246 
PULMONARY MODELS 
from a reservoir, through the controlling needle 
valve and into the pulmonary artery via the 
cannula. Perfusion was continuous except at 
the time of injection. Perfusion was stopped at 
that time to insure that the injection entered 
the artery directly, rather than into the perfu- 
sion reservoir. When necessary, perfusion ef- 
fluent could be collected through a chamber 
drain. 
Rats and guinea pigs were anesthetized by 
electroshock. The trachea was exposed and li- 
gated during an inspiration to prevent atalecta- 
sis. The animals were then exsanguinated by 
cutting the carotids. The lungs and heart were 
then excised and placed in a bath of warm 
Tyrode's. The pulmonary artery was then can- 
nulated through the right ventricle, and the 
left ventricle cut away to permit free flow of 
the effluent, and the trachea slipped over the 
tracheal cannula and tied. The whole prepara- 
tion was then sealed into the machine. Tidal 
volume, at the given negative pressures, was 
allowed to stabilize before drug administration 
was begun. Perfusate flow was stabilized at 0.2- 
0.3 ml/min for rat lungs and 0.3-0.5 ml/min 
for guinea pig lungs. Higher rates induce edema 
rapidly. At these rates, edema developed slowly, 
if at all, and mostly as a result of drug ad- 
ministration. Reduced flow rates were assumed 
to indicate vascular constriction; increased 
rate, dilatation. Such vascular responses were 
absent in non-viable lungs. 
Electroshock anesthesia was used because it 
had been shown by Heymans and his co-workers 
that after all commonly used anesthetics, in- 
halation and fixed, lung preparations were 
either short lived, unresponsive or both (pers. 
comm.). Consequently, it became of interest to 
investigate the peripheral pulmonary and pul- 
monary vascular effects of various barbiturates. 
RESULTS AND DISCUSSION 
Lungs from guinea pigs weighing 600-800 
grams were injected several successive times 
at 15 minute intervals into the pulmonary ar- 
tery with equivalent pKa solutions of pheno- 
barbital, pentobarbital, thiopental or hexobar- 
bital (Table I)." Both pulmonary and vascular 
effects were dose-related. Irreversible respira- 
tory cessation was seen at each dose level of 
each barbiturate, but more successive doses 
were needed at the lower dose levels. Visible 
edema, when it developed, occurred late. Tran- 
sient large tidal volume increases were seen 
after the second or third of the successive doses 
of each barbiturate. Eventual, irreversible, large 
reduction in tidal volume was seen in those 
lungs which remained viable. There was some 
evidence that the amount of tidal volume reduc- 
tion might also be dose-related. In every in- 
stance, effects were delayed and developed 
slowly after the injection. 
Rat lungs from animals weighing 250-400 
grams were about half the size of guinea pig 
lungs. Since doses as much as four times greater 
were required (Table I), such lungs actually 
received doses as much as eight times greater. 
Dose-related, persistent tidal volume decreases 
appeared rapidly ; increases were unusual. Res- 
piratory cessation never occurred, but tidal 
volume was reduced to 80-90 % of base volume. 
More important perhaps, was the observation 
that successive doses gave progressively lesser 
responses. In guinea pig lungs, each successive 
dose elicited a full response. 
The delayed but more intense response and 
the frequent transient tidal volume increases 
seen in guinea pig lungs suggest that these 
noticeable effects were predominantly bron- 
chiolar through the profuse anastomoses, in 
this species, between pulmonary and bronchial 
arteries. Heymans ^ stated that more than 99 % 
Table I. — Barbiturate Doses Injected Into the Pul- 
monary Artery of Isolated Lungs 
(mg/lung) 
Barbiturate 
Guinea Pig 
Rat 
Phenobarbital 
0.30 
1.2 
0.15 
0.60 
0.075 
0.30 
0.15 
Pentobarbital 
0.10 
0.40 
0.05 
0.20 
0.025 
0.10 
Thiopental 
0.10 
0.40 
0.05 
0.20 
0.025 
0.10 
Hexobarbital 
0.60 
0.80 
0.30 
0.40 
0.15 
