FREDERICK SPERLING, WILLIAM L. MARCUS AND A. A. 0. COKER 
245 
dilatation and some vasoconstriction in response 
to acetylcholine. The bronchial arteries, how- 
ever, responded as did other systemic arteries. 
Norepinephrine and isoproterenol were both re- 
ported to act on the pulmonary vasculature in 
the same manner as they did on the systemic 
vasculature.^ However, in the case of norepine- 
phrine, there may be some question (See infra). 
The in vivo action of these drugs on the bron- 
chioles are well known. Acetylcholine produced 
a slowly developing large reduction in tidal 
volume in guinea pig lungs." As discussed be- 
low, the slow development probably indicated 
airway response. Similar effects were produced 
by DFP and paraoxon.' Atropine could block 
but not reverse the effects. Epinephrine re- 
versed the effects. The effects after parathion 
i were questionable. It would have been surpris- 
I ing had parathion had the same action as para- 
oxon. 
In previously published reports on responses 
of isolated guinea pig lungs to pulmonary artery 
injections of catecholamines, Bhattacharya ^ 
found that isoproterenol and epinephrine in- 
creased tidal volume, probably by action on the 
bronchioles. Heymans and Dautrebande^ con- 
firmed this for isoproterenol and showed, in 
addition, that isoproterenol placed directly on 
the pleural surface also induced pulmonary di- 
latation, thereby demonstrating the independent 
capability of the alveoli to respond. Neither of 
these reports included investigations on the 
responses of the pulmonary vasculature, and all 
involved the guinea pig only. It thus became 
necessary to do similar studies with isolated rat 
lungs, but now the pulmonary vasculature would 
be studied as well. 
The continuously perfused, isolated lung, 
caused to inflate and deflate by cyclic negative 
pressure, is uniquely capable of distinguishing 
the activities of each of these parts of the pul- 
monary system. In such a system, the lungs in- 
flate and deflate (breathe) only to the extent 
that they are capable of doing so (Figure 8). 
Positive pressure systems overlook this capabil- 
ity. Additionally, the system as developed by 
Delaunois^ permits drugs to be administered 
either by perfusion, along with the Tyrode's, or 
by single, pulmonary artery injection, or via the 
airway in the form of gases or aerosols. The re- 
sponses of alveoli and airway to drug adminis- 
tration by pulmonary artery injection or by air- 
way may be seen by changes in tidal volume or 
by loss of capability to expand (Figure 8). Vas- 
cular effects may be -seen by changes in perfu- 
sion flow rate indicating pulmonary vascular 
constriction or dilatation. The two types of 
changes may be reversible or irreversible. When 
the changes are irreversible, the lungs are no 
longer considered viable. 
MATERIALS AND METHODS 
The system " consists of a 10 cm^ transparent 
chamber, open at top and bottom of one side to 
an accessory chamber, and at the bottom of 
another side to a negative pressure pump. The 
accessory chamber contains an airway segment, 
a heater and thermostat, and a blower. An at- 
tached aneroid manometer monitors chamber 
pressure. The chamber is sealed with a cover 
plate through which a continuation of the air- 
way passes. A tracheal cannula hangs at right 
angles from the airway. Thermistors are 
mounted in the airway on either side of the 
tracheal cannula. Temperature differences be- 
tween the two which develop during lung in- 
flation and deflation are detected by these 
thermistors and recorded on a polygraph. These 
differences are directly related to tidal volumes 
developed at a given negative pressure. Nega- 
tive pressures cycle 25-27/min from zero to a 
preset value of 6-8 mm Hg for rat lungs and 
8-10 mm Hg for guinea pig lungs. The cover 
also has a port with a needle valve continuous 
with a pulmonary artery cannula. Another port 
leads to a sidearm of the cannula through which 
injections may be made. 
Scrubbed, water-saturated air flowed at 100- 
200 ml/min at approximately ambient pressure, 
was warmed in the accessory chamber before 
flowing through the cover plate. Since the air- 
way diameter is about 10 times that of the 
tracheal cannula, the airstream was not forced 
into the trachea. A fair sample, however, en- 
tered the lung when it inflated. The airstream 
could carry vapors and gases and particulates 
such as aerosols. 
Warmed Tyrode's solution, at about 15 cm 
of water pressure, passed through a rotameter 
