The effect of the pH of perfusates on the activity of the intact urinary bladder in the rat

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THE EFFECT OF THE pH OF PERFUSATES ON THE ACTIVITY OF THE INTACT URINARY BLADDER IN THE RAT

A Thesis P resented to t h e F a c u l t y o f t h e D ep artm en t o f Zoology U n iv e r s ity of S outhern C a lif o r n ia

In P a r tia l F ulfillm en t o f th e R equirem ents f o r th e D egree M aster of S cience

t>y G lo ria G allo A u g u s t 1950

UM1 Number: EP67180

All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion.

D issertation Publishing

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This thesis, written by

f.Lar.ia-.MaLLo....................................................... under the guidance of h..?X... Faculty C om m itt ee , and a p p r o v e d by all its members, has been presented to and acce pted by the Council on Grad ua te S t u d y and Research in pa rt ia l fulfill­ ment of the requirements f o r the degree of M a s te r o f S c ie n c e

D ep artm en t o f ^ o o lo f y

Faculty Committee

Chairman

TABLE OF CONTENTS CHAPTER I.

PACE

INTRODUCTION S ta te m e n t o f th e problem Im p o rta n c e o f th e problem

II.

• • .

. • ..........................

....................................................

....................................

The p h y s i o l o g y o f m i c t u r i t i o n .............................. I n n e rv a tio n of the u r in a r y b la d d e r C o m p o n en t r e f l e x e s

of m ictu ritio n

. . . . . . ..........................

3 12 13 .1 6

EXPERIMENTAL DATA M e th o d s a n d m a t e r i a l s

........................................

M ethods o f d e c e r e b r a t i o n and r e s u l t s

obtained

25 . 26

R ecording a p p a ra tu s

................................................................... 33

R ecording p ro ced u re

...............................................................

P erfu sates used,

40

the com position of b u f fe r

s o l u t i o n s ....................................................................... P r e s e n t a t i o n o f e x p e r i m e n t a l d a t a ......................... R e s u l t s .............................. IV.

1

REVIEW OF THE LITERATURE The p h y s i o l o g y o f s m o o t h m u s c l e

III.

1

43 47 50

DISCUSSION OF EXPERIMENTAL RESULTS M i c t u r i t i o n i n t h e d e c e r e b r a t e r a t ..................................... 94 The e f f e c t o f n e m b u t a l a n e s t h e s i a

...............................

94

The e f f e c t o f a c i d a n d a l k a l i n e p e r f u s a t e s on t h e t o n e o f t h e d e t r u s o r m u s c l e a n d t h e b l a d d e r s p h i n c t e r ........................................

96

iii CHAPTER V.

VI.

PAGE

SUMMARY AND CONCLUSIONS Summary ...............................

101

C o n c l u s i o n s .............................................................

102

BIBLIOGRAPHY........................................................................................

104

LIST OF TABLES TABLE

PAGE

I . The C o m p o n e n t R e f l e x e s

of M ic tu ritio n --B arrin g to n

24

tt

II. III.

S o re n s e n ’ s B u ffe r M ixtures

..................................... . . .

44

R a t # 1 - - D e c e r e b r a t e . A n a l y s i s o f Kymogram Showing R e s u l t a n t V e s i c a l P r e s s u r e s U s in g S aline P erfu sate

IV.

........................................................................

Rat # 2 —D e c e r e b r a te . A n a ly s is

50

o f Kymogram

Showing R e s u l t a n t V e s i c a l P r e s s u r e s U s in g S aline P erfu sate V.

........................................................................

52

R a t # 2 - - D e c e r e b r a t e . A n a l y s i s o f Kymogram Showing R e s u l t a n t V e s i c a l P r e s s u r e s U s in g S aline P erfu sate

VI.

........................................................................

Rat # 2 —D e c e re b ra te . A n a ly sis

53

o f Kymogram

Showing R e s u l t a n t V e s i c a l P r e s s u r e s U s in g P erfu sate, V II.

pH 1 . 0 5 ...................................................................

Rat # 2 —D e c e re b ra te . A n aly sis

55

o f Kymogram

Showing R e s u l t a n t V e s i c a l P r e s s u r e s U s in g S aline P erfu sate V III.

........................................................................

R at #3--N em butal A n e s th e s ia . A n a ly sis

56

of

Kymogram S h o w i n g R e s u l t a n t V e s i c a l P r e s s u r e s U sing S a lin e P e r fu s a te IX.

.........................................................

R at # 3 --N em butal A n e s th e s ia . A n a ly s is

58

of

Kymogram S h o w i n g R e s u l t a n t V e s i c a l P r e s s u r e s U sing P e r f u s a te ,

pH 3 . 3 ....................................................

59

X.

Rat # 3 --D e c e re b ra te . A n aly sis

o f Kymogram

S h o w in g R e s u l t a n t V e s i c a l P r e s s u r e s U s i n g S alin o P orfuoato XI.

...................................................................

Rat # 3 - -D e c e re b r a te . A n aly sis

G1

o f Kyrnogram

Showing R e s u l t a n t V e s i c a l P r e s s u r e s U s in g P erfu sate, X II.

pH 3 . 3 ...................................................................

Rat #4--H em butal A n e s th e s ia . A n a ly s is

62

of

Kymogram S h o w i n g R e s u l t a n t V e s i c a l P r e s s u r e s U sing S a lin e P e r f u s a te X III.

.........................................................

64

Rat #4--K em butal A n e s th e s ia . A n a ly sis of Kymogram S h o w i n g R e s u l t a n t V e s i c a l P r e s s u r e s U sing S a lin e P e r f u s a te

XIV.

................................................65

Rat # 4 - -D e c e re b ra te . A n aly sis

o f Kymogram

Showing R e s u l t a n t V e s i c a l P r e s s i i r e s U sing S a lin e P e r f u s a te XV.

.........................................................

Rat #4- -D e c e r e b r a te . A n aly sis

67

o f Kymogram

Showing R e s u l t a n t V e s i c a l P r e s s u r e s U s in g P erfu sate, XVI.

pH 3 . 3 ............................................................................ 68

Rat # 4 --D e c e re b ra te . A n aly sis

o f Kymogram

Showing R e s u l t a n t V e s i c a l P r e s s u r e s U s in g P erfu sate, XVII.

pH 3 . 3 ...................................................

69

R a t # 5 - - D e c e r e b r a t e . A n a l y s i s o f Kymogram Showing R e s u l t a n t V e s i c a l P r e s s u r e s U s in g S aline P erfu sate

........................................................................

71

X V III.

R a t # 5 - - D e c e r e b r a t e . A n a l y s i s o f Kymogram Showing R e s u l t a n t V e s i c a l P r e s s u r e s U s in g P erfu sate,

XIX.

pH4 . 5 2 ...............................................................

Rat # 5 - -D e c e re b r a te . A n a ly sis

72

o f Kymogram

Showing R e s u l t a n t V e s i c a l P r e s s u r e s U s in g P erfu sate, XX.

pH8 . 4 ....................................................................

Rat # 6 - -D s c e r e b ra te . A n aly sis

73

o f Kymogram

Showing R e s u l t a n t V e s i c a l P r e s s u r e s U s in g S aline P erfu sate XXI.

........................................................................

Rat # 6 —D ec e re b ra te . A n aly sis

75

o f Kymogram

Showing R e s u l t a n t V e s i c a l P r e s s u r e s U s in g P erfu sate, XXII.

pH4 . 5 2 .......................................................................... 76

R at # 6 —D e c e r e b r a te .

A n a l y s i s o f Kymogram

Showing R e s u l t a n t V e s i c a l P r e s s u r e s U s in g P erfu sate, X X III.

pH 8 . 4 .................................................................

78

R a t i / 6 — D e c e r e b r a t e . A n a l y s i s o f Kymogram Showing R e s u l t a n t V e s i c a l P r e s s u r e s U s in g P erfu sate,

XXIV.

pH 4 . 5 2 .......................................................................79

R a t # 7 - - D e c e r e b r a t e . A n a l y s i s o f Kymogram Showing R e s u l t a n t V e s i c a l P r e s s u r e s U s in g S aline P erfu sate

XXV.

........................................................................

Rat # 7 --D e c e re b ra te . A n aly sis Showing R e s u l t a n t P erfu sate,

81

o f Kymogram

V e s ic a l P r e s s u r e s U sing

pH 4 . 5 2 .......................................................................82

XXVI.

Rat # 7 --D e c e re b ra te .

A n aly sis

o f Kymogram

Showing R e s u l t a n t V e s i c a l P r e s s u r e s U s in g P erfusate, XXVII.

pH 9 , 1

. . .

........................................

.

84

R a t # 7 - - D e c e r e b r a t e . A n a l y s i s o f Kymogram Showing R e s u l t a n t V e s i c a l P r e s s u r e s U s in g P erfu sate,

XXVIII.

pH 4 . 5 2

..............................................................

85

R a t # 8 — D e c e r e b r a t e . A n a l y s i s o f Kymogram Comparing V e s i c a l P r e s s u r e s U s in g P e r f u s a t e , pH 5 . 8 8 a n d I s o s m o l a r S a l i n e P e r f u s a t e

XXIX.

.

.

.

87

R a t # 8 - - D e c e r e b r a t e . A n a l y s i s o f Kymogram Comparing V e s i c a l P r e s s u r e s U s in g P e r f u s a t e , pH 9 . 1 a n d I s o s m o l a r S a l i n e P e r f u s a t e

XXX.

Rat # 8 - - D e c e r e b r a te . A n aly sis

.

.

. . . 89

o f Kymogram

Comparing V e s i c a l P r e s s u r e s U sin g P e r f u s a t e , pH 2 . 1 8 a n d I s o s m o l a r S a l i n e P e r f u s a t e XXXI.

Summary o f E x p e r i m e n t a l R e s u l t s

• . .

....................................

91 . 93

LIST OP FIGURES FIGURE 1.

PAGE

D i a g r a m o f t h e R e c o r d i n g A p p a r a t u s S h o w in g t h e S e t Up f o r C a l i b r a t i n g t h e S y s t e m ...............................

2.

The A p p a r a t u s As S e t Up F o r R e c o r d i n g I n t r a v e s i c a l P re ss u re s in the Rat • • • • • • • • • • • • •

3.

36

37

P h o t o g r a p h Showing t h e C o n c e n t r i c C a n n u la e I n s e r t e d In to

the U rin ary B ladder • • • • • •

.....................

4.

T y p i c a l C a l i b r a t i o n Curve

..........................................................

5.

P h o t o g r a p h o f An O r i g i n a l Kymogram S h o w i n g

38 41

R e a c tio n a ry V e s ic a l A c t i v i t y i n Response to V arious P e r f u s a te s i n D e c e re b ra te Rat #8 . 6.

.



49

Rat # 1 --D e c e re b ra te . G raphical R e la tio n s h ip of Volume I n j e c t e d a n d V e s i c a l P r e s s u r e U s i n g S aline P erfu sate

7.

• • • • • • • • • • • • • • •

51

Rat # 2 - - D e c e r e b r a te • G ra p h ic a l R e la tio n s h ip of Volume I n j e c t e d a n d V e s i c a l P r e s s u r e U s i n g S aline P erfu sates

8.

........................................................................

54

R at # 2 - - D e c e r e b r a t e . G ra p h ic a l R e l a t i o n s h i p of Volume I n j e c t e d a n d V e s i c a l P r e s s u r e U s i n g A c i d and S a l i n e P e r f u s a t e s

9.

......................................

R at # 3 —N em butal A n e s t h e s i a .

. . . . . .

57

G raphical R e la tio n sh ip

o f Volume I n j e c t e d a n d V e s i c a l P r e s s u r e U s i n g A c i d a n d S a l i n e P e r f u s a t e s ..........................................................60

10.

Rat # 3 - - D e c e r e b r a t e .

G raphical R e la tio n s h ip

o f Volume I n j e c t e d a n d V e s i c a l P r e s s u r e U s i n g A cid and S a l i n e 11.

P e r f u s a t e s ...............................................

R at # 4 —N em butal A n e s t h e s i a .

63

G raphical R e la tio n sh ip

o f Volume I n j e c t e d a n d V e s i c a l P r e s s u r e U s i n g Saline P e rfu sa te s 12.

........................................................................

66

Rat # 4 --D e c e re b ra te . G raphical R e la tio n s h ip o f Volume I n j e c t e d a n d V e s i c a l P r e s s u r e U s i n g S a l i n e a n d A c i d P e r f u s a t e s ..........................................................70

13.

Rat # 5 --D e c e re b ra te . G raphical R e la tio n s h ip o f Volume I n j e c t e d

and V e s i c a l P r e s s u r e U s in g

S a l i n e , A cid and B a sic P e r f u s a t e s 14.

Rat # 6 —D ecereb rate.

...............................

74

G raphical R e la tio n s h ip

o f Volume I n j e c t e d a n d V e s i c a l P r e s s u r e U s i n g S a l i n e a n d A c i d P e r f u s a t e s ............................................... 15.

Rat # 6 —D e c e re b ra te .

77

G raphical R e la tio n sh ip

o f Volume I n j e c t e d a n d V e s i c a l P r e s s u r e U s i n g B a s i c a n d A c i d P e r f u s a t e s .................................................... 16.

Rat # 7 —D ecereb rate.

80

G raphical R e la tio n s h ip

o f Volume I n j e c t e d a n d V e s i c a l P r e s s u r e U s i n g S a l i n e a n d A c i d P e r f u s a t e s ..........................................................83 17.

Rat # 7 --D e c e re b ra te . o f Volume I n j e c t e d

G raphical R e la tio n s h ip and V e s i c a l P r e s s u r e

U sing

B a s i c a n d A c i d P e r f u s a t e s ...................................................

86

18*

Rat # 8 --D e c e re b ra te .

G raphical R e la tio n sh ip

o f Volume I n j e c t e d a n d V e s i c a l P r e s s u r e U s i n g Iso sm o lar S alin e 19.

Rat # 8 --D e c e re b ra te .

and Acid P e r f u s a t e s

. . . . .

88

G raphical R e la tio n sh ip

o f Volume I n j e c t e d a n d V e s i c a l P r e s s u r e U s i n g Isosm olar S a lin e 20.

Rat # 8 —D e c e re b ra te .

and B a s ic P e r f u s a t e s

..................

90

G raphical R e la tio n sh ip

o f Volume I n j e c t e d a n d V e s i c a l P r e s s u r e U s i n g Iso sm o lar S a lin e

and A cid P e r f u s a t e s

.......................

92

CHAPTEH I INTRODUCTION As e a r l y a s 1 9 0 2 , D i x o n s t u d i e d

the e f f e c t s

a n d b a s e s on s m o o t h m u s c l e ; E v a n s a n d U n d e r h i l l , observed the e f f e c t s

of a lte r a tio n

on t o n e a n d c o n t r a c t i o n s gations, strip s;

of acids

i n 1923, a l s o

of hydrogen-ion c o n c e n tra tio n

o f smooth m u s c l e . I n t h e s e i n v e s t i ­

e x p e r im e n ts were c a r r i e d

o u t on e x c i s e d s m o o t h m u s c l e

b a t h i n g i n a s o l u t i o n o f a c i d pH was f o u n d t o c a u s e d e ­

c r e a s e d t o n e a n d d e c r e a s e d c o n t r a c t i o n s w h i l e a l k a l i n e pH was found to cause th e o p p o s ite e f f e c t .

The p r e s e n t i n v e s t i g a t i o n

o f t h e e f f e c t o f t h e pH o f p e r f u s a t e s

on t h e i n t a c t u r i n a r y

b la d d e r in th e r a t i s an a tte m p t to stu d y n o t only th e r e ­ a c tio n of the i n t a c t v e s i c a l m u scu latu re in s i t u b asic

so lu tio n s,

but also

to a c i d and

to observe the o v e r a l l e f f e c t of

th is r e a c tio n w ith r e l a t i o n

to the resp o n se

of the b la d d e r

s p h i n c t e r and t h e m i c t u r i t i o n r e f l e x . If

the e f f e c t of a lk a lin e p e r f u s a te s

m usculature

of the i n t a c t u r in a ry b la d d e r i s

e f f e c t on e x c i s e d s t r i p s tone,

on t h e sm ooth

o f smooth m u s c l e ,

t h e same a s t h e

th a t is increased

s u c h a n e f f e c t m i g h t be o f v a l u e c l i n i c a l l y a s t h e

p o s s ib le e t i o l o g y o f annoying f r e q u e n t m i c t u r i t i o n s in d iv id u als

sin ce i t

is

p o ssib le

i n some

th a t excessively a lk a lin e

u r i n e m i g h t a c t i n t h e same m a n n e r a s t h e a l k a l i n e p e r f u s a t e . And l i k e w i s e i f

the e f f e c t of h ig h h y d ro g en -io n c o n c e n tra tio n

be t h a t of c a u s in g d e c r e a s e d to n e o f th e b l a d d e r m u s c u la tu r e , th u s a l l o w i n g l a r g e b l a d d e r volum es and i n f r e q u e n t b u t volum inous and f o r c e f u l e l i m i n a t i o n s ,

it

seems l i k e l y

t h a t i t m ig h t be

a p p lie d as th e ra p y f o r e lim in a tin g b la d d e r c a l c u l i . p rin c ip a l,

A sim ilar

t h a t o f a l l o w i n g t h e b l a d d e r t o bec om e g r e a t l j r d i s ­

tended, has been e f f e c t i v e l y a p p lie d in e x p e llin g g a l l sto n es from the g a l l b l a d d e r . C ertain ly , means,

t h e pH o f u r i n e c a n b e c o n t r o l l e d b y d i e t a r y

sin c e c e r t a i n foods a re a c id -fo rm in g w hile o th e rs are

base-form ing.

