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The University of Chicago

The Effect Of Anoxemia On The Size Of The


Heart As Studied By The X-ray And The
Significance Of The Pericardium In
Acute Cardiac Dilatation
Produced By Anoxemia

A Dissertation
Submitted To The Graduate Faculty In
Candidacy For The Degree Doctor
of Philosophy

Department of Physiology

By
Edward Jerald Van Liere

Chicago, Illinois
March, 1928
PART I.

THE EFFECT 0F ANOXEMIA ON THE SIZE OF

THE HEART AS STUDIED BY THE X-RAY


Kaufmann and Meyer(1) clinically studied the hearts of
soldiers who had returned from campaigns in mountainous districts,
and reported that the hearts of these soldiers were greatly
increased in else; but these enlarged hearts decreas e d in si ze
wit h shor t re sts only, or m ore quick ly afte r tre at ment with
digitalis,

Whitney(2) working at Mineola found by percussion a con -


siderable dilatation of the hearts of aviators while they were
subjected to anoxemia. He states that of 10 medical officers
subjected to anoxemia by rebreathing 5 of them developed a
marked cardiac dilatation; one corresponding to an altitude of
14 , 000 feet(about 12 percent oxygen) , one to 16 , 000 feet , two to
18,000 feet and one at 20,000 feet.

LeWald and Turrel (3) , working on aviators and using the


x - r a y, r e p or te d o nl y a sl i g ht i n cr e a se in t he s i z e of t he ca r -
diac silhouette in some cases, and on the other hand, some showed
a slight decrease; in no case was there a pronounced dila tation.
Barcroft et al. (4) ascertained no cardiac enlargement
as measured by the x-ray at an altitude of 14,000 feet. In
three cases it eras found that the heart was smaller than at
sea level.
Somerwell (5) reported that all the men who went higher
than 27,000 feet had dilated hearts, from which it took from
one to three weeks to recover.
Takeuchi (6) in 1925 found that anoxemia caused an immediate
enlargement both in length and width of the heart in cats.
2
He made his observations by opening the chests administering
artificial respiration by an appropriate apparatus in which
the amount of oxygen could be regulated. The changes in the
s i z e o f t h e h e ar t w e r e t h e n s t u d ied b y m e a ns o f the c i n e -
matograph.
Jarisch and Wastl (7), using the cardiometer, found a
distinct cardiac dilatation in anoxemia.
Gremel s an d S tarl i ng (8), using the hea r t -lung pr epa r a -
t i o n r e ported th at th e cardia c dila ta tion is m ost pr onounced
below 10 percent oxygen and at the same time other signs of
cardiac failure appeared.
The present work was undertaken because of the
conflict- observations in man, and the unphysiological
experimental condi ti on s i n most of the studies on a nim a ls ° The
dog and cat, bec aus e o f t he po sit i on o f t he di ap hra gm, gi ve be tte r
x - r ay s i l h o u e t t e s o f t h e h e a r t t h a n d o e s m a n , a n d i t i s p o s s i b l e
i n animals to employ greater degrees of anoxemia.
Procedure. The anoxemia was induced by reducing the
atmospheric pressure in a steel respiratory chamber described
by Kolls and Loevenhart (9). A large mercury manometer was
mounted on a meter stick and connected to the chamber by pres -
s u r e t u bi n g , so th at th e pr essur e in the cha m ber wa s r ea d dir -
e c t l y i n m i l l im e te r s o f me r c u r y an d c o n v e r t e d t o o x y g e n p er -
centage ° A Crowell rotary pump, run 1/2 by H.P. motor was used

to reduce the pressure in the chamber. The speed of the with -


d r a w a l o f t h e a i r w a s r e g u l a t e d a t w i l l b y v a l v e s i n t h e o u t flow

