narrowing of the tracheal lumen, histological findings classified into 1 of 5 patterns, location of the ink (green or black), and presence of foreign body granuloma.
  
  
  RESULTS
  In the W-W group, we observed a gradual onset of fibrosis, notable at 21 and 28 days post-implant. In the L-W group, obliteration of the tracheal lumen was observed in all animals, with acute inflammation by day 7, and fibrosis from then on, loose fibrosis by day 14, and frank fibrosis on days 21 and 28. Green ink was observed in vascular structures, located in granulation tissue in the early phases of the BO-type lesion, then the staining becoming less clear as the histological features developed towards frank fibrosis. This trend was seen in both groups.
  
  
  CONCLUSIONS
  The obliteration and fibrosis are more extensive if the donor and recipient are from different strains (L-W). Histological findings in the L-W group corresponded to progressive fibrosis until day 21.
authors.affiliation: Department of Thoracic Surgery, University Hospital Puerta de Hierro-Majadahonda, Manuel de Falla, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Gómez-de-Antonio
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Campo-Cañaveral de la Cruz
authors.forename: Carmen
authors.initials: C
authors.lastname: Gonzalez-Lois
authors.forename: Martin
authors.initials: M
authors.lastname: Santos
authors.forename: Isabel
authors.initials: I
authors.lastname: Millán
authors.forename: Andrés
authors.initials: A
authors.lastname: Varela de Ugarte
mesh_terms: D000818:Animals; D001989:Bronchiolitis Obliterans / Q000473:pathology / Q000601:surgery*; D004195:Disease Models, Animal; D005355:Fibrosis; D006084:Graft Rejection / Q000473:pathology*; D016040:Lung Transplantation / Q000009:adverse effects*; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D014132:Trachea / Q000473:pathology / Q000637:transplantation*