V e g e ta b le s and f r u i t s

an a s h i n w hich th e b a s i c p r e d o m in a te . M eats,

on b e i n g m e t a b o l i z e d ,

e le m e n ts sodium ,

f is h foods,

leave

p o ta ssiu m and ca lc iu m

eggs and o t h e r h i g h p r o t e i n

f o o d s l e a v e an a s h i n w hich p r e d o m i n a n t l y a c i d o r f o rm in g elem ents,

ch lo rin e ,

p h o s p h o r u s a n d s u l f u r p r e d o m i n a t e . Thus

th ro u g h consum ption of e i t h e r a c id -fo rm in g or b a s e -fo rm in g foods,

t h e pH o f t h e u r i n e c o u l d be c o n t r o l l e d . U r i n a r y pH

m i g h t a l s o b e a l t e r e d b y a d m i n i s t r a t i o n o f ammonium c h l o r i d e w hich a c i d i f i e s ,

o r sodium b i c a r b o n a t e w hich a l k a l i z e s . W hile

c o n t r o l l e d pH i s u s e d t o p r e v e n t f o r m a t i o n o f u r i n a r y c a l c u l i b y e l i m i n a t i n g t h e o p ti m u m medium f o r p r e c i p i t a t i o n ,

i t m ight

a l s o be used as th e r a p e u t i c m easure f o r e x p e l l i n g a lr e a d y form ed c a l c u l i .

CHAPTER I I REVIEW OP THE LITERATURE S ince th e p r e s e n t i n v e s t i g a t i o n d e a ls w ith th e i n f l u ­ ence o f c e r t a i n f a c t o r s

on t h e a c t i v i t y

o f th e smooth m u scle

o f th e u r i n a r y b l a d d e r and th e s p h i n c t e r u r e t h r a as d e t e r ­ mined by v a r i a t i o n i n th e m i c t u r i t i o n r e f l e x , p r e s e n t a t i o n and e v a lu a t io n of the r e s u l t s sta n d in g o f the g e n e ra l p r o p e r tie s ch aracteristics

an e f f e c t i v e

r e q u i r e s an u n d e r ­

o f smooth m u s c le and t h e

o f the m i c t u r i t i o n r e f l e x .

r e v i e w o f some o f

the l i t e r a t u r e

in

m uscle p h y s io lo g y

and th e m i c t u r i t i o n

T herefore,

the f i e l d

a

o f smooth

reflex is

p resented

h erew ith . L iteratu re

on t h e p h y s i o l o g y o f s m o o t h m u s c l e . The

p h y s i o l o g y o f smooth m u sc le h a s b e e n a s u b j e c t o f q u i t e e x ­ te n s iv e i n v e s t i g a t i o n b u t as p o in te d out by F is c h e r (1944), in h is

review of v e r te b r a te

smooth m u s c l e , a g r e a t d e a l o f

d i s a g r e e m e n t and l a c k o f p r e c i s e knowledge e x i s t s C.L. Evans

(1926),

m u scle em phasized know ledge:

1).

in a review o f the two r e a s o n s f o r t h e

today.

p h y s i o l o g y o f smooth in d efin itestate

g e n e r a liz a tio n concerning p r o p e rtie s

of

of p la in

m u s c l e f r o m e x p e r i m e n t s on o n e t y p e o f a n i m a l h a v e b e e n m a d e ; 2).

p l a i n m uscle has a c o m p lic a te d r e l a t i o n s h i p

to i t s

of the t i s s u e

n e rv e s u p p ly . S t r i a t e d m u scles have been found to

d i f f e r only s l i g h t l y h i s t o l o g i c a l l y ,

p h y sio lo g ically ,

and

4 p h a r m a c o l o g i c a l l y n o t o n l y i n v a r i o u s s t r i a t e d , m u s c l e s i n one anim al b u t a ls o in o th e r c la s s e s o f v e r t e b r a t e s .

Smooth m u s c l e s

how ever, have been found to d i f f e r g r e a t l y n o t o n ly in d i f f e r e n t o r g a n s i n t h e same a n i m a l , b u t a l s o i n f u n c t i o n a l l y s i m i l a r organs of r e l a t e d

sp ecies.

In v e rte b ra te s ,

b e a r r a n g e d i n two o r m o r e l a y e r s , in d e p e n d e n t l y and w ith f i b e r s Th us i t

s m o o t h m u s c l e may

each capab le or c o n tr a c tin g

run n in g i n d i f f e r e n t d i r e c t i o n s .

c a n r e a d i l y be s e e n t h a t smooth m u s c le m ig h t e a s i l y

v a ry i n o v e r t r e a c t i o n and c a r e l e s s t o c o n f u s i o n . As m e n t i o n e d a b o v e , nerve su p p ly a ls o le a d s resu lts.

g e n e r a liz a tio n s m ight le a d

the c o m p lic a tin g f a c t o r of

to c o n fu sio n in i n t e r p r e t a t i o n of

N e a r ly a l l smooth m u s c le i n v e r t e b r a t e s r e c e i v e s a

d o u b le n e r v e s u p p ly th e com ponents o f w hich h a v e o p p o s i t e fu n ctio n s, plexuses

s u p p l y may e x i s t a s g a n g l i o n i c c e l l s

of nerve f ib e r s w ith in the

d ifficu lt utab le

and t h i s

so t h a t i t

is

to d ete rm in e w hether the observed e f f e c t s a re a t t r i b ­

to th e m uscle i t s e l f ,

trin sic

tissu e

and

nerves,

th e v e r t e b r a t e in v e rte b ra te

the a n ta g o n is tic

nerves,

or com bination of th ese f a c t o r s . smooth m u s c le h a s l e d

the i n ­

C om plexity o f

to th e u s e o f c e r t a i n

smooth m u s c le s w hich a r e f r e e

from an i n t r i n s i c

supply of n e r v e s . S m o o th m u s c l e i s

c h a r a c t e r i z e d h i s t o l o g i c a l l y by th e

absence of c r o s s - s t r i a t i o n s

a n d p h y s i o l o g i c a l l y by s l o w n e s s

o f movement. B o z l e r ,

c lassifie d

fo llo w s:

(1941)

v e r t e b r a t e m uscles as

S m ooth m u s c l e s : 1, Those a c t i v a t e d by t r u e m o to r n e r v e s 2. Those r h y t h m i c a l l y a c t i v e by v i r t u e o f t h e i r own a u t o m a t i c i t y • R e l a t i n g a l l body m u s c le s : ("many u n i t s ) ^ sk e le ta l ^m otor n e r v e s ^ S triated ^ m uscle "^ card ia c r sy n cy tial ^ (autom atic J S m o o th m u s c l e s i n t h e f i r s t

m ulti-uni t s smooth m uscle / v isceral

g r o u p c o n s i s t o f many s m a l l u n i t s

s i m i l a r to s k e l e t a l m u scle i n a r r a n g e m e n t. These a r e u n d e r m ore p r e c i s e and l o c a l i z e d c o n t r o l by a c t i o n o f th e n e r v e s , and e x h i b i t l e s s

spontaneous r h y th m ic ity .

th e group a r e blood v e s s e l s ,

of

and n i c t a t i n g m em branes. I n t h e

s e c o n d g r o u p , n e r v e s may b e p r e s e n t , for con tractio n ,

R ep resentatives

but are not in d isp en sab le

s i n c e t h e m u s c l e s t h e m s e l v e s show a u t o m a t i c i t y

and e x h i b i t r h y t h m i c a l m ovem ent. P l a i n m u s c le s o f t h e h o l l o w v isc e ra are of th is

ty p e su ch a s th e i n t e s t i n e and u r i n a r y

bladder. I t is

g e n e r a lly agreed t h a t the m a jo r ity of organs

c o n s i s t i n g of smooth m u s c le e le m e n ts r e c e i v e fib e rs

e f fe r e n t nerve

from s y m p a th e tic and p a r a s y m p a t h e t i c d i v i s i o n s o f th e

autonom ic n erv o u s

system .

The h i s t o l o g i c a l d e t a i l o f t h e r e ­

l a t i o n s h i p b etw een n e r v e s and m u scle c e l l s i s of un certain ty .

s t i l l a m atter

Some i n v e s t i g a t o r s b e l i e v e t h a t a s a r u l e ,

n e r v e e n d in g s s u p p ly a m a j o r i t y o f m u s c le c e l l s . However, th ere i s

a wide d i f f e r e n c e I n t h e d e g r e e o f d e p e n d e n c e o f t h e

s m o o t h m u s c l e on I t s

in n erv atio n .

Vi/hether o r n o t a l l t h e myons

6

are under d ire c t in fluence qu estio n .

of b o th system s i s

Gannon a n d R o s e n b l u e t h

t h a t only a f r a c t i o n o f th e c e l l s Because of th e ev id en ce smooth m u s c le c e l l s te rp re te d

th is

(1937),

p re se n te d evidence

re c e iv e nerve en dings.

t h a t only a f r a c t i o n

re c e iv e n erv e endings,

t o me an t h a t r e s p o n s e s

some h a v e i n ­

the a ll- o r - n o n e

mariner o f s t r i a t e d m u s c l e b e c a u s e c o n t r a c t i o n

and a c t i v a t e

o th er c e lls

of the

o f smooth m u s c le a r e

g r a d e d a n d m u s c l e c e l l s do n o t r e s p o n d i n

b r o u g h t a b o u t by l i b e r a t i o n

a m a tte r of

of m uscles i s

o f c h e m ic a l m e d i a t o r s w hich d i f f u s e

producing a graded re sp o n se . B o zler,

(1938), d em o n strated p h y s io lo g ic a lly t h a t c o n tr a c tio n s

from

s i n g l e shocks a r e t r a n s m i t t e d e n t i r e l y in m uscle n o t a c t i v e sp on tan eo u sly .

The g r a d i n g o f s t r e n g t h o f c o n t r a c t i o n h e

e x p l a i n e d a s b e i n g due to i n t e n s i t y conducted w ith in

the m u scle,

of d is c h a rg e of im pulses

and to t h e s i z e

of the p o t e n t i a l

w h i c h may v a r y w i t h t h e p h y s i o l o g i c a l c o n d i t i o n o f t h e t i s s u e . A c t i v i t y o f sm ooth m u s c l e ,

th en , he concluded i s

due t o d i s ­

c h a r g e s of im p u lse s w hich a r e accom panied by a c t i o n p o t e n t i a l s as i n s t r i a t e d m u sc le s . V a r i a b i l i t y of re sp o n se o c c u rs, how ever, due to f r e q u e n c y ,

number o f im p u ls e s d i s c h a r g e d ,

d u ctio n or v a r ia tio n s strated

in e x c i t a b i l i t y .

th a t e x c ita b ility in s trip s

p r e s e n c e and ab sen ce of e s t r o g e n . responses

o f smooth m u sc le i t

is

B ozler

of u te ru s

Th us i n

rate

(1941),

of con­ demon­

v a r ie s w ith the

the study of

im p o rtan t to c o n s id e r not

only th e p h t s i o l o g i c a l c o n d itio n of the m uscle, b u t a ls o i t

7 is

im p o rtan t to c o n sid e r the d iff e r e n c e s in o rg a n iz a tio n of

v a rio u s m uscles in re g a rd of a c tiv ity

of m uscle f i b e r s

m ig h t be e f f e c t e d nerves,

to th e m echanism o f c o o r d i n a t i o n s i n c e i n some o r g a n s c o o r d i n a t i o n

th ro u g h th e c e n t r a l n erv o u s system and m otor

w h i l e i n o t h e r o r g a n s c o o r d i n a t i o n m ig h t be a c c o m p l i s h ­

ed b y s y n c y t i a l c o n n e c t i o n a n d t r a n s m i s s i o n . B ozler

(1936),

in v estig ated in v erteb rate

smooth m u s c l e ,

th e r e t r a c t o r m uscle o f th e s n a i l o r t h a t o f the a d d u c to r o f P e c t e n , and c o n c lu d e d t h a t th e m echanism o f c o n t r a c t i o n o f sm ooth m u sc le and s t r i a t e d m u sc le i s In h is

stu d y ,

f u n d a m e n t a l ly th e same.

t h e m u s c l e was c o n s i d e r e d u n d e r two d i f f e r e n t

co n d itio n s: 1. R ecording th e changes o f le n g th under c o n s ta n t load. 2. R ecording th e changes o f te n s i o n a f t e r s t r e t c h i n g . Under th e f i r s t c o n d iti o n ,

i t was n o t e d t h a t a l o a d a p p l i e d t o

a m u sc le c a u s e d f i r s t a sudden e x t e n s i o n o f th e m u sc le which th e n c o n tin u e d to le n g th e n v e ry slov/ly. A f t e r u n lo a d in g th e r e was n o r e t u r n

to the form er le n g th u n le s s

stim u lated .

The

c h a n g e o f l e n g t h was v e r y s l o w i n d i c a t i n g v i s c o u s r e s i s t a n c e . The s p e e d o f r e l a x a t i o n o f the m u scle. (1924),

t h u s s e e m e d t o d e p e n d on t h e v i s c o s i t y

S i n c e i t h a s b e e n shown b y G a s s e r a n d H i l l

t h a t the v i s c o s i t y o f s k e l e t a l m uscle i s in c r e a s e d

du rin g c o n tra c tio n , betw een v i s c o s i t y co n d itio n ,

th ere is a p o s s ib ility

of re la tio n s h ip

of smooth m u sc le and t o n u s . U nder th e seco n d

the e l a s t i c

t e n s i o n p r o d u c e d w h i l e t h e m u s c l e was

8

b e i n g s t r e t c h e d was n o t e d .

I t was o b s e r v e d t h a t a s s o o n a s t h e

l e n g t h was m a i n t a i n e d c o n s t a n t ,

te n s io n dropped or d is a p p e a r ­

ed i n a few m i n u t e s w i t h a r e s u l t a n t r e l e a s e i n t e n s i o n . I t is

in terestin g

to n o te ,

th at i f

and a t t h e end o f r e l a x a t i o n its

len g th ,

it

t h e m u s c l e was f i r s t s t i m u l a t e d ,

t h e m u s c l e was s t r e t c h e d 1 0 $ o f

was f o u n d t h a t t h e r e l e a s e

of te n s io n follow ed

t h e same t i m e c o u r s e a s t h e r e l a x a t i o n o f a n i s o m e t r i c c o n t r a c t ­ io n ,

a n d a s t h e r e l a x a t i o n was made f a s t e r o r s l o w e r b y c h a n g i n g

co n d itio n s,

th e tim e r e l a t i o n s

of the r e l e a s e

of te n s io n changed

c o r r e s p o n d i n g l y . I t can be s e e n t h a t c o n t r a r y t o an e l a s t i c body,

the te n s io n d isap p e ared i f

t h e l e n g t h was m a i n t a i n e d ,

d e s i g n a t i n g th e p r o p e r t y o f p l a s t i c i t y i n smooth m u sc le and s u g g e stin g a rearran g em en t of elem en tary p a r t i c l e s w ith in the m uscle p ro to p la s m . S m o o th m u s c l e i s

s t i m u l a t e d m e c h a n ic a lly by t e n s i o n and

i n the case of th e m u sc u la tu re of the u r in a r y b la d d e r , may h a v e a t w o - f o l d e f f e c t . flu id is in jected in to i t

If

the b la d d e r i s

slo w ly ,

ten sio n

d e n e r v a t e d and

the e f f e c t of te n sio n i s

to

cau se a r e l a x a t i o n o f th e b l a d d e r w a l l so t h a t a c o n s i d e r a b l e amount o f f l u i d can be t o l e r a t e d w i t h o u t any g r e a t r i s e pressure.

There i s

i n e f f e c t an a c t i v e r e l a x a t i o n o c c u rrin g .