and inflow tubes. The inlet valves of the chamber were


3

so ar ran ge d t ha t it too k fr om 6 to G m in ute s to re a ch th e d e -


sired pressure and the animal was kept at this pressure from 3
to 4 minutes; these conditions were kept approximately uniform
in all the experiments.
D og s w ere trai n ed to lie q uietly on their ba cks on a n
appropriate animal board during the 1 to 5 second exposure of
the x-ray. The distance from the center of the tube to the
film was kept at one meter. The animals were then placed into
the respiratory chamber. The removal of the animal from the
chamber and taking the x-ray picture required from 20 to 30
sec on ds. I t w as a ime d t o pl ace t he an im al in a po si tio n i de nt -
ical with the control. As it was practically impossible to

train the rabbits and guinea pigs to lie on their backs, ap-
propriate animal boards were made to which these animals
could be fastened and they were in this way both x -rayed for
control and placed into the chamber.
In the remainder of the work barbitalized dogs and
cats were used. Barbital was given in doses of 250 to 280
mgm. per kilo b ody weight. As a rule it was give n intrav -
enously, although in a fe w cases it was given by means of a
stomack tube.
I n th e b eg in nin g of th e w or k sev er al pi ctu re s w er e tak en
of th e a ni mal i n the c our se of a d ay an d o n two a n i m a l s
pictures were t a ken on d iffere nt days. I t was s o on found,
however, that the percentage of difference in the area of the
c a r d i a c si l h o u et te w a s s o s m a l l th a t i t wa s n o t d ee m ed worth
while to take more than one or two control pictures.
4
Some of the unanesthetized animals were placed in the chamber
several times so that several pictures were made on the same
animals; in the table of results, however, only the average
figure is given.

It was realized that criticism could be made of the


results obtained as it took 20 or more seconds to remove the
animals from the respiratory chamber and place them under
the x-ray tube. It is also admitted that it is nearly impossible
to place them in exactly the same position for the two
photographs. In order to check the results in the above methods
anoxemia was induced by an appropriate mixture of oxygen and
nitrogen in an apparatus ordinarily used for clinical
administration of nitrous oxide oxygen. The tracheal can nula
of the animal was connected directly with the apparatus so it
virtually was a closed system, except for the fact that a type
of fluttler valve was inserted near the tracheal can nula, so
that the expired air could not re -enter the otherw i se c l o se d
s y s t e m . A p p r o x i m a te l y t he sa m e p e r c e n t a g e o f oxygen was
used as in the respiratory chamber and the results obtained
were, within a small per cent of experimental error the same.

The area of the heart shadow was computed by sketching


the radiographic silhouette by means of a pen and then meas-
uring the area by a planimeter, as described by Bardeen (10).
Results: The table on the following page gives the
results obtained:
Animal Comments
Cardiac area Increase
Weight in cardiac oxygen
Normal area in
Anoxemi anoxemia
kgm. a per cent per cent
Dog 1 6 28.70 33.54 18.85 4.82
sq. cm. sq. cm. No anaesthetic
Dog 2 3 17.86 20,83 16.63 4.82 No anaesthetic
Dog 3 7.8 32.89 38.05 15.68 3.0 Barbital

Dog 4 17 66.43 65.14 15.43 3.5 Barbital


Dog 5 4.25 29.02 33.02 13.77 3.20 Barbital
Dog 6 5.1 27.09 29.99 10,70 5.45 Barbital
Dog 7 3.1 19.35 20.96 8.33 5.5 Barbital
Dog 8 2.5 15.86 17.09 7.71 7 Barbital

2.4 Barbital
Cat 1 9.93 11.60 16.81 4
3 14.31 16.44 14.88 3.5 Barbital
Cat 2
Cat 3 3 13.28 14.64 10.20 5.25 Barbital

7.09 8.19 15.45 4 No anaesthetic


Rabbit
Guinea pig 490 gms. 3.22 3.74 16.00 4 No anaesthetic
6
It will be noted that the unanesthetized animals show ed
the largest increase in cardiac area, although the oxygen
percent was not as low as in some of the other animals. This is
probably due to the fact, particularly in the case of dogs, that
they showed considerable excitement when the oxygen pressure
became low; they would often bark and scratch on the glass doors
of the respiration chamber. They were thus under the influence
of exercise and in some ways their condition vas analogous to the
findings of Somervell of the Mount Everest E x p e d i t i o n . I n t h e c a se
o f t h e u n a n e s t h e t i z e d r a b b i t a n d gui ne a p ig, in sp it e of the
f a ct t ha t the y we re fa ste ne d to the animal board, they
nevertheless showed restlessness when the pressure in the
respiratory chamber became rather low.

