Lung weights of rats exposed to hyperoxic gas mixtures with He or no inert gas diluents substituting N

Weiss, H. S.

English

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1492 RF Project .................................... 
Report No ..................................... 15 
E T 
BY 
THE OHIO STATE UNIVERSITY 
RESEARCH FOUNDATION 
1314 KINNEAR RD. 
COLUMBUS, OHIO 43212 
NATIONAL AERONAUTICS & SPACE ADMINISTFiATION 
Washimton D. C . 20546 
To ............................................................................................................................................................................................. 
Grant No. NGR36-008-004 
On BIOLOGICAL EFFECTS OF PROLONGED EXPOSURE OF 
ANIMALS TO UNUSUAL GASEOUS ENVIRONMEWTS 
............................................................................................................................................................................................ 
............................................................................................................................................................................................. 
For the period 1 September 1969 - 28 February 1970 ........................................................................................................................................................... 
H ........ S Weiss 
DeTartment of Physiology 
Submitted by .................. 0 0 .................................................................................................................. 
..................................................................................................................................... 
Date ........ FSb.%.Z...28, .... &%? ........ 
https://ntrs.nasa.gov/search.jsp?R=19700024672 2020-03-11T23:14:00+00:00Z
SUB TI'JTLE: 
which H e  or no inert  gas replaces N2' 
Lung weights of rats exposed t o  hy-peroxic gas mixtures i n  
R a t s  generally survive indefintely i n  environments i n  which the 
Po, is less than 600 Torr, usually with l i t t l e  evidence of 0, toxicity 
except for  depressed food intake and decreased growth. A t  Po, greater 
than 600 Torr, respiratory symptoms of varying severity, including 
atelectasis, congestion and edema, often leading to death, are expected 
generally within a few days. 
the lower, nonlethal but s t i l l  hy-peroxic ranges had any measurable 
effect on the lungs, and whether the presence, absence or type of inert  
gas (i.e., N2 or He) associated w i t h  the 0, exerted any influence on 
the 0, effect. 
The p q o s e  of th i s  study was t o  see if 
Approximately 250 g male Sprague-Dawley (Holtzman) ra t s  were 
exposed t o  the hy-peroxic gas mixtures indicated i n  Table 1, util izing 
sealed recirculating isolators for environmental control. The LOO 0, 
exposure was carried out w i t h  the isolator held within an alt i tude cham- 
ber s e t  a t  570 torr; 570 torr of 100% 0, was calculated t o  provide an 
alveolar Po, approximately equivalent t o  74% 0, at the 750 mmHg which w a s  
taken as average ground level pressure a t  Columbus (i .e., Po, = 555 torr)  e 
Six t o  ten ra t s  were sacrificed a f te r  10 and 20 days of exposure. 
were removed and weighed fresh, then dried a t  1 0 5 O C  for  24 hrs. and re- 
weighed. one fed ad l ib ,  the other 
restricted-fed i n  an effort t o  stimulate the lower intake found w i t h  
the 0, treatments. 
Lungs 
Two control groups were run: 
The body weight measurements indicate that a l l  0, treatment depressed 
growth, w i t h  the 3.0% 0, group showing essentially GO growth at a l l  
above i ts  start ing wei@t a t  either 10 or 20 days. The N2 and He groups 
showed a l i t t l e  growth during the first 10 days but nothing further dur- 
ing the second 10 days. 
close to that of the He and N2 groups. 
The weight of the restricted-fed group was 
A t  ten days it is  evident that both wet and dry lung weights (as a 
proportion of body w e i g h t )  are greater i n  a l l  the 0, treatments than i n  
either control group, indicating some sort of lung dana,ge. 
control groups do not differ between themselves suggesting that simple 
body weight changes resulting from different food intakes does not a l t e r  
the r a t io  of either wet or dry lung weight to body weight. Since the $ 
increase i n  lung weight over that of the restricted-fed controls i s  the 
same for  the w e t  and dry measurements (Table 1) , it m u s t  be concluded 
that the ten-day 0, effect on the lungs is due essentially t o  t issue 
proliferation rather than edema, 
The two 
A t  20 days, the same relative lung weight picture is  seenbut with 
some modifications. 
body weight ra t io  although the i r  body weights are  considerably more 
divergent than at  10 days. 
The two controls again do not differ  i n  lung weight/ 
This further supports the view that lung 
1 
Table 1 - Lung and Body Weight Changes i n  Rats Exposed for 10-20 Days t o  74% 0, 
a t  One Atmosphere, with and without Inert Gas Diluents 
A V E R A G E  f S T A N D A R D  E R R O R  
T E N  D A Y S  T W E N T Y  D A Y S  
BODY 
WEIGHT 
(d 
BODY 
WEIGHT 
( g )  
WET DRY WET DRY 