W ith c o n t i n u e d I n j e c t i o n , passed,

in

if

th e l e v e l of to le r a n c e i s

the b la d d e r w a ll b e g in s

sur­

to d i s t e n d p a s s i v e l y and t h i s

in creased te n sio n stim u la te s not a re la x a tio n ,

b u t an o ccu rren ce

o f r h y th m ic c o n t r a c t i o n s o f th e w hole b l a d d e r w hich f i n a l l y

9 resu lts

i n em ptying o f th e "bladder. C h aracteristically ,

o f to n u s w hich i s and i s

smooth m u sc le e x h i b i t s

in e ffe c t a sta te

the p r o p e rty

of continued c o n tr a c tio n

c h a r a c t e r i z e d b y a v e r y s l o w c h a n g e i n m a g n i t u d e . The

d e g r e e o f t o n u s h a s b e e n shown b y W i n t o n ( 1 9 3 0 )

to vary w ith

the source of t i s s u e . C .L . Evans

(1923) showed t h a t sm ooth m u s c le i n a s t a t e

o f t o n u s h a s no h i g h e r o x y g e n c o n s u m p t i o n t h a n when i n a r e ­ la x e d s t a t e and t h a t th e p r e s e n c e o f oxygen i s

e ssen tial for

t h e m a i n t e n a n c e o f t o n u s . S u c h a lo w e x p e n d i t u r e o f e n e r g y allow s m aintenance of s u s ta in e d c o n tr a c tio n as t h a t e x h ib ite d i n a d d u c t o r m u s c l e s o f o r g a n i s m s s u c h a s c l a m s . The t o n i c c o n d i t i o n can be a l t e r e d w ith o u t ch an g in g t e n s i o n , a p r o p e r t y which i s

of p a r t i c u l a r im portance in hollow v is c e r a

such as

the u r in a r y b la d d e r. B ozler a sp ecializ ed

( 1 9 2 8 ) , p r o p o s e d t h e i d e a t h a t t o n u s was d u e t o ty p e o f f i b r i l w i t h i n th e c e l l which p ro d u c e d

to n ic c o n t r a c t i o n s w h ile a n o th e r type of f i b r i l p r e s e n t w ith ­ in

t h e same c e l l was s p e c i f i c a l l y f u n c t i o n a l i n q u i c k c o n ­

t r a c t i o n s . A new c o n c e p t was s u g g e s t e d b y t h e same i n v e s t i g a t o r (1 9 3 6 ), i n w hich he s t r e s s e d

the id e a

t h a t t h e r e i s no s p e c i f i c

t o n i c m echanism , b u t t h a t to n u s c o u ld be e x p l a i n e d by th e slow r e l a x a t i o n o f sm ooth m u sc le w hich c a n be h a s t e n e d by a c t i o n o f a n i n h i b i t o r y m e d i a t o r . One e x p l a n a t i o n f o r t o n u s b a s e d on o b serv atio n s of v arious

ty p e s of v i s c e r a l m uscle h a s been

10 s u g g e s t e d by B o z l e r

(1936) a s b e i n g due t o p e r s i s t e n t ,

w ea k

c o n t r a c t u r e b ro u g h t a b o u t by asy n c h ro n o u s a c t i v i t y i n d i f f e r ­ ent p arts

o f a m u s c l e * Prom o b s e r v a t i o n s

i t was shown t h a t t h e r e i s

of actio n p o te n tia ls ,

a n i r r e g u l a r d i s c h a r g e o f weak

im pulses c a u sin g in c o o r d in a te d c o n tr a c tio n s i n a l l p a r t s . T h is i n c o o r d i n a t i o n c a n be e x p l a i n e d by p o o r m u s c le c o n d u c t i o n r e s u l t i n g i n i n d e p e n d e n t d i s c h a r g e o f m any r e g i o n s o f t h e m uscle• As m e n t i o n e d p r e v i o u s l y , is

e x c i t a b i l i t y i n smooth m u s c le

i n f l u e n c e d by horm ones. B o z le r

(1941), by m easuring th e

rh e o b a se o f u t e r i n e m uscle d e te rm in e d th e e l e c t r i c a l e x c i t a ­ b ility

of the u te r u s i n d i f f e r e n t phases of the se x u a l c y c le .

D u r i n g a n e s t r u s , m u s c u l a r m o v e m e n t was f o u n d t o b e weak a n d in co o rd in ated ;

co n tractio n s

rem ained l o c a l i z e d .

o r i g i n a t e d i n v a r io u s re g io n s and

F ollow ing a d m in is tr a tio n of e s tr o n e ,

r i c a l e x c i t a b i l i t y was i n c r e a s e d . is

elect­

L ikew ise d u r in g e s t r u s ,

c h a r a c t e r i z e d by h ig h e s t r o g e n c o n t e n t ,

w hich

e x c i t a b i l i t y was

found to be i n c r e a s e d . I n t e r e s t i n g l y e n o u g h , W o o l s e y a n d Me B r o o k s

(1937)

fo u n d t h a t m i c t u r i t i o n volume d i m i n i s h e d m a r k e d l y d u r i n g e s t r u s in c a ts, and Brack

and i n c r e a s e d v e ry g r e a t l y p o s tp a r tu m . Langw orthy (1939) fo u n d t h a t th e u r i n a r y b l a d d e r o f p r e g n a n t

c a t s w ere c a p a b l e o f h o l d i n g l a r g e vo lu m es a t low p r e s s u r e s . These r e s u l t s volume i s

seem t o i n d i c a t e

t h a t an i n c r e a s e i n v e s i c a l

d e p e n d e n t upon d e c r e a s e d to n e o f th e m uscle and to n e

11 Is

i n f l u e n c e d by th e hormone e s t r o n e ,

w hich i s

low i n c o n c e n ­

t r a t i o n d u r in g p reg n a n c y and i s h ig h i n c o n c e n t r a t i o n a t p a r t u r i t i o n and i n th e e s t r u s phase o f th e s e x u a l cycle* I t h a s b e e n shown t h a t s m o o t h m u s c l e i s to a l t e r a t i o n s

in

very s e n s itiv e

t h e h y d r o g e n - i o n c o n c e n t r a t i o n . Dixon (1902)

d e m o n s t r a t e d t h a t v e r y s m a l l am ounts o f l a c t i c

a c id s to p the

a u t o m a t i c waves and p r o d u c e r e l a x a t i o n i n t h e sm ooth m u s c le o f f r o g sto m ach . L.C.

Evans

(1923), used v a rio u s types

smooth m u s c le t o s tu d y t h e e f f e c t s to n e and c o n t r a c t i o n s . I s o l a t e d ed i n s a l i n e

of

of

a l t e r a t i o n o f pH on t h e

strip s

o f t i s s u e s were s u s p e n d ­

s o l u t i o n a n d t h e pH o f t h e b a t h was a l t e r e d b y

a d d i t i o n o f a c id s and b a s e s .

In a l l cases,

io n c o n c e n tr a tio n w ith in the l i m i t s

In c re a se d hydrogen-

of c o m p a ta b ility caused

r e l a x a t i o n o f tone of

p l a i n m u s c le . A v a r i e t y o f a c i d s were

used,

p ro d u ced by a l l

and the e f f e c t s

a c i d s were th e same. A

s u d d e n c h a n g e t o a l k a l i n e pH c a u s e d a n i n c r e a s e i n t o n u s . G e l l h o r n ( 1 9 3 3 ) , h a s r e p o r t e d t h a t e s s e n t i a l l y t h e same e f f e c t is

produced i n s t r i a t e d m u scle. I n o r d e r to d e t e r m i n e w h e th e r th e n e r v o u s mechanism

m ig h t be r e s p o n s i b le f o r th e e f f e c t s

p r o d u c e d by a c i d , u t e r i n e

t i s s u e was p r e t r e a t e d w i t h n i c o t i n e w h i c h a b o l i s h e s b o t h m o t o r and i n h i b i t o r y e f f e c t s

of h y p o g astric

stim u latio n ,

and w ith

a t r o p i n e w h i c h p a r a l y z e s n e r v e e n d i n g s i n smootxi m u s c l e .

The

e f f e c t o f pH was e s s e n t i a l l y t n e same i n r e g a r d t o t o n u s w i t h or w ith o u t p r e -tr e a tm e n t w ith n ic o tin e

or a tro p in e .

T h i s seem s

12 to i n d i c a t e

t h a t r e l a x a t i o n p r o d u c e d b y a c i d pH i s

effected

p r i m a r i l y b y a c t i o n on t h e m u s c u l a r t i s s u e i t s e l f .

However,

H am m ett ( 1 9 2 1 ) f o u n d t h a t t r e a t i n g r a t du odenum w i t h c o c a i n e ab olished

t h e s h o r t e n i n g e f f e c t o f sodium c a r b o n a t e and c o n ­

cluded t h a t the e x t r i n s i c nerve f i b e r s

or endings i n i n t e s t ­

i n a l s e g m e n t s a r e p r i m a r i l y s t i m u l a t e d . Ho m e n t i o n i s mad e w ith r e s p e c t to r e a c ti o n L iteratu re

to a c id so lu tio n s*

on t h e p h y s i o l o g y o f m i c t u r i t i o n . A l t h o u g h

m ost of the l i t e r a t u r e

concerning the physio lo g y of m ic tu r itio n

h a s b e e n b a s e d on e x p e r i m e n t a l w o r k p e r f o r m e d on c a t s , review of th ese la tio n

s t u d i e s seems i n

a b rie f

o r d e r and a p p l i c a b l e i n r e ­

to the p re s e n t i n v e s t i g a t i o n . S ym pathetic in n e r v a tio n i s

d e r i v e d from th e lum bar

r e g i o n o f th e s p i n a l c o r d from t h e s e c o n d ,

t h i r d and f o u r t h

lum bar seg m e n ts. F ib e r s

le a v e th e s p i n a l c o rd as th e lum bar

sp lan ch n ic n e rv e s,

through the g a n g lia of th e sy m p ath etic

pass

c h a in and e n t e r th e i n f e r i o r m e s e n te r i c g a n g l i a . H ere, statio n s

o c c u r where th e p r e g a n g l i o n i c

c o n n e c tio n w ith p o s tg a n g lio n ic

fib e rs

form s y n a p t i c

f i b e r s w h i c h r u n dow nwar d a s

th e h y p o g a s t r i c n e rv e and e n t e r th e h y p o g a s t r i c , som etim es c a l l e d ,

the p e lv ic p lexu3.

v e s i c a l p le x u s which l i e s tain s

The f i b e r s

o r as i t

is

then e n t e r the

on t h e b l a d d e r w a l l a n d w h i c h c o n ­

c e l l s ta tio n s fo r p reg an g lio n ic

fib e rs

through the i n f e r i o r m e se n te ric g a n g lio n . fib e rs

cell

th a t have passed

P arasym pathetic

o r i g i n a t e i n th e s a c r a l r e g i o n o f th e s p i n a l c o r d from

13 the second,

t h i r d and f o u r t h s a c r a l segm ents and c o l l e c t i v e l y

form t h e p e l v i c n e r v e w h ich e n t e r s Short p o stg an g lio n ic f ib e rs

the h y p o g a s tric p lex u s.

arise in

the v e s i c a l g a n g lia and

p a ss to th e body and neck o f th e b l a d d e r .

The p u d i c n e r v e s ,

w hich a r e s o m a t i c , i n n e r v a t e

t h e s t r i a t e d m u s c l e o f t h e com­

pressor ureth rae;

i n th e s a c r a l r o o t s betw een th e

they a r is e

f i r s t and f o u r t h s a c r a l segm ents. L i t e r a t u r e co n cern in g the f u n c tio n s the b la d d e r i s

copious b u t i n g e n e ra l,

are c o n flic tin g .

of nerves in n e rv a tin g

re p o rte d observations

W hile t h e s y m p a t h e t i c and p a r a s y m p a t h e t i c

n erv o u s system s a r e g e n e r a l l y b e li e v e d to a c t a n t a g o n i s t i c a l l y , th e h y p o g a s tr ic s i n h i b i t i n g

th e d e t r u s o r m u scle and c o n s t r i c t ­

i n g t h e s p h i n c t e r a n d t h e p e I v i e s a c t i n g o p p o s i t e l y , m any i n ­ v e s t i g a t o r s h ave r e p o r t e d e x c e p t i o n s w hich a r e n o t i n a g re e m e n t w ith th e th e o ry of a n ta g o n is tic E llio t

(1906),

the b la d d e r v a r ie s izatio n s

actio n ,

em phasized th e f a c t t h a t i n n e r v a t i o n o f

f r o m one a n i m a l t o a n o t h e r a n d t h a t g e n e r a l ­

f r o m one s p e c i e s do n o t n e c e s s a r i l y a p p l y t o o t h e r

s p e c i e s . He m a i n t a i n e d t h a t d i f f e r i n g

o b s e r v a t i o n s w ere due

t o a r g u i n g f r o m t h e p a r t i c u l a r t o t h e g e n e r a l . I n a l l mammals he found s t i m u l a t i o n of th e p e l v i c n e rv e s b l a d d e r c o n t r a c t i o n . On t h e o t h e r h a n d ,

to cause g e n e ra l

the e f f e c t of stim ­

u l a t i o n o f t h e h y p o g a s t r i c n e r v e s was f o u n d t o d i f f e r . d o g , r a b b i t and man,

I n the

the h y p o g a s tr ic s produced c o n t r a c t i o n s

only i n a sm all a r e a a t the base of th e b la d d e r c lo s e

to the

14 sp h in cter;

i n t h e f e r r e t and t h e m ale g o a t ,

contracted.

In the c a t,

pig,

t h e whole b l a d d e r

a n d m onkey a g e n e r a l r e l a x a t i o n

was n o t e d . S tew art

(1899), d e s c rib e d u n i l a t e r a l c o n tr a c tio n s

t h e b l a d d e r w a l l f o l l o w e d by r e l a x a t i o n upon h y p o g a s t r i c u latio n .

L angw orthy, R eeves,

and T a u b e r ( 1 9 3 4 ) ,

bladder cap a c ity a f t e r h y p o g astric th e sy m p a th e tic system i n h i b i t s Denny-Brown and R o b e r t s o n

of stim ­

found d e c re a s e d

l e s i o n s and c o n c lu d e d t h a t

p arasym pathetic a c t i v i t y .

(1933) found norm al b l a d d e r f u n c t i o n

i n hum an s u b j e c t s f o l l o w i n g p r e s a c r a l n e u r e c t o m y ,

in d icatin g

no e v i d e n c e t h a t t h e h y p o g a s t r i c n e r v e s p l a y a n y p a r t i n b l a d d e r in n erv atio n . The v a l i d i t y

of stu d ie s

em ploying m ethods o f d i r e c t

f a ra d iz a tio n of nerve f ib e rs as a b a sis

o f com parison f o r

n o r m a l e f f e c t s h a s b e e n q u e s t i o n e d b y M a c D o n a ld a n d McCrea (1930).

They r e p o r t e d

t h a t th e e f f e c t of any given stim u lu s

v a r ie s w ith the e x i s t i n g c o n d itio n o f the v is c u s .

The e f f e c t

p r o d u c e d was f o u n d t o v a r y n o t o n l y w i t h t h e s t r e n g t h o f t h e s tim u lu s b u t a l s o w ith th e n a t u r e and d e p th o f a n e s t h e s i a . J.P .

Evans

( 1 9 3 6 ) , made a s t u d y o f a c t i o n c u r r e n t o f

nerves supp ly in g the u r in a ry b la d d e r.

The r e s u l t s h e o b t a i n e d

showed t h a t t h e v e s i c a l p l e x u s a c t i v i t y f o l l o w i n g s e c t i o n i n g o f t h e p e l v i c s was c o m p l e t e l y l a c k i n g ; of the h y p o g a s trie s ,

fo llo w in g s e c tio n in g

no c h a n g e was n o t e d .

T alaat

(1937),

r e p o r t e d a f f e r e n t i m p u l s e s w ere o b t a i n e d from t h e h y p o g a s t r i c

15 nerve a f t e r p e lv ic nerve d e g en eratio n . found to d is a p p e a r a f t e r i s o l a t i n g

These d i s c h a r g e s were

th e "bladder. T a l a a t su g ­

g e s t e d t h a t t h e s e i m p u l s e s h ad no r e l a t i o n

to i n t r a v e s i c a l

p r e s s u r e a n d t h a t d i s c h a r g e f r o m t h e h y p o g a s t r i c n e r v e was due l a r g e l y t o p e l v i c f i b e r s m ixed w it h h y p o g a s t r i c f i b e r s . T h is h a s b e e n d e m o n s t r a t e d a n a t o m i c a l l y by L an g w o rth y ( 1 9 3 9 ) . C u ttin g the h y p o g a s tr ic s

abolished

the r i s e

r e s u l t a n t upon s e v e re b la d d e r d i s t e n s i o n , p e lv ic s did n o t.

i n blood p r e s s u re

w h ile c u t t i n g the

T h i s , was i n t e r p r e t e d a s i n d i c a t i n g t h e

p r o b a b ility t h a t the fu n c tio n of a f f e r e n t f ib e r s in g a s tric nerves i s

the hypo­

to c a r r y p a in f u l im pulses to the c e n t r a l

nervous system . Prom t h e e v i d e n c e p r e s e n t e d , i t h y p o g a stric s play l i t t l e a rises

w o u l d seem t h a t t h e

o r no p a r t i n m i c t u r i t i o n .

The q u e s t i o n

as to w hether th e sym p ath etic n erv es a c t u a l l y in n e r v a te

th e d e t r u s o r m uscle o r w hether th e blood v e s s e l s a lo n e a r e in n erv ated .