It will also be observed that dogs of different size


were used; the smallest weighed 2.5 kilos and the largest 17
kilos. Incidentally two or three of the dogs were pups from
5 to 8 months old; they apparently withstood acute anoxemia as
well as other animals.

As Takeuchi did his work on cats, it was thought well to


try them as he reported rapid and pronounced cardiac dil-
atation in anoxemia. The results on the cats, however, did not
materially differ from those in other animals.
By the methods described, in general, it may be said
that the greater the degree of anoxemia, the greater the
cardiac dilatation, up to a certain maximum, as shown by the
following examples:
7

Ox ygen Cardiac Area Increase in Size

Cat-2.8 k i l o s

per cent sq. cm. per cent

Normal........... 14.25
Anox emia..... 8.68 14.27 0
Anox emia..... 6.89 15.09 5.89
Anox emia..... 3.31 16.44 15.41

Dog-3.5 k i l o s
Normal......... 22.09

Anox emia..... 8.27 22.54 1.95


Anox emia..... 4.0 24.18 4.22

Anox emia..... 2.6 27.86 20.66

The above r e s u l t s arc somewhat contradictory to the

findings of Takeuchi. He states that the princip l e e f f e c t on

the size of the heart seems to be in the less ex treme ranges

of anox emia. But Gremels and Starling working on the heart

lung preparation found that, in general, the greater the de -

gree of anox emia the greater the cardiac d i l a t a t i o n . They

interpret the r e s u l t s of Takeuchi as being due to vagal a c t -

ion. The question of the v a g u s in anox emia w . i l l be dealt with


in a later paper.

The present findings are not necessarily in c o n f l i c t

with those of Barcroft et a l . The a l t i t u d e at which their ob -

servations were made was 14,000 feet, corresponding approx -

imately to 12 per cent ox ygen; thin a l t i t u d e , however, caus-


ed seme of the members to be rather severely a f f l i c t e d with
8

mountain sickness. No cardiac dilatation occurred at the above


oxygen percentage by the methods employed in this work on
anaesthetized animals. The statement that in man anoxemia
actually decreases the size of the heart is also of interest. I
h a v e s o m e e v i d en c e i n t h e c a s e o f t h e d o g t h a t at r e d u c e d
atmospheric pressure corresponding to about 9 to 11 per cent
oxy ge n t he ca rd i ac ar ea i s d im ini she d. Th e de cre a se is, h ow ev e r ,
v e r y s l i g h t amoun ti n g to only a bout 1 to 1 1/2 per cent. Wh i l e
t h i s l i e s w i t h i n t h e e x p e r i m e n t a l e r r o r , i t w a s n o t i c e d in
several animals and the reports on man seem to corroborate it.
This phase of the problem ,however, needs more quantitative
work.

LeWald and Turrel working on man using less reduction in


oxy ge n p er ce nta g e t ha n i n my se ri es, re po rt ed on ly sl igh t an d
inc on sta nt ca rd i ac dil at at ion . I n one o r t wo ca se s the a n o x e m i a
w a s s u f fi c i e n t t o i n d u c e fa i n t i ng . Th e y s u g g e s t tha t the fai lu re
to d emo ns tr ate c ard ia c di la tat io n mig ht b e d ue t o vas od ila ta ti o n
in th e e pl anc hn i c a re a, he nce t he ro en tge no gram of an empty
heart. More work is needed on this particular p o i n t , I t m a y a l s o
b e m e n t i o n e d a g a i n t h a t t h e c a r d i a c s i l houette of man cannot
be so accurately outlined as in the dog or cat, because in these
animals the daiphragm lies lower and in many instances the
entire heart shadow may be easily dis c e r n e d . Th e e r r o r s d u e t o
t h e d i f f e r e n c e i n t h e t r a ns v e r s e diameter of the heart caused by
the respiratory movements as described by these authors in man
are less serious in the dog and the cat.
9

