Obliterative lesions in small airways in an immunosuppressed porcine heterotopic bronchial allograft model.
We have recently developed a heterotopic large-animal model for research into obliterative lesions in small airways caused by allograft rejection. In this model, the small airways of subcutaneously implanted allografts gradually obliterate, whereas autografts remain patient. Twenty lung fragments and 20 segments of bronchi were implanted in domestic pigs weighing 20 kg from non-related donors. The histology of five animals receiving daily cyclosporine A (CsA) (10 mg/kg), azathioprine (2 mg/kg) and methylprednisolone (20 mg), Group C, was compared with that of six animals without immunosuppression, Group A. Four animals received monotherapy with CsA (10 mg/kg) or methylprednisolone (3 mg/kg). The histological findings were graded from 0 to 3 on the basis of implants harvested repeatedly over 3 months. Epithelial destruction and bronchial obliteration was rapid and permanent in all the allografts. Inflammation and fibrosis of the bronchial wall was less prominent in Group C than in Group A and the onset of fibrosis was delayed. Cartilage degeneration and pericartilagineous inflammation were significantly less severe in Group C (P < 0.05). Monotherapy was less potent than triple therapy. This large-animal model is useful for studying the effects of immunosuppressive drugs on obliterative airway disease.
Salminen
U S
US
Department of Cardiothoracic Surgery, Helsinki University Central Hospital, Finland. ulla.s.salminen@netsonic.fi
Ikonen
T
T
Uusitalo
M
M
Taskinen
E
E
Korpela
A
A
Maasilta
P
P
Harjula
A L
AL
D000818:Animals; D001379:Azathioprine / Q000009:adverse effects*; D001980:Bronchi / Q000637:transplantation*; D001989:Bronchiolitis Obliterans / Q000276:immunology* / Q000473:pathology; D016572:Cyclosporine / Q000009:adverse effects*; D004195:Disease Models, Animal; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016040:Lung Transplantation; D008775:Methylprednisolone / Q000009:adverse effects*; D013552:Swine
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine; D008775:Methylprednisolone