To a n s w e r t h i s

q u estio n , h is to lo g ic a l i n v e s t i ­

g a t i o n s h a v e b e e n made a n d t h e s e a g a i n a r e n o t i n a g r e e m e n t . L a n g w o r t h y a n d M u rp hy ( 1 9 3 9 ) m ad e a s t u d y o f t h e n e r v e e n d i n g s i n th e v i s c u s and o b serv ed th e ty p e s

lo st a fte r d iffe re n tia l

n e r v e s e c t i o n i n g by u s in g d e g e n e r a t i v e n e rv e s t a i n i n g n ique.

tech ­

The m a j o r i t y o f n e r v e s w e r e f o u n d t o o c c u r on t h e b l o o d

v e s s e l s o f th e b l a d d e r and th e y t h e r e f o r e c o n clu d ed t h a t th e sy m p ath etic in f lu e n c e i s m ediated by changes in c o n tr a c tio n s o f t h e sm ooth m u s c u l a t u r e o f th e b lo o d v e s s e l w a l l s an d n o t

16 by d i r e c t i n n e r v a t i o n o f th e d e t r u s o r m u scle i t s e l f .

On t h e

o t h e r h a n d , K untz and Saccomanno (1944) u s i n g t h e C a j a l s i l v e r t e c h n iq u e n o t e d d i f f e r e n t i a l s t a i n i n g o f s y m p a t h e t ic and parasym pathetic

p o s tg a n g l i o n i c s i n th e v e s i c a l w a lls and c o n ­

cluded t h a t f u n c tio n a l sym pathetic in n e r v a tio n of the d e tr u s o r m uscle does o ccu r. More c o n c l u s i v e d a t a c o n c e r n i n g m i c t u r i t i o n h a v e b e e n o b t a i n e d by t h e em ploym ent o f more n a t u r a l s t i m u l i . (1914-1941) i n a s e r i e s

B arrin gton

o f p a p e r s made a s t u d y o f r e f l e x

m i c t u r i t i o n and by p ro d u c in g l e s i o n i n v a r y in g p a r t s nervous system , he n o ted th e l e v e l i n

of the

the c e n t r a l nervous

system o f th e o r i g i n o f th e m otor to n e o f th e b l a d d e r m u s c le , the p a r t s tu ritio n

of th e c e n t r a l n erv o u s system n e c e s s a r y f o r m ic ­ to tak e p la c e ,

and th e sim p le r e f l e x com ponents o f

m i c t u r i t i o n a l o n g w i t h r e f l e x c e n t e r s and p a t h s . I n o rd e r to d eterm in e the e f f e c t s t i z i n g m e t h o d s on m i c t u r i t i o n , decerebrate c a ts , eth er.

of various d e s e n si­

e x p e r i m e n t s w e r e p e r f o r m e d on

and c a t s a n e s t h e t i z e d w ith c h lo ro fo rm ,

or

The b l a d d e r was e m p t i e d by p a s s i n g a c a t h e t e r t h r o u g h

the u r e t h r a i n t o

the v is c u s .

When f l u i d f i r s t a p p e a r e d a b o u t

th e u r e t h r a l p o r tio n e n c lo s in g th e c a t h e t e r ,

t h e c a t h e t e r was

r e m o v e d f r o m t h e u r e t h r a a n d t h e v o l u m e e l i m i n a t e d was m e a s u r e d . I t was f o u n d t h a t t h e v o l u m e e l i m i n a t e d by d e ­ cereb rate

c a t s was g e n e r a l l y s l i g h t l y

e l i m i n a t e d by n o rm a l c a t s .

lo w e r t h a n t h e volume

While t h e f r e q u e n c y o f m i c t u r i t i o n

17 i n d e c e r e b r a t e c a t s was f o u n d t o b e s l i g h t l y g r e a t e r t h a n i n norm al a n im a ls;

t h e a c t o f m i c t u r i t i o n i t s e l f was e s s e n t i a l l y

th e same. I n m ost c a s e s , in decerebrate c a ts , may t a k e p l a c e i n

e l i m i n a t i o n was f o u n d t o b e c o m p l e t e

in d icatin g

t h a t norm al r e f l e x m i c t u r i t i o n

the ab sen ce o f th e f o r e b r a i n .

The b l a d d e r

v o lu m e i n c a t s a n e s t h e t i z e d w i t h e t h e r a n d c h l o r o f o r m was g e n e ra lly g r e a te r than in d e c e re b ra te anim als,

and th e s e

a n e s t h e t i c s w ere fo u n d to h a v e a d e p r e s s i n g e f f e c t on m i c t u r i t i o n . Kolb and L angw orthy (1938) fo u n d s i m i l a r d e p r e s s i n g e f f e c t s o f e t h e r a n d n e m b u t a l on t h e m i c t u r i t i o n r e f l e x a n d c o n c l u d e d th a t these a n e sth e tic s activ e

d e p r e s s s t r e t c h r e s p o n s e s and p r e v e n t

v esic al co n tractio n . D e c e r e b r a te c a t s were u se d to a n a l y s e r e f l e x m i c t u r i t i o n .

A c a t h e t e r was p a s s e d t h r o u g h t h e u r e t h r a i n t o

the b la d d e r

a n d t h e b l a d d e r was d i s t e n d e d w i t h warm w a t e r f r o m a b u r e t t e . I n t e r p o s e d b e t w e e n t h e b u r e t t e a n d t h e c a t h e t e r was a v e r t i c a l tu b e u s e d a s a w a t e r m an o m eter. E q u a l volum es o f w a t e r were run in to

th e b l a d d e r e v e r y o t h e r m in u te and p r e s s u r e s were

n o t e d a t t h e end o f one m i n u t e a f t e r e a c h i n c r e a s e i n vo lu m e. When a c e r t a i n v o l u m e was r e a c h e d , was f a i r l y c o n s i s t e n t i n

w ater escaped.

t h e same c a t .

T h i s v o lu m e

Increases in pressure

p ro d u ced by i n c r e a s e s i n volum e, w i t h i n th e l i m i t s

of the

t o l e r a t i o n volume w ere n o t g r e a t s i n c e th e b l a d d e r had tim e to adapt i t s e l f .

H o w e v e r , when t h e l i m i t was r e a c h e d ,

r o s e i n a few s e c o n d s t o f i f t e e n

tim es i t s

the p re ss u re

previous v alue,

due

18 to a c tiv e bag,

co n tractio n s

of the b la d d e r .

a g i v e n i n c r e m e n t when t h e b a g i s

a la rg e r pressure increase

In a p e rfe c tly e la s tic d isten d ed r e s u lts in

t h a n when t h e b a g i s

la x ; b u t the

p r e s s u re in c r e a s e i s n o t 200-1400^ over the p re v io u s p r e s s u r e i n c r e a s e r e s u l t a n t upon e q u a l in c re m e n t as i s

the case i n

the

u rin a ry b lad d er. The s t i m u l u s p r o d u c i n g c o n t r a c t i o n o f t h e b l a d d e r was a c t i v e d i s t e n s i o n o f the b la d d e r w a ll, s m a l l e r volum es a t s h o r t e r i n t e r v a l s ,

sin ce in tro d u c tio n of n o t allo w in g the b la d d e r

t o be c o m e a d a p t e d , was e f f e c t i v e i n e v o k i n g a c t i v e c o n t r a c t i o n s o f t h e v e s i c a l m u s c u l a t u r e . I t was n o t e d t h a t i f were p r e v i o u s l y f i l l e d

the b la d d e r

w i t h c o c a i n e h y d r o c h l o r i d e and t h e n

d i s t e n d e d w i t h w a t e r , m i c t u r i t i o n was a b o l i s h e d i n d i c a t i n g t h a t th e a f f e r e n t lim b o f th e r e f l e x a r c a r i s e s v e s i c a l w a l l and t h a t a b o l i t i o n d esen sitizatio n

i n the

o f t h e r e f l e x was d u e t o

o f th e s e n s o r y mechanism by c o c a i n e .

T h i s f i r s t r e f l e x i n t h e a c t o f m i c t u r i t i o n was f o u n d to be d e s tro y e d a f t e r d i v i s i o n of the p e lv ic n e rv e s,

or a f t e r

t r a n s e c t i o n o f the s p i n a l co rd i n th e low er th o r a c i c

or upper

c e r v i c a l r e g i o n s and n o t by s e c t i o n o f o t h e r n e rv e s o r r e g io n s o f c e n t r a l nervous system .

The r e f l e x c e n t e r ,

therefore,

concluded to la y in the re g io n of th e h in d b r a in ,

was

w ith paths

p a s s in g i n th e c e n t r a l n erv o u s system th ro u g h th e s a c r a l r o o ts to th e p e lv ic n e rv e s .

B arrin g to n lo c a liz e d

th e c e n t e r by m aking

tr a n s e c t i o n s behind a p la n e through th e p o s t e r i o r p a r t s

of

19 th e i n f e r i o r c o i l i e u l i d o r s a l l y ( l o c a t e d i n th e m esencephalon on i t s

p o s te r io r s u rfa c e o p p o site th e c e r e b ra l peduncles)

and th e m id d le o f th e pons v e n t r a l l y . tra n sectio n ,

th ere re s u lte d a loss

he co n clu d ed t h a t t h i s a r e a i s

In the m id -p o n tin e

of the r e f l e x ,

th erefo re

the h ig h e r r e f l e x c e n t e r .

p a t h s s u b s e r v i n g m i c t u r i t i o n w e r e s hown by p a r t i a l a t various

lev els

column n e a r i t s

to be i n

The

sectio n s

th e d o r s a l h a l f of the l a t e r a l

p eriphery .

A c t i v e c o n t r a c t i o n o f t h e b l a d d e r was n o t e d when t h e c a t h e t e r was moved i n p o ssib ility

the u r e t h r a .

In o rd e r to check th e

of a second r e f l e x r e s u l t a n t upon s t i m u l a t i o n of

the u r e t h r a l w a ll,

a n o t h e r m e t h o d wa s u s e d .

The b l a d d e r n e c k

was d i v i d e d p r o x i m a l t o w h e r e t h e u r e t h r a b e g i n s a n d two c a n n u l a e ,

one i n e a c h c u t e n d ,

were

tied ,

to expand allow ing

s im u lta n e o u s o b s e r v a t i o n o f b l a d d e r and u r e t h r a l p r e s s u r e s . V e r t i c a l tubes w ith a T -tube f i t t e d used as w a te r m anom eters.

at

th e lo w e r end were

One e n d o f t h e T - t u b e was c o n n e c t e d

t o t h e c a n n u l a w h i l e t h e o t h e r e n d was c o n n e c t e d t o a f i l l i n g b u rette .

P r e s s u r e s c o u l d b e r e a d when t h e c l a m p t o t h e b u r e t t e

was c l o s e d .

The b l a d d e r was d i s t e n d e d b e l o w t h a t n e c e s s a r y t o

p r o d u c e r e f l e x c o n t r a c t i o n a n d t h e u r e t h r a l p r e s s u r e was raised

g r a d u a l l y u n t i l s u f f i c i e n t to overcome r e s i s t a n c e .

It

was f o u n d t h a t when w a t e r e s c a p e d f r o m t h e e x t e r n a l m e a t u s , pow erful c o n tr a c tio n s of the b la d d e r o ccu rred producing a r is e in pressure

e q u a l to t h a t p ro d u ced by b l a d d e r d i s t e n s i o n

20

in

the f i r s t r e f l e x .

lo n g er escaped.

The p r e s s u r e r e m a i n e d u n t i l t h e w a t e r no

The r e f l e x c o u l d s t i l l b e o b t a i n e d a f t e r

c o c a i n e h a d b e e n a p p l i e d t o t h e i n t e r i o r b l a d d e r w a l l show­ ing t h a t t h is

s e c o n d r e f l e x c o n t r a c t i o n o f t h e b l a d d e r was

not in itia te d

b y t h e same s t i m u l u s a s

The r e f l e x was d e s t r o y e d b y d i v i s i o n

th a t f o r the f i r s t . of the p e lv ic n e r v e s ,

the

p u d ic s and by t r a n s e c t i o n o f th e s p i n a l c o rd i n th e lo w er th o racic

or upper c e rv ic a l re g io n s.

was c o n c l u d e d t o b e i n t h e p e l v i c s ,

Thus,

the a f f e r e n t in th e pudics

and th e r e f l e x c e n t e r i n th e h in d b r a i n . note

th a t T alaat

the e f f e r e n t p a th

It

is

in terestin g

to

( 1 9 3 7 ) , who i n v e s t i g a t e d a f f e r e n t i m p u l s e s

o f n e r v e s s u p p ly in g th e b l a d d e r and u r e t h r a ,

found t h a t flow

o f s o l u t i o n t h r o u g h t h e u r e t h r a was e f f e c t i v e

in stim u latin g

se n so ry nerv e endings i n th e u r e t h r a . D isch arg e o f a f f e r e n t i m p u l s e s was n o t e d i n t h e p u d i c n e r v e o n l y , a n d t h e d i s c h a r g e c o u ld be m a in ta in e d by th e flo w a t lo w er p r e s s u r e s

th a n were

n e c e s s a r y t o evoke a c o n t i n u o u s d i s c h a r g e due t o d i s t e n s i o n . The t h i r d

r e f l e x was d e s c r i b e d a s b e i n g d u e t o d i s ­

te n s io n of the p o s t e r i o r re g io n of the u r e t h r a ,

sin ce r is e

i n i n t r a v e s i c a l p r e s s u r e o c c u r r e d when t h e p r e s s u r e i n t h e u r e t h r a was j u s t a b o u t t h a t n e c e s s a r y t o f o r c e I t was n o t e d t h a t when t h e u r e t h r a l p r e s s u r e of w ater i t

fell

l/2

r e a c h e d 30 cm.

cm. o f v / a t e r w i t h a s u b s e q u e n t t r a n s ­

ito r y r is e in b ladder p re ssu re . u n til

the s p h in c te r.

50 cm. v / a t e r p r e s s u r e .

W ater d i d n o t e s c a p e , h o w ev er,

The r e f l e x was d e s t r o y e d o n l y

21

by d i v i d i n g

t h e h y p o g a s t r i c s a n d was n o t a f f e c t e d b y d i v i s i o n

of th e s p in a l cord as i n

the f i r s t

two r e f l e x e s .

Th e f o u r t h r e f l e x e l i c i l e d b y w a t e r r u n n i n g t h r o u g h t h e u r e t h r a was o b s e r v e d when a d d i n g v / a t e r t o t h e u r e t h r a l m anom eter a t t h e r a t e

o f 5 cm. p e r m i n u t e . W a t e r e s c a p e d v/hen

t h e p r e s s u r e was r a i s e d the p r e s s u r e f e l l

t o 34 cm. o f w a t e r a n d s t o p p e d when

t o 10 cm. o f w a t e r .

The u r e t h r a r e s i s t e d

p r e s s u r e s b e t w e e n 10 cm. o f v / a t e r a n d 35 cm. o f w a t e r when f l u i d was n o t r u n n i n g t h r o u g h , when w a t e r was e s c a p i n g .

b u t t h e r e was n o r e s i s t e n c e

This r e f l e x

t h e n c o u l d be e x p l a i n e d

a s b e i n g d u e t o r e f l e x r e l a x a t i o n o f u r e t h r a l m u s c l e s a n d v/as s tim u la te d by ru n n in g v/ater. I t

c o u ld be a b o l i s h e d o n ly by

d i v i s i o n of the p u d ic s. If h alf

th e u r e t h r a l manom eter were f i l l e d

the p r e s s u re n e c e s s a ry to s t a r t escap e,

of w ater,

and t h e b l a d d e r were d i s t e n d e d v i a

t o a b o u t one b e t w e e n 1 0 - 3 5 cm. the o th e r can n u la ,

r e s u l t i n g v e s i c a l c o n t r a c t i o n c a u s e d e s c a p e o f w a t e r from th e e x t e r n a l m eatus due to r e f l e x r e l a x a t i o n o f th e u r e t h r a . r e f l e x was d e s t r o y e d o n l y b y d i v i s i o n o f t h e p e l v i c s . e c tio n o f the s p in a l cord e f f e c te d its

The

Trans­

th e r e f l e x only through

i n f l u e n c e on t h e b l a d d e r r e f l e x c o n t r a c t i o n s . I t was

shown t h a t i f after

th e b l a d d e r were d i s t e n d e d s u f f i c i e n t l y

tran sectio n ,

I t was,

therefore,

u r e t h r a l d i l a t a t i o n could s t i l l concluded t h a t a f i f t h

take p la c e .

reflex e x ists,

the

r e f l e x c e n t e r b e in g i n th e s p in a l cord w ith the a f f e r e n t p a th

22

i n th e p e l v i c s and th e e f f e r e n t i n th e p u d ic s . B arrin g to n cut in a cat,

(1931) n o te d

th at i f

th e p e l v i c n e r v e s were

i n w hich th e s p i n a l c o r d n e a r th e l e v e l o f th e

l a s t r i b and p u d ic n e rv e s had p r e v i o u s l y been d i v i d e d , r e s u l t e d a n i n c r e a s e i n t h e volume o f r e s i d u a l u r i n e . suggested a n o th e r s p in a l r e f l e x

the s i x t h ,

i n th e p e l v i c s and e f f e c t i n g a r e l a x a t i o n

there T his

having both paths of the u r e th ra or

e f f e c t i n g b l a d d e r c o n t r a c t i o n . A n o t h e r m e t h o d was u s e d t o m easure i n c r e a s e d r e s i s t e n c e was t r a n s e c t e d i n

of the u r e th r a .

the l a s t th o ra c ic

or f i r s t

The s p i n a l c o r d lum bar segm ents

and t h e i n f e r i o r g a n g l i a w ere e x c i s e d u n d e r c h l o r o f o r m and e t h e r . A f te r th re e weeks,

t h e p u d i c n e r v e s were d i v i d e d and

th e p e l v i c s were e x p o s e d .