I t h a s b ee n r e po rt e d b y d if f e r e nt w r i t e r s t h a t a nim a l s
subjected to low atmospheric pressure in a chamber are great ly
d i s t r e s sed by th e g ases i n the stoma ch a nd intestine. The
increased intra-abdominal pressure causes the diaphragm to en -
cro ac h u po n the spa ce of t he th or aci c cav it y a nd t hus d ist or ts
t h e n o r mal con tou r of th e hea r t. This er r or wa s r uled out by the
second described method of inducing anoxemia.
Conclusions

1. Dogs, cats, rabbits and guinea pigs subjected to an -


oxemia (8.3 per cent to 2.5 percent) showed acute cardiac dil -
a t a t i o n so e v i de n c e d b y t h e x - r a y .

2, The greater the degree of anoxemia, the greater the


cardiac dilatation up to a definite. maximum.
3, There is a rather marked individual variation in this
response of the heart to anoxemia, some animals showing a
cardiac dilatation at a less reduction in oxygen percentage
than others.

Wish to express my thanks to Dr. A. S. Loevenhart for


the lo an of h is r esp ir ato ry ch am ber an d to Dr . R . S . A ll en wh o
assisted in a part of the technical work. I am also indebted to
Dr. A. J. B. Eyeter f or his he l p f u l su g g e s t i o ns and
e n c o u r a g em e n t . I especially wish to thank Dr. Carlson for
putting the equipment at my disposal which made the work
possible, and for his constructive criticism throughout the work.
10

Bibliography

(1) Kaufmann and N.H Meyer. 1917. Med, Klinik, xliv, 45.
(2) Whitney, J.L. 1918. Journ, Amer, Med. Assoc., lxxi, 1382.
(3) LeWald, L.T. and G.H. Turrel, 1920. Amer. Journ. Roent., vi i.,
no. 2, 67.
(4) Barcroft et al. 1923. Phil. Trans, Roy. Soc., B, coxi,

416.
(5) Somervell, T.H. 1925. Journ. :Physiol., London, 1x,
no. 4, 282.
(6) Takeuchi, K, 1925. Journ, Physiol., 1x, 208.
(7) Jarisch, A. and H. Wastl. 1926. Ibid., lxi, 297.
(8) Greme1s, R. and E.H. Starling. 1926. Ibid., lxi, 297.

(9) Kolls, A. C, and A. S. Loevenhart, 1915. This Journal, xxxix,


67.
(10) Bardeen, C.R. 1918, Journ, Anat.' xxiii, 423.
P A R T II.

THE SIGNIFICANCE OF THE PERICARDIUM

IN ACUTE CARDIAC DILATATION

AS PRODUCED BY ANOXEMIA
1
It has been known for a long time that the pericardium
m a y i n c er t a i n co n d i t i o n s a f f e ct th e a c t i o n o f t he h e a r t a n d
a l s o m a y a f f e c t t h e c i r c u l a t i o n . T h e i n f l u e n c e o f a n i n c r e a s e in
intrapericardial pressure was first suggested by Morgagni as
early as 1761. Cohnholm (1839), Francoie-Franck (1897), Lewis

( 1 9 0 8 ) an d others proved the physiologica l signif ica nce of a

r i s e i n i n t r a p er i ca r d i a l p r e s s u r e. Th e y f o u n d t h a t a n
i n t r a p e r ic a r d i al p r e s s u r e w h i c h is a l i t tl e a b ov e th e v e n o u s
p r e s s u r e m a y i n t e r f e r e w i t h t h e d i a s t o l i c f i l l i n g o f t h e heart.

