250 
PULMONARY MODELS 
1000 
800 
600 
400 
200- 
■% 100 
Hexoborbitol Lung 
Rat 
—Guinea Pig 
J L 
0 50 100 150 200 250 300 350 
Minutes 
Figure 7. — Lung and blood concentrations of hexobar- 
bital in rats and guinea pigs 
effects on tidal volume. The effects were blocked 
by prior atropine. Tidal volumes were also 
reduced rapidly and reversibly by 20-80 /xg of 
isoproterenol. Propranolol blocked partially or 
completely. Norepinephrine, 100-400 /xg, also 
showed dose-related rapid and reversible tidal 
volume reductions which could be blocked 
wholly or partially by dibenamine. No edema 
was seen with either isoproterenol or nore- 
pinephrine. 
Blood vessel responses with all of these auto- 
nomic drugs were also blocked by their blocking 
agents, but the responses were not typical of 
those seen in systemic vascular responses. Acet- 
ylcholine caused dose-related vascular con- 
striction. Perfusion flow rate was reduced as 
much as 50 "^r. Isoproterenol induced vascular 
dilatation, or had no effect. The dilatation in one 
case was shown by a 50'''' increase in perfusion 
flow rate. Propranolol blocked this dilatation. 
Norepinephrine showed a reverse effect. Higher 
doses and repeated doses were less constricting 
than lower doses or single doses. Vascular 
dilatation occurred after dibenamine. 
guinea pig alveoli would indicate the possibility 
of significant alveolar involvement. The imme- 
diacy of the effects of 5 gammas of histamine 
would suggest this. Serotonin was reported to 
cause pulmonary vascular constriction in the 
guinea pig lung," but the effects of the other 
autonomic drugs on the guinea pig pulmonary 
vasculature were not reported. 
Rat lungs were little affected by histamine. 
One thousand fig induced only an irreversible 
3% reduction in tidal volume which occurred 
five minutes after the injection. A second 1000 
[xg injection, 10 minutes later, reduced the tidal 
volume by another 3%. The delayed response 
indicated airway rather than alveolar effect. 
Each of the two injections caused a transient 
pulmonary vascular constriction, shown by a 
15% reduction in perfusion flow rate. 
Acetylcholine, 40-160 fig injected into the 
pulmonary arteries of rat lungs induced dose re- 
lated decreases in tidal volume. These occurred 
immediately after injection and recovered par- 
tially or entirely within five minutes (Figure 
8) . Visible edema, which developed immediately 
upon injection, seemed to have had only minimal 
SUMMARY 
In general, it is apparent that pulmonary 
artery injection of the various drugs into the 
isolated rat lung affected the alveolar bed pri- 
marily, while in the guinea pig lung the more 
conspicious effect was on the airways. The 
capability of the alveoli to inflate and deflate 
may be modified by barbiturates and by cate- 
cholamines, but the mechanism involved with 
this capability is still unknown. It may be re- 
lated to pulmonary surfactant. 
The barbiturates were retained in both spe- 
cies for prolonged periods of time in concentra- 
tions which exerted persistent inhibitory ef- 
fects. This persistence may have significance 
in treatment of barbiturate overdosage. It may 
be necessary to drive the lungs with positive 
pressure until lung concentrations have been 
reduced sufficiently. 
The pulmonary vascular system in the guinea 
pig lung has not been investigated, but in rat 
lungs it does not appear to respond in the same 
way as the systemic vasculature. 
The isolated cat lung will make an interesting 
preparation. The absence of any connection 