A c a n n u l a was t i e d

of the b la d d e r .

The c a t was d e c e r e b r a t e d u n d e r c h l o r o f o r m a n d

a f t e r an i n t e r v a l

t h e b l a d d e r was e m p t i e d b y a c a n n u l a a n d

w a t e r was t h e n i n t r o d u c e d . rise

to the fundus

t o e s c a p e was n o t e d .

be a n o t h e r s p i n a l r e f l e x

The minimum p r e s s u r e w h i c h g a v e Th us h e c o n c l u d e d t h a t t h e r e m u s t

th e s ix t h h av in g b o th p ath s in the

p e l v i c s and e f f e c t i n g r e l a x a t i o n

of the u r e t h r a .

I t was

evoked by d i s t e n s i o n of th e b l a d d e r . In i n v e s t i g a t i n g the second r e f l e x i t i n some e x p e r i m e n t s b l a d d e r c o n t r a c t i o n s ru n n in g w ater through the u r e th r a a f t e r been c u t. cuttin g

o ccu rred w hile th e pudic n e rv e s had

I n th o s e c a s e s where c o n t r a c t i o n s

the p u d ics,

co n tractio n s

was n o t i c e d t h a t

stopped a f t e r

could be e l i c i t e d by i n j e c t i n g

23 v/ater r a p i d l y i n t o d iv isio n

the u r e t h r a .

of the p e lv ic n e rv e s .

The r e f l e x was a b o l i s h e d b y While t h i s

seventh r e f l e x

c o u l d be d e s t r o y e d by d i v i s i o n o f b r a n c h e s o f t h e p e l v i c plexus to the u r e t h r a ,

the second co u ld n o t.

flow n e c e s s a r y to e l i c i t

of

t h e s e v e n t h was f o u n d t o b e a g r e a t

d e a l h i g h e r th a n t h a t n e c e s s a r y to e l i c i t

the second. A

summary o f B a r r i n g t o n 1s b r e a k d o w n o f r e f l e x e s m ictu ritio n is

The mean r a t e

involved in

p r e s e n t e d i n T able I .

A n o t h e r m e t h o d o f i n v e s t i g a t i n g m i c t u r i t i o n was i n ­ t r o d u c e d by Denny-Brown and R o b e r t s o n ( 1 9 3 3 ) ,

i n an e x t e n s i v e

s t u d y p e r f o r m e d on human s u b j e c t s . A u n i q u e s y s t e m o f d o u b l e cath eters

was u s e d . A r u b b e r c a t h e t e r was i n s e r t e d

to m easure

u r e t h r a l p r e s s u r e a n d t h r o u g h t h i s was p a s s e d a c a t h e t e r o f sm a lle r o u ts id e d iam eter to re c o rd v e s ic a l p r e s s u r e . m a n ip u la tio n o f the c a t h e t e r s , observed s im u lta n e o u s ly .

various p o rtio n s

By

c o u ld be

The two c a t h e t e r s w e r e c o n n e c t e d t o

two m a n o m e t e r s on w h i c h w e r e m o u n t e d m i r r o r s f o r r e f l e c t i n g a beam o f l i g h t on a p h o t o k y m o g r a p h . T h r e e o t h e r m a n o m e t e r s were u s e d t o r e c o r d s i m u l t a n e o u s l y a b d o m in a l m ovem ents, pressure

in the rectum ,

p resen tin g a p ic tu re

a n d m o v e m e n ts o f t h e p e r i n e u m ,

o f th e a c t u a l b l a d d e r and u r e t h r a l

a c t i v i t y along w ith secondary or supplem entary a c t i v i t y .

CABLE

I

THE COMPONENT REFLEXES OF MICTURITION REFLEX

STIMULUS

EFFEGT C ontraction of d e t r u s o r m uscle

I

D isten sio n of b la d d e r w all

II

Running w a t e r C o n tra c tio n of th ro u g h u r e t h r a d e t r u s o r m uscle

III

D isten sio n of p o ste rio r u reth ra

IV

Running w a te r R elaxation through u r e th ra of u r e th r a

V

B ladder d isten sio n

VI

D isten sio n of bladder

VII

C ontraction of Running w a te r th ro u g h u r e t h r a d e t r u s o r m uscle

C ontraction of d e t r u s o r m uscle

AFFERENT PATH

BARRINGTON EFFERENT PATH

REFLEX CENTER

pelv ics

pelv ics

h in d b ra in

pudics

p elv ics

h in d b rain

h y p o g astrics

h y p o g astrics

cord

pudics

pudics

cord

R elaxation of u reth ra

p elvics

pudics

cord

R elax atio n of u reth ra

p elvics

p elv ics

cord

b ra n c h e s from p e lv ic plexus

cord

b r a n c h e s from p e lv ic plexus

to

CHAPTER I I I EXPERIMENTAL DATA M a te r ia ls and m e th o d s. I n o r d e r to c a n n u la te th e i n ­ t a c t u r in a r y b la d d e r of the r a t ,

and i n o r d e r to r e c o r d v e s i c a l

a c t i v i t y concom itant w ith the in tr o d u c tio n of p e r f u s a te s in to the b la d d e r,

some t y p e o f d e s e u s i t i z a t i o n m u s t b e e m p l o y e d

w hich does n o t i n t e r f e r w i t h n o rm a l m i c t u r i t i o n . E t h e r and nem butal a n e s t h e s i a a r e u n s a t i s f a c t o r y . w ith e th e r ,

In ra ts

an esth etized

t h e r e i s no r e t e n t i o n o f i n j e c t e d p e r f u s a t e , b u t

ra th e r a lo ss

of f lu id

through the u r e t h r a w ith each i n t r o ­

duction of s o lu tio n in to

the b la d d e r , i n d i c a t i n g a r e l a x a t i o n

o f th e b la d d e r s p h i n c t e r . Under deep nem butal a n e s t h e s i a , b ladder p ressu re r is e s little

s t e a d i l y w ith i n c r e a s i n g volum es, w ith

o r no r e l a x a t i o n o f t h e m u s c u l a t u r e .

disten sio n ,

the

T erm inal p a s siv e

w hich n o r m a lly evokes a c t i v e c o n t r a c t i o n s

of the

d e t r u s o r m uscle w ith r e s u l t i n g r e f l e x m i c t u r i t i o n cau ses only a s lig h t lo ss

o f f l u i d when i n t r a v e s i c a l p r e s s u r e i s

enough to p a s s i v e l y f o r c e f l u i d t h u s seems t o d e p r e s s

through the u r e t h r a .

great N em butal

s t r e t c h re s p o n s e s and p r e v e n ts a s u s ta in e d

v e s i c a l c o n t r a c t i o n n e c e s s a r y f o r com plete b l a d d e r em ptying and n o rm a l m i c t u r i t i o n . K olb and Langw orthy (1938) n o te d sim ilar e ffe c ts

i n c a t s . A n o t h e r f a c t o r w h ic h makes t h e use

of nem butal u n d e s ir a b le i s

the v a r i a b i l i t y

of depth of

a n e s t h e s i a . U n le s s means a r e p r o v id e d t o i n s u r e c o n s t a n t d e p t h

26 of an esth esia, im possible,

bladder a c t i v i t y i s

v a r i a b l e , and t h i s makes

the d iscern m en t of v a r i a b i l i t y

of a c t i v i t y in

r e a c t i o n to v a rio u s p e rfu s a te s * As d i s c u s s e d i n t h e p r e v i o u s c h a p t e r ,

B a r r in g to n found

t h a t norm al m i c t u r i t i o n does ta k e p la c e i n d e c e r e b r a te c a ts i n w hich th e f o r e b r a i n h a s b e e n f u n c t i o n a l l y rem oved. S in c e th e p r e s e n t i n v e s t i g a t i o n i s o f t h e pH o f p e r f u s a t e s of m ic tu ritio n ,

an a tte m p t to stu d y th e e f f e c t

on v e s i c a l a c t i v i t y a n d t h e n o r m a l a c t

d e c e r e b r a t i o n o f a n i m a l s w o u l d t h e n se e m t o

be th e i d e a l m ethod o f d e s e n s i t i z a t i o n .

D ecerebration i s

accom plished by d i v id in g th e nervous a x is a t th e l e v e l o f the m id -b r a in . D e s tr u c tio n o f a l l p a r t s a n t e r i o r to the s e c t i o n resu lts,

and body f u n c t i o n th e n re m a in s u n d e r c o n t r o l o f th e

pons, m edulla, served,

c e re b e llu m and s p i n a l c o rd . R e fle x e s a r e p r e ­

so s u c h a p r e p a r a t i o n i s

q u its

s u ita b le f o r a study

of re fle x m ic tu ritio n . D ecerebrate r a t s , d i f f i c u l t to p rep are,

how ever,

and a v e r y low p e r c e n t a g e o f t h e a t t e m p t e d

o p e r a t i o n s were s u c c e s s f u l . resu lts

were found to be q u i t e

The v a r i o u s m e t h o d s a t t e m p t e d a n d

o b ta in e d were as f o llo w s : I.

Under e t h e r a n e s t h e s i a ,

a c a n n u l a was i n s e r t e d a n d t i e d i n .

The s k u l l b o n e s w e r e e x ­

p o s e d by d o r s a l m i d - l i n e s k i n i n c i s i o n . w ere sawed a n t e r i o r t o t h e t r a n s v e r s e a d e n t a l d r i l l were u s e d t o f r e e

t h e t r a c h e a was e x p o s e d a n d

The p a r i e t a l b o n e s

sin u s.

Bone f o r c e p s a n d

th e bone a lo n g t h e l a t e r a l

27 rid g es

o f t h e c r a n i u m . The h e m i s p h e r e s w e r e e x p o s e d a n d c a r e ­

f u l l y scooped o u t.

The c a v i t y was p a c k e d w i t h c o t t o n .

a m o d i f i c a t i o n o f t h e m ethod d e s c r i b e d by L a n d is

T his i s

(1930). A

g r e a t am ount o f h e m o rrh a g e o c c u r r e d from th e bone s i n u s e s a s a r e s u l t o f saw ing. A f t e r the s k u l l had been p e n e t r a t e d , c e s s i v e hem orrhage o c c u rre d i n

th e t r a n s v e r s e and l o n g i t u d i n a l

s i n u s e s . Upon r e m o v a l o f t h e c e r e b r a l h e m i s p h e r e s , sh ow ed s i g n s

ex­

the anim al

o f d i m i n i s h e d r e s p i r a t o r y movements and w i t h i n a

few m in u te s r e s p i r a t i o n s to p p e d c o m p l e t e l y . A p p l i c a t i o n o f a r t i f i c i a l r e s p i r a t i o n d id n o t e f f e c t r e v i v a l of the an im al. T h i s m e t h o d was t r i e d

s e v e r a l tim es w ith o u t s u c c e s s . A p p a r e n tly ,

t h e r e s p i r a t o r y c e n t e r was i m m e d i a t e l y i n j u r e d ,

p o s s i b l y due

t o t r a c t i o n c a u sed by l i f t i n g

out the c e r e b ra l hem ispheres.

Trauma p r o d u c e d by s a w in g t h e

sk u ll,

e x c e s s i v e h e m o r r h a g e may a l s o

have c o n trib u te d

case,

a n d mucus was f o u n d i n t h e

a m ix tu re o f blood c l o t

and s h o c k r e s u l t i n g from

c a n n u la and i n t h i s p a r t i c u l a r i n s t a n c e ,

t o d e a t h . I n one

resp irato ry failu re

may h a v e b e e n d u e t o a n o c c l u d e d a i r p a s s a g e . II.

U n d e r e t h e r a n e s t h e s i a a t r a c h e a l c a n n u l a was i n ­

s e r t e d by expo sin g th e a re a i n exposed by a s k i n i n c i s i o n , a n terio r

the neck r e g io n .

The s k u l l was

t h e p a r i e t a l b o n e s w e r e s aw ed

to th e r e g i o n o f th e t r a n s v e r s e s in u s and th e c e r e b r a l

h e m is p h e r e s were p a r t i a l l y

e x p o s e d . An e t h m o i d c u r e t t e was

p a s s e d do wnw ar d t o t h e f l o o r o f t h e s k u l l a t t h e l e v e l o f t h e p o s t e r i o r r e g i o n o f th e cereb ru m and by m oving t h e i n s t r u m e n t

28 la te ra lly

a c o m p l e t e t r a n s e c t i o n was a c c o m p l i s h e d .

U s in g t h i s m eth o d , 5 d e c e r e b r a t e r a t s were o b t a i n e d w ith a fairly

l o n g s u r v i v a l p e r i o d . N orm al r e s p i r a t o r y movements

w ere m a in ta in e d a f t e r

the t r a n s e c t i o n in th e se 3 c a s e s .

I n one

a n i m a l , 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 15 m i n u t e s a f t e r

tra n s­

ectio n , but i t

A great

was r e v i v e d b y a r t i f i c i a l r e s p i r a t i o n .

amount o f hem orrhage o c c u r r e d w h ile e x p o s in g th e ce re b ru m , b u t t h i s was s t o p p e d b y p a c k i n g w i t h c o t t o n . liv ed 3 hours;

t h e o t h e r r a t was k i l l e d

Two o f t h e s e a n i m a l s 6 hours a f t e r de­

cereb ra tio n . H aving s u c c e s s f u l l y p ro d u ced 3 s u c c e s s i v e d e c e r e b r a t e an im als,

t h e same m e t h o d was a t t e m p t e d on 10 o r m o r e r a t s w i t h

com plete f a i l u r e .

U s i n g a p p a r e n t l y t h e same t e c h n i q u e ,

the b r a i n

was t r a n s e c t e d i n t h e same r e g i o n . A f t e r 15 t o 30 m i n u t e s resp irato ry fa ilu re

o c c u rre d . A ttem pted r e s u s c a t a t i o n u s in g

9 5 $ O2 a n d 5$ COg g a s m i x t u r e was i n a d e q u a t e i n r e v i v i n g t h e a n i m a l . I t was t h o u g h t t h a t p e r h a p s

t h e t r a c h e a l c a n n u l a was

b e i n g o c c l u d e d b y mucus s o s e v e r a l a t t e m p t s w e r e made e l i m i n a t i n g th e use of the can n u la.

I n 1 o r 2 c a s e s t h i s d i d seem t o p r o ­

long the a n im a l!s l i f e ,

b u t o p e r a t i o n s were n o t c o n s i s t e n t l y

su ccessfu l.

P o s t mortem e x a m i n a t i o n d i d n o t r e v e a l any a p p a r e n t

d am age t o t h e m e d u l l a o r p o n s r e g i o n s . number of f a i l u r e s t h a t perhaps

The r e a s o n f o r t h e g r e a t

co u ld n o t be d e te rm in e d .

the g r e a t lo s s

of blood r a t h e r

f a i l u r e was t h e p r i m e r e a s o n .

I t was t h o u g h t than r e s p i r a t o r y

29 III,

To e l i m i n a t e

the hem orrhage f a c t o r ,

was a t t e m p t e d a f t e r i n s e r t i n g a c a n n u l a i n and th e n l i g a t i n g

the c a r o tid a r t e r i e s

d ecereh ratio n

the exposed tra c h e a

(under e th e r a n e s th e s ia ) .

The s k u l l was t h e n e x p o s e d , a n d t h e p a r i e t a l b o n e s w e r e s a w e d im m ediately a n t e r i o r to th e tra n s v e r s e

sin u s.

was t r a n s e c t e d u s i n g a n e t h m o i d c u r e t t e . tran sectio n ,

The m i d - b r a i n

Im m ediately a f t e r

t h e a n i m a l d i e d . T h i s m e t h o d was t r i e d

The r e a s o n f o r d e a t h v/as n o t d e t e r m i n e d .

only once.

P o s s ib ly the excess

traum a p ro d u ced by e x c e s s i v e h a n d l i n g o f th e a n im a l i n th e 3 su ccessiv e step s

o f p r e p a r a t i o n was a n i m p o r t a n t f a c t o r .

IV. U n d er e t h e r a n e s t h e s i a ,

t h e s k u l l was e x p o s e d b y

a m id lin e s k in i n c i s i o n . U sing a d e n t a l b u r r , d rille d in

th e l e f t p a r i e t a l bone a n t e r i o r

s in u s and l a t e r a l to th e

a h o l e was

to the tr a n s v e r s e

l o n g i t u d i n a l s i n u s . H e m o r r h a g e v/as

s l i g h t . A p i t h i n g n e e d l e v/as p a s s e d a t a b o u t a 4 5 ° a n g l e t o the r ig h t- h a n d s id e , lo n g itu d in a l sin u s. the n eed le a c ro s s sertio n .

v e n tr a l to the tr a n s v e r s e

s in u s and

T r a n s e c t i o n was a c c o m p l i s h e d b y d r a w i n g

th e f l o o r of the s k u l l to the p la c e

of in ­

The s l i g h t h e m o r r h a g e t h a t o c c u r r e d was s t o p p e d b y

p a ck in g the sm a ll h o le w ith c o tto n . The f i r s t a n i m a l l i v e d a p p r o x i m a t e l y lj- h o u r s .

