Effects of atmospheric pressure on susceptibility and resistance to infectio

Gillmore, J. D.

Gordon, F. B.

English

High and low barometric pressure effects on susceptibility and resistance to infectio

NASA Technical Reports Server

N J 
NASA A-3 0 61A (AS-1) 
Former designations: L-97,464 
R-21-010-010 
Quarterly Status Report No. 15 to 
National Aeronautics and 8pace Administration 
1 Janua.ry - 31 March 1969 
‘‘Effects of High and Low Barometric Pressures  on 
Susceptibility and Resistance to Infection1’ 
Francis B. Gordon and James D. Gfllmore 
Deparhent  of Microbiology 
Naval Medical Research Institute 
Be thes da ‘Maryland 2 00 14  
https://ntrs.nasa.gov/search.jsp?R=19690015997 2020-03-12T04:08:24+00:00Z
Abstract. 
The pulmonary imfection of mice induced by exposure to an aerosol of the chlamydial 
mouse pneumonitis agent was  definitely reduced in degree by post-challenge exposure to 
a hyperoxic environment (77% O2 in N2 at 1 atmosphere), and evidence was  obtained that 
hypoxic [110/@ O2 in N2 at 1 atmosphere) enhanced the infection. Both of these observations 
confirm or are compatible with previous findings. 
When C!dmydia &$a is injected i. p. 
when the mice are e-xposed to hypoxia. A simulated space cabin atmosphere (70% O2 in 
N2 at 5 psi@ had DO effect on the mortality curve, when compared to air-exposed controls, 
with this infecfiiicsua test-syatem. 
the resulting infection is increased in severity 
Using exposure of mice to an aerosol of influenzavirus as the test system, experiments 
demonstrated a protective effect of hypoxia applied only HOE the infectious challenge. 
This confirms ear!y investigations i n  this field-by others. A m a1 dWerence in patho- 
logic changes? but not in viral titer oE lung tissue was detected between the test and control 
groups, Although the mice may have been sacrificed at an unsatisfactory interval. Expo- 
sure to a simulated space cabin atmosphere (70% O2 in N2’ 5 psia), resulted in a greater 
mortality in the test mice khan in the controls, the same effect seen earlier with 100% O2 
8,t 3 . 3  p s h  (nlm”cPBent 160 ~ I X I  Hg). 
Great wariatio!n an the numbers of lung tumors seen in A/HeJ mice following Induction with 
dibem -anthracene eo.Tat 
kcant’dlfferences seen hetween groups i n  the last experiment of this time. 
e s  to give trouble, This fact probably contributes to the insignif- 
The status of new chambers for more precise control of parabardc environments i s  reported. 
2 
Experiment Mopn #39 was designed to determine the effect on chlamydial pulmonary 
infection in mice of post-challenge exposure to hyperoxia and hypoxia, both in normobaric 
~ ( 1  atmosphere) conditions. The mice were exposed to an infective aerosol in the usual 
manner on day 0, and then placed in! the test environments. The two parabaric environ- 
ments were 77% O2 in N, , 11% O2 in N These mixtures, and tank air for the control 
of 10 or 11 mice each were used for each Mnd of environment, one for observation of 
mortality rates,  the other for sacrifice and titration of lung tissue. 
groups, flowed through t k e one-atmosp i!le r e  chambers containing the mice. Two groups 
The results a re  presented in Table 1. Although the aerosol used was less infective 
than calculated (due to a mechanical defect discovered later) , resulting in insignificant 
mortality rates.. observations om the sacrificed mice were informative. The four factors 
assessed, weight of mouse, weight of lung, degree of oonsnlidation, and infective titer of 
lung QLFU/rnli), all point to a protective effect of 7'7% O2 in comparison to the other two 
groups. This ccPnfir.ms and extends the results seen in earlier tests (see Table 1 of QSR 
#'7$ 31 March 196'7). 
The results with mlce lander hypoxia (11% O2 at one atmosphere strongly suggest a 
somewhat greater degree of infection: particularly evident when one compares the two 
14-d.ay sacrificed. groups sf mice, This result is compatible with that of Exp. Mopn #36 
(see Tahle 1 of QSB #P3, 30 Sept 1968) i n  which the hypoxia was induced by simulated 
altitude at 7 . 3  p ~ l a ) .  