B a r n a r d (1 8 9 8 ) t o o k s t r i p s o f t h e f i b r o u s l a y e r s o f the

pericardium and subjected them to traction. He concluded t ha t


the p eri ca rdi um i s i ne xte ns ibl e. H e a ls o s ub jec te d the heart
with its pericardium removed to pressure and found that i t
ruptured at 1/2 to 1 atmo spher e, wher ea s with the per ica r d -

ium intact i t ruptured at 1 1/4 to 1 1/2 atmospheres. Hi s

conclusions from these observations were that the pericardium


is i m p o r t a n t i n n o r m a l l i f e f o r t h e p r e v e n t i o n o f a c u t e
c a r d i a c d ila ta tio n.
Kuno (1917) working with the heart -lung preparation
c o n c l u ded th at th e peri car dium is necessa r y f or the unim p -
aired working of the heart in normal life.
Felix (1 925) induced valvular and other
lesions in dogs' hearts and attempted b y modifying the
p e r i c a r dium to i nfluence these valvular defects.He found
that making he pericardium smaller hampers heart motion while
making it
lar ge r h ad fa vo ra ble in fl ue nce o n cer ta in in duc ed l esi on s,
2

particularly mitral defects.


The latest work i s that of Wilson and Heck Felix
( 1 9 2 7 ) .They made the interesting observation that in the dog
the a p p a re n t r est r a i n i n g a c t i o n of t h e p e ri c a r d ium o n t h e
d i a s t o l e a t l ow ve n o u s p r es s u e is d u e t o th e t o nus o f t h e
d i a p h r a g m, w h i ch a f f e c t s t h e h e ar t t h r o u gh t h e
p e r i c a d o -d i a p h rag m a t i c a tt a c h m en t s . With these
a t t a c h m e n t s s e ve r e d t h e y f o u n d th a t a t a n e f f e ct i ve v e n o u s
p r e s s u r e o f a b out 1 5 c m . o f w at e r t h e d o g 's h e a r t in
d i a s t o l i c c o m p le te l y f i l ls t h e p e r i ca r d i u m .
Rehn (1913) studied 5 dogs in whic h the pericardium h a d
b e e n p a r t i a l l y o r t o t a l l y r e m o v e d a n d r e p o r t e d n o i l l effects on
the health of the dog. Mazzone (1912) removed the pericardium
in 7 dogs and came to the same conclusion. Yamada ( 19 1 7 ) s l it
t h e p e r i ca r d i u m i n a s e r i e s o f 1 4 d o g s . He t h e n subjected
t h e s e a n i mal s to exerci se dur ing the post -oper a tive period. He
found no evidence of dilatation or other important pathological
changes. Yamada concluded from these experiments that t he
pro te cti ve in fl ue nce o f t he pe ri ca rdi um wa s not v e ry
i m p o r t a n t. H e di ffered, ther ef or e, f r om the views of Ba r na r d
and Kuno. Beck and Moore (1925) removed the pericardium in 5
animals and subjected them to severe exercise. These authors
f o u n d th at th e an i mal s responded to sever e exer cise ver y well
and in no way did the general health seem to be impaired. A
n u m b e r of c l in i ca l c a s e s h a v e b ee n r e p o rt e d o f p ar t i a l o r total
congenital absence of the pericardium (Moore, 1925; Grant,
1926). These conditions did not appear to produce any
3