The

s e c o n d a n i m a l l i v e d a p p r o x i m a t e l y 1 h o u r . The t h i r d a n i m a l died f hour a f t e r

tran sectio n .

f a i l u r e did n o t occur,

W hile im m e d ia te r e s p i r a t o r y

th e s u r v i v a l tim e of th e s e an im a ls

was n o t a d e q u a t e f o r t h e p u r p o s e s o f e x p e r i m e n t a t i o n ,

sin ce

30 a t l e a s t 3 o r 4 h o u r s was r e q u i r e d recordings.

to accom plish a s e r i e s

P o s t m o r t e m s r e v e a l e d no i n j u r y

of

to th e pons o r

m edulla. Under n em b u tal a n e s t h e s i a , u s in g 0 .1 3 c c . / l 7 0

gm.

body w eight a d m in is te r e d i n t r a p e r i t o n e a l l y , th e p a r i e t a l b o n e s w e r e e x p o s e d a n d d e c e r e b r a t i o n was p e r f o r m e d u s i n g t h e same t e c h n i q u e .

Two r a t s

were d e c e r e b r a t e d u n d e r n em b u tal

a n e s t h e s i a u s in g t h i s m ethod.

The f i r s t r a t h a d b e e n u n d e r

a n e s t h e s i a a p p r o x i m a t e l y 2 ,\ h o u r s d u r i n g w h i c h t i m e a n ad d itio n al

. 0 5 c c . was i n j e c t e d d i r e c t l y i n t o

the p e r i to n e a l

c a v i t y thro u g h the i n c i s i o n used to expose th e u r i n a r y b la d d e r . The r a t l i v e d 3J- h o u r s a f t e r d e c e r e b r a t i o n .

The s e c o n d r a t

h ad b e e n u n d e r a n e s t h e s i a a p p r o x i m a t e l y 2J h o u r s i n w hich tim e

. 0 5 c c . was i n j e c t e d i n

t h e same m a n n e r . T h i s r a t r e ­

m ained l i v i n g 21-24 h o u rs a f t e r d e c e r e b r a t i o n . I n b o th c a s e s , resp irato ry

fa ilu re

occu rred im m ediately a f t e r t r a n s e c t i o n ,

b u t by a p p l i c a t i o n o f a r t i f i c i a l r e s p i r a t i o n ,

the an im als

r e c o v e re d and b r e a th e d n o rm a lly w ith o u t f u r t h e r d i f f i c u l t y . U sing nem butal a n e s t h e s i a ,

2 d ecereb rate p rep aratio n s

were o b t a i n e d h a v in g lo n g s u r v i v a l .

T h i s same m e t h o d o f

d e c e r e b r a t i o n was l a t e r a t t e m p t e d on a n u m b e r o f r a t s .

The

a v e r a g e s u r v i v a l p e r i o d was 35 m i n u t e s f o r t h e f i r s t 3 r a t s . B e lie v in g th e nem butal to have to x ic e f f e c t s , c o n t r o l s were ru n u s in g th e w eight. A ll 3 r a t s

3 u noperated

same d o s a g e , 40 mg/kgm . b o d y

r e c o v e r e d from th e a n e s t h e s i a w i t h no i l l

31 effects.

The f o u r t h d e c e r e b r a t e r a t s u r v i v e d 5 h o u r s a f t e r t h e

o p eration ;

the s u rv iv a l p erio d f o r

the n e x t 3, however,

a v e r a g e d 60 m i n u t e s . S i n c e m u cu s f o r m a t i o n was n o t e d i n m o s t cases,

a t r o p i n e was a d m i n i s t e r e d t o t h e n e x t 2 a n i m a l s i n a n

a tte m p t to e lim in a te r e s p i r a t o r y d i f f i c u l t y d u rin g the c r i t i c a l p e rio d im m ediately fo llo w in g t r a n s e c t i o n .

The a n i m a l s

liv ed

50 m i n u t e s a f t e r d e c e r e b r a t i o n , A f i n a l a t t e m p t was made u s i n g a t r a c h e a l can n u la and e t h e r a n e s t h e s i a .

The a n i m a l d i e d a f t e r

1 hour. O bviously, r e s u l t s

of a l l the d e c e r e b r a tio n p ro ced u res

d e s c r i b e d ab ove were a m a t t e r o f c h a n c e i n w hich no p r e d i c t i o n c o u l d b e mad e i n r e g a r d t o s u r v i v a l p e r i o d . w ere e x tr e m e ly c o s t l y i n sin ce a l l

to taled ,

Such p r o c e d u r e s

tim e a s w e l l as i n e x p e r i m e n t a l a n i m a l s ,

t h e r e was a p p r o x i m a t e l y a n 88% m o r t a l i t y .

Two d i f f e r e n t m e t h o d s w e r e f o u n d i n p r e v io u s ly had n ot been t r i e d .

the l i t e r a t u r e

w hich

W indle and M in ea r (1 9 3 3 ),

d e s c r i b e d an anem ia method o f d e c e r e b r a t i o n i n r a t s i n which th e c a r o t i d and b a s i l a r a r t e r i e s

were l i g a t e d u s i n g a c e r v i c a l

t r a n s - p h a r y n g e a l a p p r o a c h . H o w e v e r , i t was n o t f o u n d n e c e s s a r y to u se t h i s m ethod s i n c e an e x c e l l e n t t e c h n iq u e v e ry r e c e n t l y d e v e lo p e d by A n d e rso n and Haymaker ( 1 9 4 9 ) , p ro v e d v e r y e f f e c t i v e and v e r y s i m p l e w i t h a low p e r c e n t a g e m o r t a l i t y . m o d ificatio n s,

W ith s l i g h t

t h e m e t h o d d e s c r i b e d v/as a s f o l l o w s :

V. H a t s w e r e a n e s t h e t i z e d w i t h n e m b u t a l ;

the dosage,

2 . 5 m g . / 100 gm, b o d y w e i g h t , was a d m i n i s t e r e d i n t r a p e r i t o n e a l l y .

32 P receding the o p e r a tio n ,

.05 c c .

c a l c i u m g l u c o n a t e / 1 0 0 gm.

b o d y w e i g h t was a d m i n i s t e r e d i n t r a m u s c u l a r l y t o f a c i l i t a t e ( t h e c o n c e n t r a t i o n was 1% made u p i n i s o t o n i c

clo ttin g , so lu tio n ).

Im m e d ia te ly b e f o r e m aking th e s k i n i n c i s i o n ,

s c a l p was i n f i l t r a t e d

w i t h a p p r o x i m a t e l y 0 . 4 c c . 2% p r o c a i n e

h y d r o c h lo r id e s o l u t i o n . U sing a d e n t a l b u r r , d rilled

2 h o l e s were

i n th e p a r i e t a l bones im m ed iately a n t e r i o r

tra n s v e rs e sin u s n e a r the l a t e r a l rid g e s u s in g bone f o r c e p s ,

the

to the

o f t h e c r a n i u m . Then

t h e s k u l l was c u t m e d i a l l y f r o m t h e h o l e s

im m ediately a n t e r i o r

to the

transverse sin u s,

a b o u t 4 mm. a l o n g t h e l a t e r a l r i d g e s .

and a n t e r i o r l y ,

The b o n e was l i f t e d a n d

t h e p o s t e r i o r r e g i o n o f t h e c e r e b r u m was t h u s e x p o s e d . S u c t i o n , u s i n g a w a t e r a s p i r a t o r a n d a f i n e p i p e t t e was e m p l o y e d t o remove s m a l l s e c t i o n s

o f th e cerebrum , u n t i l a com plete t r a n s ­

e c t i o n o f t h e m i d - b r a i n was p r o d u c e d ,

and t h e f l o o r o f th e

s k u l l was c o m p l e t e l y c l e a r e d o f a l l b r a i n t i s s u e .

The h o l e

was l o o s e l y p a c k e d w i t h c o t t o n s o a k e d i n c a l c i u m g l u c o n a t e so lu tio n ,

a n d t h e s k i n i n c i s i o n was c l o s e d w i t h 3 o r 4 s u t u r e s .

The a n i m a l s w e r e k e p t i n c u b a t e d u n d e r a l a m p , a t a t e m p e r a t u r e of a p p ro x im a te ly 27° C .,

a n d t h e r e c t a l t e m p e r a t u r e was

m a i n t a i n e d a t a p p r o x i m a t e l y 3 3 ° - 3 4 ° C. I n t h i s m a t t e r , decereb rate

rats

m ictu ritio n

experim ents.

the

were k e p t 8 -2 4 h o u r s u n t i l r e a d y f o r u s e i n

U sing t h i s m ethod,

6 d e c e r e b r a t e a n im a ls were p r e p a r e d .

The s u r v i v a l p e r i o d was 1 1 - 4 5 h o u r s ,

t h e a v e r a g e b e i n g 20 h o u r s .

33 In 2 in stan ces atio n ,

the r a t s

were k i l l e d a f t e r b l a d d e r e x p e r im e n t­

a n d t h e s e w o u l d h a v e no d o u b t l i v e d s e v e r a l h o u r s l o n g e r *

I n none o f th e r a t s d e c e r e b r a te d u s in g t h i s

tech n iq u e d id the

anim al d ie im m ediately a f t e r d e c e re b ra tio n *

In only 1 in s ta n c e

was r e s p i r a t o r y d i f f i c u l t y n o t e d .

The s u r v i v a l p e r i o d a f t e r

d e c e r e b r a t i o n was a d e q u a t e l y l o n g f o r t h e d u r a t i o n o f t h e experim ent i n a l l 6 cases*

The s u p e r i o r i t y o f t h i s m e t h o d

a s compared to p r e v i o u s ones i s facto rs.

probably e x p la in e d by s e v e ra l

I n f i l t r a t i o n w ith a l o c a l a n e s th e tic allow s a

s u f f i c i e n t l y low d o s a g e o f g e n e r a l a n e s t h e s i a form ation in

the r e s p i r a t o r y t r a c t ,

t o p r e v e n t m ucus

and y e t p e r m its a s u f f i c i e n t

d e g r e e o f l o c a l d e s e n s i t i z a t i o n w hich a l l e v i a t e s

s h o c k . Ad­

m i n i s t r a t i o n o f c a l c i u m g l u c o n a t e p r o v i d e s a means o f m in im izin g hem orrhage su b seq u en t to rem oval of th e s k u l l , th u s p r e v e n t i n g sh o c k . Removal o f b r a i n t i s s u e by s u c t i o n a s s u r e s r a p i d and c l e a n re m o v a l o f t i s s u e a l l o w i n g a c l e a r l y v isib le fie ld tran sectio n .

and a c c u r a t e d e t e r m i n a t i o n o f th e r e g i o n o f The w h o l e p r o c e d u r e was s i m p l e a n d d i r e c t ,

q u irin g l i t t l e

apparatus,

and l i t t l e

re­

tim e f o r th e c o m p lete

op eratio n . R e c o r d i n g a p p a r a t u s . ’/ /hen t h e e x p e r i m e n t s w e r e f i r s t b e g u n , a s e t - u p s i m i l a r t o t h a t d e s c r i b e d b y D ’ Amour a n d B l o o d ( 1 S 4 8 ) , was u s e d i n a n a t t e m p t t o r e c o r d i n t r a v e s i c a l pressures.

In th is procedure,

a s in g l e can n u la a tta c h e d to

o n e ar m o f a T - t u b e was i n s e r t e d i n t o

t h e b l a d d e r . F l u i d was

i n t r o d u c e d f r o m a s y r i n g e c o n n e c t e d t o t h e s e c o n d arm o f t h e T - t u b e . The r e m a i n i n g ar m was a t t a c h e d t o t h e r e c o r d i n g t a m ­ bour.

T h i s a r r a n g e m e n t was f o u n d t o b e e n t i r e l y i n a d e q u a t e

fo r sev eral reasons:

1 ) . upon i n j e c t i o n of p e r f u s a t e ,

there

was no i n d i c a t i o n o f t h e a m o u n t w h i c h a c t u a l l y e n t e r e d t h e b l a d d e r 2 ) . h a v i n g no t u b e i n t e r p o s e d b e tw e e n t h e r e c o r d i n g tam bour and th e s y r in g e ,

flu id

soon flow ed d i r e c t l y i n t o

th e tam bour;

3 ) . i t was r a t h e r d i f f i c u l t t o k e e p t h e c o n n e c t i n g t u b i n g fre e of a i r bu bbles. The a p p a r a t u s

f i n a l l y a s s e m b le d f o r e x p e r i m e n t a l work

was a g r e a t l y m o d i f i e d v e r s i o n o f t h e a b o v e a n d t h e a r r a n g e m e n t i s d i a g r a m m a t i c a l l y r e p r e s e n t e d i n F i g u r e 1 . No a t t e m p t was made t o d r a w t h e c o m p o n e n t s i n p r o p o r t i o n a t e s i z e s i n c e d e t a i l o f s m a l l p a r t s was e m p h a s i z e d . The d r a w i n g r e p r e s e n t e d h e r e in clu d es

th e w a te r m anom eter u s e d i n c a l i b r a t i n g

th e system

i n t e r m s o f cm. w a t e r p r e s s u r e . D u r i n g a c t u a l r e c o r d i n g o f i n t r a v e s i c a l p r e s s u r e s , however,

t h e c a n n u l a was i n s e r t e d i n t o

t h e u r i n a r y b l a d d e r a n d t h e m a n o m e t e r was e l i m i n a t e d f r o m t h e set-u p .

P hotographs o f the a p p a r a tu s used i n r e c o r d in g i n t r a ­

v e s i c a l p r e s s u r e a r e shown i n F i g u r e s 2 a n d 3 . Two c o n c e n t r i c derm ic n e e d l e s ,

c a n n u la e were c o n s t r u c t e d from 2 h y p o ­

16 a n d 22 g a u g e .

of la r g e r d iam eter,

The 16 g a u g e n e e d l e ,

t h e one

was c u t a b o u t 4 mm. d i s t a l t o t h e h u b . The

c u t p o r t i o n i n c l u d i n g t h e h u b o f t h e n e e d l e , was t h e n i n s e r t e d a t r i g h t angles

to,

and m id-way b e tw e e n t h e ends o f t h e r e -

35 m aining p o r tio n of the n e e d le ,

so t h a t a T - tu b e c o n f i g u r a t i o n

The 22 g a u g e n e e d l e was i n s e r t e d i n s i d e

resu lted .

the cross

p i e c e o f th e T -tu b e a rra n g e m e n t (th ro u g h th e lo n g a x i s ) and the

jo in ts

were s o l d e r e d a i r - t i g h t .

was d e l i v e r e d th is

The p e r f u s a t e f r o m t h e s y r i n g e

th ro u g h th e i n s i d e c a n n u la to th e b l a d d e r , and

s y ste m c o u ld be opened o r c l o s e d by means o f a 2-way

s to p - c o c k i n t e r p o s e d betw een th e s y r in g e and the hub of th e i n n e r c a n n u l a . The o u t s i d e c a n n u l a a c t e d a s a j a c k e t e n c l o s i n g th e s m a lle r can n u la, w ith the v e r t i c a l Thus,

and form ed a cham ber, a l l

tube and i n t u r n ,

th e r e c o r d i n g tam bour.

th e use of such a double c o n c e n tr ic

sim ultaneous in tro d u c in g of f lu i d

in to

cannulae enabled

the b la d d e r,

cording of re a c tio n a ry v e s ic a l a c t i v i t y ;

A v o lu m e -c a lib ra te d v e r t i c a l tube,

cumbersome t u b i n g .

in serted in to

the

c a n n u l a was i n t r o d u c e d i n t h e

a p p a r a tu s i n an a tte m p t to a s c e r t a i n en terin g

and r e ­

such an arrangem ent

a ls o e lim in a te d the n e c e s s ity of e x c e s siv e ,

hub o f th e o u ts id e c o n c e n tr ic

tim es c o n tin u o u s

t h e b l a d d e r on i n j e c t i o n

t h e volume o f p e r f u s a t e

of f lu id ,

a m o u n t o f f l u i d i n j e c t e d was f o r c e d i n t o

sin ce a c e r ta in

th e v e r t i c a l tube

b y t h e r e a c t i o n a r y i n t r a v e s i c a l p r e s s u r e . K now ing t h e v o lu m e o f p e r f u s a t e i n j e c t e d from t h e s y r i n g e , volume o f f l u i d w hich r o s e i n introduced in to

and knowing th e

the v e r t i c a l tu b e ,

t h e volume

th e b l a d d e r c o u ld be d e te rm in e d .

The a p p a r a t u s was s o c o n s t r u c t e d , and d i s c o n n e c t i o n from th e c a n n u l a e ,

t h a t c o n n e c tio n to

the s y rin g e an^ the

36

Screw clam p

R e c o rd in g tam bour niu'ui.)