Mortdity rates observed in Cm @ttagi-in&cted mice subjected to either simulated 
altitude with normal PO(, (37, OOcft ,  100% Q2) o r  hypobaric-hypoxic atmospheres (18, 000 
ft, p02 80 mm Hg) hav; been described in QSR's, No. 12  and 13. Either post-challenge 
or bsth pre- and post-challenge exposure to altered atmospheres were utilized. Evidence 
that departures from the nsrmal host-agent effect are primarily dependent upon alteration 
of the parabaric conditions followi.ng, rather than preceding, challenge was  presented in 
QSR No. 14 (Exp- Bsirtt $6). when hyperoxic-normobaric (7'7% O2 at 1 atm) and correspond- 
ing flowing line air and shelf control animals were utilized. The reduced mortality 
observed in the hyperoxie groups was  as pronounced in animals exposed post-challenge 
only, as in those exposed both pre- and post-challenge. On this basis, experiment Psit t  #7, 
utilizing a s-hulated space cabin atmosphere ('70% Q2 in %a2, 5 psia), a hypobaric-normoxic 
atmosphere (18,0100 Pt, p02 80 mm Hg): and line air controls, 1 atm, was designed to 
determine the effect of only past-challenge e-qosure to the parabaric environment. Tan 
mice were used in each group. 
3 
As before the b. p. challenge consisted of 0.25 ml of a 2 x dilution in phosphate 
buffered saline (one LIB50 dose) of C. psitga, strain 6BC - #3305. Survival rates for 
each parabaric group and. controls are presented in Figure 1. 
The effect ob post-challenge exposure to hypoxia is again clearly indicated by the de- 
creased survival time and 100% mortality observed in mice (Group 6) subjected to the 
hypobaric-hypoxic environment. The same ef€ect was  seen in  earlier experiments (Psitt #1 
and #2) reported in QSRqs #12 and #13. 
The resulte (Group B) with simulated space-cabin atmosphere (70% 0 in NZ, 5 psia) 
are the f i rs t  reported, using this host-microbe model. It is reassuring &at the survival 
curre seen in mice under this condition is almost exactly the same as that of the controls. 
This result is i n  contrast to the greater mortality seen in mice exposed to an aerosol of 
influenza virus and placed in 70% O2 in SiZ9 5 psia [Exp. PR-8 # lo ,  see below), and 
emphasizes the meed for attention to pulmonary infections In parabaric conditions. Com- 
parison of this result using 1. p. injected & R2aittaci and that of aerosol-induced 
chlamydial infectbn (mouse pneumonitis strain9 in 8 similar environment, must await 
performance of additional experiments. A.lthough we have assumed that our regularly used 
hypobaric-norrnnxic environment (100% 02" 8 . 3  psia) was closely similar to the 70% O2 in 
X2> 5 pela, atmosphe.re, an asaumptiom supported by the similar results with influenza 
v i ra l  infection in the two types of environment, the results of the current experiment, 
Psitt #72 differ rnwkedly from those of Psitt Ql? in which the 100% O2 environment 
appeared to pr oa.ide some protection from i, p. = induced chlamydial infection in contrast 
to the greater mortality of mice fn this enviromnent following aerosol exposure to 
ehlarnydiae (mouse puenmmitis). This question, too, can be resolved only by additional 
experirneints. 
3 .  Effect o f p g 4 x m m @  qn pulmonary infection of mice with influenza virus. ---- - - -- 
Three experiments have been performed. in which groups of mice were placed in para- 
baric environments before o r  after exposure to selected doses of influenza virus QPR-8) in 
an aerosol, 
for observation of mortality, and the other for sacrifice at intervals , observation and 
titration sf lungs, 
TWO groups of 10-12 mice were placed in  each of the environments, one group 
In Expo PB-3 #9 the test mdee were exposed to parabaric conditions before infection. 
They were placed in chambers with flowing air at '7 e 3 psia (p0 
18,000 f t  altitude), i. e. 
chambers in air at one atmosphere (normobaric, normoxic condition). After 2 weeks they 
were  removed from the chambers! subjected to the aerosol challenge, and returned to a 
shelf in the animal roo= (norrnobaric, normoxic conditions) 
80 mm Hg; simulated 
in hypobaric, hypoxic conditions, an2 the controls in similar 
4 
Figure 2 depicts the survivor-curve of PR-8 #9, and it may be seen that mortality in  
the control group was  7'0% ("/IO mice). In contrast, 2 only of the test group of mice died. 
This result is similar to that reported for mice exposed to influenza virus aerosol and 
placed in a hypobaric-hypoxic chamber ( E q .  PR-8 #3, Fig. 5, QSR #12), 
and directly confirms the earlier e-xperimentlts of gaiter, et at, 1952, 1955, and of Berry, 
et at ,  1955, cited in QSR #12. 
