248 
PULMONARY MODELS 
between 95-105%. Total recovery from lung 
and from perfusate effluent in the experimental 
isolated lungs was in the same range. 
Pentobarbital concentration was the most 
persistent in both species. More than 40% of 
the amount injected was present 60 minutes 
later. This concentration persisted in guinea pig 
lungs to the end of the experiment at 120 min- 
utes. In rat lungs, however, in the next 40 min- 
utes the concentration fell to 25% of the initial. 
In rat lungs also, the other three barbiturates 
showed typical half-life decay curves which 
were parallel to each other. In each of these in- 
stances, about 25% of the initial concentration 
remained at the conclusion. Thus, in this 
species, all four barbiturates eventually had the 
same residue ratio. In guinea pig lungs, hexo- 
barbital showed a rapid rate of decline : almost 
all was lost in about 120 minutes. The other two 
barbiturates had half-life decay curves parallel 
to each other, parallel to those seen in the rat, 
and eventual residues similar to those found in 
the rat lungs: 25% of the initial concentration 
(Figure 3) . 
The parallel concentration declines in the 
lungs within each species would suggest me- 
tabolic similarity. The parallelism between the 
species, in the rate of decline of thiopental and 
phenobarbital, and the similarity of their resi- 
due ratios together with the maintenance of the 
level of pentobarbital, may indicate metabolic 
similarity between these two species. Nonethe- 
less, relatively high concentrations of all except 
guinea pig hexobarbital remained for as long 
as 120 minutes after a single injection. This 
would suggest that successive injections or per- 
fusion would increase this concentration suf- 
ficiently so that the lung might lose its inflation 
capability. 
In vivo circulating barbiturate may be con- 
sidered to be perfusing the lung. Assuming 
equal initial concentration of barbiturate in all 
tissues after intraperitoneal injection, the lungs 
of both species showed initial concentrations 
two to ten times higher than this. The in vivo 
concentration of pentobarbital in rat and guinea 
pig lungs remained at high levels for up to six 
hours, despite decreasing blood concentrations. 
In guinea pig lungs, the concentration fell only 
from 600% to 350 and in rat lungs the concen- 
tration remained at 200% for the first four 
hours, and then fell to 60% in the two following 
hours. The retention was similar to that seen in 
vitro (Figure 4). The concentration of each of 
the other barbiturates, in the lungs of both spe- 
cies, also remained high, but showed progres- 
sive declines (Figures 5-7). Enough remained 
after six hours, however, to have had serious 
effects on the in vitro lungs. 
These findings confirmed the observation men- 
tioned above, that after barbiturate overdosage, 
lung function needs to be maintained while 
other therapy is in progress. This must be done 
with positive pressure respiration, since, as was 
shown above, the lung loses its capability to 
inflate and deflate by negative pressure. The 
positive pressure augmentation should be con- 
tinued until inhibitory lung concentrations have 
been reduced. 
The alveoli inflate and deflate without muscle 
CONCN 
to 
100 
80 
60 
401- 
20- 
% \o\- 
8 
6 
41- 
Guineo Pig 
\ 
\ 
\ 
\ 
\. 
Thiopental 
\ 
% 
A-—- Hexobarbital 

1 1 1 1 1 
1 
4 6 810 20 40 60 100 120 140 
Minutes 
Figure 3. — In vitro rat and guinea pig lung concentra- 
tions of indicated barbiturates. 