Kymograph

.V e rtic a l tube (c a lib ra te d in

.25 c c . )

W ater m anom eter Removable f i t t i n g s Rubber n i p p l e Two-way s t o p - c o c k C o n cen tric cannulae S yringe

FIGURE 1 RECORDING APPARATUS SET-UP FOR CALIBRATION

37

4

_

R ecording tambour

V e r t i c a l tube

. W ater m a n o m e t e r

C oncentric cannulae

FIGURE 2 THE APPARATUS AS SET UP FOR RECORDING INTRAVESICAL PRESSURES IN THE RAT

38

t e r manom eter

o i 3 t chamber oncentric cannulae

FIGURE 3 PHOTOGRAPH SHOWING THE CONCENTRIC CANNULAE INSERTED INTO THE URINARY BLADDER

39 v e r t i c a l c o l u m n was s i m p l e a n d q u i c k . A t f i r s t these

j u n c t i o n s o c c u r r e d when p r e s s u r e i n

f a i r l y h ig h , how ever,

leakage a t

th e system ro se

i t was l a t e r f o u n d t h a t a p p l i c a t i o n o f

a s m a ll amount o f s to p - c o c k g r e a s e aro u n d th e f i t t i n g s

was

a s i m p l e a n d q u i c k m e a n s o f a s s u r i n g a l e a k p r o o f s y s t e m . The v e r t i c a l c o l u m n was e a s i l y f l u s h e d by m e a n s o f o p e n i n g t h e clam ped r u b b e r t u b i n g a t th e

to p o f th e colum n.

In th e r e c o r d i n g a p p a r a t u s u s e d by B a r r in g to n in h is

stu d ies in c a ts ,

by Lew is,

and i n th e r e c o r d in g a p p a r a tu s u se d

L a n g w o rth y , and Dees

f o r m e d on human s u b j e c t s , u reth ra in to flu id

(1914),

(1935), i n ex p erim en ts p e r ­

a c a t h e t e r was p a s s e d t h r o u g h t h e

t h e b l a d d e r a n d t h e b l a d d e r was d i s t e n d e d w i t h

from a r e s e r v o i r . A v e r t i c a l

tube i n t e r p o s e d betw een

t h e r e s e r v o i r a n d t h e c a t h e t e r was u s e d a s a w a t e r m a n o m e t e r . No a c c o u n t was made o f t h e v o l u m e o f f l u i d i n

the v e r t i c a l

tu b e i n o r d e r t o d e te r m in e th e a c t u a l volume o f t h e b l a d d e r co n ten ts.

Perhaps i n l a r g e r a n im a ls,

th is

a m o u n t was com­

p a r a t i v e l y n e g l i g i b l e . However, i n t h e r a t i n w hich in c r e m e n ts were o n ly

.2 c c . ,

v o lu m e i n

th e v e r t i c a l colum n.

It

i s noted

it

w o u l d seem i m p o r t a n t t o a c c o u n t f o r

th at in

( 1 9 1 4 ) , and by Lewis e t a l

th e m ethods d e s c r i b e d by B a r r i n g t o n (1935),

the i n t r a v e s i c a l p r e s s u re s

w ere r e a d d i r e c t l y from th e v e r t i c a l colum n. I n t h e p r e s e n t i n v e s t i g a t i o n , however,

t h e s y s t e m was c a l i b r a t e d i n t e r m s

o f w a t e r p r e s s u r e u s i n g t h e s e t - u p shown i n F i g u r e 1 . W a t e r

40 was i n t r o d u c e d i n t o

t h e w a t e r m anom eter from t h e s y r i n g e ,

way o f t h e c a n n u l a e

j o i n e d by a r u b b e r n i p p l e

to the h o r iz o n ta l

ar m o f t h e m a n o m e t e r . A t 5 cm. w a t e r p r e s s u r e i n t e r v a l s , i n d i c a t e d by th e m anom eter r e a d i n g s ,

by

as

the c o rre sp o n d in g r i s e

o f t h e . w r i t i n g ar m o f t h e t a m b o u r was r e c o r d e d k y m o g r a p h i c a l l y . The c a l i b r a t i o n c u r v e was p l o t t e d , rise

i n mm. o f t h e w r i t i n g a r m ,

the o r d in a te r e p r e s e n t i n g

t h e a b s c i s s a r e p r e s e n t i n g cm.

w ater p r e s s u r e . A t y p i c a l c a l i b r a t i o n curve i s 4.

show n i n F i g u r e

The kymogram r e c o r d s o b t a i n e d i n r e c o r d i n g i n t r a v e s i c a l

p r e s s u r e s were m easu red and th e h e i g h t s c o r d in g s were i n t e r p r e t e d i n

term s

t h e c a l i b r a t i o n c u r v e . With t h i s

i n mm. o f t h e r e ­

o f cm. w a t e r p r e s s u r e u s i n g

arrangem ent, a given p re s s u re

i n th e w a t e r m anom eter r e p r e s e n t e d

the a c t u a l b la d d e r p r e s s u r e

c o r r e c t e d f o r h y d r o s t a t i c p r e s s u r e o f th e v e r t i c a l colum n. A reading in pressure,

th e w a te r m anom eter,

f o r e x a m p l e 5 cm. w a t e r

r e p r e s e n t e d a p p r o x i m a t e l y 2 5 - 3 0 cm. w a t e r i n t h e

v e r t i c a l colum n,

thus i n c o r r e c t l y r e p r e s e n t i n g b la d d e r p r e s s u r e .

R ecording p ro c e d u re . A f te r d e c e r e b r a tin g the an im al,

a

minimum o f 1 h o u r was a l l o w e d f o r r e c o v e r y f r o m a n e s t h e s i a b e f o re p e r f u s in g the b la d d e r and r e c o r d in g th e r e a c t i o n a r y b ladder a c tiv ity .

The d e c e r e b r a t e r a t was f a s t e n e d s e c u r e l y

to th e anim al b o ard , m id-line in c is io n ,

a n d t h r o u g h a lov; v e n t r a l a b d o m i n a l

a p p r o x i m a t e l y 2 cm. i n l e n g t h ,

the u r in a r y

b l a d d e r was e x p o s e d . A s m a l l s n i p was made i n t h e b l a d d e r w all,

on t h e d o r s a l s i d e n e a r t h e a p e x .

The c o n c e n t r i c

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42 c a n n u la e were i n s e r t e d and u s i n g a s m a l l c u r v e d c u t t i n g - n e e d l e , s e v e r a l s m a l l s t i t c h e s were p a s s e d a ro u n d th e b l a d d e r i n c i s i o n and th e

t h r e a d en d s were t i e d a r o u n d t h e c a n n u l a e . With t h e

cannulae i n p la c e ,

1 sin g le

bladder in c is io n ,

to the c a n n u la e ,

enough o f t h e b l a d d e r t i s s u e system .

in jectio n ,

ju st

o f t h e v e r t i c a l tu b e were

th e r e s p e c t i v e hubs of th e c a n n u la e . At 2

m inute i n t e r v a l s , the b la d d e r .

w ith care to in c lu d e

to a s su re a com pletely le a k -p ro o f

The s y r i n g e a n d t h e t i p

in serted in to

w ritin g

t h r e a d was t h e n t i e d a r o u n d t h e

0 . 2 c c . p e r f u s a t e was s l o w l y i n j e c t e d i n t o

The s t o p - c o c k b e i n g c l o s e d i m m e d i a t e l y a f t e r

b l a d d e r p r e s s u r e s w e r e r e c o r d e d by m e a n s o f t h e

t a m b o u r o n a k y m o g r a p h drum r e v o l v i n g a t t h e r a t e

o f 8 m m . / s e c o n d . The v o l u m e i n t h e v e r t i c a l c o l u m n was r e a d 1 m inute a f t e r i n j e c t i o n of f l u i d i n t o first

series

of experim ents,

and i n

the b la d d e r i n th e

th e rem ain in g e x p e rim e n ts,

r e a d i n g s were ta k e n im m e d ia te ly a f t e r i n j e c t i o n as w e l l a s 1 m inute a f t e r i n j e c t i o n . At f i r s t ,

th e exposed b l a d d e r and s u rro u n d in g t i s s u e s

w ere k e p t m o i s t e n e d by s a l i n e - s o a k e d c o t t o n c o v e r i n g t h e a r e a * This o f c o u rs e o b sc u re d th e b l a d d e r so t h a t o b s e r v a t i o n of i t s sta te

o f d i s t e n s i o n o r c o n t r a c t i o n was i m p o s s i b l e . L a t e r ,

sm all m oist-cham ber

(made b y c u t t i n g t h e r o u n d e d - e n d o f a

tra n sp aren t p la s tic

test-tu b e)

a

was u s e d w h i c h was e f f e c t i v e

i n p re v e n tin g d ry in g out of the b la d d e r t i s s u e , p erm itted o b serv atio n of blad d er a c tiv ity *

and s t i l l

43 In the f i r s t

series

of experim ents, u sin g 4 r a t s ,

(T a b le s I II-X V I) 3 s o l u t i o n s were i n j e c t e d i n t o f o r com parison of b la d d e r a c t i v i t y : n pH 5 . 2 ; S o r e n s e n Ts b u f f e r m i x t u r e s , In the second s e r i e s

iso to n ic

the b la d d e r

salin e

0.85$,

pH 1 . 0 5 a n d pH 3 . 3 2 .

of ex p e rim e n ts, u s in g 3 r a t s ,

( T a b l e s X V I I - X X V I I ) , i s o t o n i c s a l i n e , 0 . 8 5 $ , pH 5 . 2 , a n d !! S o r e n s e n Ts b u f f e r m i x t u r e s , pH 4 . 5 2 , pH 8 . 4 , a n d pH 9 . 1 w e r e used in a com parative stu d y of b la d d e r a c t i v i t y . In the p re v io u s e x p e rim e n ts, w ith s a lin e ,

t h e b l a d d e r was p e r f u s e d

is o s m o t i c w ith th e serum ;

the b u f f e r m ix tu re

p e r f u s a t e s used were e i t h e r h y p e ro s m o tic o r hyp o o sm o tic w ith th e serum . I n o r d e r to d e te rm in e w h eth er v a r i a t i o n i n b la d d e r a c t i v i t y u s i n g d i f f e r e n t b u f f e r s o l u t i o n s was d u e p r i m a r i l y t o d i f f e r e n c e s i n pH o r t o d i f f e r e n c e s i n o s m o t i c p r e s s u r e s of the s o lu t io n s ,

the l a s t exp erim en t, u s in g 1 r a t

XXVTII-XXX), was r u n t o c o m p a r e t h e e f f e c t s b u ffer so lu tio n , so lu tio n ,

of p e r fu s io n w ith

pH 5 . 8 8 a n d i s o s m o l a r s a l i n e ,

pH 9 . 1 a n d i s o s m o l a r s a l i n e ,

pH 2 . 1 8 a n d i s o s m o l a r s a l i n e ,

(T ables

pH 5 . 1 ; b u f f e r

pH 5 . 3 ; b u f f e r s o l u t i o n ,

pH 5 . 1 . A Beckman pH m e t e r was

u s e d t o d e t e r m i n e t h e pH o f t h e s a l i n e

so lu tio n s.

The b u f f e r s o l u t i o n s w e r e p r e p a r e d f r o m t h e f o l l o w i n g m a te ria ls in

t h e a m o u n t s shown i n T a b l e I I .

a) M ix tu re 7 .5 0 5 g.

G ly c in e ; 5 .8 5 g. N aC l/ l i t e r

b ) E x a c t l y 0 . 1 N HG1 s o l u t i o n c ) E x a c t l y 0 . 1 N HaOH s o l u t i o n

44

TABLE I I 11

SOREKSEN' S BUFFER MIXTURES

pH

G lycine/N aC I m ixture cc.

2.18

240

5.88

400

9 .1

320

NaOH cc.

HG1 cc.

160

80

R atio Iso sm o lar conc. o s m o l a r c o n c . KaGl g m . / 4 0 0 c c . b u f f e r and iso to n ic salin e b u ffer/salin e

0.906

3.08

1.04

3.536

____

0.96

3.264

1.05

40

360

0.37

3.52

360

40

0.66

4.52

396

4

0.68

8.4

380

20

0.67

45 The r a t i o

o f th e osm olar c o n c e n tr a tio n o f the b u f f e r m ix tu re

and th e osm olar c o n c e n t r a t i o n o f th e i s o t o n i c is

in d icated in

the ta b le .

NaCl i n g . / 4 0 0 c c . i s th ird

salin e

so lu tio n

The i s o s m o l a r c o n c e n t r a t i o n o f

in d ic a te d f o r the s o lu tio n s i n

the

experim ent. The c o n c e n t r a t i o n o f NaCl i n g . / 4 0 0 c c . ,

isosm o tic

w i t h t h e b u f f e r m i x t u r e was d e t e r m i n e d b y c a l c u l a t i n g t h e number o f m oles o f o s m o t i c a l l y a c t i v e p a r t i c l e s

present in

400 c c . b u f f e r s o l u t i o n .

for buffer

s o l u t i o n pH 2 . 1 8 , 1.

A sample c a l c u l a t i o n ,

was a s f o l l o w s :

Grams o f E a c h C o n s t i t u e n t / 400 c c . S o l u t i o n = ( c c . x g r a m s ) 1000

G lycine

240 x 7 .5 0 5 g.

- 1.801 g ./2 4 0 c c .

1006

2.

NaCl

240 x 5 . 8 5 g. 1000

= 1.404 g ./2 4 0 c c .

HC1

160 x 3 . 6 4 6 g . 1000

= 0.584 g . / l 6 0 c c .

O sm olar C o n c e n t r a t i o n s grams x number o s m o t i c a l l y M o le c u la r w t. activ e p a rtic le s produced by 1 m o lecu le B uffer M ix tu re: G lycine

1.801 = 0.0239 x 1 = 0.0239 75.05

NaCl

1.404 = 0.0241 58.45

x 2 = 0.0482

HC1

0.584 = 0.0 1 6 3-6747

x 2 = 0,032 0 .1 0 4 1 T o t a l number o f m oles of so m o tically a c tiv e p a r tic le s /4 0 0 cc.

46 Iso to n ic

S aline:

8 .5 g ./l* $$745 3.

=

•1436 x 400 x 2 = 0 .1 1 4 8 8 100$

S a l i n e I s o s m o t i c W ith B u f f e r S o l u t i o n = o s m o la r c o n c . b u f f e r x ( g . NaCl / osm olar conc. s a l i n e 0.1041 - 0.906 x 3 .4 g ./4 0 0 c c . 0.11488

400 c c . )

- 3.08 g ./4 0 0 c c .

P r e s e n t a t i o n o f e x p e r i m e n t a l d a t a . D ata from th e s e r i e s of experim ents u sin g 8 r a t s and g r a p h s . I n 7 r a t s ,

appear in the fo llo w in g ta b le s

several tr ia ls

were r u n and b la d d e r

p r e s s u r e s w e r e r e c o r d e d u s i n g t h e same r a t i n o r d e r t o compare th e r e a c t i o n s

of a s in g le b la d d e r to v a rio u s p e r f u s a te s .

D ata from e a c h t r i a l a p p e a r i n t a b l e s i n the t r i a l s

were r u n .

th e o r d e r i n w hich

The kymogr ams o b t a i n e d d u r i n g e a c h p e r ­

f u s i o n o f th e b l a d d e r were m e a su re d ,

and th e h e i g h t o f th e

t r a c i n g s were i n t e r p r e t e d i n term s of v e s i c a l p r e s s u r e i n cm. w a t e r , u s i n g t h e c a l i b r a t i o n c u r v e . A t y p i c a l kymogram record i s

shown i n F i g u r e 5 . From e a c h r e c o r d ,

the i n i t i a l

p r e s s u r e i n cm. w a t e r r e s u l t i n g u p o n c o m p l e t i o n o f e a c h i n ­ je c tio n of p e r fu s a te , th e end o f 2 m in u te s in jectio n ), tab les.

and th e f i n a l p r e s s u r e ,

resu ltin g a t

(im m ediately p re c e d in g the fo llo w in g

w ere d e te r m in e d and c o m p ile d i n t h e r e s p e c t i v e

To f a c i l i t a t e

a n a ly z in g and com paring o f r e s u l t s ,

t h e s e v a l u e s were th e n p l o t t e d

g rap h ically ,

the o rd in a te

r e p r e s e n t i n g v e s i c a l p r e s s u r e s i n t e r m s o f cm. w a t e r ,

the

a b s c i s s a r e p r e s e n t i n g volume o f p e r f u s a t e i n t r o d u c e d i n t o t h e s y s te m . I n i t i a l and f i n a l p r e s s u r e s were p l o t t e d a s illu stra te d

in

the f o llo w in g diagram .