Lungs were harvested f'mn test and control groups on days 4, 5, 6 and 7 ,  as indicated 
in Fig. 2,  and the observations on these harvests are recorded in  Table 2. These intervals 
were not optimal and this experiment, and probably not satisfactory, as previous evidence 
indicates that the highest viral titers are found in the lungs just before the mice begin to 
die. %a this experiment the first death did not occur until the 11th day, and there is little 
or no evidence in Table 2 for a significant difference between the test and control groups. 
En E-q. PR-8 # I O  two parabaric conditions were used only y_p after aerosol challenge, a 
simulated space cabin atmosphere (70% O2 in N2' 5 psia, and tank air at 7 . 3  psia, as in  
the preceding experiment. Figure 3 indicates the results of observations on survival. The 
space-cabin atmosphere (Group B) had the same effect, i. e. , increased mortality, as ob- 
Herved before in  our regular hypobaric, normoxic environment (100% O2 at 3.3 psia). The 
latter result was observed Ea Exp. ' s  PR-8 #3, #4, and #8 in QSR's 812 and 14. 
Again the hypobaric, hypoxic environment (Group C) exerted a protective effect, con- 
firming previous experiments described and cited above. 
Although not indicated in Fig. 3 ,  lung harvests were taken from parallel groups of mice 
on days 4: 5, 6 ,  7, and the usual observations were made (Table 3). Again: the last lung 
har17est occurred 3 days before the first death in the parallel group and interpretation of 
the data in Table 3 is difficult. There is very little evidence of differences among the 
groups except when the average degree of lung consolidation for entire groups is calculated. 
The lung more for Group C, in  which the parallel group had the least mortality, was 
about one-half that of the control, Group D, as well  as that of Group B. 
The mice of Em. PR-8 #11 w e r e  held at  one atmosphere pressure, but the 3 groups 
were subjected to hyperoxia (77% in Sa,), hypoxia (11% in  N29 and to a iP  (controls) before 
aerosol challenge. They were then put on the shelf. The challenge dose of aerosol was 
less than predicted (a mechanical deficiency) and .mortality was negligible. The slight 
differences observed (recorded io Table 4) cannot be regarded as significant compatible 
with wkat has been seen before, Group e ,  e-xposed to hypoxia, appeared to have definitely 
less lung consolidation than the other 2 groups. 
5 
4. -of parabarosis on induction of pulmonary tumors in  A/HeJ strain mice 
The cumulative loss of A/HeJ mice in hypobaric-normoxic or hypobaric-hypoxic envir- 
onments following induction by dibenz-anthracene , made statistical evaluation impossible 
(QSW #14, Dec. , 1968)). Similar parabaric conditions were again employed in the present 
experiment. Equal weight groups of 14 or 15 mice each were again exposed to the various 
parabarfa: conditions, as recorded i n  Table 5 immediately following d. v. injection of 0.1 mg 
of dibenz -anthracene 
After exposure to the various altered atmospheres for the times indicated, the mice 
were held in  ambient room atmosphere for four months and then sacrificed under anesthesia. 
The lungs were infiltrated in situ and tumor nodules counted as before. 
Although all animals in the various experimental groups survived in this instance, the 
resulting incidence of lung tumors observed at sacrifice was  very erratic within each 
experimental group. As indicated in Table 5 the mean value for tumor incidence in each 
group is generally low but individual animals ranged from no tumors present to over 50 in  
same instances. This  is reflected in the large standard e r ro r s  calculated for each para- 
haric group. No hference of alteration in tumor incidence can be made at the level of sig- 
nificance calculated by Student's t i n  comparing the various parabaric groups. 
Steps have been taken to control more vigorously several factors possibly resgcrnsible 
f o r  the withia-group variations that have occurred in this type of experiment. Hf this 
d.ifficulty canaot be overcome in experiments now underway, this line of inquiry will be 
3,bandoned 0 
A s h i p i ~ g  accident has again delayed delivery of two additional animal chambers that 
will allow more extensive experiments both at sirnulated altitude and depth. These will be 
delivered in April, 1969. In the meantime, the one chamber of this type has been employed 
for  exploratory short-term tests. Present evidence indicates that these chambers will  
indeed extend the range of parabaric conditions that can be satisfactorily investigated. 
Also plans a re  underway to construct similar chambers, but without the capacity to 
a,llow marked departures from normal pressures. These will serve to house the control 
animals, thus allowhg more efficient use of t,he pressure chambers only for increased or 
decreasedpressures. 
