Histopathology of one-stage bilateral lung allografts

Morphological features of modified and unmodified bilateral lung allografts were studied in 87 dogs. Immunosuppressive treatment consisted of various combinations of azathioprine, methotrexate, prednisolone, methylprednisolone and antilymphocyte serum. The classic acute rejection was observed in the unmodified dogs, which died between 4 and 9 days. Progression of the lesion was confined to a certain stage in these lung allografts charged with providing total pulmonary function, so that hemorrhagic necrosis was never encountered. Immunosuppressive drugs decrease the speed and intensity of classic rejection, and increase the complications of respiratory infection in the protracted course. Of 14 dogs surviving more than 14 days, 4 died of chronic rejection at 72, 84, 177, and 396 days after transplantation. Death of the remaining animals was attributed to acute rejection (3 dogs); severe anemia (3 dogs); pulmonary infection and sepsis (3 dogs); and arterial thromboembolism (1 dog). In these long-functioning lung allografts, the alveolar lining cells were frequently replaced by very atypical cells presumed to be type 2 pneumocytes. The bronchus was occluded by mucus plugs, and the alveolar surface was covered with hyaline membrane, or obliterated by organized fibrocellular precipitate. The alveolar walls and perivascular area were thickened by fibrosis. Obliterative intimal thickening of pulmonary arteries was not observed. Although the immunologic and non-immunologic mechanisms responsible for the development of these lesions are difficult to separate, these cumulative changes apparently accompany the deterioration of the vital function of the graft until ultimate death.