48 Where a d r o p i n p r e s s u r e i s of flu id

shown, w i t h no i n d i c a t i o n o f l o s s

from th e b l a d d e r th r o u g h th e u r e t h r a ,

the b la d d e r o ccu rred .

ad ap tatio n of

"D h i n d i c a t e s d r i b b l i n g o c c u r r e d ,

"M .R." i n d i c a t e s m i c t u r i t i o n r e f l e x . Where p o s s i b l e ,

t h e v o lu m e o f f l u i d e l i m i n a t e d

through

t h e u r e t h r a was d e t e r m i n e d a n d i n c l u d e d i n t h e t a b l e s . H o w e v e r , i n some i n s t a n c e s when t h e h i g h f r e q u e n c y o f d r i b b l i n g a n d t h e h y p e r a c t i v i t y o f t h e a n i m a l made c o l l e c t i o n d i f f i c u l t , i t was m e r e l y i n d i c a t e d

t h a t l o s s o f f l u i d h a d o c c u r r e d . Two

term s h av e been u se d to i n d i c a t e l o s s u reth ra:

of f lu id

"dribble"and r e f le x m ic tu r itio n .

was u s e d t o i n d i c a t e

through th e

R eflex m ic tu r itio n

e m p ty in g o f t h e b l a d d e r i n c a s e s when,

as i n R at # 1, a s u s t a i n e d c o n t r a c t i o n r e s u l t e d i n a lo n g e l i m i n a t i o n p e r i o d i n w hich th e b l a d d e r p r e s s u r e d ro p p e d a t t h e c o m p l e t i o n o f t h e a c t t o a low a p p r o x i m a t i n g t h e i n i t i a l p r e s s u r e . W hereas, flu id

in o ther cases,

where f r e q u e n t l o s s

of

o c c u r r e d from t h e u r e t h r a i n am ounts o f 1 o r 2 d r o p s ,

d u ra tio n being very s h o rt, stream in g of f l u i d

and where no a p p a r e n t f o r c e f u l

from t h e u r e t h r a o c c u r r e d ,

th e term

" d r i b b l e " was a p p l i e d . The r e s u l t s

o b t a i n e d from a l l

the ex p erim en tal r a t s

w e r e a n a l y z e d a n d c o n s o l i d a t e d a n d a p p e a r i n T a b l e XXXI, page 93.

FIGURE 5 PHOTOGRAPH OF AN ORIGINAL KYMOGRAM SHOWING REACTIONARY VESICAL ACTIVITY I I RESPONSE TO VARIOUS PERFUSATES IN DECEREBRATE RAT # 8

50 TABLE I I I RAT # 1 --DECEREBRATE, ANALYSIS OP KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING SALINE PERFUSATE

F luid in jected cc •

0 .2

Volume i n v e r t i c a l tube cc •

F luid re le a se d from b l a d d e r through u r e t h r a

*-

3C* *5c

H t . i n mm. recorded in itial fin a l

Pressure cm. w a t e r in itia l fin a l

2.0

2 .0

2 .5

2 .5

0.4

2.9

2 .5

4.0

3.0

0 .6

3.7

3.0

5.5

4.0

0.8

4.0

3.4

6 .0

5.0

1.0

5.0

4 .5

7.5

6.5

1 .2

5.8

5.2

8 .5

7 .7

1 .4

6 .0

6.5

9.0

9.8

1.6

8 .0

7.0

12.7

11.0

1 .8

8 .6

7.5

14.0

12.0

2.0

12.0

10.0

22.0

17.0

2.2

12.6

11.0

18.5

19.5

2.0

22.5

2.5

2.3

R eflex m ictu ritio n

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52 TABLE IV RAT # 2 - -DECEREBRATE, ANALYSIS OF KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING SALINE PERFUSATE

Fluid in jected cc •

Volume i n v e r t i c a l tube cc.

0 .2



0.4

F luid re le a se d from b l a d d e r through u r e th ra cc.

H t . i n mm. recorded in itial fin a l

P ressure cm. w a t e r in itial fin a l

0

1 .5

1.5

1 .5

1.5

0.12

0

3 .0

3.0

4 .0

4 .0

0.6

0.24

0

5.0

5.0

7 .5

7.5

0.8

0.4 0

0.2

7.0

7 .0

11.0

11.0

1.0

0.52

0

8.0

8 .0

12.6

12.6

1.2

0.58

0

9 .5

8 .0

16.0

12.6

1.4

0.58

0.2

9.6

8 .5

16.2

13.5

1.6

0.42

0

10.0

10.0

17.0

17.0

1.8

0.65

0.3

11.6

9.0

21.0

15.0

2.0

0.63

0

10.0

9.0

17.0

15.0

2.2

0.52

0

11.0

11.0

19.5

19.5

2.4

0.52

0.3

12.0

8 .9

22.0

14.5

2.6

0.63

0.2

10.0

9.0

17.0

15.0

2.8

0.77

11.0

10.0

19.5

17.0

3.0

0.48

12.0

9.5

22.0

16.0

3.2

0.65

11.0

9.0

19.5

15.0

3.4

0.50

10.0

5.5

17.0

8 .0

Loss of f l u i d

Tv0 .5 ?*»• 0 .3

thro u g h u r e t h r a ;

volum e e l i m i n a t e d unknown.

TABLE V RAT # 2 --DECEREBRATE, ANALYSIS OP KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING SALINE PERFUSATE

F luid in jected cc.

Volume i n v e r t i c a l tube cc •

F luid re le a se d from b l a d d e r through u r e th r a cc •

H t . i n mm, recorded in itial fin a l

Pressure cm, w a t e r in itial fin a l

0.2



0

3.5

3 .5

5.0

5.0

0.4

0 .5

0

6.0

6.0

9.0

9.0

0 .6

0 .7

0

9.0

9 .0

15.0

15.0

o

00 •

0.83

0

10.5

10.5

18.0

18.0

1.0

1.05

0

13.0

12.6

25.0

21.8

1.2

1.2

0

15.0

14.1

3 0.0

27.5

1.4

1.2

0

16.0

14.0

33.0

27.5

1.6

1.03

13.0

12.0

25.0

22.0

1.8

0.85

0.2

14.0

10.0

27.5

17.0

2.0

0.83

0

13.0

10.0

25.0

17.0

2.2

0.98

0

12.0

12.0

22.0

22.0

2.4

0.90

0.2

13.0

11.0

25.0

19.5

2.6

0.91

0,4

12.0

9.5

22.0

16.0

2 .8

0.93

0

12.0

11.8

22.0

21.6

3 .0

0.95

0

13.5

11.5

26.5

21.0

3 .2

0 .7

0.4

13.0

9.0

25.0

15.0

3 .4

0.5

0

10.0

6.5

17.0

9.8

3.6

0.6 5

0

9.3

8.5

15.5

13.5

to

CO



0.80

0

10.0

9.0

17.0

15.0

4 .0

0.78

0.4

12.0

8.0

22.0

■"* L o s s o f f l u i d

through u r e t h r a ;

volume e l i m i n a t e d unknown.

12. J

Iu

a .* /

O' *

). i*

/. C

H o . & 2 .D 1 T , U n i v e r s i t y B a n ic s r o R E , L c ;s a n r e l e s

55

TABLE VT RAT #2—DECEREBRATE, ANALYSIS OP KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING PERFUSATE, pH 1.05

F luid in jected cc •

Volume i n v e r t i c a l tube cc.

0.2

F luid re le a se d from b l a d d e r through u r e th r a

H t . i n mm. recorded in itial fin a l

Pressure cm. w a t e r in itial fin a l

0

3 .5

3 .0

5.0

4.0

0.4

0.36

0

6.0

4.7

9.0

7.0

0 .6

0.45

0

7.0

5.0

11.0

7.5

0.8

0.24

0

6.0

2.0

9.0

2.5

1.0

0.24

0

5.0

3.5

7.5

5.0

1.2

0.24

0

5.5

3.3

8.0

4.8

1.4

0.32

0

5.0

4.7

7.5

7 .0

1.6

0 .55

0

7.6

7 .6

12.0

12.0

1.8

0.73

0

10.0

10.0

17.0

17.0

2.0

0.53

0

13.0

4.8

25.0

2.2

0.50

0

7.2

7 .0

11.0

10.0

2.4

0.45

0

8.3

6.3

13.5

9.5

2 .6

0.24

0

8.0

3.0

12.5

4.0

2.8

0.32

0

5.0

5.0

7.5

7.5

3.0

0.24

0

6 .5

1.0

10.0

0 .5

3.2

0.24

0

3.5

2.0

5.0

2.5

** S l i g h t l e a k a g e o c c u r r e d a t t h e and th e c a n n u la .

ju n c tio n of th e v e r t i c a l tube

7.0**

56

TABLE VII RAT # 2 - -DECEREBRATE, ANALYSIS OP KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING SALINE PERFUSATE

F luid in jected cc.

0.2

Volume i n v e r t i c a l tube cc.



0.4

F luid re le a se d from b l a d d e r through u r e th r a cc.

H t . i n mm. recorded in itia l fin a l

P ressure cm. w a t e r in itia l fin a l

0

2 .5

2.5

3.0

3.0

0

4.0

4.0

6.0

6.0

0.6

0.42

0

5.5

5.5

8.0

8 .0

0 .8

0 .55

0

7.2

7.2

11.3

11.3

1.0

0.70

0

9 .5

9.0

16.0

15.0

1.2

0.67

0

10.5

9.0

18.0

15.0

1.4

0.73

0

10.0

9.5

17.0

16.0

1 .6

0.73

?-*

11.0

9.0

19.5

15.0

H

CO



0.80

0

11.0

10.5

19.5

18.0

2.0

0 .45

0 .4

11.5

9.0

21.0

15.0

2.2

0.58

0

11.0

10.5

19.5

18.0

2 .4

0.70

0

12.0

8.0

22.0

12.5

2.6

0.65

0.4

10.0

7 .5

17.0

12.0

2.8

0.72

0

10.0

10.0

17.0

17.0

3.0

0.83

0

12.0

11.0

22.0

19.5

3.2

0.90

0

12.0

11.5

22.0

21.0

3.4

0.83

0 .2

14.0

10.0

27.5

17.0

3 .6

0.83

?*-

19.0

8.0

27.5

12.5

3.8

0.70

0

9.0

9.0

15.0

15.0

4.0

0.85

0

11.0

11.0

19.5

19.5

4.2

1.03

0

14.0

11.0

27.5

19.5

# Loss o f f l u i d

through u r e th r a ;

v o lu m e e l i m i n a t e d u n k n o w n .

No. 6201-T, U niversity Bookstore, Los A ngeles

58

TABLE VIII

RAT #3—NEMBUTAL ANESTHESIA. ANALYSIS OP KYMOGRAM SHOEING RESULTANT VESICAL PRESSURES USING SALINE PERFUSATE

F luid in jected cc.

Volume i n v e r t i c a l tube cc.

0 .2

F luid released f ro m b l a d d e r through u r e th r a cc.

H t . i n mm. recorded in itia l fin a l

Pressure cm. w a t e r in itial fin a l

0

1.3

1.3

1.0

1 .0

0.4

0.28

0

4.0

4.0

6.0

6.0

0.6

0.48

0

5.6

5.6

8.3

8.3

0 .8

0.55

0

6.8

6.0

10.5

9.0

1.0

0.60

0

7 .9

7.0

12.5

11.0

1.2

0.70

0

9.2

8.0

15.3

12.5

1.4

0.70

?*

11.0

8 .0

19.5

12.5

1.6

0.78

0

10.0

8.0

17.0

12.5

1.8

0.68

?*

11.2

8.0

20.1

12.5

2.0

0.65

0.4

11.2

7 .9

20.1

12.5

2.2

0.70

0

10.3

8 .2

17.6

13.0

2.4

0.65

0

11.0

8.0

19.5

12.5

2.6

*•*

0.3

8.5

4.0

13.5

6.0**

2.8

0.54

0

7.0

6.0

11.0

9.0

3.0

—'■

0

9.0

6.0

15.0

9.0**

* Loss o f f l u i d

through u r e t h r a ;

v o lu m e e l i m i n a t e d u n k n o w n .

** L e ak ag e o c c u r r e d a t t h e v e r t i c a l tu b e c a n n u l a j u n c t i o n .

TABLE IX

59

RAT #3—NEMBUTAL ANESTHESIA, ANALYSIS OP KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING PERFUSATE, pH 3 .3

F luid in jected cc •

Volume i n v e r t i c a l tube cc.

0.2

F luid re le a se d from b l a d d e r through u r e th r a cc.

H t . i n mm. recorded in itial fin a l

Pressure cm. w a t e r in itial fin a l

0

2 .7

2.7

3.5

3 .5

0.4

0 .20

0

5.0

4.2

7.5

6.0

0.6

0.48

0

6.2

6.0

9.3

9.0

0.8

0.78

0

9.0

7.0

15.0

11.0

1.0

0.60

0

10.0

7.0

17.0

11.0

1.2

0.73

0

10.0

8.3

17.0

13.5**

1.4

0.70

?*

12.1

5.5

22.5

1.6

0.65

0

8 .7

7.7

14.0

12.0***

1.8

0.70

0

9.0

7.0

15.0

11.0

2.0

0.78

0

10.0

9.0

17.0

15.0

2.2

0.90

0.4

11.6

6.0

21.0

9 .0

2.4

0.50

0

6.3

6.3

9.5

9.0

2.6

0.58

0

7.2

6.9

11.0

10.5

2.8

0.60

0

8.2

6.9

13.0

10.5

3.0

0.58

0

8.2

7.0

13.0

11.0

3.2

0.60

0

8 .5

7.0

13.5

11.0

3 .4

0 .6 0

0

8 .2

7.0

13.0

11.0

3.6

0.63

0

8.2

7.0

13.0

11.0

3.8

0.60

0

8.0

7 .0

12.5

11.0

4 .0

0.60

0

8 .2

3.0

13.0

4 .0

* L o s s o f f l u i d t h r o u g h u r e t h r a ; v o l u m e e l i m i n a t e d u nknow n *-*• A n i m a l u n d e r v e r y l i g h t a n e s t h e s i a *** I n j e c t i o n o f 0 . 0 5 c c . n e m b u ta l

8.0

■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■! itIf*If,ItarfHf lf «iil^UlOlii{lt^Uair;i

n jacted 0.1



I-a-

1,1c

No. 6201-T, U niversity Bookstore, Los A ngeles

61

TABLE X RAT #3 —DECEREBRATE, ANALYSIS OP KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING SALINE PERFUSATE

F luid in jected cc.

Volume i n v e r t i c a l tube cc.

F luid re le a se d .from b l a d d e r through u r e th r a cc •

H t . i n mm* recorded in itial fin a l

P ressure cm* w a t e r in itia l fin a l

0.2

_

0

3.0

2 .5

4 .0

3.0

0.4

0.20

0

4.5

4.0

6.5

4 .5

0 .6

0.48

0

6.0

5.4

9.0

8 .0

0.8

0.58

0

8.0

7.0

12.5

11.0

1.0

0 .6 5

0

9.2

8 .0

15.5

12.5

1.2

0.75

?*

10.2

8 .0

17.5

12.5

1.4

0.60

?-*

10.0

7.5

17.0

12.0

1.6

0.60

0

10.0

7.8

17.0

12.3

1.8

0.55

0

9.8

6.5

16.5

9.8

2.0

0.55

0

8.2

8 .0

13.0

12.5

2.2

0.53

0

9.0

6.6

15.0

10.0

2.4

0 .4 5

0

9.0

6.2

15.0

9.3

2 .6

0.53

0

8.5

7.0

13.5

11.0

* Loss o f f l u i d

through u r e t h r a ;

volume e l i m i n a t e d unknown.

TABLE XI RAT #3 —DECEREBRATE, ANALYSIS OP KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING PERFUSATE, pH 3 .3

F luid in jected cc •

Volume i n v e r t i c a l tube cc .

Fluid re le a se d from b l a d d e r th ro u g h u r e t h r a cc.

*0.4

H t . i n mm. recorded in itia l fin a l

P ressure cm. w a t o r in itia l fin a l

0

2.0

2 .0

2 .5

2 .5

0.6

0.4-5

0

3 .4

3.0

5.0

4 .0

0 .8

0.58

0

5 .0

5.0

7.5

7.5

1.0

0.73

0

7 .0

4 .0

11.0

6 .0

1.2

0 .55

0

6.9

4 .0

10.5

6.0

1.4

0.48

0

7 .0

3 .3

11.0

4.9

1 .6

0.58

0

5.0

4.0

7.5

6.0

1.8

0.60

0

5.7

3 .0

8 .5

4 .0

2 .0

0 .4 5

?**

6.0

3.0

9.0

4.0

2 .2

0.50

0

4.3

3 .0

6.5

4 .0

2 .4

0.53

0

4 .3

3 .0

6 .5

4 .0

2.6

0.55

0

5.0

3 .7

7 .5

5.5***

2.8

0 .55

0

5 .0

3 ,5

7 .5

5.0

3.0

0,45

0

6 .0

6.0

9.0

9 .0

* R ecording began a t ** Loss o f f l u i d

.4 c c .

through u r e t h r a ;

volum e e l i m i n a t e d unknown,

*•** L e a k a g e a r o u n d t h e c a n n u l a a t t h e p l a c e o f i n s e r t i o n i n t h e b l a d d e r .

curv