Small airway obliteration in a new swine heterotopic lung and bronchial allograft model.
BACKGROUND
We studied a heterotopic large-animal model with obliterative airway lesions caused by allograft rejection.


METHODS
Lung fragments (1 cm3) with airways (LB), and 1 to 2 mm diameter bronchi alone (B) were implanted subcutaneously in 11 domestic piglets weighing 20 kg. Six animals each received 40 implants from nonrelated donors without immunosuppression (group A). Another 5 animals had autograft implants (group U). The implants were harvested consecutively for histologic analysis over 3 months in group A and 6 months in group U.


RESULTS
In group U, the initial ischemia caused mild to moderate epithelial damage with moderate metaplasia but with a return to normal ciliary epithelium within 1 month. Transient mild luminal obliteration with granulation tissue and mononuclear cells was observed during the first weeks, but after 4 weeks the lumen was patent and filled with mucus. In the bronchial wall, moderate fibrosis developed in LB implants, whereas mild fibrosis was seen in B implants. In group A, the epithelium was totally absent by 2 weeks, and mild inflammation, fibrosis, and destruction of the cartilage with pericartilaginous mononuclear accumulation were observed in the bronchial wall. Small airways were gradually obliterated between days 7 and 21, initially by granulation tissue and mononuclear cells and later by progressive fibrosis.


CONCLUSIONS
In this model, autografted airway implants stayed patent for at least 6 months, whereas total luminal obliteration histologically resembling obliterative bronchiolitis developed in allografts within 21 days. Because small airways, including bronchioli, can be transplanted with the use of this model, it may be useful for research into the causes of airway obliteration, which may be relevant to the pathogenesis of obliterative bronchiolitis in lung recipients.
Ikonen
T
T
Department of Surgery, Helsinki University, Finland.
Uusitalo
M
M
Taskinen
E
E
Korpela
A
A
Salminen
U S
US
Morris
R E
RE
Harjula
A L
AL
D000818:Animals; D001980:Bronchi / Q000473:pathology / Q000637:transplantation*; D001989:Bronchiolitis Obliterans / Q000473:pathology* / Q000601:surgery; D004195:Disease Models, Animal; D004848:Epithelium / Q000473:pathology; D006084:Graft Rejection / Q000473:pathology* / Q000601:surgery; D016040:Lung Transplantation / Q000473:pathology*; D012086:Reoperation; D013552:Swine; D016042:Transplantation, Heterotopic / Q000473:pathology*; D014184:Transplantation, Homologous