338 
SURGERY AND TRANSPLANTATION 
Figure 12c. 
sociates '^^"•^^ studied rejection extensively, 
with and without methotrexate suppression. 
Animals exhibited evidence of a progressively 
more severe reaction after the second day, 
characterized by listlessness, cough, and a thin 
foamy sputum. These workers were later to 
describe long-term survival in several animals 
using methotrexate as the immunosuppressive 
agent. The histologic features of lung allograft 
rejection have been well described in the litera- 
ture and certain of these features are presented 
in Figure 14. Vascular changes are impor- 
tant.65.«6 
Our initial studies of lung allotransplantation 
were performed in a series of 138 dogs with the 
particular objective of determining the efficacy 
of various means of immunosuppression.''^ The 
treated groups all lived longer than did the con- 
trols, the control animals living an average of 
7.4 days. Twenty of 34 animals treated with 
azathioprine (Imuran) in a dosage of 4.0 mg 
per kg per day by mouth survived the imme- | 
diate postoperative period and lived an aver- 
age of 30.4 days. Incidentally, the angiograms 
in one animal which was a permanent survivor I 
were remarkably normal on the day prior to j 
sacrifice, despite the fact that the lung was 
found to have been encased in a fibrous envelope 
and essentially rejected. This again emphasized j 
that only by differential lung function studies, 
or by ligation of the contralateral pulmonary 
artery or by contralateral pneumonectomy, could 
one be certain of the functional status of the al- 
lografted lung when one of the animal's own 
lungs remained in situ. 
Various other immunosuppressive regimens 
have been employed in our laboratory, including 
radiation to the mediastinum, horse anti-dog | 
lymphocyte serum (or globulin) and predni- | 
sone. The best average survival rate that we 
have achieved in any series has been 35 days, 
this being accomplished with a combination of 
Figure 12d. 
i 