A few observations have been made on temperatures of mice taken to simulated altitude, 
as projected in the former QSR. These will  'be continued with new thermistors designed 
for use in the new chambers. 
Table 1. Experiment Mopn #39. Effect of post-challenge parabarosis on mouse lung infection 
with C. - trachomatis (strain mouse pneumonitis) 
Observations on sacrificed mice 
Day of Av. mouse Av. lung Lung Lung titer Environment 
(1 atxn pressure) Mortality sacrifice" wt. (gm9 wt. (gm) consol. IFU/ml~x104) 
77% O2 in N2 0/11 11 21.8 0.26 0.8** 5.2+ - 0 . 1  
(3, 1 , 0 , 0 , 0 )  
14 24.5 0.20 0.06 1.5+ - 0.6  
@.3 ,0 ,0 ,0 ,  0) 
1/11 11 17.3  0.34 1 .7  92 - +19 
44,3,1,0.5,0)  
2 
11% O2 in N 
259 +18 
_3 
14 16.4 0.41 2.4 
W 9  3,2,2,1D 
64 .i. 4 - Air (control) 1/10 11 17.9 0.26 1 .5  
(4, 1,1,1,O95P 
36 4. 3.5  - 14 18.3 0.36 1.3 
fd9 2,1 ,0 .5 ,0)  
* 5 mice were sacrificed in each group. 
*>) Average score, and (individual scores) on an arbitrary 0-5 scale. 
IFU =: Inc%usiom-forming units. 
Table 2 0  E q .  PR8-9. Effect of two weeks pre-challenge parabaric exposure with 
aerosol of PR-8 influenza virua on mouse lung infection. 
Day of NO. Infectivity titer 
Environment sacrifiam of A V ,  lung Lung of lung 
post- halle en get mice wta [gm9 cowssol. * @ID50 ;K&ber) 
Group B 
Tank air9 
7.8 psla 
4 2 0.20 0.0 
402 09 
(09 09 0) 
5 8 0.24 0 .0  
6 
lo6*  
lo6*  
a 3 0.28 
Group C 
Line air, 
1 atmosphere 
4 2 0.26 0.0 
( 0 9  09 
5 
6 3 0.27 1 . 3  
@,I2 1) 
7 3 0.27 1. a 
104. 6 
* Arbitrary 0-5 scoring for degree of lung involvement. 
t Aerosol exposure. 20 minutes using 1 : l O O  dilution of BR-8, pool A, at 0 . 3  ml/ 
min, RH 93% e 
Table 3. Exp. PW8-PO. Effect of parabaric cond8tioms on mouse lung infection 
following aerosol challenge with PR-8 influenza vlrus 
Day of NO.  Infectivity titer 
post- challenge T mice wt* Qgm9 scores* groupQ12) QElID50;K%rber) 
Ewvirament sacrifice , Of lung Individual Av. of of lung 
70% Q2 5 3 0.24 0.0 lo7.  
(0, Q? 0) 
5 psaa t% 191) 
in N2 0.83 
2 6 3 0.33 1 .25  
7 3 0.31 2.0 
a ,  3 psia 6 3 0.26 8.5 
@,5,@. 5, e. 5 )  
8.5 a 3 0.27 1.2 > 10 
-1 3 0.25 0.0 IO7* 
5 3 8.21 0. a IO7' 
1 a h  6 3 0.28 0, a > lo8* 
(07@!, 0) 
Group D 
Tank air control Ql? 1 , @ )  
0 .92  
(1,O. 5,o.  5 j  
8.3 7 3 8.26 2 . 3  2 10 
$' Arbitrary 0-85 scoririg €or degree of lung involvementnt. 
t Aerosol exposure. 20 minutes us in^ IA00 di1ution of PW-8, pool A, at 0.31 ml/min, 
BH 
Table 4. E-. PR8-11. E€€ect of pre-exposure to altered atmospheres on mouse lung 
infection f'ollowing aerosol challenge with PR-8 influenza virus e 
Observations on sacrificed mice 
E nvir onment Day of No. Av. mouse Av. lung Lung Infectivity titer 
(pipre- Mortality sacrifice of wt. I(gm) wt. Qgm) cons0l. . of lung 
challenge) (post- mice 
Group B 
1 at.m 
2/10 4 3 18.2 0.20 0 .1  lo7*  1 
(090 ,  0.3) 
5 3 18.3 8.20 0.4 1 0 ~ 0  
6 3 16 .8  0.21 1,2 l o a e  O 
a 3 21.0 0.28 1 . 5  lo6.  
