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PHYSIOLOGY 
differences is esophageal tone or other varia- 
tions. 
We've compared values, say, for carbon diox- 
ide obtained with our end tidal sampler and the 
breath by breath peak method, and they're very 
close. Now, we feel that we can get legitimate 
end tidal samples to frequencies up around 50. 
In our dogs with radiation damage, of course, 
the frequency continues to climb until death. 
Certainly we place no reliance on frequencies of 
80 to 100, and in fact, stop our measurements of 
diffusing capacities when frequencies reach that 
high. However, the plunger, that I noted in the 
pressure chamber, allows the collection of a pre- 
set volume. Therefore, if we have an idea of the 
tidal volume of the dog (most of our dogs are 
about the same size) and know the frequency, 
we can guess fairly closely the tidal volume and 
we usually set the collection at about 10 % ; so 
you can see we're well up on the alveolar pla- 
teau. End tidal measurements or alveolar meas- 
urements are a big bucket of worms in pulmo- 
nary physiology. Here again, I think you have to 
set your conditions, and decide how you're 
going to do it in your laboratory. It may or may 
not compare closely with what someone else is 
doing, but you're all familiar with the problems 
of the definition of true alveolar gas, mean al- 
veolar gas and so forth. So we've set our condi- 
tions and we're making our measurements. We 
feel that we get good samples with it. They com- 
pare very favorably to those obtained in hu- 
mans. 
H. Calderwood, University of Florida, 
Gainsville: How reproducible are your steady 
state diffusing capacities within the same dogs? 
We're doing pulmonary function tests on anes- 
thetized beagles and had to give up the steady 
state and go to the single breath to get reproduc- 
ibility. 
Dr. Mauderly: Well this is very true. The 
reproducibility is not good. There is quite a 
high variation. The variation within a dog on 
sequential measurements is lower than it is 
within the colony. Of course, here when I men- 
tion colony, I'm not talking about a large range of 
sizes, as you could see with pound dogs, but 
with a fairly narrow range of sizes that we see 
in our beagles. The fluctuation of this value 
within an individual dog is less, but it is still 
quite large. We place very little reliance on a 
single measurement. But here again performing 
the measurements in the conscious state, we 
have these variations and therefore we rely on 
numbers, and our tests don't take very long. 
They're relatively innocuous and we can per- 
form them repeatedly with very little trouble. 
So we rely on two or three tests on the same 
animal and come up with a mean value. But 
there is a considerable variation by method and 
I'm sure more variation than others' have seen 
with single breath method. 
C. G. La Farge, Children's Hospital, Boston, 
Mass. : In this very nifty animal model that 
you've shown so beautifully this morning, are 
there important gravitational effects on ventila- 
tion and profusion? I notice that you do some of 
your experiments in what might be called a nor- 
mal dog position and others in the inverse? 
Dr. Mauderly : This is very true, and it's a 
question which I feel we'll have to address very 
soon. We have not done specific experiments de- 
signed to answer that question. I'm sure that 
there must be some gravitational effects as 
there are in humans. I think the effects are 
quite possibly less because of the rather hori- 
zontal axis of the dog's lung and the relation- 
ship of the lung to the heart. So, therefore, if 
you turn the dog on its back, you really aren't 
changing the position of the heart and the lungs 
too much. Now, quite possibly some of the dif- 
ferences we see here in pH and in the carbon 
dioxide parameters may be related to the fact 
that they're restrained on their backs, but we 
have not specifically addressed that question, 
A. AzAR, E. I, DuPont, Newark, Delaware: 
During the course of your toxicity testing, 
have you had an opportunity to use this 
technique where you've exposed animals to com- 
pounds known to effect pulmonary function; 
and if you have, would you comment on the sen- 
sitivity of the method in detecting changes 
where animals have been exposed to, say, a TDI 
or a compound known to effect pulmonary func- 
tion? 
Dr. Mauderly: Yes, as a matter of fact, 
most of our work is with radioactive aerosols. 
The effects are very similar to what you find 
from external radiation. We have found that 
the occurrence of lung damage can be picked up 
