FREDERICK SPERLING, WILLIAM L. MARCUS AND A. A. 0. COKER 
247 
of the perfusate in such lung preparations 
flowed through the pulmonary artery. However, 
the relatively high injection pressure could 
have forced retrograde flow through the anasto- 
moses into the bronchiolar circulation. 
Pulmonary and bronchiolar arterial blood mix 
in the capillary bed in humans (Figure 1) and 
may do so in guinea pigs also.'* The appearance 
of the effluent would be as though it were al- 
most completely pulmonary artery circulation. 
However, bronchiolar effects after pulmonary 
artery injection would appear after some delay, 
as they did in guinea pig lungs. The barbiturates 
could open the airways transiently. Plugging 
might follow secondarily. Commonly used bron- 
chiodilators have been shown to be frequently 
associated with secondary respiratory distress 
and death in man, due to the mucus plugging of 
the smaller bronchioles.^^ In rat lungs, bron- 
chiolar involvement would be minimal, and the 
noticeable effects would be predominantly al- 
veolar. These effects would occur quickly, as 
they did, and would involve the expansion capa- 
bility or perhaps the elasticity of the alveoli. 
There would then be a great, but not complete, 
reduction in tidal volume. These considerations 
are consistent with the described morphology. 
Simultaneously, the pulmonary vascular sys- 
tem generally constricted in guinea pig lungs. 
Dilatation was infrequent and small. The 
amount of constriction, as measured by perfu- 
sion flow rate, was dose-related. Successive 
doses gave progressively lesser effects, similar 
to that seen in the tidal volume responses in 
rat lungs. The pulmonary vasculature of the 
rat also showed constriction, but transient di- 
latation was frequent and only thiopental 
showed lesser constriction after smaller doses. 
These in vitro responses appear to differ from 
the generally accepted systemic vascular re- 
sponses. 
These observations indicated that the bar- 
biturates exerted strong and persistent peri- 
pheral effects on the bronchioles, the alveoli 
and the pulmonary vasculature. This in turn 
suggested that treatment of barbiturate over- 
dosage should include vigorous support of peri- 
pheral pulmonary function to augment central 
stimulation and dialysis. Therefore, it was nec- 
essary to know whether persistance of pulmo- 
nary peripheral effects were correlated with the 
presence of barbiturate in the lung. 
Pulmonary artery injections of single doses 
of the four barbiturates (Table 11) were ad- 
ministered to rat and guinea pig lungs and the 
concentration in lung and perfusate determined 
at various time intervals up to 120 minutes. The 
lungs remained viable during the entire ex- 
periment. These were compared to the concen- 
trations found after various time intervals up to 
360 minutes after single intraperitoneal anes- 
thetic doses (Table III). Blood concentrations 
were also determined. The weights of the guinea 
pigs and rats were in the same range as noted 
above. 
Barbiturate recovery was confirmed by add- 
ing known quantities to homogenized, untreated 
lung, excised from electroshocked animals. In 
contradiction to the concentrations later found 
in experimental lungs, above 90% remained in 
the lungs despite repeated, numerous wash- 
ings. Total recovery in lung and wash ranged 
Table II. — In Vit7-o Dose of Barbiturates in Rats and 
Guinea Pigs 
Guinea pigs Rats 
Barbiturates pKa Number Number 
Dose of Dose of 
(y) Lungs (7) Lungs 
Phenbbarbital 7.3 100 15 150 15 
Pentobarbital 8.1 100 15 50 22 
Thiopental 7.6 100 19 100 19 
Hexobarbital 8.2 337.5 18 337. B 25 
Table III. — In Vivo Dose of Barbiturates in Rats and Guinea Pigs 
Guinea Pigs Bats 
Barbiturate Number Induction Number Induction 
Dose of Time Dose of Time 
mg/Kg Animals (min) mg/Kg Animals (min) 
Phenobarbital- _ 150 18 12 125 18 12 
Pentobarbital 40 18 5 40 24 5 
Thiopental _ 40 18 3 40 20 3 
Hexabarbital 125 22 2.5 125 24 2.5 