(0. 6,O. 3,O. 3) 
c2, 1,0,69 
l / 9  4 3 15. a 8.18 0 - 2  PO7. a 
(0, 090.69 
GrQUp &r 
5 3 14.8 0.18 0.2 lo6 -  
11% o2 (0- a ,  0 . 3 ~ 0 9  
7 1 atrn 6 3 16.2 0.18 0 . 3  
(0 .6 ,0 ,3 ,  0)  
a 2 14.0 0.21 0. a 1 8  
011 0 4 3 20.5 0.19 0.2 I O 6 .  El 
(0.3,O. 3,og 
Group D 
5 3 18.8 0.21 0.4 1 8  
Air control (0- 6,O. 6,O) 
1 atrn 6 3 18.3 0.22 0.7 lo6*  
a 3 20. a 0.27 2-37 lo6. O 
Q1,O.  6? 0-6)  
No. mice at Type and. duratfon of No. mice at Average No. 
Group challenge eaxiiron Ament sacrifice tu.mors 
15 
g: '15 
D 14 
E 13 
F ra 
100% cIz9 3 . 3  peda 15 4.5 (9 0,9 
2 weeks 
Tank air9 a 0 3 paia 15 3 .3  (9 1.0 
2 weeks 
11% 0 inN,, 1 a.tm 8 weeks 14 
4.7- 0 1.3 
Tank ai.?, I afm 14 7.4 g 3.7 
2 weeks 
EFFECT OF ALTERED ATMOSPHCRES ON SURVIVAL OF MICE 
FOLLOWING 1.P CHALLENGE WITH C.psittaci 
--e-- 
--o-.-. 
GROUP B- 70% 4 IN N;! ,SpliO 
GROUP C- TANK AIR, 7.3 PSI0 - G R , W  D- TANK AIR CONTROL,lolm. 
io0 
Bo 
-1 
E 6 0  
3 
u) 
\ 
$ 40 
z W 
w 20 n 
0 
DAYS POST CHALLENGE 
Figure 1. Exp. Psitt-7. Strain 6BC injected in an estimated 
dose of 1 LDs0. 
EFFECT OF ALTERED ATMOSPHERE BEFCRE AEROSOL CHALLENGE WITH 
PR-8 INFLUENZA VIRUS ON MOUSE SURVIVAL 
- * - W P C -  TANKAIR ZSWCp02 80mnHg) 
-0- uxwp D- AIR CONTRa, I otm 
100 
BO 
-1 
60 
5 
f 40 
5 
2 20 
L 
w 
0 
DAYS POST CHALLENGE 
Figure& Exp. PR8-9. 
EFFECT OF ALTERED ATWHERE ON SURVIVAL OF MICE 
FOLLOWINO AEROSOL CHALLENGE WITH pR8 INFLUENZA VlRUS 
0 
AUERU) AMSPHERE D 
l I I I 1 1 I l l I  1 1 1  
ZWLEKS 0 I 2 3 4 5 6 7 8 9 IO II 12 13 14 IS 16 
DAYS WST-WALLEM 
Figure3. Eq. PR8-10. 
EFFECT OF PARABARIC CONDITIONS ON SURVIVAL OF 
MICE FOLLOWING AEROSOL CHALLENGE WITH A CHLAMYDIAL 
AGENT( MOUSE PNEUMONITISY 
0 % 
0 I 2 3 4 5 6 -  k Ib /I ;2 /3 Id lk I; I‘i. 1 ‘ 8  1‘9 h 
DAYS POST CHALLENGE UNDER ALTERED ATMOSPHERES 
Figure 19. C. trachomatis pulmonary infection at simulated 
altitude (36,000 ft) and 100% 02- 
EFFECTS OF ALTERED ATMOSPHERES ON MORTALrm RATES OF 
EXPERIMENTAL MICE 
- 
100% 02, KyPoxrA 
(AIR, 7.3 PSIA, 
or 11% O,, 1 ATM) 
3.2 PSIA 
DISEASE 
AGENT (77YcO21 I ATM) 
INFLUENZA 
VIRUS 
C. TRACHOMATIS 
(mouse pneumo.) 
- 
C. PSITTACI 
-I__ i” 
COXSACKIE B 
VIRUS _I, 
7,  b ,Is MORTALITY INCREASED, DECREASED, OR NOT CHANGED. 
Figure 20. 
of experimental mice. 
Effects of altered atmospheres on mortality rates 


Effects of high and low barometric pressures on susceptibility and resistance to infection Quarterly status report, 1 Apr. - 30 Jun. 1969

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