F. J. VEITH, S. B. P. SINHA, S. S. SIEGELMAN AND J. W. C. HAGSTROM 
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some blood flow to the opposite lung will prob- 
ably be maintained, and because of prior right 
ventricular hypertrophy. It is, of course, also 
necessary to avoid technical errors in both the 
bronchial and venous anastomoses in order to 
obtain animals that can survive solely on the 
function of a single transplanted lung. Techni- 
cal details which have facilitated these impor- 
tant aspects of the procedure have been pre- 
viously detailed by our groups and by Alican 
and his coworkers. 
The present results show that 10 per cent of 
allografted lungs, under treatment with aza- 
thioprine, antilymphocyte serum and corticos- 
teroids, could provide total pulmonary function 
for more than one month. However, all allograft 
recipients were dead 100 days after operation. 
This is in contrast to a 50 per cent three month 
survival after autotransplantation and contra- 
lateral pulmonary artery ligation. Clearly, the 
functional defects produced by rejection or the 
toxicity of the immunosuppressive agents were 
a major cause of mortality. Since many allo- 
grafted dogs died with minimal changes in their 
allograft, we believe that both factors played a 
role. Obviously better immunosuppression is 
needed. 
The blood gas and hemodynamic data in the 
present report provide information concerning 
the late respiratory and vascular function of 
lung transplants chronically charged with pro- 
viding total pulmonary function. Clearly such 
transplanted lungs alone can maintain normal 
arterial and venous partial pressures of oxygen 
and carbon dioxide and pH at all times up to 44 
months after operation (Table II). In addition, 
these transplanted lungs were able to vasodilate 
with increased blood flow so that the pulmonary 
artery pressure did not rise more than it does in 
normal dogs subjected to simple right pulmo- 
nary artery ligation (Table II). This is an im- 
portant observation since many other workers 
have suggested that transplanted lungs have a 
fixed high vascular resistance and are incapable 
of vasodilating normally with increased pul- 
monary blood flows. Furthermore as shown in 
Table II, no late or progressive rise in pulmo- 
nary artery pressure or in the vascular resist- 
ance of the transplanted lungs occurred for pe- 
riods up to two years after operation despite 
their increased blood flow. This is important 
since several other investigators have noted a 
progressive rise in pulmonary artery pressure 
after lung transplantation and delayed ablation 
of the function of the opposite lung. It is still 
unclear what would happen to vascular resist- 
ance in these lungs if cardiac output was in- 
creased further, although Ebert has presented 
evidence that transplant vascular resistance is 
higher than normal with very high cardiac out- 
puts up to 42 days after operation. 
The sustained normal respiratory and vascu- 
lar function of these transplanted lungs is con- 
sistent with the normal angiographic and mi- 
croscopic structure that we observed up to 2V2 
years after they were charged with providing 
total pulmonary function. Many workers have 
claimed that autografted lungs, with time, de- 
velop marked histologic abnormalities charac- 
terized by fibrosis, foci of bronchopneumonia, 
and tnickening of alveolar walls. Review of the 
sections from the transplanted lungs in our 
dogs that died from 2-30 months after opera- 
tion revealed widespread areas of completely 
normal lung in all animals. We, therefore, be- 
lieve that transplanted lungs do not necessarily 
develop late pathologic lesions, and the changes 
observed by other workers are misleading and 
probably related to endemic disease in the recip- 
ient animals or to the studies themselves. This 
conclusion, which is supported by the work of 
Lempert and his colleagues," is most important 
since it means that lung grafts can, if rejection 
is controlled, maintain morphologic integrity 
for protracted periods and probably indefi- 
nitely. 
CONCLUSIONS 
We believe that we have shown that a single 
transplanted lung can provide total pulmonary 
function while carrying the entire cardiac out- 
put in dogs, if the arterial anastomosis is dis- 
tensible and if all other technical details are 
perfect. This functional adequacy can be 
achieved in a high percentage of autografts and 
is well maintained for over ZV2 years. With au- 
tografts there is no deterioration in respiratory 
function, vascular function, or pulmonary mi- 
croscopic morphology for at least 2-3 years. 