255 f 5.6 1) 100% 0, (570 torr)  
(as % of restricted-fed 
0.64 f 0.02 
(126) 
0.87 f 0.17 
(147) 
0.19 f 0.02 
(167) 
2) 74% 0 ~ ~ 2 6 %  N2 (1 Atm 
(as % of restricted-fed 
279 f 49 
(101 L) 
0.63 f 0.01 
(124) 
0.62 f 0.02 
(104) 
3) 74% 0,-26% H e  (1 A t m  
(as % of restricted-fed: 
277 f 2.6 
- 
0.11 f 0,Ol 4) Room air  controls, restricted-fed 0.12 f 0.01 272 f 5.8 0.58 f 0.05 
305 f 3.1 0.12 f 0.01 336 f 9.4 0.12 1. 0.01 
5) Room air controls, 
ad lib-fed 
0.53 f 0.01 
weight tends t o  remain proportional t o  body weight when the depression 
of body weight is  due mainly t o  decreased feed intake. 
0, enriched groups have proportionally higher lung weights, both wet 
and dry, but now the helium group is clearly the least  affected. In 
fact ,  lung weight of the H e  group, while higher, does not appear t o  
differ  significantly from either of the controls, whereas it is  decidedly 
lower than either of the other two 0, groups. 
the lungs of the 10% 0, and the 74% 0,-26% N2 groups over that of the 
restricted controls is now greater than a t  10 days, indicating a further 
exaggeration of the lung damage by these treatments. The lung weight 
increment s t i l l  seems t o  be due primarily t o  t issue proliferation, since 
i n  comparison t o  controls the dry w e i g h t  changes are now even more pro- 
nounced than the w e t  w e i g h t s .  
weight of the lungs was  practically the same for  a l l  f ive groups i n  each 
time period, further showing that the 0, effect results frm an increase 
of t issue similar i n  moisture content t o  that  of normal lung components. 
Again the three 
The % weight increase of 
A supplemental calculation of the % dry 
Several observations i n  this study appear worthy of comment. F i r s t ,  
it is evident from the increased lung weightbody weight ratios that 
ambient Po2 i n  the 555-570 t o r r  range does have an deleterious effect 
on the lungs. 
essentially one of' t issue proliferation, as indicated by the fact  that  
the dry weight increases are equal t o  or greater than the wet weight 
changes, and % dry matter remains the same. One would have speculated 
perhaps from past observations that edema might have been the f irst  and 
most marked effect of 0, toxicity. Thirdly, it would appear that by 
20 days a t  least ,  the effect of the nonlethalhyperoxia on the lmgs 
has been altered by the inert  gas diluent present, being clearly less 
severe i n  the He group. 
Secondly, and perhaps surprisingly, the 0, effect is 
An explanation for  the apparent helium inhibition of 0, pulmonary 
toxicity is  not immediately evident. 
O,-He mixture is less dense than either 100% 0, or O,-N, and theoreti- 
cally this might reduce the work of breathing, particularly i n  a damaged 
pulmonary system. 
pulmonary membrane may be enhanced by He, i n  perhaps the same manner 
that 0, uptake i n  some biological systems appears t o  be increased i n  
the presence of heliwn This too should decrease the work of breathing. 
Both of these views, hawever, would require the somewhat unlikely situa- 
t ion  that the increased lung t issue proliferation is  i n  response t o  
increased work of breathing i n  a damaged lung. 
would be that hy-peroxia directly stimulated t issue proliferation, pos- 
sibly i n  the form of capillary hyperplasia, which w a s  i n  turn inhibited 
by helium through some as yet unclear mechanism. 
On a purely physical basis, the 
Another possibility i s  that 0, diffusion through the 
The more direct view 
The improved lung picture i n  the He ra t s  also appears t o  be associ- 
ated w i t h  a slightly better body w e i g h t  than i n  either the 100% 0, or 
02-N2. 
t o  that  on the lungs (e.g., He body weight i s  only 8% higher than i n  
02-N2) , whereas lung dry weight/body weight is 37% less. 
However, the effect on body weight is  relatively small compared 
Other studies 
3 
have shown that the effect of hy-peroxia on food intake andbody weight 
may be distinct from i t s  lethal and pulmonary effects, 
Regardless of the mechanisms, the possibility that  helium may have 
some moderating effect on pulmonary oxygen toxicity should be of suffi- 
cient practical importance to warrant further pursuit of this  problem. 
It may be added that wet and dry heart, l iver  and kidney weights, includ- 
ing l iver  l ipid,  were also exmined for  a l l  groups of rats and fowid t o  
be relatively unaffected by the 0, or inert  gas treatment, Thus the 
effect on the lungs is a fa i r ly  specific response to both 0, and He. 
/ Date Investigator .............. .......... ............................. .......... 
Supervisor ...................................................................................................................................... Date .................................................................. 
For The Ohio St rch Foundation 
Executive Director ............... Date. .................................. u ?; ..... [..e.? 
4 


Biological effects of prolonged exposure of animals to unusual gaseous environments Semiannual report, 1 Sep. 1969 - 28 Feb. 1970

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