clinical symptoms and the death of these patients seemed in


no way or hastened b y these congenital defects.
S i n ce th ere i s sti l l a diver gence of opinion in r ega r d to
the importance of the pericardium, it was thought worth while
to study the influence of the pericardium on the acute
dilatation of the heart induced by anoxemia, endeavoring to
m a i n t a i n th e an i mal s i n a s nor ma l physiologic condition a s
possible.
Procedure. Barbitalized dogs, cats and monkeys were used. In
the case of dogs and cats barbital was given intra venously; in
the monkeys intramuscularly . An x-ray picture was now taken
for the control. The distance from the plate to the center of the
tube was one meter. The length of exposure va r ied f r om 2 to 3
s e c o n d s. I mmediatel y afte r the contr ol p i c t u r e w a s t a k e n , th e
a n i m a l w as p l a ced in a s t e e l r e s p ir atory chamber (Kolls and
Loevenhart, 1915) and subjected to anoxemia. The same
apparatus and methods were used as des c r i b e d b y t he s e n i o r
a u t h o r i n a p r ev io u s p a p e r ( V a n Li e r e , l927). Eight minutes
were allowed to bring the pressure down to the desir ed level
a n d i t was h el d th ere for 2 minutes. The animal was removed
and the x-ray picture taken again; removing the a nim a l a nd
t a k i n g th e x-ray pi cture r ecq uir ed a ppr ox i m a t e l y 2 5 s e c o n d s .
It was aimed to place the animal in the identical position as
the control.

A tracheal cannula was now inserted and artificial


respiration vas administered. A small opening was made in
the 4th or 5th interspace in the approximate region of the
cardiac
4
apex. The pericardium was grasped with a small hemostat and
WAS slit longitudinally its entire length or it was entirely
removed- generally the latter was done. The wound was par tia lly
clo se d, th e l un gs we re th en ex pa n ded a nd he ld th u s f or a f e w
s e c o n d s u n t i l t h e r e m a i n d e r o f t h e w o u n d w a s c l o s e d . The
artificial respiration was now discontinued and the ani - mal .
allowed to resume its normal breathing.
The animals were allowed two hours to recover from t h e
effects of the operation. A c o n t r o l p i c t u r e w a s a g a i n taken.
The animal was placed in the respiratory chamber and
subjec ted to an o xemi a. I t wa s a imed to duplica t e a s closely
as possible the procedure previous to the removal of the
pericardium as described above.
I n o r d e r t o c h e c k t h e r e s u l t s o b t a i n e d w i t h t h e u s e of
the respiratory chamber, the nitrous -oxide oxygen appa ratus
was used as described in a previous pa per (Van Liere 1 9 2 7 ) .
Th e r e s u l t s c o mpa r e d f a v or a b l y t o t h o s e o bt a i n e d w i t h the
respiratory chamber.
C o n s i d e r ab l e d i ffi c u l t y w as e x p e r ie n c e d i n t ak i n g x-ray
p i c t u r e s of th e h eart afte r r em ova l of the per ica r dium as the
heart would often rotate. The fluoros cope was used
b e f o r e th e pi cture was ta ken in or der to see whether the
hea rt wa s in it s nor ma l p os iti on .

The cardiac silho uette was traced vith a pen and the
area measured by means of a planimeter.
R e s u l t s . T h e t a b l e o n t h e f o l l o wi n g p a g e g i v e s t h e .

results obtained.
Table 1
Cardiac area Pericardium
Cardiac area Increase Cut
Anoxemia oxygen Increase
cardiac in Anoxemia
Animal Weight Normal
in area in cardiac
Anoxemia anoxemia Normal Anox. area in oxygen
anoxemi
per a
kgm sq. cm. per cent p e r c e n t p e r c en t
sq.cm. cent
.
Dog 1 7.8 32.89 38.05 15.68 3.0 32.25 36.95 14.60 3.0
Dog 2 17. 56.43 65.14 15.43 3.50 63.85 70.62 10.61 4.0
Dog 3 3.1 19.35 20.96 8.33 4.50 22.38 24.63 10.08 4.50
Dog 4 5.1 27.09 29.99 10.71 4.45 27.41 . 29.34 7.06 5.40

Dog 5 4.5 24.18 27.60 29.67 7.5 0 5.0


Dog 6 6.3 32.50 33.41 35.60 6.55 5.0

Cat 1 2. 10.32 10.50 12.12 15.32 4.0

Cat 2 2.5 13.41 13.54 15.15 11.90 4c0


Cat 3 2.3 12.38 14.83 16.25 9.57 5.0

M o n ke y 1 2.3 10.64 12.64 18.79 3.0 10.64 13.22 24.24 3.0

Monkey 2 2.8 11.73 15.15 29.04 3.0 11.93 16.77 40.57 3.0
Monkey no.
Table 2
1; weight 2.3 kg m,
Cardiac area in sq. cm. Increase in cardiac
Date Normal Anoxemia area in per cent. Comments
5% 0 4% 0 3% 0 3% 0
5% 0 4% 0
11.15 12.06 12.64 12.64 8.06 13.26 13.26 No anesthetic
May 2
May 4 11.03 11.93 12.32 12.32 8.20 11.70 11.70 No anecthetic

May 5 11.09 12.58 13.77 12.77 13.44 15.15 15.15 No anesthetic

11.09 12.19 12.64 12.64 9.92 1307 13.97 NO anesthetic


May 10
10.64 12.25 12.25 12.64 15.13 15,13 18.79 Barbital.
May 12
10.64 12.26 12.58 13.22 15.13 18.23 24.24 Pericardium cut
May 12
Monkey no. 2; weight 2.8 kgm.
13.87 15.09 16.90 17.22 8.80 21.85 24.15 No anesthetic
May 9
14.19 16.45 17.42 18.05 15.92 22.76 27.27 No anesthetic
May 10
13.55 16.13 16.77 17.09 19.04 26.76 26.12 No anesthetic
May 14
11.74 12.53 13.22 15.15 7.15 12.60 29.04 Barbital
May 25
May 25 11.93 13.22 13.55 16.77 10.81 13.57 40.56 Pericardium cut
7

Discussion. It appears from the data obtained from the


c a t s a n d d o g s (t ab l e 1 ) th a t t h e he a r t w i th t h e p e ri c a r d i u m
removed seems to withstand anoxemia as well as the heart with

the pericardium intact. This is, however, more apparent than

real. On the whole less severe degrees of anoxemia were used in


the cases where the pericardium had be en removed. It must also
be pointed out that unless approximately 2 hours were a l l o w e d t o
elapse after the operation for the removal of the pericardium,
the heart would not be back to its normal size. I n so me of

t h e s e a n i m a l s , p a r t i c u l a r l y i n t h e e a r l y w o r k , where the

i m p o r t a n ce of th is f a c t o r w a s n ot f u l l y r ec o g n i z ed , a s u f f i c i e n t
time was not allowed for the heart to return to its normal size.
This also then in part explains the rather small increase in

c a r d i a c a r e a i n s o m e o f t h e a n i m a l s w i t h the pericardium

removed. In some of the animals, moreover, 2 h o u r s w a s n o t


s u f f i c i e n t t i m e f o r t h e h e a r t t o r e t u r n t o i t s no rm a l s i z e , b u t as
t h e s e we r e a c u t e e x p e r im e n t s w i th t h e a n i m a l s und e r b a rb i t a l it
w a s t h o u g h t a d vis a b l e n o t t o w ai t o v e r 2 h o u r s , a s i f a l o n g e r
time was allowed to elapse the physiologic condition might be
impaired. Obviously the proper way to check this is to allow
c o m p l e t e r e c o v e r y ; t h i s w o r k i s contemplated in the near future.

I n t h e a ni m a l s , fu r t h e r m o re , w it h t h e p e r ic a r d i um r e -
moved if the anoxemia was produced somewhat too rapidly or i f
t h e g r a d e o f a n o x e m i a w a s a l i t t l e s e v e r e , r e s p i r a t o r y f a ilure
o c c u r r ed earl i er, th an in the nor m a l a nim a ls, a nd in som e of
the se an im als a n an ox emi a of 7 to 10 p er ce nt
0
oxygen produced a sudden and acute cardiac dilatation from which
the heart did not recover. This was never seen with the
p e r i c a r di um i n tact. I n th e f or mer ca ses the ca r dia c silhouette
showed an enormous increase (35 to 40 per cent) above the
normal. These data were not included in the table. There is thus
considerable individual variation.

Table 2 shows the results obtained with monkeys ( Lac -


acus rhesus ). It will be noted that controls were run on
different days. On the whole it will be seen that the normal
cardiac area obtained on different days check very closely.
The reason for this is that several control x-ray pictures
were taken at the time of each experiment and the average
cardiac area was used. In m a n y instances, furthermore, sev e r a l
x - r a y p i c t u r e s w e r e t a k e n o f t h e h e a r t u n d e r a d e f i n i t e per ce n t
o f a n o x emi a; ag ai n , h owever , only the a ver a ge f igur e i s g i v e n i n
t h e t a b l e . I t w i l l b e f u r t h e r n o t i c e d t h a t t h e heart in the
barbitalized monkeys showed a smaller area than t h e
unanesthetized animals. A pos sible explanation for this is that
these latter animals were as a rule frightened and r e s t l e s s
w h e n t h e y w e r e s u b j e c t e d t o t h e e x p e r i m e n t . T h e results
obtained with monkeys seem to show more clearly than in the
other animals that the pericardium is perhaps only impor ta nt in
sev er e s tr ess . I n ord in ary c irc um s tan ce s i t p r o b a b l y i s n o t v e r y
important in regard to the prevention of cardiac dilatation, but
in conditions which throw a great s t r e s s o n t h e h e a r t i t
p r o b a b l y p l a y s a p r o t e c t i v e r o l e i n that it prevents the c ar d ia c
muscle from undue stretching.
9

which might permanently injure the muscle fibers.

The table below . shows the effects of extreme anoxemia on


the heart.
Pericardium intact Pericardims cut

Animal 1 . . . . . . 1 8 . 6 4 % Animal 1 . . . . . . . . . 2 9 . 6 8 %

Aminal 2.......20.67% Animal 2 . . . . . . . . . 3 0 . 7 6 %


Animal 3 . . . . . . . 2 5 . 7 3 % Animal 3 . . . . . . . . . . . 3 6 . 0 %

Animal4.......40.0%(cat)

The animals of t he above table were subjected to


anoxemia in the respiratory chamber and kept there until
r e s p i r a t o r y f a i l u r e o c c u r r e d . T h e y w e r e t h e n q u i c k l y r e moved
and the x -ray picture was taken. The heart was still beating
when the animals were removed and in most cases ar t i f i c i a l
r e s p i r a t i o n w o u l d r e s t o r e t h e m t o n o r m a l b r e a t h ing. The
r e s t o r a t i on of n ormal breathing could be m a ter ia lly h e l p e d , o f
c o u r s e , b y f o r c i n g p u r e o x y g e n i n t o t h e l u n g s . As a rule
when this was done the heart would almost immed ia tel y s ta rt to
bea t str on ger a n d m or e r ap idl y. The an ima ls used above were
dogs except animal no. 4 which was a cat. Th e l a t t e r a n i m a l
i n c i d e n t a l l y s h o w e d a g r e a t e r c a r d i a c d i l at ati on ; alt ho ugh a s
pre vi ous ly po in te d o ut ca ts di d no t dif f er m a ter ia ll y f r om dogs
i n r e s p on se to an oxemi a.

Conclusions
1. Animals with the pericardium removed tend to show a
greater cardiac dilatation in severe degrees of anoxemia;
10

especially in monkeys.
2. The protective action of the pericardium as re -
gards the prevention of acute cardiac dilatation probably
never comes into play in the normal animal, except possibly i n
ins ta nce s of ex tr eme s tre ss on t h e h ea rt.

We take great pleasure in thanking Professor Carlson


f o r h i s con stru cti ve c r iticism thr oughout this wor k.

Notes. This paper was written with Mr. R. S. Allen,


who was the Junior author; it was accepted for publication
in the American Journal of Physiology, September 21, 1927.
11

Bibliography
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Beck, C. S. and R. L. Moore. 1926. Arch. Surg., xi, 550. Cohnheim,
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